I was a resident, on morning rounds. The attending neurologist was young and ambitious (weren’t we all once?), trying to get the hospital to help him fund a research program in his subspecialty of interest.

One of the patients we saw that morning was a locally known successful businessman who’d been admitted, fortunately not for anything too serious.

Pretty standard up to that point.

After answering questions, however, the attending suddenly went into a sales pitch on his new research program, asking the guy for a financial donation, and giving him the card for the person at his office handling the funding.

I don’t remember anymore if he repeated that with other patients, but even now it still leaves a bad taste in my mouth. As a resident I wasn’t in a position to criticize him, nor did I want to endanger my own standing in the program by talking to someone higher up.

He was, fortunately, the only attending I ever worked with who did that. It still stands out in my mind, perhaps as an example of what not to do, and sometimes I still think about it.

Perhaps I’m naive, but I assumed he was an aberration. Apparently not, as the American College of Physicians recently issued a position paper advising its members not to ask patients for donations to the doctor’s workplace. There’s actually an acronym, GPF (Grateful Patient Fundraising) for this.

I understand a lot of these doctors are in academics and need funding for research and other programs. I know that a lot of good comes from this research, and I fully support it.

But this seems to be a bad way of doing it. Standing at the bedside on that long-ago morning, I remember thinking the patient (who looked kind of surprised) was going to wonder if this was a vague sort of hint: You’ll get better care if you pay up. Or a veiled threat that you may not get decent care if you don’t. I have no idea if he donated.

There must be a better way to get funding than hitting up a patient as part of the care plan. Perhaps discharge materials might include a brochure about how to make a donation, if interested. Or the ubiquitous portal might have a “donate” box in the task bar.

If the patient were to initiate this on his own, I wouldn’t have an issue with it. He gets out of the hospital, is grateful for his care, and calls the physician’s office to say he’d like to make a donation to whatever his program is (or just goes online to do it). That’s fine. I’ve even had the occasional patient call my office to say they’d like to make a donation to my favorite charity, and I give them a list of various neurology research foundations (none of which I’m affiliated with, for the record).

But to actively solicit donations from someone under your care is tasteless and inappropriate. It creates a conflict of interest for both parties.

The patient may believe he’ll get better care, and is obligated to keep giving – or else. The physician may feel like he’s stuck going beyond what’s really needed, ordering unnecessary tests and such to keep the financial VIP happy. And what happens if the big donor patient calls in because he hurt his ankle and needs a Percocet refill that another doctor won’t give him?

The statement by the ACP is appropriate. The only thing that bothers me about it is that it had to be made at all.

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

I was a resident, on morning rounds. The attending neurologist was young and ambitious (weren’t we all once?), trying to get the hospital to help him fund a research program in his subspecialty of interest.

One of the patients we saw that morning was a locally known successful businessman who’d been admitted, fortunately not for anything too serious.

Pretty standard up to that point.

After answering questions, however, the attending suddenly went into a sales pitch on his new research program, asking the guy for a financial donation, and giving him the card for the person at his office handling the funding.

I don’t remember anymore if he repeated that with other patients, but even now it still leaves a bad taste in my mouth. As a resident I wasn’t in a position to criticize him, nor did I want to endanger my own standing in the program by talking to someone higher up.

He was, fortunately, the only attending I ever worked with who did that. It still stands out in my mind, perhaps as an example of what not to do, and sometimes I still think about it.

Perhaps I’m naive, but I assumed he was an aberration. Apparently not, as the American College of Physicians recently issued a position paper advising its members not to ask patients for donations to the doctor’s workplace. There’s actually an acronym, GPF (Grateful Patient Fundraising) for this.

I understand a lot of these doctors are in academics and need funding for research and other programs. I know that a lot of good comes from this research, and I fully support it.

But this seems to be a bad way of doing it. Standing at the bedside on that long-ago morning, I remember thinking the patient (who looked kind of surprised) was going to wonder if this was a vague sort of hint: You’ll get better care if you pay up. Or a veiled threat that you may not get decent care if you don’t. I have no idea if he donated.

There must be a better way to get funding than hitting up a patient as part of the care plan. Perhaps discharge materials might include a brochure about how to make a donation, if interested. Or the ubiquitous portal might have a “donate” box in the task bar.

If the patient were to initiate this on his own, I wouldn’t have an issue with it. He gets out of the hospital, is grateful for his care, and calls the physician’s office to say he’d like to make a donation to whatever his program is (or just goes online to do it). That’s fine. I’ve even had the occasional patient call my office to say they’d like to make a donation to my favorite charity, and I give them a list of various neurology research foundations (none of which I’m affiliated with, for the record).

But to actively solicit donations from someone under your care is tasteless and inappropriate. It creates a conflict of interest for both parties.

The patient may believe he’ll get better care, and is obligated to keep giving – or else. The physician may feel like he’s stuck going beyond what’s really needed, ordering unnecessary tests and such to keep the financial VIP happy. And what happens if the big donor patient calls in because he hurt his ankle and needs a Percocet refill that another doctor won’t give him?

The statement by the ACP is appropriate. The only thing that bothers me about it is that it had to be made at all.

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

I was a resident, on morning rounds. The attending neurologist was young and ambitious (weren’t we all once?), trying to get the hospital to help him fund a research program in his subspecialty of interest.

One of the patients we saw that morning was a locally known successful businessman who’d been admitted, fortunately not for anything too serious.

Pretty standard up to that point.

After answering questions, however, the attending suddenly went into a sales pitch on his new research program, asking the guy for a financial donation, and giving him the card for the person at his office handling the funding.

I don’t remember anymore if he repeated that with other patients, but even now it still leaves a bad taste in my mouth. As a resident I wasn’t in a position to criticize him, nor did I want to endanger my own standing in the program by talking to someone higher up.

He was, fortunately, the only attending I ever worked with who did that. It still stands out in my mind, perhaps as an example of what not to do, and sometimes I still think about it.

Perhaps I’m naive, but I assumed he was an aberration. Apparently not, as the American College of Physicians recently issued a position paper advising its members not to ask patients for donations to the doctor’s workplace. There’s actually an acronym, GPF (Grateful Patient Fundraising) for this.

I understand a lot of these doctors are in academics and need funding for research and other programs. I know that a lot of good comes from this research, and I fully support it.

But this seems to be a bad way of doing it. Standing at the bedside on that long-ago morning, I remember thinking the patient (who looked kind of surprised) was going to wonder if this was a vague sort of hint: You’ll get better care if you pay up. Or a veiled threat that you may not get decent care if you don’t. I have no idea if he donated.

There must be a better way to get funding than hitting up a patient as part of the care plan. Perhaps discharge materials might include a brochure about how to make a donation, if interested. Or the ubiquitous portal might have a “donate” box in the task bar.

If the patient were to initiate this on his own, I wouldn’t have an issue with it. He gets out of the hospital, is grateful for his care, and calls the physician’s office to say he’d like to make a donation to whatever his program is (or just goes online to do it). That’s fine. I’ve even had the occasional patient call my office to say they’d like to make a donation to my favorite charity, and I give them a list of various neurology research foundations (none of which I’m affiliated with, for the record).

But to actively solicit donations from someone under your care is tasteless and inappropriate. It creates a conflict of interest for both parties.

The patient may believe he’ll get better care, and is obligated to keep giving – or else. The physician may feel like he’s stuck going beyond what’s really needed, ordering unnecessary tests and such to keep the financial VIP happy. And what happens if the big donor patient calls in because he hurt his ankle and needs a Percocet refill that another doctor won’t give him?

The statement by the ACP is appropriate. The only thing that bothers me about it is that it had to be made at all.

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

In discussions between health care providers and patients, the words “regularity” and “irregularity” come up primarily in reference to either constipation or menstrual cycles. However, the participants in a recent panel convened by the National Sleep Foundation think we should also be discussing irregularity when we are discussing sleep with our patients.

The sleep experts on the panel began by considering 40,000 papers that directly or tangentially dealt with the topic of irregular sleep patterns. The reviewers uncovered numerous references to an association between sleep irregularity and a wide variety of adverse health outcomes, including obesity and metabolic disorders, hypertension and other cardiovascular disorders, and elevations in several inflammatory markers. Not surprisingly, the investigators also found an abundance of references supporting an association between irregular sleep and a suite of mental health problems, including depression, mood disorders, lower self esteem, poor academic performance, and deficits in attention. For example, several of the studies the panel reviewed found that in college students, GPA was lower when their sleep pattern was irregular. There were some papers that found no significant association between irregular sleep and other adverse health outcomes, but none of the studies demonstrated an association with better or improved health outcomes.

There is currently no universally accepted definition of an irregular sleep pattern. The experts pointed to some papers that used a standard deviation of 1 hour from the patient’s usual bed time determined by averaging over an interval measured in weeks. You and I shouldn’t be surprised that irregular sleep is unhealthy, but the breadth of the panel’s findings is impressive.

Although it has been long in coming, sleep is finally beginning to get some attention by the media. The focus is usually on the optimal number of hours we need each night. This panel’s findings suggest that total sleep time is only part of the story, and may even be less important than the regularity of our sleep patterns.

For those of us in pediatrics, the place where irregularity raises its ugly head is with teenagers and weekends. Although the numbers are far from clear, the question remains of how effective is catch-up sleep after a week of too-early mornings and too-late bedtimes for the chronically under-slept adolescent.

In some studies in which patients had the demonstrable effects of sleep deprivation (e.g., metabolic and cardiovascular) there was some improvement when weekend sleep was extended by 1 or 2 hours, but none beyond 2 hours.

The panel’s findings, while certainly significant, merely add weight and nuance to the existing evidence of importance of sleep and the damage done by sleep deprivation. As one of the panel members has said, “Sleep is the third pillar of health, equally important as diet and exercise, if not more.” However, this message is not getting out, or at least it is not being heeded. Like obesity, our efforts as advisers to our patients isn’t working. Unfortunately, this is because our advice is often whispered and given halfheartedly.

There was some evidence of improvement as a result of the pandemic, when those fortunate enough to be able to work from home were taking advantage of the flexibility in their schedules and getting more sleep. But health care providers certainly can’t take responsibility for what was an accident of nature.

Those of you who have been reading Letters from Maine for the last 3 decades may tire of my beating the tired horse of sleep deprivation. But I will not be deterred. I see very little evidence among health care professionals in taking the importance of sleep seriously. Sure, they may include it buried in the list of potential contributors to their patient’s complaint, but I see very little effort to move it higher on their list of priorities and almost no movement toward making substantive recommendations and then reinforcing them with follow-up.

Like obesity, sleep deprivation is a societal problem. We can lay some of the blame on Thomas Edison, but until we as health care professionals take sleep deprivation seriously, we will be undertreating and mistreating our patients who would benefit from a serious discussion of their sleep habits. Until that time you will continue to read columns like this one when I encounter significant studies on the importance of sleep.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In discussions between health care providers and patients, the words “regularity” and “irregularity” come up primarily in reference to either constipation or menstrual cycles. However, the participants in a recent panel convened by the National Sleep Foundation think we should also be discussing irregularity when we are discussing sleep with our patients.

The sleep experts on the panel began by considering 40,000 papers that directly or tangentially dealt with the topic of irregular sleep patterns. The reviewers uncovered numerous references to an association between sleep irregularity and a wide variety of adverse health outcomes, including obesity and metabolic disorders, hypertension and other cardiovascular disorders, and elevations in several inflammatory markers. Not surprisingly, the investigators also found an abundance of references supporting an association between irregular sleep and a suite of mental health problems, including depression, mood disorders, lower self esteem, poor academic performance, and deficits in attention. For example, several of the studies the panel reviewed found that in college students, GPA was lower when their sleep pattern was irregular. There were some papers that found no significant association between irregular sleep and other adverse health outcomes, but none of the studies demonstrated an association with better or improved health outcomes.

There is currently no universally accepted definition of an irregular sleep pattern. The experts pointed to some papers that used a standard deviation of 1 hour from the patient’s usual bed time determined by averaging over an interval measured in weeks. You and I shouldn’t be surprised that irregular sleep is unhealthy, but the breadth of the panel’s findings is impressive.

Although it has been long in coming, sleep is finally beginning to get some attention by the media. The focus is usually on the optimal number of hours we need each night. This panel’s findings suggest that total sleep time is only part of the story, and may even be less important than the regularity of our sleep patterns.

For those of us in pediatrics, the place where irregularity raises its ugly head is with teenagers and weekends. Although the numbers are far from clear, the question remains of how effective is catch-up sleep after a week of too-early mornings and too-late bedtimes for the chronically under-slept adolescent.

In some studies in which patients had the demonstrable effects of sleep deprivation (e.g., metabolic and cardiovascular) there was some improvement when weekend sleep was extended by 1 or 2 hours, but none beyond 2 hours.

The panel’s findings, while certainly significant, merely add weight and nuance to the existing evidence of importance of sleep and the damage done by sleep deprivation. As one of the panel members has said, “Sleep is the third pillar of health, equally important as diet and exercise, if not more.” However, this message is not getting out, or at least it is not being heeded. Like obesity, our efforts as advisers to our patients isn’t working. Unfortunately, this is because our advice is often whispered and given halfheartedly.

There was some evidence of improvement as a result of the pandemic, when those fortunate enough to be able to work from home were taking advantage of the flexibility in their schedules and getting more sleep. But health care providers certainly can’t take responsibility for what was an accident of nature.

Those of you who have been reading Letters from Maine for the last 3 decades may tire of my beating the tired horse of sleep deprivation. But I will not be deterred. I see very little evidence among health care professionals in taking the importance of sleep seriously. Sure, they may include it buried in the list of potential contributors to their patient’s complaint, but I see very little effort to move it higher on their list of priorities and almost no movement toward making substantive recommendations and then reinforcing them with follow-up.

Like obesity, sleep deprivation is a societal problem. We can lay some of the blame on Thomas Edison, but until we as health care professionals take sleep deprivation seriously, we will be undertreating and mistreating our patients who would benefit from a serious discussion of their sleep habits. Until that time you will continue to read columns like this one when I encounter significant studies on the importance of sleep.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In discussions between health care providers and patients, the words “regularity” and “irregularity” come up primarily in reference to either constipation or menstrual cycles. However, the participants in a recent panel convened by the National Sleep Foundation think we should also be discussing irregularity when we are discussing sleep with our patients.

The sleep experts on the panel began by considering 40,000 papers that directly or tangentially dealt with the topic of irregular sleep patterns. The reviewers uncovered numerous references to an association between sleep irregularity and a wide variety of adverse health outcomes, including obesity and metabolic disorders, hypertension and other cardiovascular disorders, and elevations in several inflammatory markers. Not surprisingly, the investigators also found an abundance of references supporting an association between irregular sleep and a suite of mental health problems, including depression, mood disorders, lower self esteem, poor academic performance, and deficits in attention. For example, several of the studies the panel reviewed found that in college students, GPA was lower when their sleep pattern was irregular. There were some papers that found no significant association between irregular sleep and other adverse health outcomes, but none of the studies demonstrated an association with better or improved health outcomes.

There is currently no universally accepted definition of an irregular sleep pattern. The experts pointed to some papers that used a standard deviation of 1 hour from the patient’s usual bed time determined by averaging over an interval measured in weeks. You and I shouldn’t be surprised that irregular sleep is unhealthy, but the breadth of the panel’s findings is impressive.

Although it has been long in coming, sleep is finally beginning to get some attention by the media. The focus is usually on the optimal number of hours we need each night. This panel’s findings suggest that total sleep time is only part of the story, and may even be less important than the regularity of our sleep patterns.

For those of us in pediatrics, the place where irregularity raises its ugly head is with teenagers and weekends. Although the numbers are far from clear, the question remains of how effective is catch-up sleep after a week of too-early mornings and too-late bedtimes for the chronically under-slept adolescent.

In some studies in which patients had the demonstrable effects of sleep deprivation (e.g., metabolic and cardiovascular) there was some improvement when weekend sleep was extended by 1 or 2 hours, but none beyond 2 hours.

The panel’s findings, while certainly significant, merely add weight and nuance to the existing evidence of importance of sleep and the damage done by sleep deprivation. As one of the panel members has said, “Sleep is the third pillar of health, equally important as diet and exercise, if not more.” However, this message is not getting out, or at least it is not being heeded. Like obesity, our efforts as advisers to our patients isn’t working. Unfortunately, this is because our advice is often whispered and given halfheartedly.

There was some evidence of improvement as a result of the pandemic, when those fortunate enough to be able to work from home were taking advantage of the flexibility in their schedules and getting more sleep. But health care providers certainly can’t take responsibility for what was an accident of nature.

Those of you who have been reading Letters from Maine for the last 3 decades may tire of my beating the tired horse of sleep deprivation. But I will not be deterred. I see very little evidence among health care professionals in taking the importance of sleep seriously. Sure, they may include it buried in the list of potential contributors to their patient’s complaint, but I see very little effort to move it higher on their list of priorities and almost no movement toward making substantive recommendations and then reinforcing them with follow-up.

Like obesity, sleep deprivation is a societal problem. We can lay some of the blame on Thomas Edison, but until we as health care professionals take sleep deprivation seriously, we will be undertreating and mistreating our patients who would benefit from a serious discussion of their sleep habits. Until that time you will continue to read columns like this one when I encounter significant studies on the importance of sleep.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

The poster child for a burned-out physician is a young woman practicing in primary care, according to a new study of more than 1,300 clinicians.

The study, published in JAMA Network Open. investigated patterns in physician burnout among 1,373 physicians at Massachusetts General Physicians Organization, a hospital-owned group practice. It assessed burnout in 3 years: 2017, 2019, and 2021.

Rates of burnout appear to be worsening; they increased from 44% to 50% between 2017 and 2021. Respondents were queried about their satisfaction with their career and compensation, as well as their well-being, administrative workload, and leadership and diversity.

Female physicians exhibited a higher burnout rate than male physicians (odds ratio, 1.47; 95% confidence interval, 1.02-2.12), while among primary care physicians (PCPs), the burnout rate was almost three times higher than among those in internal medicine (OR, 2.82; 95% CI, 1.76-4.50). Among physicians with 30 or more years of experience, the burnout rate was lower than among those with 10 years of experience or less (OR, 0.21; 95% CI, 0.13-0.35).

The fact that burnout disproportionately affects female physicians could reflect the additional household and family obligations women are often expected to handle, as well as their desire to form relationships with their patients, according to Timothy Hoff, PhD, a professor of management, healthcare systems, and health policy at Northeastern University, Boston.

“Female physicians tend to practice differently than their male counterparts,” said Dr. Hoff, who studies primary care. “They may focus more on the relational aspects of care, and that could lead to a higher rate of burnout.”

The study used the Maslach Burnout Inventory and three burnout subscales: exhaustion, cynicism, and reduced personal efficacy. The cohort was composed of 50% men, 67% White respondents, and 87% non-Hispanic respondents. A little over two-thirds of physicians had from 11 to 20 years of experience.

About 93% of those surveyed responded; by comparison, response rates were between 27% and 32% in previous analyses of physician burnout, the study authors say. They attribute this high participation rate to the fact that they compensated each participant with $850, more than is usually offered.

Hilton Gomes, MD, a partner at a concierge primary care practice in Miami – who has been practicing medicine for more than 15 years – said the increased rates of burnout among his younger colleagues are partly the result of a recent shift in what is considered the ideal work-life balance.

“Younger generations of doctors enter the profession with a strong desire for a better work-life balance. Unfortunately, medicine does not typically lend itself to achieving this balance,” he said.

Dr. Gomes recalled a time in medical school when he tried to visit his former pediatrician, who couldn’t be found at home.

“His wife informed me that he was tending to an urgent sick visit at the hospital, while his wife had to deal with their own grandson’s fracture being treated at urgent care,” Dr. Gomes said. “This illustrates, in my experience, how older generations of physicians accepted the demands of the profession as part of their commitment, and this often involved putting our own families second.”

Dr. Gomes, like many other PCPs who have converted to concierge medicine, previously worked at a practice where he saw nearly two dozen patients a day for a maximum of 15 minutes each.

“The structure of managed care often results in primary care physicians spending less time with patients and more time on paperwork, which is not the reason why physicians enter the field of medicine,” Dr. Gomes said.

Physicians are not alone in their feelings of physical and mental exhaustion. In the Medscape Physician Assistant Burnout Report 2023, 16% of respondents said the burnout they experienced was so severe that they were thinking of leaving medicine.

In 2022, PCP burnout cost the United States $260 million in excess health care expenditures. Burnout has also increased rates of physician suicide over the past 50 years and has led to a rise in medical errors.

Physicians say that programs that teach them to perform yoga and take deep breaths – which are offered by their employers – are not the solution.

“We sort of know what the realities of physician burnout are now; the imperative is to address it,” Dr. Hoff said. “We need studies that focus on the concepts of sustainability.”

The study was funded by the Massachusetts General Physicians Organization. A coauthor reports receiving a grant from the American Heart Association. No other disclosures were reported.

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

The poster child for a burned-out physician is a young woman practicing in primary care, according to a new study of more than 1,300 clinicians.

The study, published in JAMA Network Open. investigated patterns in physician burnout among 1,373 physicians at Massachusetts General Physicians Organization, a hospital-owned group practice. It assessed burnout in 3 years: 2017, 2019, and 2021.

Rates of burnout appear to be worsening; they increased from 44% to 50% between 2017 and 2021. Respondents were queried about their satisfaction with their career and compensation, as well as their well-being, administrative workload, and leadership and diversity.

Female physicians exhibited a higher burnout rate than male physicians (odds ratio, 1.47; 95% confidence interval, 1.02-2.12), while among primary care physicians (PCPs), the burnout rate was almost three times higher than among those in internal medicine (OR, 2.82; 95% CI, 1.76-4.50). Among physicians with 30 or more years of experience, the burnout rate was lower than among those with 10 years of experience or less (OR, 0.21; 95% CI, 0.13-0.35).

The fact that burnout disproportionately affects female physicians could reflect the additional household and family obligations women are often expected to handle, as well as their desire to form relationships with their patients, according to Timothy Hoff, PhD, a professor of management, healthcare systems, and health policy at Northeastern University, Boston.

“Female physicians tend to practice differently than their male counterparts,” said Dr. Hoff, who studies primary care. “They may focus more on the relational aspects of care, and that could lead to a higher rate of burnout.”

The study used the Maslach Burnout Inventory and three burnout subscales: exhaustion, cynicism, and reduced personal efficacy. The cohort was composed of 50% men, 67% White respondents, and 87% non-Hispanic respondents. A little over two-thirds of physicians had from 11 to 20 years of experience.

About 93% of those surveyed responded; by comparison, response rates were between 27% and 32% in previous analyses of physician burnout, the study authors say. They attribute this high participation rate to the fact that they compensated each participant with $850, more than is usually offered.

Hilton Gomes, MD, a partner at a concierge primary care practice in Miami – who has been practicing medicine for more than 15 years – said the increased rates of burnout among his younger colleagues are partly the result of a recent shift in what is considered the ideal work-life balance.

“Younger generations of doctors enter the profession with a strong desire for a better work-life balance. Unfortunately, medicine does not typically lend itself to achieving this balance,” he said.

Dr. Gomes recalled a time in medical school when he tried to visit his former pediatrician, who couldn’t be found at home.

“His wife informed me that he was tending to an urgent sick visit at the hospital, while his wife had to deal with their own grandson’s fracture being treated at urgent care,” Dr. Gomes said. “This illustrates, in my experience, how older generations of physicians accepted the demands of the profession as part of their commitment, and this often involved putting our own families second.”

Dr. Gomes, like many other PCPs who have converted to concierge medicine, previously worked at a practice where he saw nearly two dozen patients a day for a maximum of 15 minutes each.

“The structure of managed care often results in primary care physicians spending less time with patients and more time on paperwork, which is not the reason why physicians enter the field of medicine,” Dr. Gomes said.

Physicians are not alone in their feelings of physical and mental exhaustion. In the Medscape Physician Assistant Burnout Report 2023, 16% of respondents said the burnout they experienced was so severe that they were thinking of leaving medicine.

In 2022, PCP burnout cost the United States $260 million in excess health care expenditures. Burnout has also increased rates of physician suicide over the past 50 years and has led to a rise in medical errors.

Physicians say that programs that teach them to perform yoga and take deep breaths – which are offered by their employers – are not the solution.

“We sort of know what the realities of physician burnout are now; the imperative is to address it,” Dr. Hoff said. “We need studies that focus on the concepts of sustainability.”

The study was funded by the Massachusetts General Physicians Organization. A coauthor reports receiving a grant from the American Heart Association. No other disclosures were reported.

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

The poster child for a burned-out physician is a young woman practicing in primary care, according to a new study of more than 1,300 clinicians.

The study, published in JAMA Network Open. investigated patterns in physician burnout among 1,373 physicians at Massachusetts General Physicians Organization, a hospital-owned group practice. It assessed burnout in 3 years: 2017, 2019, and 2021.

Rates of burnout appear to be worsening; they increased from 44% to 50% between 2017 and 2021. Respondents were queried about their satisfaction with their career and compensation, as well as their well-being, administrative workload, and leadership and diversity.

Female physicians exhibited a higher burnout rate than male physicians (odds ratio, 1.47; 95% confidence interval, 1.02-2.12), while among primary care physicians (PCPs), the burnout rate was almost three times higher than among those in internal medicine (OR, 2.82; 95% CI, 1.76-4.50). Among physicians with 30 or more years of experience, the burnout rate was lower than among those with 10 years of experience or less (OR, 0.21; 95% CI, 0.13-0.35).

The fact that burnout disproportionately affects female physicians could reflect the additional household and family obligations women are often expected to handle, as well as their desire to form relationships with their patients, according to Timothy Hoff, PhD, a professor of management, healthcare systems, and health policy at Northeastern University, Boston.

“Female physicians tend to practice differently than their male counterparts,” said Dr. Hoff, who studies primary care. “They may focus more on the relational aspects of care, and that could lead to a higher rate of burnout.”

The study used the Maslach Burnout Inventory and three burnout subscales: exhaustion, cynicism, and reduced personal efficacy. The cohort was composed of 50% men, 67% White respondents, and 87% non-Hispanic respondents. A little over two-thirds of physicians had from 11 to 20 years of experience.

About 93% of those surveyed responded; by comparison, response rates were between 27% and 32% in previous analyses of physician burnout, the study authors say. They attribute this high participation rate to the fact that they compensated each participant with $850, more than is usually offered.

Hilton Gomes, MD, a partner at a concierge primary care practice in Miami – who has been practicing medicine for more than 15 years – said the increased rates of burnout among his younger colleagues are partly the result of a recent shift in what is considered the ideal work-life balance.

“Younger generations of doctors enter the profession with a strong desire for a better work-life balance. Unfortunately, medicine does not typically lend itself to achieving this balance,” he said.

Dr. Gomes recalled a time in medical school when he tried to visit his former pediatrician, who couldn’t be found at home.

“His wife informed me that he was tending to an urgent sick visit at the hospital, while his wife had to deal with their own grandson’s fracture being treated at urgent care,” Dr. Gomes said. “This illustrates, in my experience, how older generations of physicians accepted the demands of the profession as part of their commitment, and this often involved putting our own families second.”

Dr. Gomes, like many other PCPs who have converted to concierge medicine, previously worked at a practice where he saw nearly two dozen patients a day for a maximum of 15 minutes each.

“The structure of managed care often results in primary care physicians spending less time with patients and more time on paperwork, which is not the reason why physicians enter the field of medicine,” Dr. Gomes said.

Physicians are not alone in their feelings of physical and mental exhaustion. In the Medscape Physician Assistant Burnout Report 2023, 16% of respondents said the burnout they experienced was so severe that they were thinking of leaving medicine.

In 2022, PCP burnout cost the United States $260 million in excess health care expenditures. Burnout has also increased rates of physician suicide over the past 50 years and has led to a rise in medical errors.

Physicians say that programs that teach them to perform yoga and take deep breaths – which are offered by their employers – are not the solution.

“We sort of know what the realities of physician burnout are now; the imperative is to address it,” Dr. Hoff said. “We need studies that focus on the concepts of sustainability.”

The study was funded by the Massachusetts General Physicians Organization. A coauthor reports receiving a grant from the American Heart Association. No other disclosures were reported.

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

TOPLINE:

Metabolic dysfunction–associated steatotic liver disease (MASLD) significantly raises the risk for cardiovascular, metabolic, oncologic, and other outcomes, a new meta-analysis suggests.

METHODOLOGY:

• Researchers conducted a comprehensive meta-analysis of studies to investigate longitudinal clinical outcomes associated with MASLD, previously known as nonalcoholic fatty liver disease.
• They identified 129 original studies that evaluated the longitudinal risks for incident clinical outcomes in patients with MASLD vs those without the disease.
• Investigators calculated pooled risk estimates for clinical outcomes in patients with MASLD and those without MASLD, with MASLD being diagnosed by imaging, biopsy, blood tests, or ICD codes.

TAKEAWAY:

• MASLD was associated with a significant increased risk for cardiovascular disease outcomes (hazard ratio, 1.43), metabolic outcomes such as incident hypertension (HR, 1.75), prediabetes (HR, 1.69), diabetes (HR, 2.56), metabolic syndrome (HR, 2.57), chronic kidney disease (HR, 1.38), and various liver-related outcomes (HR, 3.92).
• Patients with advanced MASLD had a significantly greater risk (P = .02) of developing diabetes than did their peers with less severe MASLD (HR, 1.63), compared with persons without MASLD.
• MASLD was also associated with all cancers (HR, 1.54); the highest risk was seen for hepatocellular carcinoma (HR, 4.37).
• Subgroup analyses stratified by sex found no significant differences in the risks observed between men and women with MASLD.

IN PRACTICE:

“It is imperative to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to recognition and treatment beyond that of the hepatologist alone,” the authors wrote. “The growing prevalence of MASLD will remain a major global health threat that requires effective disease management frameworks to be put in place.”

SOURCE:

The study, with co–first authors Kai En Chan and Elden Yen Hng Ong, National University of Singapore, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The results depend on the validity of the original studies, and residual confounding factors may have biased the reported results. The study is also limited in its inclusion of large population-based studies using ICD codes that may result in misclassification bias. There was no examination of longitudinal outcomes in patients with histologically confirmed MASLD.

DISCLOSURES:

The study had no funding. Some authors reported research support, consulting fees, or stock options from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Metabolic dysfunction–associated steatotic liver disease (MASLD) significantly raises the risk for cardiovascular, metabolic, oncologic, and other outcomes, a new meta-analysis suggests.

METHODOLOGY:

• Researchers conducted a comprehensive meta-analysis of studies to investigate longitudinal clinical outcomes associated with MASLD, previously known as nonalcoholic fatty liver disease.
• They identified 129 original studies that evaluated the longitudinal risks for incident clinical outcomes in patients with MASLD vs those without the disease.
• Investigators calculated pooled risk estimates for clinical outcomes in patients with MASLD and those without MASLD, with MASLD being diagnosed by imaging, biopsy, blood tests, or ICD codes.

TAKEAWAY:

• MASLD was associated with a significant increased risk for cardiovascular disease outcomes (hazard ratio, 1.43), metabolic outcomes such as incident hypertension (HR, 1.75), prediabetes (HR, 1.69), diabetes (HR, 2.56), metabolic syndrome (HR, 2.57), chronic kidney disease (HR, 1.38), and various liver-related outcomes (HR, 3.92).
• Patients with advanced MASLD had a significantly greater risk (P = .02) of developing diabetes than did their peers with less severe MASLD (HR, 1.63), compared with persons without MASLD.
• MASLD was also associated with all cancers (HR, 1.54); the highest risk was seen for hepatocellular carcinoma (HR, 4.37).
• Subgroup analyses stratified by sex found no significant differences in the risks observed between men and women with MASLD.

IN PRACTICE:

“It is imperative to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to recognition and treatment beyond that of the hepatologist alone,” the authors wrote. “The growing prevalence of MASLD will remain a major global health threat that requires effective disease management frameworks to be put in place.”

SOURCE:

The study, with co–first authors Kai En Chan and Elden Yen Hng Ong, National University of Singapore, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The results depend on the validity of the original studies, and residual confounding factors may have biased the reported results. The study is also limited in its inclusion of large population-based studies using ICD codes that may result in misclassification bias. There was no examination of longitudinal outcomes in patients with histologically confirmed MASLD.

DISCLOSURES:

The study had no funding. Some authors reported research support, consulting fees, or stock options from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Metabolic dysfunction–associated steatotic liver disease (MASLD) significantly raises the risk for cardiovascular, metabolic, oncologic, and other outcomes, a new meta-analysis suggests.

METHODOLOGY:

• Researchers conducted a comprehensive meta-analysis of studies to investigate longitudinal clinical outcomes associated with MASLD, previously known as nonalcoholic fatty liver disease.
• They identified 129 original studies that evaluated the longitudinal risks for incident clinical outcomes in patients with MASLD vs those without the disease.
• Investigators calculated pooled risk estimates for clinical outcomes in patients with MASLD and those without MASLD, with MASLD being diagnosed by imaging, biopsy, blood tests, or ICD codes.

TAKEAWAY:

• MASLD was associated with a significant increased risk for cardiovascular disease outcomes (hazard ratio, 1.43), metabolic outcomes such as incident hypertension (HR, 1.75), prediabetes (HR, 1.69), diabetes (HR, 2.56), metabolic syndrome (HR, 2.57), chronic kidney disease (HR, 1.38), and various liver-related outcomes (HR, 3.92).
• Patients with advanced MASLD had a significantly greater risk (P = .02) of developing diabetes than did their peers with less severe MASLD (HR, 1.63), compared with persons without MASLD.
• MASLD was also associated with all cancers (HR, 1.54); the highest risk was seen for hepatocellular carcinoma (HR, 4.37).
• Subgroup analyses stratified by sex found no significant differences in the risks observed between men and women with MASLD.

IN PRACTICE:

“It is imperative to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to recognition and treatment beyond that of the hepatologist alone,” the authors wrote. “The growing prevalence of MASLD will remain a major global health threat that requires effective disease management frameworks to be put in place.”

SOURCE:

The study, with co–first authors Kai En Chan and Elden Yen Hng Ong, National University of Singapore, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The results depend on the validity of the original studies, and residual confounding factors may have biased the reported results. The study is also limited in its inclusion of large population-based studies using ICD codes that may result in misclassification bias. There was no examination of longitudinal outcomes in patients with histologically confirmed MASLD.

DISCLOSURES:

The study had no funding. Some authors reported research support, consulting fees, or stock options from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Compared with supervised treadmill workouts at a gym, which is considered first-line therapy for walking impairment in lower extremity peripheral artery disease (PAD), exercising at home significantly improves 6-minute walking (6MW) distance, but not maximal treadmill walking distance, results of a new meta-analysis show.

METHODOLOGY:

• The analysis included five randomized clinical trials with a total of 719 participants, mean age 68.6 years, all led by researchers at Northwestern University, Chicago, that compared either supervised treadmill or home-based walking exercise with a nonexercise control group in people with PAD (defined as Ankle Brachial Index ≤ 0.90).
• All trials measured 6-minute walk (6MW) distance (walking as far as possible in 6 minutes), treadmill walking performance, and outcomes from the Walking Impairment Questionnaire (WIQ), which includes distance, walking speed, and stair-climbing domains, at baseline and at 6 months.
• Supervised treadmill exercise interventions included three individualized exercise sessions per week with an exercise physiologist at an exercise center, and home-based exercises involved walking near home 5 days per week, both for up to 50 minutes per session.

TAKEAWAY:

• After adjusting for study, age, sex, race, smoking, history of myocardial infarction, heart failure, and baseline 6MW distance, the study found both exercise interventions were better than nonexercise controls for 6MW distance.
• Compared with supervised treadmill exercise, home-based walking was associated with significantly improved mean 6MW distance (31.8 m vs. 55.6 m; adjusted between-group difference: −23.8 m; 95% confidence interval, −44.0 to −3.6; P = .021), and significantly improved WIQ walking speed score.
• However, home-based walking was associated with significantly less improvement in maximal treadmill walking distance, compared with supervised treadmill exercise (adjusted between-group difference: 132.5 m; 95% CI, 72.1-192.9; P < .001).

IN PRACTICE:

Home-based walking exercise “circumvents” barriers to accessing supervised exercise such as having to travel to a facility, said the authors, who noted the new data “demonstrated a large and consistent effect of home-based walking exercise on improved 6MW distance and also significantly improved the WIQ walking speed score, compared with supervised treadmill exercise.”

SOURCE:

The study was conducted by Neela D. Thangada, MD, Northwestern University, Chicago, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

Data were combined from different randomized clinical trials that were led by one investigative team, and reported comparisons were not prespecified. Comparisons between supervised and home-based exercise lacked statistical power for the WIQ distance and stair-climbing measures.

DISCLOSURES:

The study was sponsored by the National Center for Research Resources and the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Thangada reports no relevant financial relationships. Disclosures for study coauthors can be found with the original article.

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

TOPLINE:

Compared with supervised treadmill workouts at a gym, which is considered first-line therapy for walking impairment in lower extremity peripheral artery disease (PAD), exercising at home significantly improves 6-minute walking (6MW) distance, but not maximal treadmill walking distance, results of a new meta-analysis show.

METHODOLOGY:

• The analysis included five randomized clinical trials with a total of 719 participants, mean age 68.6 years, all led by researchers at Northwestern University, Chicago, that compared either supervised treadmill or home-based walking exercise with a nonexercise control group in people with PAD (defined as Ankle Brachial Index ≤ 0.90).
• All trials measured 6-minute walk (6MW) distance (walking as far as possible in 6 minutes), treadmill walking performance, and outcomes from the Walking Impairment Questionnaire (WIQ), which includes distance, walking speed, and stair-climbing domains, at baseline and at 6 months.
• Supervised treadmill exercise interventions included three individualized exercise sessions per week with an exercise physiologist at an exercise center, and home-based exercises involved walking near home 5 days per week, both for up to 50 minutes per session.

TAKEAWAY:

• After adjusting for study, age, sex, race, smoking, history of myocardial infarction, heart failure, and baseline 6MW distance, the study found both exercise interventions were better than nonexercise controls for 6MW distance.
• Compared with supervised treadmill exercise, home-based walking was associated with significantly improved mean 6MW distance (31.8 m vs. 55.6 m; adjusted between-group difference: −23.8 m; 95% confidence interval, −44.0 to −3.6; P = .021), and significantly improved WIQ walking speed score.
• However, home-based walking was associated with significantly less improvement in maximal treadmill walking distance, compared with supervised treadmill exercise (adjusted between-group difference: 132.5 m; 95% CI, 72.1-192.9; P < .001).

IN PRACTICE:

Home-based walking exercise “circumvents” barriers to accessing supervised exercise such as having to travel to a facility, said the authors, who noted the new data “demonstrated a large and consistent effect of home-based walking exercise on improved 6MW distance and also significantly improved the WIQ walking speed score, compared with supervised treadmill exercise.”

SOURCE:

The study was conducted by Neela D. Thangada, MD, Northwestern University, Chicago, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

Data were combined from different randomized clinical trials that were led by one investigative team, and reported comparisons were not prespecified. Comparisons between supervised and home-based exercise lacked statistical power for the WIQ distance and stair-climbing measures.

DISCLOSURES:

The study was sponsored by the National Center for Research Resources and the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Thangada reports no relevant financial relationships. Disclosures for study coauthors can be found with the original article.

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

TOPLINE:

Compared with supervised treadmill workouts at a gym, which is considered first-line therapy for walking impairment in lower extremity peripheral artery disease (PAD), exercising at home significantly improves 6-minute walking (6MW) distance, but not maximal treadmill walking distance, results of a new meta-analysis show.

METHODOLOGY:

• The analysis included five randomized clinical trials with a total of 719 participants, mean age 68.6 years, all led by researchers at Northwestern University, Chicago, that compared either supervised treadmill or home-based walking exercise with a nonexercise control group in people with PAD (defined as Ankle Brachial Index ≤ 0.90).
• All trials measured 6-minute walk (6MW) distance (walking as far as possible in 6 minutes), treadmill walking performance, and outcomes from the Walking Impairment Questionnaire (WIQ), which includes distance, walking speed, and stair-climbing domains, at baseline and at 6 months.
• Supervised treadmill exercise interventions included three individualized exercise sessions per week with an exercise physiologist at an exercise center, and home-based exercises involved walking near home 5 days per week, both for up to 50 minutes per session.

TAKEAWAY:

• After adjusting for study, age, sex, race, smoking, history of myocardial infarction, heart failure, and baseline 6MW distance, the study found both exercise interventions were better than nonexercise controls for 6MW distance.
• Compared with supervised treadmill exercise, home-based walking was associated with significantly improved mean 6MW distance (31.8 m vs. 55.6 m; adjusted between-group difference: −23.8 m; 95% confidence interval, −44.0 to −3.6; P = .021), and significantly improved WIQ walking speed score.
• However, home-based walking was associated with significantly less improvement in maximal treadmill walking distance, compared with supervised treadmill exercise (adjusted between-group difference: 132.5 m; 95% CI, 72.1-192.9; P < .001).

IN PRACTICE:

Home-based walking exercise “circumvents” barriers to accessing supervised exercise such as having to travel to a facility, said the authors, who noted the new data “demonstrated a large and consistent effect of home-based walking exercise on improved 6MW distance and also significantly improved the WIQ walking speed score, compared with supervised treadmill exercise.”

SOURCE:

The study was conducted by Neela D. Thangada, MD, Northwestern University, Chicago, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

Data were combined from different randomized clinical trials that were led by one investigative team, and reported comparisons were not prespecified. Comparisons between supervised and home-based exercise lacked statistical power for the WIQ distance and stair-climbing measures.

DISCLOSURES:

The study was sponsored by the National Center for Research Resources and the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Thangada reports no relevant financial relationships. Disclosures for study coauthors can be found with the original article.

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

Damaged mitochondrial DNA (mtDNA) initiates and spreads Parkinson’s disease (PD) pathology, potentially opening new avenues for early diagnosis, disease monitoring, and drug development.

While defects in mitochondrial functions and in mitochondrial DNA have been implicated in PD in the past, the current study demonstrates “for the first time how damaged mitochondrial DNA can underlie the mechanisms of PD initiation and spread in brain,” lead investigator Shohreh Issazadeh-Navikas, PhD, with the University of Copenhagen, told this news organization.

“This has direct implication for clinical diagnosis” – if damaged mtDNA can be detected in blood, it could serve as an early biomarker for disease, she explained.

The study was published online in Molecular Psychiatry.
 

“Infectious-like” spread of PD pathology

In earlier work, the researchers identified dysregulated interferon-beta (IFN-beta) signaling as a “top candidate pathway” associated with sporadic PD and its progression to PD with dementia (PDD).

In mice PD models that were deficient in IFN-beta signaling, the investigators showed that neuronal IFN-beta is required to maintain mitochondrial homeostasis and metabolism.

Lack of neuronal IFN-beta or disruption of its downstream signaling causes the accumulation of damaged mitochondria with excessive oxidative stress and insufficient adenosine triphosphate production.

In the current study, using postmortem brain tissue samples from patients with sporadic PD, they confirmed that there were deletions of mtDNA in the medial frontal gyrus, a region implicated in cognitive impairments in PD, suggesting a potential role of damaged mtDNA in disease pathophysiology.

They also identified mtDNA deletions in a “hotspot” in complex I respiratory chain subunits that were associated with dysregulation of oxidative stress and DNA damage response pathways in cohorts with sporadic PD and PDD.

They confirmed the contribution of mtDNA damage to PD pathology in the PD mouse models. They showed that lack of neuronal IFN-beta signaling leads to oxidative damage and mutations in mtDNA in neurons, which are subsequently released outside the neurons.

Injecting damaged mtDNA into mouse brain induced PDD-like behavioral symptoms, including neuropsychiatric, motor, and cognitive impairments. It also caused neurodegeneration in brain regions distant from the injection site, suggesting that damaged mtDNA triggers spread of PDD characteristics in an “infectious-like” manner, the researchers report.

Further study revealed that the mechanism through which damaged mtDNA causes pathology in healthy neurons involves dual activation of Toll-like receptor (TLR) 9 and 4 pathways, leading to increased oxidative stress and neuronal cell death, respectively.

“Our proteomic analysis of extracellular vesicles containing damaged mtDNA identified the TLR4 activator, ribosomal protein S3, as a key protein involved in recognizing and extruding damaged mtDNA,” the investigators write.

In the future they plan to investigate how mtDNA damage can serve as a predictive marker for different disease stages and progression and to explore potential therapeutic strategies aimed at restoring normal mitochondrial function to rectify the mitochondrial dysfunctions implicated in PD.
 

Making a comeback?

Commenting on the research for this news organization, James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, noted that the role of mitochondria in PD is “like a starlet that burst onto the scene in the 80s, faded into obscurity, and through diligence and continued research has moved beyond being a solid character actor and is reemerging as a force to reckon with.

“This paper only adds to the allure that mitochondria may have in contributing to PD by providing evidence of a novel process by which mitochondria may be not only contributing to PD and loss of dopamine neurons but may play a larger role in the subsequent effects that many people with PD experience – dementia,” Dr. Beck said.

He noted that the authors identified several proteins as facilitating the neurodegeneration that is wrought by damaged mitochondrial DNA.

“These could be potential targets for future drug development. In addition, this work implicates alterations in immune signaling and drugs in development to target inflammatory responses may also bring ancillary benefit,” Dr. Beck said.

However, he said, “while very interesting findings, this is really the first effort that demonstrates how damaged mitochondrial DNA may contribute to neurodegeneration in the context of PD and PD dementia. Further work needs to validate these findings as well as to elucidate mechanisms underlying the propagation of the mitochondrial DNA from cell to cell.”

Funding for this research was provided by the European Union’s Horizon 2020 Research and Innovation Program, the Lundbeck Foundation, and the Danish Council for Independent Research–Medicine. Dr. Issazadeh-Navikas and Dr. Beck have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Damaged mitochondrial DNA (mtDNA) initiates and spreads Parkinson’s disease (PD) pathology, potentially opening new avenues for early diagnosis, disease monitoring, and drug development.

While defects in mitochondrial functions and in mitochondrial DNA have been implicated in PD in the past, the current study demonstrates “for the first time how damaged mitochondrial DNA can underlie the mechanisms of PD initiation and spread in brain,” lead investigator Shohreh Issazadeh-Navikas, PhD, with the University of Copenhagen, told this news organization.

“This has direct implication for clinical diagnosis” – if damaged mtDNA can be detected in blood, it could serve as an early biomarker for disease, she explained.

The study was published online in Molecular Psychiatry.
 

“Infectious-like” spread of PD pathology

In earlier work, the researchers identified dysregulated interferon-beta (IFN-beta) signaling as a “top candidate pathway” associated with sporadic PD and its progression to PD with dementia (PDD).

In mice PD models that were deficient in IFN-beta signaling, the investigators showed that neuronal IFN-beta is required to maintain mitochondrial homeostasis and metabolism.

Lack of neuronal IFN-beta or disruption of its downstream signaling causes the accumulation of damaged mitochondria with excessive oxidative stress and insufficient adenosine triphosphate production.

In the current study, using postmortem brain tissue samples from patients with sporadic PD, they confirmed that there were deletions of mtDNA in the medial frontal gyrus, a region implicated in cognitive impairments in PD, suggesting a potential role of damaged mtDNA in disease pathophysiology.

They also identified mtDNA deletions in a “hotspot” in complex I respiratory chain subunits that were associated with dysregulation of oxidative stress and DNA damage response pathways in cohorts with sporadic PD and PDD.

They confirmed the contribution of mtDNA damage to PD pathology in the PD mouse models. They showed that lack of neuronal IFN-beta signaling leads to oxidative damage and mutations in mtDNA in neurons, which are subsequently released outside the neurons.

Injecting damaged mtDNA into mouse brain induced PDD-like behavioral symptoms, including neuropsychiatric, motor, and cognitive impairments. It also caused neurodegeneration in brain regions distant from the injection site, suggesting that damaged mtDNA triggers spread of PDD characteristics in an “infectious-like” manner, the researchers report.

Further study revealed that the mechanism through which damaged mtDNA causes pathology in healthy neurons involves dual activation of Toll-like receptor (TLR) 9 and 4 pathways, leading to increased oxidative stress and neuronal cell death, respectively.

“Our proteomic analysis of extracellular vesicles containing damaged mtDNA identified the TLR4 activator, ribosomal protein S3, as a key protein involved in recognizing and extruding damaged mtDNA,” the investigators write.

In the future they plan to investigate how mtDNA damage can serve as a predictive marker for different disease stages and progression and to explore potential therapeutic strategies aimed at restoring normal mitochondrial function to rectify the mitochondrial dysfunctions implicated in PD.
 

Making a comeback?

Commenting on the research for this news organization, James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, noted that the role of mitochondria in PD is “like a starlet that burst onto the scene in the 80s, faded into obscurity, and through diligence and continued research has moved beyond being a solid character actor and is reemerging as a force to reckon with.

“This paper only adds to the allure that mitochondria may have in contributing to PD by providing evidence of a novel process by which mitochondria may be not only contributing to PD and loss of dopamine neurons but may play a larger role in the subsequent effects that many people with PD experience – dementia,” Dr. Beck said.

He noted that the authors identified several proteins as facilitating the neurodegeneration that is wrought by damaged mitochondrial DNA.

“These could be potential targets for future drug development. In addition, this work implicates alterations in immune signaling and drugs in development to target inflammatory responses may also bring ancillary benefit,” Dr. Beck said.

However, he said, “while very interesting findings, this is really the first effort that demonstrates how damaged mitochondrial DNA may contribute to neurodegeneration in the context of PD and PD dementia. Further work needs to validate these findings as well as to elucidate mechanisms underlying the propagation of the mitochondrial DNA from cell to cell.”

Funding for this research was provided by the European Union’s Horizon 2020 Research and Innovation Program, the Lundbeck Foundation, and the Danish Council for Independent Research–Medicine. Dr. Issazadeh-Navikas and Dr. Beck have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Damaged mitochondrial DNA (mtDNA) initiates and spreads Parkinson’s disease (PD) pathology, potentially opening new avenues for early diagnosis, disease monitoring, and drug development.

While defects in mitochondrial functions and in mitochondrial DNA have been implicated in PD in the past, the current study demonstrates “for the first time how damaged mitochondrial DNA can underlie the mechanisms of PD initiation and spread in brain,” lead investigator Shohreh Issazadeh-Navikas, PhD, with the University of Copenhagen, told this news organization.

“This has direct implication for clinical diagnosis” – if damaged mtDNA can be detected in blood, it could serve as an early biomarker for disease, she explained.

The study was published online in Molecular Psychiatry.
 

“Infectious-like” spread of PD pathology

In earlier work, the researchers identified dysregulated interferon-beta (IFN-beta) signaling as a “top candidate pathway” associated with sporadic PD and its progression to PD with dementia (PDD).

In mice PD models that were deficient in IFN-beta signaling, the investigators showed that neuronal IFN-beta is required to maintain mitochondrial homeostasis and metabolism.

Lack of neuronal IFN-beta or disruption of its downstream signaling causes the accumulation of damaged mitochondria with excessive oxidative stress and insufficient adenosine triphosphate production.

In the current study, using postmortem brain tissue samples from patients with sporadic PD, they confirmed that there were deletions of mtDNA in the medial frontal gyrus, a region implicated in cognitive impairments in PD, suggesting a potential role of damaged mtDNA in disease pathophysiology.

They also identified mtDNA deletions in a “hotspot” in complex I respiratory chain subunits that were associated with dysregulation of oxidative stress and DNA damage response pathways in cohorts with sporadic PD and PDD.

They confirmed the contribution of mtDNA damage to PD pathology in the PD mouse models. They showed that lack of neuronal IFN-beta signaling leads to oxidative damage and mutations in mtDNA in neurons, which are subsequently released outside the neurons.

Injecting damaged mtDNA into mouse brain induced PDD-like behavioral symptoms, including neuropsychiatric, motor, and cognitive impairments. It also caused neurodegeneration in brain regions distant from the injection site, suggesting that damaged mtDNA triggers spread of PDD characteristics in an “infectious-like” manner, the researchers report.

Further study revealed that the mechanism through which damaged mtDNA causes pathology in healthy neurons involves dual activation of Toll-like receptor (TLR) 9 and 4 pathways, leading to increased oxidative stress and neuronal cell death, respectively.

“Our proteomic analysis of extracellular vesicles containing damaged mtDNA identified the TLR4 activator, ribosomal protein S3, as a key protein involved in recognizing and extruding damaged mtDNA,” the investigators write.

In the future they plan to investigate how mtDNA damage can serve as a predictive marker for different disease stages and progression and to explore potential therapeutic strategies aimed at restoring normal mitochondrial function to rectify the mitochondrial dysfunctions implicated in PD.
 

Making a comeback?

Commenting on the research for this news organization, James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, noted that the role of mitochondria in PD is “like a starlet that burst onto the scene in the 80s, faded into obscurity, and through diligence and continued research has moved beyond being a solid character actor and is reemerging as a force to reckon with.

“This paper only adds to the allure that mitochondria may have in contributing to PD by providing evidence of a novel process by which mitochondria may be not only contributing to PD and loss of dopamine neurons but may play a larger role in the subsequent effects that many people with PD experience – dementia,” Dr. Beck said.

He noted that the authors identified several proteins as facilitating the neurodegeneration that is wrought by damaged mitochondrial DNA.

“These could be potential targets for future drug development. In addition, this work implicates alterations in immune signaling and drugs in development to target inflammatory responses may also bring ancillary benefit,” Dr. Beck said.

However, he said, “while very interesting findings, this is really the first effort that demonstrates how damaged mitochondrial DNA may contribute to neurodegeneration in the context of PD and PD dementia. Further work needs to validate these findings as well as to elucidate mechanisms underlying the propagation of the mitochondrial DNA from cell to cell.”

Funding for this research was provided by the European Union’s Horizon 2020 Research and Innovation Program, the Lundbeck Foundation, and the Danish Council for Independent Research–Medicine. Dr. Issazadeh-Navikas and Dr. Beck have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This month we will discuss "migraine plus" conditions: menstrual migraine as well as migraine-associated symptoms, including allodynia, photophobia, and nausea.

Migraine is one of the most common and disabling conditions worldwide, and it is three times more likely to be found in women than men. This is even more so during reproductive years, where many women experience hormonally triggered migraine attacks. Although some women will experience migraine exclusively perimenstrually, most women who experience menstrual migraine attacks also will have migraine attacks that are not hormonally triggered. It is often challenging to find the correct acute treatment for specific kinds of migraine attacks, and many women will describe specific acute medications as more effective for their nonmenstrual or "regular" migraine attacks compared with their perimenstrual attacks. The study by MacGregor and colleagues investigated the use of ubrogepant and compared its effect between these two subtypes of attacks.

This trial was an extension of the initial phase 3 trial of ubrogepant, called ACHIEVE II. Initial investigators enrolled over 700 patients into an open-label extension, and the participants were randomly assigned 1:1:1 to their "usual care," 50 mg ubrogepant, or 100 mg ubrogepant. Participants were blinded to the dose of ubrogepant even though they knew that they were taking ubrogepant or their standard acute medication. The purpose of the "usual care" arm was not to collect efficacy results; rather, it was for safety, specifically to evaluate the long-term hepatic safety with ubrogepant.

Participants were allowed to treat up to eight migraine attacks per 4-week interval. The duration of the trial was 52 weeks, and a second dose of medication was allowed, identical to the initial dose. Women in this trial recorded their menstrual start date and whether they treated menstrually related attacks. An attack was considered menstrually related if the headache was within a 5-day window of the onset of menstruation. Of the 734 women enrolled in the intention-to-treat population, 354 reported at least one menstrual cycle start date with a headache day. Efficacy outcome measures included pain freedom at 2 hours post-dose, pain relief at 2 hours post-dose, absence of photophobia, phonophobia, and nausea at 2 hours post-dose, normal function at 2 hours post-dose, and use of rescue medication within 24 hours of the initial dose. All information was collected via an electronic diary.

There was no statistically significant difference between 2-hour pain freedom outcomes of menstrual and nonmenstrual migraine attacks, although there was a numerically higher mean percentage of menstrual attacks that was not statistically significant. This was noted for both doses of ubrogepant. This was also the case for 2-hour pain relief; the migraine-associated symptoms of photophobia, phonophobia, and nausea; for functional disability; and the use of a rescue medication. Among all outcomes it appears that both doses of ubrogepant are equally effective for both menstrual and nonmenstrual migraine attacks. On the basis of this evidence, clinicians may be able to consolidate different acute medications for different migraine subtypes and consider the use of this calcitonin gene-related peptide (CGRP) antagonist for all the patient's attacks.

Allodynia is a condition whereby a nonpainful stimulus is perceived as painful. In the context of migraine, this often will occur in the head and neck region and as a result of the chronification of migraine — headache frequency increasing to > 15 days per month. One significant risk factor for the development of chronic migraine is medication overuse, when an acute medication for migraine is used more often than its recommended use. Pijpers and colleagues sought to determine whether the presence of allodynia was predictive for the prognosis of chronic migraine complicated by medication overuse.

This study was a subset of the Chronification And Reversibility of Migraine (CHARM) study, a randomized, double-blind, placebo-controlled trial that aimed to investigate whether treatment with botulinum toxin A was of added value in addition to withdrawal therapy in chronic migraine patients with medication overuse headache. Diagnoses were made in consultation with headache experts and confirmed by a headache diary. Exclusion criteria were: (1) other primary headache or neurologic disorders; (2) other chronic pain disorders with medium to high pain intensity or requiring pain medication; (3) major psychiatric disorders other than depression; (4) major cognitive, behavioral, or oncologic disorders; (5) contraindications for treatment or inability to adhere to the study protocol; (6) (planned) pregnancy or breastfeeding; (7) use of ergots, opioids, or barbiturates; or (8) abuse of drugs in the past 12 months. Allodynia was determined by the Allodynia Symptom Checklist (ASC) .

The primary outcome was reversion from chronic to episodic migraine; secondary outcomes were > 50% reduction in monthly migraine days and reduction in number of monthly headache days. A total of 173 participants in the CHARM trial provided baseline allodynia data and were included in this current study. Participants with cutaneous allodynia were mainly women and did not differ significantly in age, number of monthly migraine or headache days, age of onset, use of acute or prophylactic treatment, or being treated with botulinum toxin.

The absence of cutaneous allodynia was predictive for good outcome after 12 weeks. For the primary endpoint, the odds for reversion from chronic migraine to episodic migraine were 2.5 times higher for participants without allodynia vs with allodynia. In all, 75.0% of participants without allodynia vs 57.4% of participants with allodynia reverted to episodic migraine. These helpful data will allow us to better predict accurately the disease process and better set expectations for our patients with chronic migraine.

In the earlier days of headache treatment, the focus for both acute and preventive medications was a decrease in the severity or frequency of pain. As time has progressed and our understanding of migraine has broadened, we now consider pain one of the many features of migraine, albeit usually the most prominent feature. The CGRP antagonist class of migraine medications has revolutionized how migraine is treated, both acutely and preventively; however, the initial studies all focused on pain-related outcomes. Alpuente and colleagues sought to better determine the effect of CGRP monoclonal antibody medications on other migraine-associated symptoms, specifically photophobia, photophobia, nausea, dizziness, and aura.

All injectable CGRP antibody medications were studied. Responses were recorded in an electronic diary. Patients were followed at 3 and 6 months and were excluded if their diary was < 80% complete; a total of 158 patients were included in this study. At 3 months, groups of patients were further divided between those who had > 50% decrease in monthly headache days and those that had < 50% reduction.

The > 50% group showed statistically significant reductions in the ratios of photophobia, phonophobia, and aura after 6 months of treatment, and, of note, these symptoms decreased at a higher rate than the reduction in headache days per month after 6 months. Rates of nausea and dizziness only reduced proportionally to the monthly headache days. For the < 50% group, there was a rebound of dizziness in between months 3 and 6, but all other outcomes decreased in proportion to the monthly headache days.

Our patients all experience symptoms other than headache pain as part of their migraine attacks. When we discuss the risks and benefits of a new treatment, we can now more accurately address many of the other associated symptoms and explain what our patients are likely to expect when starting a new medication. Similar studies have described these findings with the oral CGRP antagonists as well, and most acute migraine studies now use "most bothersome symptom" rather than pain severity as their primary outcome.

This month we will discuss "migraine plus" conditions: menstrual migraine as well as migraine-associated symptoms, including allodynia, photophobia, and nausea.

Migraine is one of the most common and disabling conditions worldwide, and it is three times more likely to be found in women than men. This is even more so during reproductive years, where many women experience hormonally triggered migraine attacks. Although some women will experience migraine exclusively perimenstrually, most women who experience menstrual migraine attacks also will have migraine attacks that are not hormonally triggered. It is often challenging to find the correct acute treatment for specific kinds of migraine attacks, and many women will describe specific acute medications as more effective for their nonmenstrual or "regular" migraine attacks compared with their perimenstrual attacks. The study by MacGregor and colleagues investigated the use of ubrogepant and compared its effect between these two subtypes of attacks.

This trial was an extension of the initial phase 3 trial of ubrogepant, called ACHIEVE II. Initial investigators enrolled over 700 patients into an open-label extension, and the participants were randomly assigned 1:1:1 to their "usual care," 50 mg ubrogepant, or 100 mg ubrogepant. Participants were blinded to the dose of ubrogepant even though they knew that they were taking ubrogepant or their standard acute medication. The purpose of the "usual care" arm was not to collect efficacy results; rather, it was for safety, specifically to evaluate the long-term hepatic safety with ubrogepant.

Participants were allowed to treat up to eight migraine attacks per 4-week interval. The duration of the trial was 52 weeks, and a second dose of medication was allowed, identical to the initial dose. Women in this trial recorded their menstrual start date and whether they treated menstrually related attacks. An attack was considered menstrually related if the headache was within a 5-day window of the onset of menstruation. Of the 734 women enrolled in the intention-to-treat population, 354 reported at least one menstrual cycle start date with a headache day. Efficacy outcome measures included pain freedom at 2 hours post-dose, pain relief at 2 hours post-dose, absence of photophobia, phonophobia, and nausea at 2 hours post-dose, normal function at 2 hours post-dose, and use of rescue medication within 24 hours of the initial dose. All information was collected via an electronic diary.

There was no statistically significant difference between 2-hour pain freedom outcomes of menstrual and nonmenstrual migraine attacks, although there was a numerically higher mean percentage of menstrual attacks that was not statistically significant. This was noted for both doses of ubrogepant. This was also the case for 2-hour pain relief; the migraine-associated symptoms of photophobia, phonophobia, and nausea; for functional disability; and the use of a rescue medication. Among all outcomes it appears that both doses of ubrogepant are equally effective for both menstrual and nonmenstrual migraine attacks. On the basis of this evidence, clinicians may be able to consolidate different acute medications for different migraine subtypes and consider the use of this calcitonin gene-related peptide (CGRP) antagonist for all the patient's attacks.

Allodynia is a condition whereby a nonpainful stimulus is perceived as painful. In the context of migraine, this often will occur in the head and neck region and as a result of the chronification of migraine — headache frequency increasing to > 15 days per month. One significant risk factor for the development of chronic migraine is medication overuse, when an acute medication for migraine is used more often than its recommended use. Pijpers and colleagues sought to determine whether the presence of allodynia was predictive for the prognosis of chronic migraine complicated by medication overuse.

This study was a subset of the Chronification And Reversibility of Migraine (CHARM) study, a randomized, double-blind, placebo-controlled trial that aimed to investigate whether treatment with botulinum toxin A was of added value in addition to withdrawal therapy in chronic migraine patients with medication overuse headache. Diagnoses were made in consultation with headache experts and confirmed by a headache diary. Exclusion criteria were: (1) other primary headache or neurologic disorders; (2) other chronic pain disorders with medium to high pain intensity or requiring pain medication; (3) major psychiatric disorders other than depression; (4) major cognitive, behavioral, or oncologic disorders; (5) contraindications for treatment or inability to adhere to the study protocol; (6) (planned) pregnancy or breastfeeding; (7) use of ergots, opioids, or barbiturates; or (8) abuse of drugs in the past 12 months. Allodynia was determined by the Allodynia Symptom Checklist (ASC) .

The primary outcome was reversion from chronic to episodic migraine; secondary outcomes were > 50% reduction in monthly migraine days and reduction in number of monthly headache days. A total of 173 participants in the CHARM trial provided baseline allodynia data and were included in this current study. Participants with cutaneous allodynia were mainly women and did not differ significantly in age, number of monthly migraine or headache days, age of onset, use of acute or prophylactic treatment, or being treated with botulinum toxin.

The absence of cutaneous allodynia was predictive for good outcome after 12 weeks. For the primary endpoint, the odds for reversion from chronic migraine to episodic migraine were 2.5 times higher for participants without allodynia vs with allodynia. In all, 75.0% of participants without allodynia vs 57.4% of participants with allodynia reverted to episodic migraine. These helpful data will allow us to better predict accurately the disease process and better set expectations for our patients with chronic migraine.

In the earlier days of headache treatment, the focus for both acute and preventive medications was a decrease in the severity or frequency of pain. As time has progressed and our understanding of migraine has broadened, we now consider pain one of the many features of migraine, albeit usually the most prominent feature. The CGRP antagonist class of migraine medications has revolutionized how migraine is treated, both acutely and preventively; however, the initial studies all focused on pain-related outcomes. Alpuente and colleagues sought to better determine the effect of CGRP monoclonal antibody medications on other migraine-associated symptoms, specifically photophobia, photophobia, nausea, dizziness, and aura.

All injectable CGRP antibody medications were studied. Responses were recorded in an electronic diary. Patients were followed at 3 and 6 months and were excluded if their diary was < 80% complete; a total of 158 patients were included in this study. At 3 months, groups of patients were further divided between those who had > 50% decrease in monthly headache days and those that had < 50% reduction.

The > 50% group showed statistically significant reductions in the ratios of photophobia, phonophobia, and aura after 6 months of treatment, and, of note, these symptoms decreased at a higher rate than the reduction in headache days per month after 6 months. Rates of nausea and dizziness only reduced proportionally to the monthly headache days. For the < 50% group, there was a rebound of dizziness in between months 3 and 6, but all other outcomes decreased in proportion to the monthly headache days.

Our patients all experience symptoms other than headache pain as part of their migraine attacks. When we discuss the risks and benefits of a new treatment, we can now more accurately address many of the other associated symptoms and explain what our patients are likely to expect when starting a new medication. Similar studies have described these findings with the oral CGRP antagonists as well, and most acute migraine studies now use "most bothersome symptom" rather than pain severity as their primary outcome.

This month we will discuss "migraine plus" conditions: menstrual migraine as well as migraine-associated symptoms, including allodynia, photophobia, and nausea.

Migraine is one of the most common and disabling conditions worldwide, and it is three times more likely to be found in women than men. This is even more so during reproductive years, where many women experience hormonally triggered migraine attacks. Although some women will experience migraine exclusively perimenstrually, most women who experience menstrual migraine attacks also will have migraine attacks that are not hormonally triggered. It is often challenging to find the correct acute treatment for specific kinds of migraine attacks, and many women will describe specific acute medications as more effective for their nonmenstrual or "regular" migraine attacks compared with their perimenstrual attacks. The study by MacGregor and colleagues investigated the use of ubrogepant and compared its effect between these two subtypes of attacks.

This trial was an extension of the initial phase 3 trial of ubrogepant, called ACHIEVE II. Initial investigators enrolled over 700 patients into an open-label extension, and the participants were randomly assigned 1:1:1 to their "usual care," 50 mg ubrogepant, or 100 mg ubrogepant. Participants were blinded to the dose of ubrogepant even though they knew that they were taking ubrogepant or their standard acute medication. The purpose of the "usual care" arm was not to collect efficacy results; rather, it was for safety, specifically to evaluate the long-term hepatic safety with ubrogepant.

Participants were allowed to treat up to eight migraine attacks per 4-week interval. The duration of the trial was 52 weeks, and a second dose of medication was allowed, identical to the initial dose. Women in this trial recorded their menstrual start date and whether they treated menstrually related attacks. An attack was considered menstrually related if the headache was within a 5-day window of the onset of menstruation. Of the 734 women enrolled in the intention-to-treat population, 354 reported at least one menstrual cycle start date with a headache day. Efficacy outcome measures included pain freedom at 2 hours post-dose, pain relief at 2 hours post-dose, absence of photophobia, phonophobia, and nausea at 2 hours post-dose, normal function at 2 hours post-dose, and use of rescue medication within 24 hours of the initial dose. All information was collected via an electronic diary.

There was no statistically significant difference between 2-hour pain freedom outcomes of menstrual and nonmenstrual migraine attacks, although there was a numerically higher mean percentage of menstrual attacks that was not statistically significant. This was noted for both doses of ubrogepant. This was also the case for 2-hour pain relief; the migraine-associated symptoms of photophobia, phonophobia, and nausea; for functional disability; and the use of a rescue medication. Among all outcomes it appears that both doses of ubrogepant are equally effective for both menstrual and nonmenstrual migraine attacks. On the basis of this evidence, clinicians may be able to consolidate different acute medications for different migraine subtypes and consider the use of this calcitonin gene-related peptide (CGRP) antagonist for all the patient's attacks.

Allodynia is a condition whereby a nonpainful stimulus is perceived as painful. In the context of migraine, this often will occur in the head and neck region and as a result of the chronification of migraine — headache frequency increasing to > 15 days per month. One significant risk factor for the development of chronic migraine is medication overuse, when an acute medication for migraine is used more often than its recommended use. Pijpers and colleagues sought to determine whether the presence of allodynia was predictive for the prognosis of chronic migraine complicated by medication overuse.

This study was a subset of the Chronification And Reversibility of Migraine (CHARM) study, a randomized, double-blind, placebo-controlled trial that aimed to investigate whether treatment with botulinum toxin A was of added value in addition to withdrawal therapy in chronic migraine patients with medication overuse headache. Diagnoses were made in consultation with headache experts and confirmed by a headache diary. Exclusion criteria were: (1) other primary headache or neurologic disorders; (2) other chronic pain disorders with medium to high pain intensity or requiring pain medication; (3) major psychiatric disorders other than depression; (4) major cognitive, behavioral, or oncologic disorders; (5) contraindications for treatment or inability to adhere to the study protocol; (6) (planned) pregnancy or breastfeeding; (7) use of ergots, opioids, or barbiturates; or (8) abuse of drugs in the past 12 months. Allodynia was determined by the Allodynia Symptom Checklist (ASC) .

The primary outcome was reversion from chronic to episodic migraine; secondary outcomes were > 50% reduction in monthly migraine days and reduction in number of monthly headache days. A total of 173 participants in the CHARM trial provided baseline allodynia data and were included in this current study. Participants with cutaneous allodynia were mainly women and did not differ significantly in age, number of monthly migraine or headache days, age of onset, use of acute or prophylactic treatment, or being treated with botulinum toxin.

The absence of cutaneous allodynia was predictive for good outcome after 12 weeks. For the primary endpoint, the odds for reversion from chronic migraine to episodic migraine were 2.5 times higher for participants without allodynia vs with allodynia. In all, 75.0% of participants without allodynia vs 57.4% of participants with allodynia reverted to episodic migraine. These helpful data will allow us to better predict accurately the disease process and better set expectations for our patients with chronic migraine.

In the earlier days of headache treatment, the focus for both acute and preventive medications was a decrease in the severity or frequency of pain. As time has progressed and our understanding of migraine has broadened, we now consider pain one of the many features of migraine, albeit usually the most prominent feature. The CGRP antagonist class of migraine medications has revolutionized how migraine is treated, both acutely and preventively; however, the initial studies all focused on pain-related outcomes. Alpuente and colleagues sought to better determine the effect of CGRP monoclonal antibody medications on other migraine-associated symptoms, specifically photophobia, photophobia, nausea, dizziness, and aura.

All injectable CGRP antibody medications were studied. Responses were recorded in an electronic diary. Patients were followed at 3 and 6 months and were excluded if their diary was < 80% complete; a total of 158 patients were included in this study. At 3 months, groups of patients were further divided between those who had > 50% decrease in monthly headache days and those that had < 50% reduction.

The > 50% group showed statistically significant reductions in the ratios of photophobia, phonophobia, and aura after 6 months of treatment, and, of note, these symptoms decreased at a higher rate than the reduction in headache days per month after 6 months. Rates of nausea and dizziness only reduced proportionally to the monthly headache days. For the < 50% group, there was a rebound of dizziness in between months 3 and 6, but all other outcomes decreased in proportion to the monthly headache days.

Our patients all experience symptoms other than headache pain as part of their migraine attacks. When we discuss the risks and benefits of a new treatment, we can now more accurately address many of the other associated symptoms and explain what our patients are likely to expect when starting a new medication. Similar studies have described these findings with the oral CGRP antagonists as well, and most acute migraine studies now use "most bothersome symptom" rather than pain severity as their primary outcome.

Lead is significantly more harmful to the health of children and adults across the world than previously thought. This conclusion is suggested by a modeling study presented by Norwegian development economist Bjorn Larsen and the Colombian environmental specialist for lead Ernesto Sánchez-Triana, PhD, in a presentation to the World Bank. Their work was published in The Lancet Planetary Health.

As Mr. Larsen and Mr. Sánchez-Triana report, the economic consequences of increased exposure to lead are already immense, especially in low- and middle-income countries (LMICs). The study was financed by the Korea Green Growth Trust Fund and the World Bank’s Pollution Management and Environmental Health Program.
 

Intellectual, cardiovascular effects

“It is a very important publication that affects all of us,” pediatrician Stephan Böse-O’Reilly, MD, of the Institute and Polyclinic for Occupational, Social, and Environmental Health at Ludwig Maximilian University Hospital in Munich, Germany, said in an interview. “The study, the results of which I think are very reliable, shows that elevated levels of lead in the blood have a much more drastic effect on children’s intelligence than we previously thought.”

It is well known that lead affects the antenatal and postnatal cognitive development of children, Dr. Böse-O’Reilly explained. But the extent of this effect has quite clearly been underestimated before now.

On the other hand, Mr. Larsen and Mr. Sánchez-Triana’s work could prove that lead may lead to more cardiovascular diseases in adulthood. “We already knew that increased exposure to lead increased the risk of high blood pressure and, as a result, mortality,” said Dr. Böse-O’Reilly. “This study now very clearly shows that the risk of arteriosclerosis, for example, also increases through lead exposure.”
 

Figures from 2019

“For the first time, to our knowledge, we aimed to estimate the global burden and cost of IQ loss and cardiovascular disease mortality from lead exposure,” wrote Mr. Larsen and Mr. Sánchez-Triana. For their calculations, the scientists used blood lead level estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.

They estimated IQ loss in children younger than 5 years using the internationally recognized blood lead level–IQ loss function. The researchers subsequently estimated the cost of this IQ loss based on the loss in lifetime income, presented as cost in U.S. dollars and percentage of gross domestic product (GDP).

Mr. Larsen and Mr. Sánchez-Triana estimated cardiovascular deaths caused by lead exposure in adults aged 25 years or older using a model that captures the effects of lead exposure on cardiovascular disease mortality that is mediated through mechanisms other than hypertension.

Finally, they used the statistical life expectancy to estimate the welfare cost of premature mortality, also presented as cost in U.S. dollars and percentage of GDP. All estimates were calculated according to the World Bank income classification for 2019.
 

Millions of deaths

As reported by Mr. Larsen and Mr. Sánchez-Triana, children younger than 5 years lost an estimated 765 million IQ points worldwide because of lead exposure in this period. In 2019, 5,545,000 adults died from cardiovascular diseases caused by lead exposure. The scientists recorded 729 million of the IQ points lost (95.3%) and 5,004,000 (90.2%) of the deaths as occurring in LMICs.

The IQ loss here was nearly 80% higher than a previous estimate, wrote Mr. Larsen and Mr. Sánchez-Triana. The number of cardiovascular disease deaths they determined was six times higher than the GBD 2019 estimate.

“These are results with which the expert societies, especially the German Society of Pediatrics and Adolescent Medicine and the German Cardiac Society, and the corresponding professional associations need to concern themselves,” said Dr. Böse-O’Reilly.

Although blood lead concentrations have declined substantially since the phase-out of leaded gasoline, especially in Western countries, lead still represents a major health issue because it stays in the bones for decades.

European situation moderate

“We need a broad discussion on questions such as whether lead levels should be included in prophylactic assessments in certain age groups, what blood level is even tolerable, and in what situation medicinal therapy with chelating agents would possibly be appropriate,” said Dr. Böse-O’Reilly.

“Of course, we cannot answer these questions on the basis of one individual study,” he added. “However, the work in question definitely illustrates how dangerous lead can be and that we need further research into the actual burden and the best preventive measures.”

In this respect, the situation in Europe is still comparatively moderate. “Globally, lead exposure has risen in recent years,” said Dr. Böse-O’Reilly. According to an investigation by the Planet Earth Foundation, outside of the European Union, lead can increasingly be found in toys, spices, and cooking utensils, for example.

“Especially in lower-income countries, there is a lack of consumer protection or a good monitoring program like we have here in the EU,” said Dr. Böse-O’Reilly. In these countries, lead is sometimes added to spices by unscrupulous retailers to make the color more intense or to simply add to its weight to gain more profit.

Recycling lead-acid batteries or other electrical waste, often transferred to poorer countries, constitutes a large problem. “In general, children in Germany have a blood lead level of less than 1 mcg/dL,” explained Dr. Böse-O’Reilly. “In some regions of Indonesia, where these recycling factories are located, more than 50% of children have levels of more than 20 mcg/dL.”
 

Particulate matter

According to Mr. Larsen and Mr. Sánchez-Triana, the global cost of increased lead exposure was around $6 trillion USD in 2019, which was equivalent to 6.9% of global GDP. About 77% of the cost ($4.62 trillion USD) comprised the welfare costs of cardiovascular disease mortality, and 23% ($1.38 trillion USD) comprised the present value of future income losses because of IQ loss in children.

“Our findings suggest that global lead exposure has health and economic costs on par with PM2.5 air pollution,” wrote the authors. This places lead as an environmental risk factor on par with particulate matter and above that of air pollution from solid fuels, ahead of unsafe drinking water, unhygienic sanitation, or insufficient handwashing.

“This finding is in contrast to that of GBD 2019, which ranked lead exposure as a distant fourth environmental risk factor, due to not accounting for IQ loss in children – other than idiopathic developmental intellectual disability in a small subset of children – and reporting a substantially lower estimate of adult cardiovascular disease mortality,” wrote Mr. Larsen and Mr. Sánchez-Triana.

“A central implication for future research and policy is that LMICs bear an extraordinarily large share of the health and cost burden of lead exposure,” wrote the authors. Consequently, improved quality of blood lead level measurements and identification of sources containing lead are urgently needed there.
 

Improved recycling methods

Dr. Böse-O’Reilly would like an increased focus on children. “If children’s cognitive skills are lost, this of course has a long-term effect on a country’s economic position,” he said. “Precisely that which LMICs actually need for their development is being stripped from them.

“We should think long and hard about whether we really need to send so much of our electrical waste and so many old cars to poorer countries, where they are incorrectly recycled,” he warned. “We should at least give the LMICs the support necessary for them to be able to process lead-containing products in the future so that less lead makes it into the environment.

“Through these global cycles, we all contribute a lot toward the worldwide lead burden,” Dr. Böse-O’Reilly said. “In my opinion, the German Supply Chain Act is therefore definitely sensible. Not only does it protect our own economy, but it also protects the health of people in other countries.”

This article was translated from Medscape’s German Edition. A version of this article appeared on Medscape.com.

Lead is significantly more harmful to the health of children and adults across the world than previously thought. This conclusion is suggested by a modeling study presented by Norwegian development economist Bjorn Larsen and the Colombian environmental specialist for lead Ernesto Sánchez-Triana, PhD, in a presentation to the World Bank. Their work was published in The Lancet Planetary Health.

As Mr. Larsen and Mr. Sánchez-Triana report, the economic consequences of increased exposure to lead are already immense, especially in low- and middle-income countries (LMICs). The study was financed by the Korea Green Growth Trust Fund and the World Bank’s Pollution Management and Environmental Health Program.
 

Intellectual, cardiovascular effects

“It is a very important publication that affects all of us,” pediatrician Stephan Böse-O’Reilly, MD, of the Institute and Polyclinic for Occupational, Social, and Environmental Health at Ludwig Maximilian University Hospital in Munich, Germany, said in an interview. “The study, the results of which I think are very reliable, shows that elevated levels of lead in the blood have a much more drastic effect on children’s intelligence than we previously thought.”

It is well known that lead affects the antenatal and postnatal cognitive development of children, Dr. Böse-O’Reilly explained. But the extent of this effect has quite clearly been underestimated before now.

On the other hand, Mr. Larsen and Mr. Sánchez-Triana’s work could prove that lead may lead to more cardiovascular diseases in adulthood. “We already knew that increased exposure to lead increased the risk of high blood pressure and, as a result, mortality,” said Dr. Böse-O’Reilly. “This study now very clearly shows that the risk of arteriosclerosis, for example, also increases through lead exposure.”
 

Figures from 2019

“For the first time, to our knowledge, we aimed to estimate the global burden and cost of IQ loss and cardiovascular disease mortality from lead exposure,” wrote Mr. Larsen and Mr. Sánchez-Triana. For their calculations, the scientists used blood lead level estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.

They estimated IQ loss in children younger than 5 years using the internationally recognized blood lead level–IQ loss function. The researchers subsequently estimated the cost of this IQ loss based on the loss in lifetime income, presented as cost in U.S. dollars and percentage of gross domestic product (GDP).

Mr. Larsen and Mr. Sánchez-Triana estimated cardiovascular deaths caused by lead exposure in adults aged 25 years or older using a model that captures the effects of lead exposure on cardiovascular disease mortality that is mediated through mechanisms other than hypertension.

Finally, they used the statistical life expectancy to estimate the welfare cost of premature mortality, also presented as cost in U.S. dollars and percentage of GDP. All estimates were calculated according to the World Bank income classification for 2019.
 

Millions of deaths

As reported by Mr. Larsen and Mr. Sánchez-Triana, children younger than 5 years lost an estimated 765 million IQ points worldwide because of lead exposure in this period. In 2019, 5,545,000 adults died from cardiovascular diseases caused by lead exposure. The scientists recorded 729 million of the IQ points lost (95.3%) and 5,004,000 (90.2%) of the deaths as occurring in LMICs.

The IQ loss here was nearly 80% higher than a previous estimate, wrote Mr. Larsen and Mr. Sánchez-Triana. The number of cardiovascular disease deaths they determined was six times higher than the GBD 2019 estimate.

“These are results with which the expert societies, especially the German Society of Pediatrics and Adolescent Medicine and the German Cardiac Society, and the corresponding professional associations need to concern themselves,” said Dr. Böse-O’Reilly.

Although blood lead concentrations have declined substantially since the phase-out of leaded gasoline, especially in Western countries, lead still represents a major health issue because it stays in the bones for decades.

European situation moderate

“We need a broad discussion on questions such as whether lead levels should be included in prophylactic assessments in certain age groups, what blood level is even tolerable, and in what situation medicinal therapy with chelating agents would possibly be appropriate,” said Dr. Böse-O’Reilly.

“Of course, we cannot answer these questions on the basis of one individual study,” he added. “However, the work in question definitely illustrates how dangerous lead can be and that we need further research into the actual burden and the best preventive measures.”

In this respect, the situation in Europe is still comparatively moderate. “Globally, lead exposure has risen in recent years,” said Dr. Böse-O’Reilly. According to an investigation by the Planet Earth Foundation, outside of the European Union, lead can increasingly be found in toys, spices, and cooking utensils, for example.

“Especially in lower-income countries, there is a lack of consumer protection or a good monitoring program like we have here in the EU,” said Dr. Böse-O’Reilly. In these countries, lead is sometimes added to spices by unscrupulous retailers to make the color more intense or to simply add to its weight to gain more profit.

Recycling lead-acid batteries or other electrical waste, often transferred to poorer countries, constitutes a large problem. “In general, children in Germany have a blood lead level of less than 1 mcg/dL,” explained Dr. Böse-O’Reilly. “In some regions of Indonesia, where these recycling factories are located, more than 50% of children have levels of more than 20 mcg/dL.”
 

Particulate matter

According to Mr. Larsen and Mr. Sánchez-Triana, the global cost of increased lead exposure was around $6 trillion USD in 2019, which was equivalent to 6.9% of global GDP. About 77% of the cost ($4.62 trillion USD) comprised the welfare costs of cardiovascular disease mortality, and 23% ($1.38 trillion USD) comprised the present value of future income losses because of IQ loss in children.

“Our findings suggest that global lead exposure has health and economic costs on par with PM2.5 air pollution,” wrote the authors. This places lead as an environmental risk factor on par with particulate matter and above that of air pollution from solid fuels, ahead of unsafe drinking water, unhygienic sanitation, or insufficient handwashing.

“This finding is in contrast to that of GBD 2019, which ranked lead exposure as a distant fourth environmental risk factor, due to not accounting for IQ loss in children – other than idiopathic developmental intellectual disability in a small subset of children – and reporting a substantially lower estimate of adult cardiovascular disease mortality,” wrote Mr. Larsen and Mr. Sánchez-Triana.

“A central implication for future research and policy is that LMICs bear an extraordinarily large share of the health and cost burden of lead exposure,” wrote the authors. Consequently, improved quality of blood lead level measurements and identification of sources containing lead are urgently needed there.
 

Improved recycling methods

Dr. Böse-O’Reilly would like an increased focus on children. “If children’s cognitive skills are lost, this of course has a long-term effect on a country’s economic position,” he said. “Precisely that which LMICs actually need for their development is being stripped from them.

“We should think long and hard about whether we really need to send so much of our electrical waste and so many old cars to poorer countries, where they are incorrectly recycled,” he warned. “We should at least give the LMICs the support necessary for them to be able to process lead-containing products in the future so that less lead makes it into the environment.

“Through these global cycles, we all contribute a lot toward the worldwide lead burden,” Dr. Böse-O’Reilly said. “In my opinion, the German Supply Chain Act is therefore definitely sensible. Not only does it protect our own economy, but it also protects the health of people in other countries.”

This article was translated from Medscape’s German Edition. A version of this article appeared on Medscape.com.

Lead is significantly more harmful to the health of children and adults across the world than previously thought. This conclusion is suggested by a modeling study presented by Norwegian development economist Bjorn Larsen and the Colombian environmental specialist for lead Ernesto Sánchez-Triana, PhD, in a presentation to the World Bank. Their work was published in The Lancet Planetary Health.

As Mr. Larsen and Mr. Sánchez-Triana report, the economic consequences of increased exposure to lead are already immense, especially in low- and middle-income countries (LMICs). The study was financed by the Korea Green Growth Trust Fund and the World Bank’s Pollution Management and Environmental Health Program.
 

Intellectual, cardiovascular effects

“It is a very important publication that affects all of us,” pediatrician Stephan Böse-O’Reilly, MD, of the Institute and Polyclinic for Occupational, Social, and Environmental Health at Ludwig Maximilian University Hospital in Munich, Germany, said in an interview. “The study, the results of which I think are very reliable, shows that elevated levels of lead in the blood have a much more drastic effect on children’s intelligence than we previously thought.”

It is well known that lead affects the antenatal and postnatal cognitive development of children, Dr. Böse-O’Reilly explained. But the extent of this effect has quite clearly been underestimated before now.

On the other hand, Mr. Larsen and Mr. Sánchez-Triana’s work could prove that lead may lead to more cardiovascular diseases in adulthood. “We already knew that increased exposure to lead increased the risk of high blood pressure and, as a result, mortality,” said Dr. Böse-O’Reilly. “This study now very clearly shows that the risk of arteriosclerosis, for example, also increases through lead exposure.”
 

Figures from 2019

“For the first time, to our knowledge, we aimed to estimate the global burden and cost of IQ loss and cardiovascular disease mortality from lead exposure,” wrote Mr. Larsen and Mr. Sánchez-Triana. For their calculations, the scientists used blood lead level estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.

They estimated IQ loss in children younger than 5 years using the internationally recognized blood lead level–IQ loss function. The researchers subsequently estimated the cost of this IQ loss based on the loss in lifetime income, presented as cost in U.S. dollars and percentage of gross domestic product (GDP).

Mr. Larsen and Mr. Sánchez-Triana estimated cardiovascular deaths caused by lead exposure in adults aged 25 years or older using a model that captures the effects of lead exposure on cardiovascular disease mortality that is mediated through mechanisms other than hypertension.

Finally, they used the statistical life expectancy to estimate the welfare cost of premature mortality, also presented as cost in U.S. dollars and percentage of GDP. All estimates were calculated according to the World Bank income classification for 2019.
 

Millions of deaths

As reported by Mr. Larsen and Mr. Sánchez-Triana, children younger than 5 years lost an estimated 765 million IQ points worldwide because of lead exposure in this period. In 2019, 5,545,000 adults died from cardiovascular diseases caused by lead exposure. The scientists recorded 729 million of the IQ points lost (95.3%) and 5,004,000 (90.2%) of the deaths as occurring in LMICs.

The IQ loss here was nearly 80% higher than a previous estimate, wrote Mr. Larsen and Mr. Sánchez-Triana. The number of cardiovascular disease deaths they determined was six times higher than the GBD 2019 estimate.

“These are results with which the expert societies, especially the German Society of Pediatrics and Adolescent Medicine and the German Cardiac Society, and the corresponding professional associations need to concern themselves,” said Dr. Böse-O’Reilly.

Although blood lead concentrations have declined substantially since the phase-out of leaded gasoline, especially in Western countries, lead still represents a major health issue because it stays in the bones for decades.

European situation moderate

“We need a broad discussion on questions such as whether lead levels should be included in prophylactic assessments in certain age groups, what blood level is even tolerable, and in what situation medicinal therapy with chelating agents would possibly be appropriate,” said Dr. Böse-O’Reilly.

“Of course, we cannot answer these questions on the basis of one individual study,” he added. “However, the work in question definitely illustrates how dangerous lead can be and that we need further research into the actual burden and the best preventive measures.”

In this respect, the situation in Europe is still comparatively moderate. “Globally, lead exposure has risen in recent years,” said Dr. Böse-O’Reilly. According to an investigation by the Planet Earth Foundation, outside of the European Union, lead can increasingly be found in toys, spices, and cooking utensils, for example.

“Especially in lower-income countries, there is a lack of consumer protection or a good monitoring program like we have here in the EU,” said Dr. Böse-O’Reilly. In these countries, lead is sometimes added to spices by unscrupulous retailers to make the color more intense or to simply add to its weight to gain more profit.

Recycling lead-acid batteries or other electrical waste, often transferred to poorer countries, constitutes a large problem. “In general, children in Germany have a blood lead level of less than 1 mcg/dL,” explained Dr. Böse-O’Reilly. “In some regions of Indonesia, where these recycling factories are located, more than 50% of children have levels of more than 20 mcg/dL.”
 

Particulate matter

According to Mr. Larsen and Mr. Sánchez-Triana, the global cost of increased lead exposure was around $6 trillion USD in 2019, which was equivalent to 6.9% of global GDP. About 77% of the cost ($4.62 trillion USD) comprised the welfare costs of cardiovascular disease mortality, and 23% ($1.38 trillion USD) comprised the present value of future income losses because of IQ loss in children.

“Our findings suggest that global lead exposure has health and economic costs on par with PM2.5 air pollution,” wrote the authors. This places lead as an environmental risk factor on par with particulate matter and above that of air pollution from solid fuels, ahead of unsafe drinking water, unhygienic sanitation, or insufficient handwashing.

“This finding is in contrast to that of GBD 2019, which ranked lead exposure as a distant fourth environmental risk factor, due to not accounting for IQ loss in children – other than idiopathic developmental intellectual disability in a small subset of children – and reporting a substantially lower estimate of adult cardiovascular disease mortality,” wrote Mr. Larsen and Mr. Sánchez-Triana.

“A central implication for future research and policy is that LMICs bear an extraordinarily large share of the health and cost burden of lead exposure,” wrote the authors. Consequently, improved quality of blood lead level measurements and identification of sources containing lead are urgently needed there.
 

Improved recycling methods

Dr. Böse-O’Reilly would like an increased focus on children. “If children’s cognitive skills are lost, this of course has a long-term effect on a country’s economic position,” he said. “Precisely that which LMICs actually need for their development is being stripped from them.

“We should think long and hard about whether we really need to send so much of our electrical waste and so many old cars to poorer countries, where they are incorrectly recycled,” he warned. “We should at least give the LMICs the support necessary for them to be able to process lead-containing products in the future so that less lead makes it into the environment.

“Through these global cycles, we all contribute a lot toward the worldwide lead burden,” Dr. Böse-O’Reilly said. “In my opinion, the German Supply Chain Act is therefore definitely sensible. Not only does it protect our own economy, but it also protects the health of people in other countries.”

This article was translated from Medscape’s German Edition. A version of this article appeared on Medscape.com.

TOPLINE:

People with a history of depression or stress were significantly more likely to be diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) later in life compared with those without either condition, a new study found.

METHODOLOGY:

• Longitudinal cohort study of 1,362,548 people with records in the Region Stockholm administrative health care database with a diagnosis of stress-induced exhaustion disorder (SED), depression, or both between 2012 and 2013.
• Cohort followed for diagnosis of MCI or AD between 2014 and 2022.

TAKEAWAY:

• SED diagnosed in 0.3%, depression in 2.9% and both SED and depression in 0.1%
• Compared with people without SED or depression, AD risk was more than double in patients with SED (adjusted odds ratio [aOR], 2.45; 99% confidence interval [CI], 1.22-4.91) or depression (aOR, 2.32; 99% CI, 1.85-2.90) and four times higher in patients with both SED and depression (aOR, 4.00; 99% CI, 1.67-9.58)
• Risk for MCI was also higher in people with SED (aOR, 1.87; 99% CI,1.20-2.91), depression (aOR, 2.85; 99% CI, 2.53-3.22) or both SED and depression (aOR, 3.87; 99% CI, 2.39-6.27) vs patients with no history of SED or depression.
• Only patients with depression had a higher risk for another dementia type (aOR, 2.39; 99% CI, 1.92-2.96).

IN PRACTICE:

“Future studies should examine the possibility that symptoms of depression and/or chronic stress could be prodromal symptoms of dementia rather than risk factors,” study authors wrote.

SOURCE:

The study was conducted by Johanna Wallensten, doctoral student, department of clinical sciences, Danderyd Hospital, Stockholm, and colleagues and funded by the Karolinska Institute. It was published online in Alzheimer’s Research and Therapy.

LIMITATIONS:

Use of a health care registry could have led to over- or underestimation of depression, MCI and AD. The study probably captures most people with depression but not most people with depressive symptoms.

DISCLOSURES:

The authors reported no relevant conflicts.

A version of this article appeared on Medscape.com.

TOPLINE:

People with a history of depression or stress were significantly more likely to be diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) later in life compared with those without either condition, a new study found.

METHODOLOGY:

• Longitudinal cohort study of 1,362,548 people with records in the Region Stockholm administrative health care database with a diagnosis of stress-induced exhaustion disorder (SED), depression, or both between 2012 and 2013.
• Cohort followed for diagnosis of MCI or AD between 2014 and 2022.

TAKEAWAY:

• SED diagnosed in 0.3%, depression in 2.9% and both SED and depression in 0.1%
• Compared with people without SED or depression, AD risk was more than double in patients with SED (adjusted odds ratio [aOR], 2.45; 99% confidence interval [CI], 1.22-4.91) or depression (aOR, 2.32; 99% CI, 1.85-2.90) and four times higher in patients with both SED and depression (aOR, 4.00; 99% CI, 1.67-9.58)
• Risk for MCI was also higher in people with SED (aOR, 1.87; 99% CI,1.20-2.91), depression (aOR, 2.85; 99% CI, 2.53-3.22) or both SED and depression (aOR, 3.87; 99% CI, 2.39-6.27) vs patients with no history of SED or depression.
• Only patients with depression had a higher risk for another dementia type (aOR, 2.39; 99% CI, 1.92-2.96).

IN PRACTICE:

“Future studies should examine the possibility that symptoms of depression and/or chronic stress could be prodromal symptoms of dementia rather than risk factors,” study authors wrote.

SOURCE:

The study was conducted by Johanna Wallensten, doctoral student, department of clinical sciences, Danderyd Hospital, Stockholm, and colleagues and funded by the Karolinska Institute. It was published online in Alzheimer’s Research and Therapy.

LIMITATIONS:

Use of a health care registry could have led to over- or underestimation of depression, MCI and AD. The study probably captures most people with depression but not most people with depressive symptoms.

DISCLOSURES:

The authors reported no relevant conflicts.

A version of this article appeared on Medscape.com.

TOPLINE:

People with a history of depression or stress were significantly more likely to be diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) later in life compared with those without either condition, a new study found.

METHODOLOGY:

• Longitudinal cohort study of 1,362,548 people with records in the Region Stockholm administrative health care database with a diagnosis of stress-induced exhaustion disorder (SED), depression, or both between 2012 and 2013.
• Cohort followed for diagnosis of MCI or AD between 2014 and 2022.

TAKEAWAY:

• SED diagnosed in 0.3%, depression in 2.9% and both SED and depression in 0.1%
• Compared with people without SED or depression, AD risk was more than double in patients with SED (adjusted odds ratio [aOR], 2.45; 99% confidence interval [CI], 1.22-4.91) or depression (aOR, 2.32; 99% CI, 1.85-2.90) and four times higher in patients with both SED and depression (aOR, 4.00; 99% CI, 1.67-9.58)
• Risk for MCI was also higher in people with SED (aOR, 1.87; 99% CI,1.20-2.91), depression (aOR, 2.85; 99% CI, 2.53-3.22) or both SED and depression (aOR, 3.87; 99% CI, 2.39-6.27) vs patients with no history of SED or depression.
• Only patients with depression had a higher risk for another dementia type (aOR, 2.39; 99% CI, 1.92-2.96).

IN PRACTICE:

“Future studies should examine the possibility that symptoms of depression and/or chronic stress could be prodromal symptoms of dementia rather than risk factors,” study authors wrote.

SOURCE:

The study was conducted by Johanna Wallensten, doctoral student, department of clinical sciences, Danderyd Hospital, Stockholm, and colleagues and funded by the Karolinska Institute. It was published online in Alzheimer’s Research and Therapy.

LIMITATIONS:

Use of a health care registry could have led to over- or underestimation of depression, MCI and AD. The study probably captures most people with depression but not most people with depressive symptoms.

DISCLOSURES:

The authors reported no relevant conflicts.

A version of this article appeared on Medscape.com.

SAN DIEGO – In low- and middle-income countries with high incidence and mortality from head and neck cancer, resources remain limited. Patients often can’t travel far for treatment or afford to stay near a treatment center for the length of time required for conventionally fractionated radiotherapy.

A hypofractionated radiotherapy regimen with or without weekly cisplatin may be a viable alternative for patients with locally advanced head and neck cancer in these settings.

The phase 3 randomized HYPNO trial, conducted in 10 low- and middle-income countries, revealed that the hypofractionated regimen shortened total treatment time by a median of 11.5 days and was noninferior to conventional fractionation for tumor control and safety.

The primary trial results were presented by Søren Bentzen, PhD, DMSc, at the annual meeting of the American Society for Radiation Oncology.

“It was Usain Bolt who said, ‘I train for 4 years to run 9 seconds,’ and that was the feeling that I had when we did the noninferiority test,” said Dr. Bentzen, from the University of Maryland School of Medicine in Baltimore. “We had not looked at the data while the data were being accumulated, and guess what? It actually turned out that we had noninferiority with respect to both locoregional control and the late effects.”

In the HYPNO trial, Dr. Bentzen and colleagues wanted to determine whether a streamlined approach to the treatment of patients in low- and middle-income countries could improve access to care and still achieve strong outcomes.

The investigators used mathematical modeling to devise a strategy to reduce the number of fractions and put this hypothesis to the test in a pragmatic trial.

Patients from Uruguay, Brazil, Argentina, Cuba, South Africa, India, Pakistan, Thailand, Indonesia, and the Philippines were enrolled. After stratification by performance status, tumor subsite, institution, and previous treatment with chemotherapy, the 792 patients in the trial were randomly assigned in a 1:1 ratio to receive either 66 Gy in 33 fractions 6 days each week over 5.5 weeks, or 55 Gy in 20 fractions 5 days per week over 4 weeks. In both groups, weekly cisplatin was optional.

Compliance with the regimens was high in both arms, with 95% of patients assigned to conventional fractionation and 99% assigned to hypofractionation receiving the total planned doses.

At 3 years’ follow-up, the rates of locoregional control were 50.7% in the hypofractionation arm and 51.2% in the conventional fractionation arm (P = .40). No significant differences between the groups have emerged over 5 years, Dr. Bentzen said.

Rates of late toxicities of grade 3 or greater at 3 years’ follow-up were similar between the groups, at 18.8% in the hypofractionation arm and 20.2% in the conventional fractionation arm (P = .68).

Three-year overall survival rates also did not differ between the groups – 54.1% in the hypofractionation arm vs. 55.5% in the conventional arm (P = .62) – nor did rates of progression-free survival – 44.0% vs. 45.3%.

“Head and neck cancer caused by factors other than the human papillomavirus (HPV) remains a significant burden especially in lower- and middle-income countries,” Dr. Bentzen said in a press release. “This is a trial that directly informs how you can effectively deliver radiation therapy to patients in a resource-scarce environment.”

Beth Beadle, MD, PhD, the invited discussant at a media briefing where Dr. Bentzen summarized the findings, said, “I think this trial is going to change practice in low- and middle-income countries and will improve access to care.”

Although the approach used in the HYPNO trial will likely allow more patients to receive treatment and will save lives in countries with limited resources, the strategy likely won’t apply to U.S. practice, noted Dr. Beadle, a professor of radiation oncology at Stanford University, California.

“The one thing I do caution, and that Dr. Bentzen brought up, is that this is a very different population than the one that we see in the United States now,” Dr. Beadle said. “In fact, it’s very challenging to find a similar patient population to even serve as a comparison in the modern era and modern techniques.”

The HYPNO trial was sponsored by the International Atomic Energy Agency. Dr. Bentzen and Dr. Beadle have disclosed no relevant financial relationships.

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

SAN DIEGO – In low- and middle-income countries with high incidence and mortality from head and neck cancer, resources remain limited. Patients often can’t travel far for treatment or afford to stay near a treatment center for the length of time required for conventionally fractionated radiotherapy.

A hypofractionated radiotherapy regimen with or without weekly cisplatin may be a viable alternative for patients with locally advanced head and neck cancer in these settings.

The phase 3 randomized HYPNO trial, conducted in 10 low- and middle-income countries, revealed that the hypofractionated regimen shortened total treatment time by a median of 11.5 days and was noninferior to conventional fractionation for tumor control and safety.

The primary trial results were presented by Søren Bentzen, PhD, DMSc, at the annual meeting of the American Society for Radiation Oncology.

“It was Usain Bolt who said, ‘I train for 4 years to run 9 seconds,’ and that was the feeling that I had when we did the noninferiority test,” said Dr. Bentzen, from the University of Maryland School of Medicine in Baltimore. “We had not looked at the data while the data were being accumulated, and guess what? It actually turned out that we had noninferiority with respect to both locoregional control and the late effects.”

In the HYPNO trial, Dr. Bentzen and colleagues wanted to determine whether a streamlined approach to the treatment of patients in low- and middle-income countries could improve access to care and still achieve strong outcomes.

The investigators used mathematical modeling to devise a strategy to reduce the number of fractions and put this hypothesis to the test in a pragmatic trial.

Patients from Uruguay, Brazil, Argentina, Cuba, South Africa, India, Pakistan, Thailand, Indonesia, and the Philippines were enrolled. After stratification by performance status, tumor subsite, institution, and previous treatment with chemotherapy, the 792 patients in the trial were randomly assigned in a 1:1 ratio to receive either 66 Gy in 33 fractions 6 days each week over 5.5 weeks, or 55 Gy in 20 fractions 5 days per week over 4 weeks. In both groups, weekly cisplatin was optional.

Compliance with the regimens was high in both arms, with 95% of patients assigned to conventional fractionation and 99% assigned to hypofractionation receiving the total planned doses.

At 3 years’ follow-up, the rates of locoregional control were 50.7% in the hypofractionation arm and 51.2% in the conventional fractionation arm (P = .40). No significant differences between the groups have emerged over 5 years, Dr. Bentzen said.

Rates of late toxicities of grade 3 or greater at 3 years’ follow-up were similar between the groups, at 18.8% in the hypofractionation arm and 20.2% in the conventional fractionation arm (P = .68).

Three-year overall survival rates also did not differ between the groups – 54.1% in the hypofractionation arm vs. 55.5% in the conventional arm (P = .62) – nor did rates of progression-free survival – 44.0% vs. 45.3%.

“Head and neck cancer caused by factors other than the human papillomavirus (HPV) remains a significant burden especially in lower- and middle-income countries,” Dr. Bentzen said in a press release. “This is a trial that directly informs how you can effectively deliver radiation therapy to patients in a resource-scarce environment.”

Beth Beadle, MD, PhD, the invited discussant at a media briefing where Dr. Bentzen summarized the findings, said, “I think this trial is going to change practice in low- and middle-income countries and will improve access to care.”

Although the approach used in the HYPNO trial will likely allow more patients to receive treatment and will save lives in countries with limited resources, the strategy likely won’t apply to U.S. practice, noted Dr. Beadle, a professor of radiation oncology at Stanford University, California.

“The one thing I do caution, and that Dr. Bentzen brought up, is that this is a very different population than the one that we see in the United States now,” Dr. Beadle said. “In fact, it’s very challenging to find a similar patient population to even serve as a comparison in the modern era and modern techniques.”

The HYPNO trial was sponsored by the International Atomic Energy Agency. Dr. Bentzen and Dr. Beadle have disclosed no relevant financial relationships.

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

SAN DIEGO – In low- and middle-income countries with high incidence and mortality from head and neck cancer, resources remain limited. Patients often can’t travel far for treatment or afford to stay near a treatment center for the length of time required for conventionally fractionated radiotherapy.

A hypofractionated radiotherapy regimen with or without weekly cisplatin may be a viable alternative for patients with locally advanced head and neck cancer in these settings.

The phase 3 randomized HYPNO trial, conducted in 10 low- and middle-income countries, revealed that the hypofractionated regimen shortened total treatment time by a median of 11.5 days and was noninferior to conventional fractionation for tumor control and safety.

The primary trial results were presented by Søren Bentzen, PhD, DMSc, at the annual meeting of the American Society for Radiation Oncology.

“It was Usain Bolt who said, ‘I train for 4 years to run 9 seconds,’ and that was the feeling that I had when we did the noninferiority test,” said Dr. Bentzen, from the University of Maryland School of Medicine in Baltimore. “We had not looked at the data while the data were being accumulated, and guess what? It actually turned out that we had noninferiority with respect to both locoregional control and the late effects.”

In the HYPNO trial, Dr. Bentzen and colleagues wanted to determine whether a streamlined approach to the treatment of patients in low- and middle-income countries could improve access to care and still achieve strong outcomes.

The investigators used mathematical modeling to devise a strategy to reduce the number of fractions and put this hypothesis to the test in a pragmatic trial.

Patients from Uruguay, Brazil, Argentina, Cuba, South Africa, India, Pakistan, Thailand, Indonesia, and the Philippines were enrolled. After stratification by performance status, tumor subsite, institution, and previous treatment with chemotherapy, the 792 patients in the trial were randomly assigned in a 1:1 ratio to receive either 66 Gy in 33 fractions 6 days each week over 5.5 weeks, or 55 Gy in 20 fractions 5 days per week over 4 weeks. In both groups, weekly cisplatin was optional.

Compliance with the regimens was high in both arms, with 95% of patients assigned to conventional fractionation and 99% assigned to hypofractionation receiving the total planned doses.

At 3 years’ follow-up, the rates of locoregional control were 50.7% in the hypofractionation arm and 51.2% in the conventional fractionation arm (P = .40). No significant differences between the groups have emerged over 5 years, Dr. Bentzen said.

Rates of late toxicities of grade 3 or greater at 3 years’ follow-up were similar between the groups, at 18.8% in the hypofractionation arm and 20.2% in the conventional fractionation arm (P = .68).

Three-year overall survival rates also did not differ between the groups – 54.1% in the hypofractionation arm vs. 55.5% in the conventional arm (P = .62) – nor did rates of progression-free survival – 44.0% vs. 45.3%.

“Head and neck cancer caused by factors other than the human papillomavirus (HPV) remains a significant burden especially in lower- and middle-income countries,” Dr. Bentzen said in a press release. “This is a trial that directly informs how you can effectively deliver radiation therapy to patients in a resource-scarce environment.”

Beth Beadle, MD, PhD, the invited discussant at a media briefing where Dr. Bentzen summarized the findings, said, “I think this trial is going to change practice in low- and middle-income countries and will improve access to care.”

Although the approach used in the HYPNO trial will likely allow more patients to receive treatment and will save lives in countries with limited resources, the strategy likely won’t apply to U.S. practice, noted Dr. Beadle, a professor of radiation oncology at Stanford University, California.

“The one thing I do caution, and that Dr. Bentzen brought up, is that this is a very different population than the one that we see in the United States now,” Dr. Beadle said. “In fact, it’s very challenging to find a similar patient population to even serve as a comparison in the modern era and modern techniques.”

The HYPNO trial was sponsored by the International Atomic Energy Agency. Dr. Bentzen and Dr. Beadle have disclosed no relevant financial relationships.

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