Guilt reduction, now in deceptive and open-secret forms

Guilt plagues a lot of us, sometimes regularly. Maybe you felt bad about eating the leftovers that your partner was looking forward to eating at the end of the day. Or for not saving a seat for your friend who was running late to the movies. Maybe even hiding a secret that you know would hurt a person’s feelings. We’ve all felt it, and it doesn’t feel good.

Annie Spratt/Unsplash

But what if there was a pill that would make those feelings seem to hurt less? There’s already a pill for almost everything, right?

Well, researchers from the University of Basel are on the case and have conducted a study suggesting that a placebo might work. They asked participants to write down a time they felt super guilty about something, just to stir up those feelings again, then they were divided into three groups. One group was told they would receive real medication that was actually a placebo, one was told they would get a placebo, and one got nothing. The subjects’ guilty feelings were reduced in both the medication-that-was-really-a-placebo group and placebo-that-was-a-placebo group.

“Our study therefore supports the intriguing finding that placebos work even when they are administered openly, and that explanation of the treatment is key to its effectiveness,” lead author Dilan Sezer said in a written statement.

More research is needed, but the human mind is a very interesting place. It seems like we can convince ourselves of just about anything. Especially to feel less guilty.
 

It’s a mad, mad, mad, mad scientist’s world

Mad scientists. Life’s just more interesting with a few of them running around, but they’re mostly relegated to works of fiction. Real life is boring; we don’t actually have neurosurgeons going around claiming human brain transplant is technically feasible.

Oh, wait a minute.

Best of all, this isn’t even Dr. Sergio Canavero’s first rodeo with mad science: In 2015 he claimed human head transplants were technically feasible, and in the past few years has claimed to have rehearsed head transplants on cadavers and successfully repaired spinal cord injuries in animals. Lots of claims in there, but precious little evidence. And contrary to what everyone at the head enhancement clinic says, people will notice if you start going around with a new head.

But let’s get back to brains. Ignoring the fact that brain transplant sounds like a zombie with a PhD nibbling on your skull, the article does appear in a peer-reviewed journal. So surely there’s some level of legitimacy. After all, it’s not like Dr. Canavero is an editor for this journal. [Editor’s note: By that we mean he is an editor for the journal.]

Man, he’s taking all the fun out of this.

Anyway, now that we’ve prefaced this with the mother of all caveats, what exactly is Dr. Canavero proposing with his brain transplant? It’s pretty simple: Just have a robot scoop out the first brain and place it into a fresh body, either a donated but moribund younger body or a cloned body. Reconnect all the nerves and vasculature and you’re good to go. Enjoy your wine and laugh in the face of death.

Naturally, such a … bold proposal is lacking in the details, but who cares about details, anyway? This is mad science, not respectable science. Professionals have standards. And if we hear that a human brain transplant was successfully completed on a non–dark and stormy night and the doctor didn’t cackle madly “It’s alive! It’s alive!” then honestly, what even was the point?

Ambivalence rules!

As the office’s unofficial Sith lord/Star Wars nerd, LOTME takes notice when science extols the benefits of unhappiness: “It’s good to be grumpy: Bad moods make us more detail-oriented, study shows.”

Ryan Franco/Unsplash

The investigators manipulated the emotions of participants by having them watch a clip from “Sophie’s Choice” or one from “Friends.” Then the subjects listened to short, emotionally neutral stories, some of which contained inconsistencies, with the text displayed on a computer screen. Sorry to say, gang at Central Perk, but round one went to the sad movie.

“When people are in a negative mood, they are more careful and analytical. They scrutinize what’s actually stated in a text, and they don’t just fall back on their default world knowledge,” lead author Vicky Lai, PhD, of the University of Arizona said in a statement from the school.

Negative mood. Careful and analytical. Grumpy is good.

You’ve fallen into Darth Science’s little trap, and we have you now.

A study conducted at the University of Geneva offers a slightly different conclusion. And by slightly different, we mean completely different. People over age 65 who watched a series of short TV clips depicting people in a state of emotional suffering experienced excessive modification of their neuronal connections, compared with those who watched emotionally neutral videos.

The brains of these subjects remained “frozen in a negative state by relating the suffering of others to their own emotional memories,” lead author Sebastian Baez Lugo said in a written release from the university.

Emotional suffering. Frozen brains. Grumpy is … not good?

So there you have it. Darth Science’s lesson for the day: A negative mood makes you careful and analytical, but negative thoughts are bad for your brain.

Guilt reduction, now in deceptive and open-secret forms

Guilt plagues a lot of us, sometimes regularly. Maybe you felt bad about eating the leftovers that your partner was looking forward to eating at the end of the day. Or for not saving a seat for your friend who was running late to the movies. Maybe even hiding a secret that you know would hurt a person’s feelings. We’ve all felt it, and it doesn’t feel good.

Annie Spratt/Unsplash

But what if there was a pill that would make those feelings seem to hurt less? There’s already a pill for almost everything, right?

Well, researchers from the University of Basel are on the case and have conducted a study suggesting that a placebo might work. They asked participants to write down a time they felt super guilty about something, just to stir up those feelings again, then they were divided into three groups. One group was told they would receive real medication that was actually a placebo, one was told they would get a placebo, and one got nothing. The subjects’ guilty feelings were reduced in both the medication-that-was-really-a-placebo group and placebo-that-was-a-placebo group.

“Our study therefore supports the intriguing finding that placebos work even when they are administered openly, and that explanation of the treatment is key to its effectiveness,” lead author Dilan Sezer said in a written statement.

More research is needed, but the human mind is a very interesting place. It seems like we can convince ourselves of just about anything. Especially to feel less guilty.
 

It’s a mad, mad, mad, mad scientist’s world

Mad scientists. Life’s just more interesting with a few of them running around, but they’re mostly relegated to works of fiction. Real life is boring; we don’t actually have neurosurgeons going around claiming human brain transplant is technically feasible.

Oh, wait a minute.

Best of all, this isn’t even Dr. Sergio Canavero’s first rodeo with mad science: In 2015 he claimed human head transplants were technically feasible, and in the past few years has claimed to have rehearsed head transplants on cadavers and successfully repaired spinal cord injuries in animals. Lots of claims in there, but precious little evidence. And contrary to what everyone at the head enhancement clinic says, people will notice if you start going around with a new head.

But let’s get back to brains. Ignoring the fact that brain transplant sounds like a zombie with a PhD nibbling on your skull, the article does appear in a peer-reviewed journal. So surely there’s some level of legitimacy. After all, it’s not like Dr. Canavero is an editor for this journal. [Editor’s note: By that we mean he is an editor for the journal.]

Man, he’s taking all the fun out of this.

Anyway, now that we’ve prefaced this with the mother of all caveats, what exactly is Dr. Canavero proposing with his brain transplant? It’s pretty simple: Just have a robot scoop out the first brain and place it into a fresh body, either a donated but moribund younger body or a cloned body. Reconnect all the nerves and vasculature and you’re good to go. Enjoy your wine and laugh in the face of death.

Naturally, such a … bold proposal is lacking in the details, but who cares about details, anyway? This is mad science, not respectable science. Professionals have standards. And if we hear that a human brain transplant was successfully completed on a non–dark and stormy night and the doctor didn’t cackle madly “It’s alive! It’s alive!” then honestly, what even was the point?

Ambivalence rules!

As the office’s unofficial Sith lord/Star Wars nerd, LOTME takes notice when science extols the benefits of unhappiness: “It’s good to be grumpy: Bad moods make us more detail-oriented, study shows.”

Ryan Franco/Unsplash

The investigators manipulated the emotions of participants by having them watch a clip from “Sophie’s Choice” or one from “Friends.” Then the subjects listened to short, emotionally neutral stories, some of which contained inconsistencies, with the text displayed on a computer screen. Sorry to say, gang at Central Perk, but round one went to the sad movie.

“When people are in a negative mood, they are more careful and analytical. They scrutinize what’s actually stated in a text, and they don’t just fall back on their default world knowledge,” lead author Vicky Lai, PhD, of the University of Arizona said in a statement from the school.

Negative mood. Careful and analytical. Grumpy is good.

You’ve fallen into Darth Science’s little trap, and we have you now.

A study conducted at the University of Geneva offers a slightly different conclusion. And by slightly different, we mean completely different. People over age 65 who watched a series of short TV clips depicting people in a state of emotional suffering experienced excessive modification of their neuronal connections, compared with those who watched emotionally neutral videos.

The brains of these subjects remained “frozen in a negative state by relating the suffering of others to their own emotional memories,” lead author Sebastian Baez Lugo said in a written release from the university.

Emotional suffering. Frozen brains. Grumpy is … not good?

So there you have it. Darth Science’s lesson for the day: A negative mood makes you careful and analytical, but negative thoughts are bad for your brain.

Guilt reduction, now in deceptive and open-secret forms

Guilt plagues a lot of us, sometimes regularly. Maybe you felt bad about eating the leftovers that your partner was looking forward to eating at the end of the day. Or for not saving a seat for your friend who was running late to the movies. Maybe even hiding a secret that you know would hurt a person’s feelings. We’ve all felt it, and it doesn’t feel good.

Annie Spratt/Unsplash

But what if there was a pill that would make those feelings seem to hurt less? There’s already a pill for almost everything, right?

Well, researchers from the University of Basel are on the case and have conducted a study suggesting that a placebo might work. They asked participants to write down a time they felt super guilty about something, just to stir up those feelings again, then they were divided into three groups. One group was told they would receive real medication that was actually a placebo, one was told they would get a placebo, and one got nothing. The subjects’ guilty feelings were reduced in both the medication-that-was-really-a-placebo group and placebo-that-was-a-placebo group.

“Our study therefore supports the intriguing finding that placebos work even when they are administered openly, and that explanation of the treatment is key to its effectiveness,” lead author Dilan Sezer said in a written statement.

More research is needed, but the human mind is a very interesting place. It seems like we can convince ourselves of just about anything. Especially to feel less guilty.
 

It’s a mad, mad, mad, mad scientist’s world

Mad scientists. Life’s just more interesting with a few of them running around, but they’re mostly relegated to works of fiction. Real life is boring; we don’t actually have neurosurgeons going around claiming human brain transplant is technically feasible.

Oh, wait a minute.

Best of all, this isn’t even Dr. Sergio Canavero’s first rodeo with mad science: In 2015 he claimed human head transplants were technically feasible, and in the past few years has claimed to have rehearsed head transplants on cadavers and successfully repaired spinal cord injuries in animals. Lots of claims in there, but precious little evidence. And contrary to what everyone at the head enhancement clinic says, people will notice if you start going around with a new head.

But let’s get back to brains. Ignoring the fact that brain transplant sounds like a zombie with a PhD nibbling on your skull, the article does appear in a peer-reviewed journal. So surely there’s some level of legitimacy. After all, it’s not like Dr. Canavero is an editor for this journal. [Editor’s note: By that we mean he is an editor for the journal.]

Man, he’s taking all the fun out of this.

Anyway, now that we’ve prefaced this with the mother of all caveats, what exactly is Dr. Canavero proposing with his brain transplant? It’s pretty simple: Just have a robot scoop out the first brain and place it into a fresh body, either a donated but moribund younger body or a cloned body. Reconnect all the nerves and vasculature and you’re good to go. Enjoy your wine and laugh in the face of death.

Naturally, such a … bold proposal is lacking in the details, but who cares about details, anyway? This is mad science, not respectable science. Professionals have standards. And if we hear that a human brain transplant was successfully completed on a non–dark and stormy night and the doctor didn’t cackle madly “It’s alive! It’s alive!” then honestly, what even was the point?

Ambivalence rules!

As the office’s unofficial Sith lord/Star Wars nerd, LOTME takes notice when science extols the benefits of unhappiness: “It’s good to be grumpy: Bad moods make us more detail-oriented, study shows.”

Ryan Franco/Unsplash

The investigators manipulated the emotions of participants by having them watch a clip from “Sophie’s Choice” or one from “Friends.” Then the subjects listened to short, emotionally neutral stories, some of which contained inconsistencies, with the text displayed on a computer screen. Sorry to say, gang at Central Perk, but round one went to the sad movie.

“When people are in a negative mood, they are more careful and analytical. They scrutinize what’s actually stated in a text, and they don’t just fall back on their default world knowledge,” lead author Vicky Lai, PhD, of the University of Arizona said in a statement from the school.

Negative mood. Careful and analytical. Grumpy is good.

You’ve fallen into Darth Science’s little trap, and we have you now.

A study conducted at the University of Geneva offers a slightly different conclusion. And by slightly different, we mean completely different. People over age 65 who watched a series of short TV clips depicting people in a state of emotional suffering experienced excessive modification of their neuronal connections, compared with those who watched emotionally neutral videos.

The brains of these subjects remained “frozen in a negative state by relating the suffering of others to their own emotional memories,” lead author Sebastian Baez Lugo said in a written release from the university.

Emotional suffering. Frozen brains. Grumpy is … not good?

So there you have it. Darth Science’s lesson for the day: A negative mood makes you careful and analytical, but negative thoughts are bad for your brain.

Mothers with intellectual or developmental disabilities are less likely to initiate breastfeeding and to receive in-hospital breastfeeding support than are those without a disability, new data suggest.

In a population-based cohort study of more than 600,000 mothers, patients with an intellectual or developmental disability were about 18% less likely to have a chance to initiate breastfeeding during their hospital stay.

“Overall, we did see lower rates of breastfeeding practices and supports in people with intellectual and developmental disabilities, as well as those with multiple disabilities, compared to people without disabilities,” study author Hilary K. Brown, PhD, assistant professor of health and society at University of Toronto Scarborough in Ontario, told this news organization.

The study was published in The Lancet Public Health.
 

Disparities in breastfeeding

“There hasn’t been a lot of research on breastfeeding outcomes in people with disabilities,” said Dr. Brown, who noted that the study outcomes were based on the WHO-UNICEF Baby Friendly Hospital Initiative guidelines. “There have been a number of qualitative studies that have suggested that they do experience barriers accessing care related to breastfeeding and different challenges related to breastfeeding. But as far as quantitative outcomes, there has only been a handful of studies.”

To examine these outcomes, the investigators analyzed health administrative data from Ontario. They included in their analysis all birthing parents aged 15-49 years who had a single live birth between April 1, 2012, and March 31, 2018. Patients with a physical disability, sensory disability, intellectual or developmental disability, or two or more disabilities were identified via diagnostic algorithms and were compared with individuals without disabilities with respect to the opportunity to initiate breastfeeding, to engage in in-hospital breastfeeding, to engage in exclusive breastfeeding at hospital discharge, to have skin-to-skin contact, and to be provided with breastfeeding assistance.

The investigators considered a physical disability to encompass conditions such as congenital anomalies, musculoskeletal disorders, neurologic disorders, or permanent injuries. They defined sensory disability as hearing loss or vision loss. Intellectual or developmental disability was defined as having autism spectrum disorder, chromosomal anomaly, fetal alcohol spectrum disorder, or other intellectual disability. Patients with multiple disabilities had two or more of these conditions.

The study population included 634,111 birthing parents, of whom 54,476 (8.6%) had a physical disability, 19,227 (3.0%) had a sensory disability, 1,048 (0.2%) had an intellectual or developmental disability, 4,050 (0.6%) had multiple disabilities, and 555,310 (87.6%) had no disability.

The investigators found that patients with intellectual or developmental disabilities were less likely than were those without a disability to have an opportunity to initiate breastfeeding (adjusted relative risk [aRR], 0.82), to engage in any in-hospital breastfeeding (aRR, 0.85), to be breastfeeding exclusively at hospital discharge (aRR, 0.73), to have skin-to-skin contact (aRR, 0.90), and to receive breastfeeding assistance (aRR, 0.85) compared with patients without a disability.

They also found that individuals with multiple disabilities were less likely to have an opportunity to initiate breastfeeding (aRR, 0.93), to engage in any in-hospital breastfeeding (aRR, 0.93), to be exclusively breastfeeding at hospital discharge (aRR, 0.90), to have skin-to-skin contact (aRR, 0.93), and to receive breastfeeding assistance (aRR, 0.95) compared with patients without a disability.
 

An understudied population

Commenting on the study, Lori Feldman-Winter, MD, MPH, professor of pediatrics at Rowan University in Camden, N.J., said that one of its strengths is that it included patients who may be excluded from studies of breastfeeding practices. The finding of few differences in breastfeeding practices and supports for people with physical and sensory disabilities, compared with those without disabilities, was positive, she added.

“This is an understudied population, and it is important to call out that there may be practices related to breastfeeding care that suffer, due to implicit bias regarding persons with intellectual and multiple disabilities,” said Dr. Feldman-Winter. “The good news is that other disabilities did not show the same disparities. This study also shows how important it is to measure potential gaps in care across multiple sociodemographic and other variables, such as disabilities, to ensure equitable and inclusive care.”

Health care professionals need to be aware of disparities in breastfeeding care, she added. They need to be open to exploring potential biases when it comes to providing equitable care.

R. Douglas Wilson, MD, president of the Society of Obstetricians and Gynaecologists of Canada and professor emeritus of obstetrics and gynecology at the University of Calgary in Alberta, noted that the size of the cohort represents a strength of the study and that the findings suggest the possible need for closer follow-up of a new mother who is breastfeeding and who has an intellectual disability or multiple disabilities.

“You might keep that patient in hospital for an extra day, and then the home care nurse may look in on them more frequently than they would for someone who does not need that extra oversight,” said Dr. Wilson. When their patients are pregnant, obstetricians and gynecologists can find out whether their patients intend to breastfeed and put them in touch with nurses or lactation consultants to assist them, he added.

The study was funded by the National Institutes of Health and the Canada Research Chairs Program. Dr. Brown, Dr. Feldman-Winter, and Dr. Wilson reported no relevant financial relationships.

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

Mothers with intellectual or developmental disabilities are less likely to initiate breastfeeding and to receive in-hospital breastfeeding support than are those without a disability, new data suggest.

In a population-based cohort study of more than 600,000 mothers, patients with an intellectual or developmental disability were about 18% less likely to have a chance to initiate breastfeeding during their hospital stay.

“Overall, we did see lower rates of breastfeeding practices and supports in people with intellectual and developmental disabilities, as well as those with multiple disabilities, compared to people without disabilities,” study author Hilary K. Brown, PhD, assistant professor of health and society at University of Toronto Scarborough in Ontario, told this news organization.

The study was published in The Lancet Public Health.
 

Disparities in breastfeeding

“There hasn’t been a lot of research on breastfeeding outcomes in people with disabilities,” said Dr. Brown, who noted that the study outcomes were based on the WHO-UNICEF Baby Friendly Hospital Initiative guidelines. “There have been a number of qualitative studies that have suggested that they do experience barriers accessing care related to breastfeeding and different challenges related to breastfeeding. But as far as quantitative outcomes, there has only been a handful of studies.”

To examine these outcomes, the investigators analyzed health administrative data from Ontario. They included in their analysis all birthing parents aged 15-49 years who had a single live birth between April 1, 2012, and March 31, 2018. Patients with a physical disability, sensory disability, intellectual or developmental disability, or two or more disabilities were identified via diagnostic algorithms and were compared with individuals without disabilities with respect to the opportunity to initiate breastfeeding, to engage in in-hospital breastfeeding, to engage in exclusive breastfeeding at hospital discharge, to have skin-to-skin contact, and to be provided with breastfeeding assistance.

The investigators considered a physical disability to encompass conditions such as congenital anomalies, musculoskeletal disorders, neurologic disorders, or permanent injuries. They defined sensory disability as hearing loss or vision loss. Intellectual or developmental disability was defined as having autism spectrum disorder, chromosomal anomaly, fetal alcohol spectrum disorder, or other intellectual disability. Patients with multiple disabilities had two or more of these conditions.

The study population included 634,111 birthing parents, of whom 54,476 (8.6%) had a physical disability, 19,227 (3.0%) had a sensory disability, 1,048 (0.2%) had an intellectual or developmental disability, 4,050 (0.6%) had multiple disabilities, and 555,310 (87.6%) had no disability.

The investigators found that patients with intellectual or developmental disabilities were less likely than were those without a disability to have an opportunity to initiate breastfeeding (adjusted relative risk [aRR], 0.82), to engage in any in-hospital breastfeeding (aRR, 0.85), to be breastfeeding exclusively at hospital discharge (aRR, 0.73), to have skin-to-skin contact (aRR, 0.90), and to receive breastfeeding assistance (aRR, 0.85) compared with patients without a disability.

They also found that individuals with multiple disabilities were less likely to have an opportunity to initiate breastfeeding (aRR, 0.93), to engage in any in-hospital breastfeeding (aRR, 0.93), to be exclusively breastfeeding at hospital discharge (aRR, 0.90), to have skin-to-skin contact (aRR, 0.93), and to receive breastfeeding assistance (aRR, 0.95) compared with patients without a disability.
 

An understudied population

Commenting on the study, Lori Feldman-Winter, MD, MPH, professor of pediatrics at Rowan University in Camden, N.J., said that one of its strengths is that it included patients who may be excluded from studies of breastfeeding practices. The finding of few differences in breastfeeding practices and supports for people with physical and sensory disabilities, compared with those without disabilities, was positive, she added.

“This is an understudied population, and it is important to call out that there may be practices related to breastfeeding care that suffer, due to implicit bias regarding persons with intellectual and multiple disabilities,” said Dr. Feldman-Winter. “The good news is that other disabilities did not show the same disparities. This study also shows how important it is to measure potential gaps in care across multiple sociodemographic and other variables, such as disabilities, to ensure equitable and inclusive care.”

Health care professionals need to be aware of disparities in breastfeeding care, she added. They need to be open to exploring potential biases when it comes to providing equitable care.

R. Douglas Wilson, MD, president of the Society of Obstetricians and Gynaecologists of Canada and professor emeritus of obstetrics and gynecology at the University of Calgary in Alberta, noted that the size of the cohort represents a strength of the study and that the findings suggest the possible need for closer follow-up of a new mother who is breastfeeding and who has an intellectual disability or multiple disabilities.

“You might keep that patient in hospital for an extra day, and then the home care nurse may look in on them more frequently than they would for someone who does not need that extra oversight,” said Dr. Wilson. When their patients are pregnant, obstetricians and gynecologists can find out whether their patients intend to breastfeed and put them in touch with nurses or lactation consultants to assist them, he added.

The study was funded by the National Institutes of Health and the Canada Research Chairs Program. Dr. Brown, Dr. Feldman-Winter, and Dr. Wilson reported no relevant financial relationships.

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

Mothers with intellectual or developmental disabilities are less likely to initiate breastfeeding and to receive in-hospital breastfeeding support than are those without a disability, new data suggest.

In a population-based cohort study of more than 600,000 mothers, patients with an intellectual or developmental disability were about 18% less likely to have a chance to initiate breastfeeding during their hospital stay.

“Overall, we did see lower rates of breastfeeding practices and supports in people with intellectual and developmental disabilities, as well as those with multiple disabilities, compared to people without disabilities,” study author Hilary K. Brown, PhD, assistant professor of health and society at University of Toronto Scarborough in Ontario, told this news organization.

The study was published in The Lancet Public Health.
 

Disparities in breastfeeding

“There hasn’t been a lot of research on breastfeeding outcomes in people with disabilities,” said Dr. Brown, who noted that the study outcomes were based on the WHO-UNICEF Baby Friendly Hospital Initiative guidelines. “There have been a number of qualitative studies that have suggested that they do experience barriers accessing care related to breastfeeding and different challenges related to breastfeeding. But as far as quantitative outcomes, there has only been a handful of studies.”

To examine these outcomes, the investigators analyzed health administrative data from Ontario. They included in their analysis all birthing parents aged 15-49 years who had a single live birth between April 1, 2012, and March 31, 2018. Patients with a physical disability, sensory disability, intellectual or developmental disability, or two or more disabilities were identified via diagnostic algorithms and were compared with individuals without disabilities with respect to the opportunity to initiate breastfeeding, to engage in in-hospital breastfeeding, to engage in exclusive breastfeeding at hospital discharge, to have skin-to-skin contact, and to be provided with breastfeeding assistance.

The investigators considered a physical disability to encompass conditions such as congenital anomalies, musculoskeletal disorders, neurologic disorders, or permanent injuries. They defined sensory disability as hearing loss or vision loss. Intellectual or developmental disability was defined as having autism spectrum disorder, chromosomal anomaly, fetal alcohol spectrum disorder, or other intellectual disability. Patients with multiple disabilities had two or more of these conditions.

The study population included 634,111 birthing parents, of whom 54,476 (8.6%) had a physical disability, 19,227 (3.0%) had a sensory disability, 1,048 (0.2%) had an intellectual or developmental disability, 4,050 (0.6%) had multiple disabilities, and 555,310 (87.6%) had no disability.

The investigators found that patients with intellectual or developmental disabilities were less likely than were those without a disability to have an opportunity to initiate breastfeeding (adjusted relative risk [aRR], 0.82), to engage in any in-hospital breastfeeding (aRR, 0.85), to be breastfeeding exclusively at hospital discharge (aRR, 0.73), to have skin-to-skin contact (aRR, 0.90), and to receive breastfeeding assistance (aRR, 0.85) compared with patients without a disability.

They also found that individuals with multiple disabilities were less likely to have an opportunity to initiate breastfeeding (aRR, 0.93), to engage in any in-hospital breastfeeding (aRR, 0.93), to be exclusively breastfeeding at hospital discharge (aRR, 0.90), to have skin-to-skin contact (aRR, 0.93), and to receive breastfeeding assistance (aRR, 0.95) compared with patients without a disability.
 

An understudied population

Commenting on the study, Lori Feldman-Winter, MD, MPH, professor of pediatrics at Rowan University in Camden, N.J., said that one of its strengths is that it included patients who may be excluded from studies of breastfeeding practices. The finding of few differences in breastfeeding practices and supports for people with physical and sensory disabilities, compared with those without disabilities, was positive, she added.

“This is an understudied population, and it is important to call out that there may be practices related to breastfeeding care that suffer, due to implicit bias regarding persons with intellectual and multiple disabilities,” said Dr. Feldman-Winter. “The good news is that other disabilities did not show the same disparities. This study also shows how important it is to measure potential gaps in care across multiple sociodemographic and other variables, such as disabilities, to ensure equitable and inclusive care.”

Health care professionals need to be aware of disparities in breastfeeding care, she added. They need to be open to exploring potential biases when it comes to providing equitable care.

R. Douglas Wilson, MD, president of the Society of Obstetricians and Gynaecologists of Canada and professor emeritus of obstetrics and gynecology at the University of Calgary in Alberta, noted that the size of the cohort represents a strength of the study and that the findings suggest the possible need for closer follow-up of a new mother who is breastfeeding and who has an intellectual disability or multiple disabilities.

“You might keep that patient in hospital for an extra day, and then the home care nurse may look in on them more frequently than they would for someone who does not need that extra oversight,” said Dr. Wilson. When their patients are pregnant, obstetricians and gynecologists can find out whether their patients intend to breastfeed and put them in touch with nurses or lactation consultants to assist them, he added.

The study was funded by the National Institutes of Health and the Canada Research Chairs Program. Dr. Brown, Dr. Feldman-Winter, and Dr. Wilson reported no relevant financial relationships.

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

Children with hyperdiploid acute lymphoblastic leukemia (ALL) are much more likely to also have congenital cytomegalovirus (CMV) infection, according to an analysis published in JAMA Network Open.

Although researchers found no association between ALL and congenital CMV infection overall, pediatric patients diagnosed with hyperdiploid ALL had sixfold greater odds of being positive for congenital CMV than cancer-free controls.

“These findings suggest mixed evidence for an association between congenital CMV infection and ALL” and that “a CMV-ALL association may be specific to hyperdiploid ALL,” said investigators, led by Jennifer Geris, PhD, a postdoctoral associate at Baylor College of Medicine, Houston.

A growing body of evidence suggests that CMV, a member of the herpesvirus family, may be a risk factor for ALL. Although the mechanism remains unclear, congenital CMV may encourage proliferation of CD34+ hematopoietic progenitor cells in bone marrow that are vulnerable to oncogenic transformation.

Two prior independent studies have suggested that prenatal CMV infection is associated with an increased risk of childhood ALL. However, given how common CMV infection is (more than 80% seropositivity worldwide) and the relatively rarity of pediatric ALL, Joseph Wiemels, PhD, argued in an accompanying editorial that CMV can’t be a direct cause of leukemia.

“Instead, CMV may play a supportive role” with infection in some infants altering immune function in a way that increases vulnerability to more direct causes of ALL, explained Dr. Wiemels, professor of population and public health sciences at the University of Southern California, Los Angeles. In other words, “exposure to CMV early rather than fulminant infection” at birth “may be the key epidemiologic feature.”

In the current study, Dr. Geris and colleagues tested dried newborn blood spots from 1189 children with ALL and 4,756 controls matched on age, sex, and mother’s race and ethnicity for the presence of cytomegalovirus at birth. Children were born in Michigan on or after Oct. 1, 1987.

Across the entire study population, congenital CMV was detected in 6 ALL cases (0.5%) and 21 controls (0.4%), with no difference in the odds of congenital CMV infection between the two groups. Among subjects positive for congenital CMV, it was not clear who had fulminant, clinically recognized disease and who did not.

Overall, 2 of 74 cases (2.7%) of hyperdiploid ALL were positive for congenital CMV. Compared with all controls in an unmatched analysis, those with hyperdiploid ALL were 6.26 times more likely to be CMV positive.

Overall, the investigators concluded that the current findings, in combination with previous evidence showing a similar connection, “strongly suggest CMV is associated specifically to hyperdiploid ALL.”

Although “the evidence supporting an association between CMV and ALL is tantalizing and mounting rapidly,” Dr. Wiemels noted that “much additional research attention is required to mechanistically describe pathways by which CMV may influence leukemia before the virus could be considered a potential target for prevention or clinical management of ALL.”

“We are still in the early chapters of the book describing the role of CMV and ALL,” but the virus might emerge as a clinical target “with much future promise for the health and well-being of our children,” he said.

The work was funded by the National Institutes of Health, the University of Minnesota, and the Department of Defense. The investigators and editorialist have disclosed no relevant financial relationships.

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

Children with hyperdiploid acute lymphoblastic leukemia (ALL) are much more likely to also have congenital cytomegalovirus (CMV) infection, according to an analysis published in JAMA Network Open.

Although researchers found no association between ALL and congenital CMV infection overall, pediatric patients diagnosed with hyperdiploid ALL had sixfold greater odds of being positive for congenital CMV than cancer-free controls.

“These findings suggest mixed evidence for an association between congenital CMV infection and ALL” and that “a CMV-ALL association may be specific to hyperdiploid ALL,” said investigators, led by Jennifer Geris, PhD, a postdoctoral associate at Baylor College of Medicine, Houston.

A growing body of evidence suggests that CMV, a member of the herpesvirus family, may be a risk factor for ALL. Although the mechanism remains unclear, congenital CMV may encourage proliferation of CD34+ hematopoietic progenitor cells in bone marrow that are vulnerable to oncogenic transformation.

Two prior independent studies have suggested that prenatal CMV infection is associated with an increased risk of childhood ALL. However, given how common CMV infection is (more than 80% seropositivity worldwide) and the relatively rarity of pediatric ALL, Joseph Wiemels, PhD, argued in an accompanying editorial that CMV can’t be a direct cause of leukemia.

“Instead, CMV may play a supportive role” with infection in some infants altering immune function in a way that increases vulnerability to more direct causes of ALL, explained Dr. Wiemels, professor of population and public health sciences at the University of Southern California, Los Angeles. In other words, “exposure to CMV early rather than fulminant infection” at birth “may be the key epidemiologic feature.”

In the current study, Dr. Geris and colleagues tested dried newborn blood spots from 1189 children with ALL and 4,756 controls matched on age, sex, and mother’s race and ethnicity for the presence of cytomegalovirus at birth. Children were born in Michigan on or after Oct. 1, 1987.

Across the entire study population, congenital CMV was detected in 6 ALL cases (0.5%) and 21 controls (0.4%), with no difference in the odds of congenital CMV infection between the two groups. Among subjects positive for congenital CMV, it was not clear who had fulminant, clinically recognized disease and who did not.

Overall, 2 of 74 cases (2.7%) of hyperdiploid ALL were positive for congenital CMV. Compared with all controls in an unmatched analysis, those with hyperdiploid ALL were 6.26 times more likely to be CMV positive.

Overall, the investigators concluded that the current findings, in combination with previous evidence showing a similar connection, “strongly suggest CMV is associated specifically to hyperdiploid ALL.”

Although “the evidence supporting an association between CMV and ALL is tantalizing and mounting rapidly,” Dr. Wiemels noted that “much additional research attention is required to mechanistically describe pathways by which CMV may influence leukemia before the virus could be considered a potential target for prevention or clinical management of ALL.”

“We are still in the early chapters of the book describing the role of CMV and ALL,” but the virus might emerge as a clinical target “with much future promise for the health and well-being of our children,” he said.

The work was funded by the National Institutes of Health, the University of Minnesota, and the Department of Defense. The investigators and editorialist have disclosed no relevant financial relationships.

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

Children with hyperdiploid acute lymphoblastic leukemia (ALL) are much more likely to also have congenital cytomegalovirus (CMV) infection, according to an analysis published in JAMA Network Open.

Although researchers found no association between ALL and congenital CMV infection overall, pediatric patients diagnosed with hyperdiploid ALL had sixfold greater odds of being positive for congenital CMV than cancer-free controls.

“These findings suggest mixed evidence for an association between congenital CMV infection and ALL” and that “a CMV-ALL association may be specific to hyperdiploid ALL,” said investigators, led by Jennifer Geris, PhD, a postdoctoral associate at Baylor College of Medicine, Houston.

A growing body of evidence suggests that CMV, a member of the herpesvirus family, may be a risk factor for ALL. Although the mechanism remains unclear, congenital CMV may encourage proliferation of CD34+ hematopoietic progenitor cells in bone marrow that are vulnerable to oncogenic transformation.

Two prior independent studies have suggested that prenatal CMV infection is associated with an increased risk of childhood ALL. However, given how common CMV infection is (more than 80% seropositivity worldwide) and the relatively rarity of pediatric ALL, Joseph Wiemels, PhD, argued in an accompanying editorial that CMV can’t be a direct cause of leukemia.

“Instead, CMV may play a supportive role” with infection in some infants altering immune function in a way that increases vulnerability to more direct causes of ALL, explained Dr. Wiemels, professor of population and public health sciences at the University of Southern California, Los Angeles. In other words, “exposure to CMV early rather than fulminant infection” at birth “may be the key epidemiologic feature.”

In the current study, Dr. Geris and colleagues tested dried newborn blood spots from 1189 children with ALL and 4,756 controls matched on age, sex, and mother’s race and ethnicity for the presence of cytomegalovirus at birth. Children were born in Michigan on or after Oct. 1, 1987.

Across the entire study population, congenital CMV was detected in 6 ALL cases (0.5%) and 21 controls (0.4%), with no difference in the odds of congenital CMV infection between the two groups. Among subjects positive for congenital CMV, it was not clear who had fulminant, clinically recognized disease and who did not.

Overall, 2 of 74 cases (2.7%) of hyperdiploid ALL were positive for congenital CMV. Compared with all controls in an unmatched analysis, those with hyperdiploid ALL were 6.26 times more likely to be CMV positive.

Overall, the investigators concluded that the current findings, in combination with previous evidence showing a similar connection, “strongly suggest CMV is associated specifically to hyperdiploid ALL.”

Although “the evidence supporting an association between CMV and ALL is tantalizing and mounting rapidly,” Dr. Wiemels noted that “much additional research attention is required to mechanistically describe pathways by which CMV may influence leukemia before the virus could be considered a potential target for prevention or clinical management of ALL.”

“We are still in the early chapters of the book describing the role of CMV and ALL,” but the virus might emerge as a clinical target “with much future promise for the health and well-being of our children,” he said.

The work was funded by the National Institutes of Health, the University of Minnesota, and the Department of Defense. The investigators and editorialist have disclosed no relevant financial relationships.

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

A common sentiment shared by patients who are happy with their health care professionals is, “I feel heard and understood.” How do we become those professionals and make sure that we are doing a good job connecting and communicating with our patients?

Here are a few suggestions on how to do this.
 

Practice intent listening

When a patient shares their symptoms with you, show genuine curiosity and concern. Ask clarifying questions. Ask how the symptom or problem is affecting their day-to-day life. Avoid quick, rapid-fire questions back at the patient. Do not accept a patient self-diagnosis.

When a patient with a first-time headache says they are having a migraine headache, for example, ask many clarifying questions to make sure you can make a diagnosis of headache type, then use all the information you have gathered to educate the patient on what you believe they have.

It is easy to jump to treatment, but we always want to make sure we have the diagnosis correct first. By intently listening, it also makes it much easier to tell a patient you do not know what is causing their symptoms, but that you and the patient will be vigilant for any future clues that may lead to a diagnosis.
 

Use terminology that patients understand

Rachael Gotlieb, MD, and colleagues published an excellent study with eye-opening results on common phrases we use as health care providers and how often patients do not understand them.

Only 9% of patients understood what was meant when they were asked if they have been febrile. Only 2% understood what was meant by “I am concerned the patient has an occult infection.” Only 21% understood that “your xray findings were quite impressive” was bad news.

It is easy to avoid these medical language traps, we just have to check our doctor speak. Ask, “Do you have a fever?” Say, “I am concerned you may have an infection that is hard to find.”

Several other terms we use all the time in explaining things to patients that I have found most patients do not understand are the terms bilateral, systemic, and significant. Think carefully as you explain things to patients and check back to have them repeat to you what they think you said.
 

Be comfortable saying you don’t know

Many symptoms in medicine end up not being diagnosable. When a patient shares symptoms that do not fit a pattern of a disease, it is important to share with them why you think it is okay to wait and watch, even if you do not have a diagnosis.

Patients find it comforting that you are so honest with them. Doing this also has the benefit of gaining patients’ trust when you are sure about something, because it tells them you don’t have an answer for everything.
 

Ask your patients what they think is causing their symptoms

This way, you know what their big fear is. You can address what they are worried about, even if it isn’t something you are considering.

Patients are often fearful of a disease a close friend or relative has, so when they get new symptoms, they fear diseases that we might not think of. By knowing what they are fearful of, you can reassure when appropriate.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

A common sentiment shared by patients who are happy with their health care professionals is, “I feel heard and understood.” How do we become those professionals and make sure that we are doing a good job connecting and communicating with our patients?

Here are a few suggestions on how to do this.
 

Practice intent listening

When a patient shares their symptoms with you, show genuine curiosity and concern. Ask clarifying questions. Ask how the symptom or problem is affecting their day-to-day life. Avoid quick, rapid-fire questions back at the patient. Do not accept a patient self-diagnosis.

When a patient with a first-time headache says they are having a migraine headache, for example, ask many clarifying questions to make sure you can make a diagnosis of headache type, then use all the information you have gathered to educate the patient on what you believe they have.

It is easy to jump to treatment, but we always want to make sure we have the diagnosis correct first. By intently listening, it also makes it much easier to tell a patient you do not know what is causing their symptoms, but that you and the patient will be vigilant for any future clues that may lead to a diagnosis.
 

Use terminology that patients understand

Rachael Gotlieb, MD, and colleagues published an excellent study with eye-opening results on common phrases we use as health care providers and how often patients do not understand them.

Only 9% of patients understood what was meant when they were asked if they have been febrile. Only 2% understood what was meant by “I am concerned the patient has an occult infection.” Only 21% understood that “your xray findings were quite impressive” was bad news.

It is easy to avoid these medical language traps, we just have to check our doctor speak. Ask, “Do you have a fever?” Say, “I am concerned you may have an infection that is hard to find.”

Several other terms we use all the time in explaining things to patients that I have found most patients do not understand are the terms bilateral, systemic, and significant. Think carefully as you explain things to patients and check back to have them repeat to you what they think you said.
 

Be comfortable saying you don’t know

Many symptoms in medicine end up not being diagnosable. When a patient shares symptoms that do not fit a pattern of a disease, it is important to share with them why you think it is okay to wait and watch, even if you do not have a diagnosis.

Patients find it comforting that you are so honest with them. Doing this also has the benefit of gaining patients’ trust when you are sure about something, because it tells them you don’t have an answer for everything.
 

Ask your patients what they think is causing their symptoms

This way, you know what their big fear is. You can address what they are worried about, even if it isn’t something you are considering.

Patients are often fearful of a disease a close friend or relative has, so when they get new symptoms, they fear diseases that we might not think of. By knowing what they are fearful of, you can reassure when appropriate.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

A common sentiment shared by patients who are happy with their health care professionals is, “I feel heard and understood.” How do we become those professionals and make sure that we are doing a good job connecting and communicating with our patients?

Here are a few suggestions on how to do this.
 

Practice intent listening

When a patient shares their symptoms with you, show genuine curiosity and concern. Ask clarifying questions. Ask how the symptom or problem is affecting their day-to-day life. Avoid quick, rapid-fire questions back at the patient. Do not accept a patient self-diagnosis.

When a patient with a first-time headache says they are having a migraine headache, for example, ask many clarifying questions to make sure you can make a diagnosis of headache type, then use all the information you have gathered to educate the patient on what you believe they have.

It is easy to jump to treatment, but we always want to make sure we have the diagnosis correct first. By intently listening, it also makes it much easier to tell a patient you do not know what is causing their symptoms, but that you and the patient will be vigilant for any future clues that may lead to a diagnosis.
 

Use terminology that patients understand

Rachael Gotlieb, MD, and colleagues published an excellent study with eye-opening results on common phrases we use as health care providers and how often patients do not understand them.

Only 9% of patients understood what was meant when they were asked if they have been febrile. Only 2% understood what was meant by “I am concerned the patient has an occult infection.” Only 21% understood that “your xray findings were quite impressive” was bad news.

It is easy to avoid these medical language traps, we just have to check our doctor speak. Ask, “Do you have a fever?” Say, “I am concerned you may have an infection that is hard to find.”

Several other terms we use all the time in explaining things to patients that I have found most patients do not understand are the terms bilateral, systemic, and significant. Think carefully as you explain things to patients and check back to have them repeat to you what they think you said.
 

Be comfortable saying you don’t know

Many symptoms in medicine end up not being diagnosable. When a patient shares symptoms that do not fit a pattern of a disease, it is important to share with them why you think it is okay to wait and watch, even if you do not have a diagnosis.

Patients find it comforting that you are so honest with them. Doing this also has the benefit of gaining patients’ trust when you are sure about something, because it tells them you don’t have an answer for everything.
 

Ask your patients what they think is causing their symptoms

This way, you know what their big fear is. You can address what they are worried about, even if it isn’t something you are considering.

Patients are often fearful of a disease a close friend or relative has, so when they get new symptoms, they fear diseases that we might not think of. By knowing what they are fearful of, you can reassure when appropriate.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

Ralph L. Sacco, MD, the first neurologist to serve as president of the American Heart Association and the only physician to serve as president of both the AHA and the American Academy of Neurology, died Jan. 17 at the age of 65.

He died of a brain tumor at his home in Amagansett, N.Y., according to an obituary published in Neurology, Circulation, and Stroke.

University of Miami

“Ralph was one of a kind,” Nancy Brown, chief executive officer for the AHA and American Stroke Association, said in a statement. “His leadership was unparalleled, and his warm, generous heart and care transcended his research and clinic to every person fortunate to meet him and likely become a friend,” Ms. Brown said.

In a tweet, Natalia S. Rost, MD, professor of neurology at Harvard Medical School, Boston, called him, “a dear friend, an inspiring colleague, a generous mentor, an astute scientist, a consummate advocate for brain health worldwide.” 
 

Dedicated to improving stroke care

Dr. Sacco was chair of the University of Miami Miller School of Medicine in the department of neurology; the Olemberg Family Chair in Neurological Disorders; professor of neurology, public health sciences, human genetics, and neurosurgery; executive director of the Evelyn F. McKnight Brain Institute; director and multi-principal investigator of the Miami Clinical and Translational Science Institute; and senior associate dean for clinical and translational science.

Dr. Sacco was a population-based researcher in the field of cerebrovascular diseases.

As founder of the Northern Manhattan Study, he paved the way for examining the differences in stroke risk related to race, ethnicity, sex, and neighborhood, and realizing the impact of modifiable lifestyle behaviors, such as alcohol consumption and physical activity, on stroke risk.

Dr. Sacco’s work led to more targeted stroke prevention programs and his “drive and dedication fueled changes that improved stroke research and fostered the development of targeted stroke care delivery, ultimately improving stroke recovery and post-stroke quality of life for many,” the AHA statement said.

Dr. Sacco was also founder and executive director of the Florida Stroke Registry, which consists of 167 Florida stroke centers. He was a member of the National Academy of Medicine.

In an obituary written by Orly Avitzur, MD, current president of the AAN, she notes that he “was the only physician to have become both the president of the AHA (2010-2011) and the AAN (2017-2019), positions that reflected the respect and admiration of professional colleagues earned over the years.”

During his tenure as AAN president, Dr. Sacco led an initiative to ensure that academic neurology, from department chairs to professors to students, knew about the abundance of academy resources available to them, the AAN noted in a statement. 

Dr. Sacco was a “strong proponent of enlarging the neurology workforce through the academic pipeline and promoted the concept of the ‘newrologist’ to get people excited in careers in neurology, moving beyond just diagnosis and treatments to include interventions, preventative care, and the future of regenerative care,” the AAN said.

Dr. Sacco received numerous awards throughout his career, most recently the AHA 2022 Distinguished Scientist award. He also received the 2015 Gold Heart Award, the 2011 Distinguished National Leadership Award, and the 2006 William Feinberg Award.

In addition to his husband, Scott Dutcher, Dr. Sacco is survived by his father, Anthony P. Sacco, and his father’s wife, Rosemary; and his four siblings and their families, along with many nieces and nephews.

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

Ralph L. Sacco, MD, the first neurologist to serve as president of the American Heart Association and the only physician to serve as president of both the AHA and the American Academy of Neurology, died Jan. 17 at the age of 65.

He died of a brain tumor at his home in Amagansett, N.Y., according to an obituary published in Neurology, Circulation, and Stroke.

University of Miami

“Ralph was one of a kind,” Nancy Brown, chief executive officer for the AHA and American Stroke Association, said in a statement. “His leadership was unparalleled, and his warm, generous heart and care transcended his research and clinic to every person fortunate to meet him and likely become a friend,” Ms. Brown said.

In a tweet, Natalia S. Rost, MD, professor of neurology at Harvard Medical School, Boston, called him, “a dear friend, an inspiring colleague, a generous mentor, an astute scientist, a consummate advocate for brain health worldwide.” 
 

Dedicated to improving stroke care

Dr. Sacco was chair of the University of Miami Miller School of Medicine in the department of neurology; the Olemberg Family Chair in Neurological Disorders; professor of neurology, public health sciences, human genetics, and neurosurgery; executive director of the Evelyn F. McKnight Brain Institute; director and multi-principal investigator of the Miami Clinical and Translational Science Institute; and senior associate dean for clinical and translational science.

Dr. Sacco was a population-based researcher in the field of cerebrovascular diseases.

As founder of the Northern Manhattan Study, he paved the way for examining the differences in stroke risk related to race, ethnicity, sex, and neighborhood, and realizing the impact of modifiable lifestyle behaviors, such as alcohol consumption and physical activity, on stroke risk.

Dr. Sacco’s work led to more targeted stroke prevention programs and his “drive and dedication fueled changes that improved stroke research and fostered the development of targeted stroke care delivery, ultimately improving stroke recovery and post-stroke quality of life for many,” the AHA statement said.

Dr. Sacco was also founder and executive director of the Florida Stroke Registry, which consists of 167 Florida stroke centers. He was a member of the National Academy of Medicine.

In an obituary written by Orly Avitzur, MD, current president of the AAN, she notes that he “was the only physician to have become both the president of the AHA (2010-2011) and the AAN (2017-2019), positions that reflected the respect and admiration of professional colleagues earned over the years.”

During his tenure as AAN president, Dr. Sacco led an initiative to ensure that academic neurology, from department chairs to professors to students, knew about the abundance of academy resources available to them, the AAN noted in a statement. 

Dr. Sacco was a “strong proponent of enlarging the neurology workforce through the academic pipeline and promoted the concept of the ‘newrologist’ to get people excited in careers in neurology, moving beyond just diagnosis and treatments to include interventions, preventative care, and the future of regenerative care,” the AAN said.

Dr. Sacco received numerous awards throughout his career, most recently the AHA 2022 Distinguished Scientist award. He also received the 2015 Gold Heart Award, the 2011 Distinguished National Leadership Award, and the 2006 William Feinberg Award.

In addition to his husband, Scott Dutcher, Dr. Sacco is survived by his father, Anthony P. Sacco, and his father’s wife, Rosemary; and his four siblings and their families, along with many nieces and nephews.

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

Ralph L. Sacco, MD, the first neurologist to serve as president of the American Heart Association and the only physician to serve as president of both the AHA and the American Academy of Neurology, died Jan. 17 at the age of 65.

He died of a brain tumor at his home in Amagansett, N.Y., according to an obituary published in Neurology, Circulation, and Stroke.

University of Miami

“Ralph was one of a kind,” Nancy Brown, chief executive officer for the AHA and American Stroke Association, said in a statement. “His leadership was unparalleled, and his warm, generous heart and care transcended his research and clinic to every person fortunate to meet him and likely become a friend,” Ms. Brown said.

In a tweet, Natalia S. Rost, MD, professor of neurology at Harvard Medical School, Boston, called him, “a dear friend, an inspiring colleague, a generous mentor, an astute scientist, a consummate advocate for brain health worldwide.” 
 

Dedicated to improving stroke care

Dr. Sacco was chair of the University of Miami Miller School of Medicine in the department of neurology; the Olemberg Family Chair in Neurological Disorders; professor of neurology, public health sciences, human genetics, and neurosurgery; executive director of the Evelyn F. McKnight Brain Institute; director and multi-principal investigator of the Miami Clinical and Translational Science Institute; and senior associate dean for clinical and translational science.

Dr. Sacco was a population-based researcher in the field of cerebrovascular diseases.

As founder of the Northern Manhattan Study, he paved the way for examining the differences in stroke risk related to race, ethnicity, sex, and neighborhood, and realizing the impact of modifiable lifestyle behaviors, such as alcohol consumption and physical activity, on stroke risk.

Dr. Sacco’s work led to more targeted stroke prevention programs and his “drive and dedication fueled changes that improved stroke research and fostered the development of targeted stroke care delivery, ultimately improving stroke recovery and post-stroke quality of life for many,” the AHA statement said.

Dr. Sacco was also founder and executive director of the Florida Stroke Registry, which consists of 167 Florida stroke centers. He was a member of the National Academy of Medicine.

In an obituary written by Orly Avitzur, MD, current president of the AAN, she notes that he “was the only physician to have become both the president of the AHA (2010-2011) and the AAN (2017-2019), positions that reflected the respect and admiration of professional colleagues earned over the years.”

During his tenure as AAN president, Dr. Sacco led an initiative to ensure that academic neurology, from department chairs to professors to students, knew about the abundance of academy resources available to them, the AAN noted in a statement. 

Dr. Sacco was a “strong proponent of enlarging the neurology workforce through the academic pipeline and promoted the concept of the ‘newrologist’ to get people excited in careers in neurology, moving beyond just diagnosis and treatments to include interventions, preventative care, and the future of regenerative care,” the AAN said.

Dr. Sacco received numerous awards throughout his career, most recently the AHA 2022 Distinguished Scientist award. He also received the 2015 Gold Heart Award, the 2011 Distinguished National Leadership Award, and the 2006 William Feinberg Award.

In addition to his husband, Scott Dutcher, Dr. Sacco is survived by his father, Anthony P. Sacco, and his father’s wife, Rosemary; and his four siblings and their families, along with many nieces and nephews.

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

Simulation-based teaching of transesophageal echocardiography (TEE) improved cardiology fellows’ knowledge, skills, and comfort with the procedure, compared with traditional training, a new study shows.

“TEE learning may be hampered by the lack of availability of teachers and equipment and by the need for esophageal intubation, which is semi-invasive,” Augustin Coisne, MD, PhD, of the Cardiovascular Research Foundation in New York, said in an interview. “In this setting, simulation emerges as a key educational tool, but we were lacking evidence supporting simulation-based educational programs.”

Fellows in the simulation group achieved higher theoretical test scores and practical test scores after the training than did those in the traditional group.

Furthermore, Dr. Coisne said, “the results of the subgroup analyses were surprising and unexpected. The effect of the simulation-based training was greater among fellows at the beginning of fellowship – i.e., 2 years or less of training – in both theoretical and practical tests and in women [versus men] for the theoretical test.”

Their results, from the randomized SIMULATOR study, were published online in JAMA Cardiology.
 

More ready, more confident

The researchers randomly assigned 324 cardiology fellows (mean age, 26.4 years; about 30% women) inexperienced in TEE from 42 French university centers to TEE training with or without simulation support. Both groups participated in traditional didactic training using e-learning with an online course that is compulsory for all cardiology fellows in France.

The simulation group also participated in two 2-hour teaching sessions using a TEE simulator.

Each fellow completed a theoretical and a practical test prior to training to assess their baseline TEE level and again 3 months after the end of the training program. A TEE simulator (U/S Mentor Simulator; 3D Systems Simbionix) was used for all tests, and 24 certified echocardiography teachers served as both trainers and raters.

The theoretical tests included 20 online video-based questions to evaluate recognition of standard TEE views, normal anatomy, and some pathological cases. Fellows had 90 seconds to choose the best answer for each question from five multiple-choice options.

For the practical tests, fellows had 3 minutes to familiarize themselves with the handling of the simulator, without specific training and before the probe introduction.

They were asked to show 10 basic views on the simulator and had a maximum of 1 minute for each view.

The coprimary outcomes were the scores in the final theoretical and practical tests. TEE duration and the fellows’ self-assessment of their proficiency were also evaluated.

At baseline, the theoretical and practical test scores were similar between the groups (33.0 for the simulator group vs. 32.5 for the traditional group, and 44.2 vs. 46.1, respectively).

After training, the fellows in the simulation group had higher theoretical and practical test scores than those in the traditional group (47.2% vs. 38.3% and 74.5% vs. 59.0%, respectively).

Score changes were consistently higher when the pretraining scores were lower, an association that was stronger in the simulation group.

Dr. Coisne noted that subgroup analyses showed that the effectiveness of the simulation training was greater when performed at the beginning of the fellowship. On the theoretical test, the point increase was 11.9 for the simulation group versus 4.25 points for the traditional training group; for the practical test, the increases were 24.0 points versus 10.1 points.

After training, it took significantly less time for the simulation group to complete a TEE than it did the traditional group (8.3 vs. 9.4 minutes).

Furthermore, simulation group fellows reported that they felt more ready (mean score, 3.0 vs. 1.7) and more confident (mean score, 3.3 vs. 2.4) about performing a TEE alone after training.

“The simulation approach is definitively scalable to every institution,” Dr. Coisne said. “However, a medico-economic analysis should be interesting because the cost of the simulator and its maintenance might be a limitation to spread simulation-based teaching. The possibility for smaller hospitals to pool their financial input to share a TEE simulator could be considered to increase its cost-effectiveness.”
 

Real-world outcomes required

Commenting on the study, S. Justin Szawlewicz, MD, chair of cardiovascular medicine at Deborah Heart and Lung Center in Brown Mills, N.J., pointed out that the authors indicated that the number of TEEs performed by the trainees was not collected.

“This would be useful information to determine if those who received simulator training sought out and performed more TEEs, and also to determine if cardiology trainees in France perform a similar number of TEEs as cardiology trainees in the United States.”

In addition, he said, “the 4 hours of simulator training in TEE is extra education and experience that the standard trainees didn’t get. Would 4 extra hours of standard training didactics also improve trainees’ scores?”

Noting that the fellows’ ability to perform TEE in real patients was not assessed, Dr. Szawlewicz said, “a study could be designed that evaluated TEE images from real patients to see if trainees receiving simulator training performed better, more comprehensive and efficient TEEs than standard training.”

Nevertheless, he concluded, “Four hours of simulator training appears to improve TEE knowledge and skills. This is something we would consider at our institution.”

Like Dr. Szawlewicz, Michael Spooner, MD, MBA, of Mercy One North Iowa Heart Center in Mason City, and Kathryn Bertlacher, MD, of the University of Pittsburgh Medical Center, noted in a related editorial, “data are not provided about change in the learner’s behavior or performance on an actual TEE after the course, nor are there data about clinical outcomes such as patient safety or completeness of subsequent TEEs.

“This limitation, which is a limitation of most of the existing TEE simulation literature, is a high bar to cross,” they concluded. “Reaching this bar will require studies such as this to provide foundational understanding.”

Twin-Medical provided the TEE simulators. No relevant conflicts of interest were disclosed.

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

Simulation-based teaching of transesophageal echocardiography (TEE) improved cardiology fellows’ knowledge, skills, and comfort with the procedure, compared with traditional training, a new study shows.

“TEE learning may be hampered by the lack of availability of teachers and equipment and by the need for esophageal intubation, which is semi-invasive,” Augustin Coisne, MD, PhD, of the Cardiovascular Research Foundation in New York, said in an interview. “In this setting, simulation emerges as a key educational tool, but we were lacking evidence supporting simulation-based educational programs.”

Fellows in the simulation group achieved higher theoretical test scores and practical test scores after the training than did those in the traditional group.

Furthermore, Dr. Coisne said, “the results of the subgroup analyses were surprising and unexpected. The effect of the simulation-based training was greater among fellows at the beginning of fellowship – i.e., 2 years or less of training – in both theoretical and practical tests and in women [versus men] for the theoretical test.”

Their results, from the randomized SIMULATOR study, were published online in JAMA Cardiology.
 

More ready, more confident

The researchers randomly assigned 324 cardiology fellows (mean age, 26.4 years; about 30% women) inexperienced in TEE from 42 French university centers to TEE training with or without simulation support. Both groups participated in traditional didactic training using e-learning with an online course that is compulsory for all cardiology fellows in France.

The simulation group also participated in two 2-hour teaching sessions using a TEE simulator.

Each fellow completed a theoretical and a practical test prior to training to assess their baseline TEE level and again 3 months after the end of the training program. A TEE simulator (U/S Mentor Simulator; 3D Systems Simbionix) was used for all tests, and 24 certified echocardiography teachers served as both trainers and raters.

The theoretical tests included 20 online video-based questions to evaluate recognition of standard TEE views, normal anatomy, and some pathological cases. Fellows had 90 seconds to choose the best answer for each question from five multiple-choice options.

For the practical tests, fellows had 3 minutes to familiarize themselves with the handling of the simulator, without specific training and before the probe introduction.

They were asked to show 10 basic views on the simulator and had a maximum of 1 minute for each view.

The coprimary outcomes were the scores in the final theoretical and practical tests. TEE duration and the fellows’ self-assessment of their proficiency were also evaluated.

At baseline, the theoretical and practical test scores were similar between the groups (33.0 for the simulator group vs. 32.5 for the traditional group, and 44.2 vs. 46.1, respectively).

After training, the fellows in the simulation group had higher theoretical and practical test scores than those in the traditional group (47.2% vs. 38.3% and 74.5% vs. 59.0%, respectively).

Score changes were consistently higher when the pretraining scores were lower, an association that was stronger in the simulation group.

Dr. Coisne noted that subgroup analyses showed that the effectiveness of the simulation training was greater when performed at the beginning of the fellowship. On the theoretical test, the point increase was 11.9 for the simulation group versus 4.25 points for the traditional training group; for the practical test, the increases were 24.0 points versus 10.1 points.

After training, it took significantly less time for the simulation group to complete a TEE than it did the traditional group (8.3 vs. 9.4 minutes).

Furthermore, simulation group fellows reported that they felt more ready (mean score, 3.0 vs. 1.7) and more confident (mean score, 3.3 vs. 2.4) about performing a TEE alone after training.

“The simulation approach is definitively scalable to every institution,” Dr. Coisne said. “However, a medico-economic analysis should be interesting because the cost of the simulator and its maintenance might be a limitation to spread simulation-based teaching. The possibility for smaller hospitals to pool their financial input to share a TEE simulator could be considered to increase its cost-effectiveness.”
 

Real-world outcomes required

Commenting on the study, S. Justin Szawlewicz, MD, chair of cardiovascular medicine at Deborah Heart and Lung Center in Brown Mills, N.J., pointed out that the authors indicated that the number of TEEs performed by the trainees was not collected.

“This would be useful information to determine if those who received simulator training sought out and performed more TEEs, and also to determine if cardiology trainees in France perform a similar number of TEEs as cardiology trainees in the United States.”

In addition, he said, “the 4 hours of simulator training in TEE is extra education and experience that the standard trainees didn’t get. Would 4 extra hours of standard training didactics also improve trainees’ scores?”

Noting that the fellows’ ability to perform TEE in real patients was not assessed, Dr. Szawlewicz said, “a study could be designed that evaluated TEE images from real patients to see if trainees receiving simulator training performed better, more comprehensive and efficient TEEs than standard training.”

Nevertheless, he concluded, “Four hours of simulator training appears to improve TEE knowledge and skills. This is something we would consider at our institution.”

Like Dr. Szawlewicz, Michael Spooner, MD, MBA, of Mercy One North Iowa Heart Center in Mason City, and Kathryn Bertlacher, MD, of the University of Pittsburgh Medical Center, noted in a related editorial, “data are not provided about change in the learner’s behavior or performance on an actual TEE after the course, nor are there data about clinical outcomes such as patient safety or completeness of subsequent TEEs.

“This limitation, which is a limitation of most of the existing TEE simulation literature, is a high bar to cross,” they concluded. “Reaching this bar will require studies such as this to provide foundational understanding.”

Twin-Medical provided the TEE simulators. No relevant conflicts of interest were disclosed.

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

Simulation-based teaching of transesophageal echocardiography (TEE) improved cardiology fellows’ knowledge, skills, and comfort with the procedure, compared with traditional training, a new study shows.

“TEE learning may be hampered by the lack of availability of teachers and equipment and by the need for esophageal intubation, which is semi-invasive,” Augustin Coisne, MD, PhD, of the Cardiovascular Research Foundation in New York, said in an interview. “In this setting, simulation emerges as a key educational tool, but we were lacking evidence supporting simulation-based educational programs.”

Fellows in the simulation group achieved higher theoretical test scores and practical test scores after the training than did those in the traditional group.

Furthermore, Dr. Coisne said, “the results of the subgroup analyses were surprising and unexpected. The effect of the simulation-based training was greater among fellows at the beginning of fellowship – i.e., 2 years or less of training – in both theoretical and practical tests and in women [versus men] for the theoretical test.”

Their results, from the randomized SIMULATOR study, were published online in JAMA Cardiology.
 

More ready, more confident

The researchers randomly assigned 324 cardiology fellows (mean age, 26.4 years; about 30% women) inexperienced in TEE from 42 French university centers to TEE training with or without simulation support. Both groups participated in traditional didactic training using e-learning with an online course that is compulsory for all cardiology fellows in France.

The simulation group also participated in two 2-hour teaching sessions using a TEE simulator.

Each fellow completed a theoretical and a practical test prior to training to assess their baseline TEE level and again 3 months after the end of the training program. A TEE simulator (U/S Mentor Simulator; 3D Systems Simbionix) was used for all tests, and 24 certified echocardiography teachers served as both trainers and raters.

The theoretical tests included 20 online video-based questions to evaluate recognition of standard TEE views, normal anatomy, and some pathological cases. Fellows had 90 seconds to choose the best answer for each question from five multiple-choice options.

For the practical tests, fellows had 3 minutes to familiarize themselves with the handling of the simulator, without specific training and before the probe introduction.

They were asked to show 10 basic views on the simulator and had a maximum of 1 minute for each view.

The coprimary outcomes were the scores in the final theoretical and practical tests. TEE duration and the fellows’ self-assessment of their proficiency were also evaluated.

At baseline, the theoretical and practical test scores were similar between the groups (33.0 for the simulator group vs. 32.5 for the traditional group, and 44.2 vs. 46.1, respectively).

After training, the fellows in the simulation group had higher theoretical and practical test scores than those in the traditional group (47.2% vs. 38.3% and 74.5% vs. 59.0%, respectively).

Score changes were consistently higher when the pretraining scores were lower, an association that was stronger in the simulation group.

Dr. Coisne noted that subgroup analyses showed that the effectiveness of the simulation training was greater when performed at the beginning of the fellowship. On the theoretical test, the point increase was 11.9 for the simulation group versus 4.25 points for the traditional training group; for the practical test, the increases were 24.0 points versus 10.1 points.

After training, it took significantly less time for the simulation group to complete a TEE than it did the traditional group (8.3 vs. 9.4 minutes).

Furthermore, simulation group fellows reported that they felt more ready (mean score, 3.0 vs. 1.7) and more confident (mean score, 3.3 vs. 2.4) about performing a TEE alone after training.

“The simulation approach is definitively scalable to every institution,” Dr. Coisne said. “However, a medico-economic analysis should be interesting because the cost of the simulator and its maintenance might be a limitation to spread simulation-based teaching. The possibility for smaller hospitals to pool their financial input to share a TEE simulator could be considered to increase its cost-effectiveness.”
 

Real-world outcomes required

Commenting on the study, S. Justin Szawlewicz, MD, chair of cardiovascular medicine at Deborah Heart and Lung Center in Brown Mills, N.J., pointed out that the authors indicated that the number of TEEs performed by the trainees was not collected.

“This would be useful information to determine if those who received simulator training sought out and performed more TEEs, and also to determine if cardiology trainees in France perform a similar number of TEEs as cardiology trainees in the United States.”

In addition, he said, “the 4 hours of simulator training in TEE is extra education and experience that the standard trainees didn’t get. Would 4 extra hours of standard training didactics also improve trainees’ scores?”

Noting that the fellows’ ability to perform TEE in real patients was not assessed, Dr. Szawlewicz said, “a study could be designed that evaluated TEE images from real patients to see if trainees receiving simulator training performed better, more comprehensive and efficient TEEs than standard training.”

Nevertheless, he concluded, “Four hours of simulator training appears to improve TEE knowledge and skills. This is something we would consider at our institution.”

Like Dr. Szawlewicz, Michael Spooner, MD, MBA, of Mercy One North Iowa Heart Center in Mason City, and Kathryn Bertlacher, MD, of the University of Pittsburgh Medical Center, noted in a related editorial, “data are not provided about change in the learner’s behavior or performance on an actual TEE after the course, nor are there data about clinical outcomes such as patient safety or completeness of subsequent TEEs.

“This limitation, which is a limitation of most of the existing TEE simulation literature, is a high bar to cross,” they concluded. “Reaching this bar will require studies such as this to provide foundational understanding.”

Twin-Medical provided the TEE simulators. No relevant conflicts of interest were disclosed.

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

Patients who received an injection of inclisiran (Leqvio), a small interfering RNA (siRNA) agent, every 6 months for as long as 4 years safely maintained about a 45% reduction from baseline in their level of low-density lipoprotein cholesterol (LDL-C) in an open-label extension study with 382 patients.

In addition to providing the longest reported treatment experience with inclisiran, which received Food and Drug Administration marketing approval a little over a year ago, the results also suggest with the most definitive evidence to date that inclisiran is less effective for lowering LDL-C, compared with a class of medications that reduce LDL-C by a related but distinct mechanism: antibodies that directly inhibit activity of the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, a drug class that includes alirocumab (Praluent) and evolocumab (Repatha). Inclisiran cuts PCSK9 activity by blocking this enzyme’s gene transcription in liver cells thereby interfering with PCSK9 production.

Mitchel L. Zoler/MDedge News

Results from this study, the ORION-3 trial, provide “the first prospective long-term evaluation of the durability and safety of an siRNA-based therapy to provide clinically meaningful reductions in LDL cholesterol with a convenient dosing schedule,” wrote Kausik K. Ray, MD, and coauthors in a report in The Lancet Diabetes & Endocrinology.

The findings “provide assurance that siRNA-based therapies are safe and have the potential to provide a convenient approach to managing” LDL-C, wrote Dr. Ray, a cardiologist and professor of public health at Imperial College London, and his associates.
 

Evolocumab surpasses inclisiran in crossover cohort

The new data from ORION-3 study included findings from 92 patients first treated with evolocumab injections every 2 weeks for a year, an intervention that lowered their LDL-C levels by an average of about 60%, compared with their pretreatment level. ORION-3’s study design then crossed these patients to treatment with injections of inclisiran twice a year during 3 further years of follow-up, during which their average LDL levels reset to a roughly 45% drop from baseline, a potentially clinically meaningful difference, commented Robert S. Rosenson, MD, a lipid management specialist who was not involved in the ORION-3 study.

“This is the first evidence that compared the two classes” within a single study, thereby avoiding a problematic cross-study comparison. “That’s why the data are important. They underscore that the monoclonal antibodies are more effective for lowering LDL-C,” compared with inclisiran, said Dr. Rosenson, professor and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai in New York.

The findings “confirm in a trial that the PCSK9 monoclonal antibodies are indeed more potent,” he said in an interview.

But Dr. Rosenson acknowledged that, while this analysis used data on patients treated with evolocumab and then switched to inclisiran collected prospectively in a single study, it has the limitation of involving a comparison that was not prespecified. The primary goal of the evolocumab-to-inclisiran switch included in ORION-3 was to assess the ease, safety, and efficacy of a switch to inclisiran from treatment with a PCSK9 antibody and was not intended to compare the two drug classes. 

The roughly 15% absolute difference in LDL-C lowering between the two tested drug classes can have substantial clinical implications for patients who start treatment with highly elevated levels of LDL-C, more than 190 mg/dL, because they have heterozygous familial hypercholesterolemia, are unable to take a statin because of intolerance, or both. The difference in LDL-C reduction with an antibody or with inclisiran could mean the difference between whether or not a patient like this achieves their LDL-C goal level, Dr. Rosenson explained.

Inclisiran’s upside

On the other hand, inclisiran has a couple of important advantages. First, its mechanism of action means that effective treatment involves one injection every 6 months following a patient’s first two injections at onset and after 90 days, with all injections administered in a clinician’s office. In contrast, both of the monoclonal antibodies require injections every other week, a schedule that depends on patient self-injections using prefilled syringes obtained from a pharmacy.

Mitchel L. Zoler/MDedge News

Twice-a-year dosing by a clinician can be a major attraction because it helps ensure treatment compliance, aids patients with physical or psychological limitations to self-injection, reduces the pill burden for patients who require multiple medications, and facilitates frequent travelers who would otherwise need to carry syringes with them on trips, Dr. Rosenson noted.

The second big advantage of office-based administration of inclisiran for U.S. Medicare patients is that the treatment is billed under a patient’s part B coverage, usually resulting in easier coverage and a significantly lower patient co-pay, compared with Medicare’s coverage for a pharmacy-dispensed agent, which is covered under Medicare part D. “Part B coverage is financially more doable” for most Medicare patients, said Dr. Rosenson.

The administration schedule for inclisiran as well as its superior Medicare coverage makes the agent “transformative” for LDL-C lowering in patients for whom treatment delivery, frequency, and payment are issues, he said.
 

Inclisiran uptake modest after FDA approval

Despite these pluses, uptake of inclisiran has been modest since it received U.S. marketing approval in December 2021. In its most recent quarterly financial filing, in October 2022, Novartis reported total worldwide income from inclisiran (Leqvio) of $70 million during the first 9 months of 2022, although a Novartis spokesperson noted that the company has seen “positive trends in uptake” over the course of 2022. Inclisiran is labeled as an “adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering” of LDL-C.

During 2022, inclisiran uptake lagged because of the usual problems that slow the introduction of new drugs and new drug classes, especially ones that require dosing by a clinician. Months were spent waiting for billing codes to roll out, for clinical staffs to incorporate inclisiran injections into their routines, and for commercial insurers to get up to speed on their coverage, Dr. Rosenson said.

Also, a key step for widespread uptake of a new medication for improving cardiovascular disease outcomes – results from phase 3 studies that document safety and efficacy for these outcomes – remains several years off. The ORION-4 trial and the VICTORION-2P trial, each assessing the impact of inclisiran on cardiovascular disease events in roughly 15,000 people, will need about another 3-4 years before their results become available.

Professional medical societies that issue cardiovascular-disease management guidelines “prefer agents with proven benefits in phase 3 trials,” Dr. Rosenson noted.

Hence, the most recent update to U.S. LDL-C–management guidelines, released in the second half of 2022 by the American College of Cardiology as an Expert Consensus Decision Pathway, said this about the current role for inclisiran: “At the present time, a PCSK9 monoclonal antibody is preferred as the initial PCSK9 inhibitor of choice in view of its demonstrated safety, efficacy, and benefits for cardiovascular outcomes in the FOURIER [for evolocumab] and ODYSSEY Outcomes [for alirocumab] trials. The ORION-4 and VICTORION-2P cardiovascular outcomes trials with inclisiran are currently underway, and their completion is anticipated in 2026 and 2027, respectively. In view of the twice-yearly dosing regimen, inclisiran may be considered in patients with demonstrated poor adherence to PCSK9 monoclonal antibodies. Patients with adverse effects from both PSCK9 monoclonal antibodies or those who may be unable to self-inject may also be considered for therapy with inclisiran.”
 

ORION-3 extended the ORION-1 trial

The ORION-1 study was a phase 2 placebo-controlled, dose-ranging safety and efficacy assessment of inclisiran that gave patients two injections of the drug, at day zero and 90 days, and followed them for an additional 120 days (210 days total follow-up duration), and in some cases for as long as 360 days total. Of the 370 patients who received inclisiran in ORION-1, 290 agreed to continue inclisiran in the open-label extension, ORION-3. ORION-1 also included 127 patients randomized to initial placebo treatment, and 92 of these patients agreed to continue in ORION-3 and became the patients initially treated with evolocumab injections every other week for 1 year followed by initiation of an inclisiran regimen.

The primary outcome of ORION-3 was the change in LDL-C from baseline (the ORION-1 baseline) after 210 days of receiving inclisiran in ORION-3 (or a total of roughly 570 days after the start of ORION-1). The primary endpoint showed that, at day 210 of ORION-3 the average reduction in LDL-C from the original baseline level was 47.5%.

But a “more important” outcome, said Dr. Ray when he first reported the ORION-3 results during the American Heart Association scientific sessions in Chicago in November 2022, was that, overall, during 4 years on inclisiran this cohort showed an average cut in LDL-C from baseline of about 45% that consistently remained at this level throughout the 4 years of treatment.

“This provides us with an idea of what happens with chronic inclisiran dosing,” Dr. Ray explained. “There was no loss of biological efficacy, and we achieved these clinically meaningful, time-averaged reductions with a good safety profile. The great thing is that when patients get their injections [every 6 months] you see a consistent LDL-C reduction. A twice-annual injection is an opportunity to redesign” the way patients receive preventive cardiology care and treatment to lower LDL-C, Dr Ray said.

ORION-1 was sponsored by The Medicines Company. ORION-3 was sponsored by Novartis (which acquired The Medicines Company). Dr. Ray has received consulting fees, personal fees, and research grants from Novartis, as well as consulting fees and research grants from Amgen, the company that markets evolocumab (Repatha), and research grants from Regeneron, the company that markets alirocumab (Praluent). He has also received consulting fee, personal fees, and research grants from numerous other companies. Dr. Rosenson has been a consultant to and has received research funding from Amgen, Novartis, and Regeneron, and he has received speaking fees from Amgen and Regeneron, and has ties to several other pharmaceutical companies.
 

This article was updated on 1/26/2023.

Patients who received an injection of inclisiran (Leqvio), a small interfering RNA (siRNA) agent, every 6 months for as long as 4 years safely maintained about a 45% reduction from baseline in their level of low-density lipoprotein cholesterol (LDL-C) in an open-label extension study with 382 patients.

In addition to providing the longest reported treatment experience with inclisiran, which received Food and Drug Administration marketing approval a little over a year ago, the results also suggest with the most definitive evidence to date that inclisiran is less effective for lowering LDL-C, compared with a class of medications that reduce LDL-C by a related but distinct mechanism: antibodies that directly inhibit activity of the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, a drug class that includes alirocumab (Praluent) and evolocumab (Repatha). Inclisiran cuts PCSK9 activity by blocking this enzyme’s gene transcription in liver cells thereby interfering with PCSK9 production.

Mitchel L. Zoler/MDedge News

Results from this study, the ORION-3 trial, provide “the first prospective long-term evaluation of the durability and safety of an siRNA-based therapy to provide clinically meaningful reductions in LDL cholesterol with a convenient dosing schedule,” wrote Kausik K. Ray, MD, and coauthors in a report in The Lancet Diabetes & Endocrinology.

The findings “provide assurance that siRNA-based therapies are safe and have the potential to provide a convenient approach to managing” LDL-C, wrote Dr. Ray, a cardiologist and professor of public health at Imperial College London, and his associates.
 

Evolocumab surpasses inclisiran in crossover cohort

The new data from ORION-3 study included findings from 92 patients first treated with evolocumab injections every 2 weeks for a year, an intervention that lowered their LDL-C levels by an average of about 60%, compared with their pretreatment level. ORION-3’s study design then crossed these patients to treatment with injections of inclisiran twice a year during 3 further years of follow-up, during which their average LDL levels reset to a roughly 45% drop from baseline, a potentially clinically meaningful difference, commented Robert S. Rosenson, MD, a lipid management specialist who was not involved in the ORION-3 study.

“This is the first evidence that compared the two classes” within a single study, thereby avoiding a problematic cross-study comparison. “That’s why the data are important. They underscore that the monoclonal antibodies are more effective for lowering LDL-C,” compared with inclisiran, said Dr. Rosenson, professor and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai in New York.

The findings “confirm in a trial that the PCSK9 monoclonal antibodies are indeed more potent,” he said in an interview.

But Dr. Rosenson acknowledged that, while this analysis used data on patients treated with evolocumab and then switched to inclisiran collected prospectively in a single study, it has the limitation of involving a comparison that was not prespecified. The primary goal of the evolocumab-to-inclisiran switch included in ORION-3 was to assess the ease, safety, and efficacy of a switch to inclisiran from treatment with a PCSK9 antibody and was not intended to compare the two drug classes. 

The roughly 15% absolute difference in LDL-C lowering between the two tested drug classes can have substantial clinical implications for patients who start treatment with highly elevated levels of LDL-C, more than 190 mg/dL, because they have heterozygous familial hypercholesterolemia, are unable to take a statin because of intolerance, or both. The difference in LDL-C reduction with an antibody or with inclisiran could mean the difference between whether or not a patient like this achieves their LDL-C goal level, Dr. Rosenson explained.

Inclisiran’s upside

On the other hand, inclisiran has a couple of important advantages. First, its mechanism of action means that effective treatment involves one injection every 6 months following a patient’s first two injections at onset and after 90 days, with all injections administered in a clinician’s office. In contrast, both of the monoclonal antibodies require injections every other week, a schedule that depends on patient self-injections using prefilled syringes obtained from a pharmacy.

Mitchel L. Zoler/MDedge News

Twice-a-year dosing by a clinician can be a major attraction because it helps ensure treatment compliance, aids patients with physical or psychological limitations to self-injection, reduces the pill burden for patients who require multiple medications, and facilitates frequent travelers who would otherwise need to carry syringes with them on trips, Dr. Rosenson noted.

The second big advantage of office-based administration of inclisiran for U.S. Medicare patients is that the treatment is billed under a patient’s part B coverage, usually resulting in easier coverage and a significantly lower patient co-pay, compared with Medicare’s coverage for a pharmacy-dispensed agent, which is covered under Medicare part D. “Part B coverage is financially more doable” for most Medicare patients, said Dr. Rosenson.

The administration schedule for inclisiran as well as its superior Medicare coverage makes the agent “transformative” for LDL-C lowering in patients for whom treatment delivery, frequency, and payment are issues, he said.
 

Inclisiran uptake modest after FDA approval

Despite these pluses, uptake of inclisiran has been modest since it received U.S. marketing approval in December 2021. In its most recent quarterly financial filing, in October 2022, Novartis reported total worldwide income from inclisiran (Leqvio) of $70 million during the first 9 months of 2022, although a Novartis spokesperson noted that the company has seen “positive trends in uptake” over the course of 2022. Inclisiran is labeled as an “adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering” of LDL-C.

During 2022, inclisiran uptake lagged because of the usual problems that slow the introduction of new drugs and new drug classes, especially ones that require dosing by a clinician. Months were spent waiting for billing codes to roll out, for clinical staffs to incorporate inclisiran injections into their routines, and for commercial insurers to get up to speed on their coverage, Dr. Rosenson said.

Also, a key step for widespread uptake of a new medication for improving cardiovascular disease outcomes – results from phase 3 studies that document safety and efficacy for these outcomes – remains several years off. The ORION-4 trial and the VICTORION-2P trial, each assessing the impact of inclisiran on cardiovascular disease events in roughly 15,000 people, will need about another 3-4 years before their results become available.

Professional medical societies that issue cardiovascular-disease management guidelines “prefer agents with proven benefits in phase 3 trials,” Dr. Rosenson noted.

Hence, the most recent update to U.S. LDL-C–management guidelines, released in the second half of 2022 by the American College of Cardiology as an Expert Consensus Decision Pathway, said this about the current role for inclisiran: “At the present time, a PCSK9 monoclonal antibody is preferred as the initial PCSK9 inhibitor of choice in view of its demonstrated safety, efficacy, and benefits for cardiovascular outcomes in the FOURIER [for evolocumab] and ODYSSEY Outcomes [for alirocumab] trials. The ORION-4 and VICTORION-2P cardiovascular outcomes trials with inclisiran are currently underway, and their completion is anticipated in 2026 and 2027, respectively. In view of the twice-yearly dosing regimen, inclisiran may be considered in patients with demonstrated poor adherence to PCSK9 monoclonal antibodies. Patients with adverse effects from both PSCK9 monoclonal antibodies or those who may be unable to self-inject may also be considered for therapy with inclisiran.”
 

ORION-3 extended the ORION-1 trial

The ORION-1 study was a phase 2 placebo-controlled, dose-ranging safety and efficacy assessment of inclisiran that gave patients two injections of the drug, at day zero and 90 days, and followed them for an additional 120 days (210 days total follow-up duration), and in some cases for as long as 360 days total. Of the 370 patients who received inclisiran in ORION-1, 290 agreed to continue inclisiran in the open-label extension, ORION-3. ORION-1 also included 127 patients randomized to initial placebo treatment, and 92 of these patients agreed to continue in ORION-3 and became the patients initially treated with evolocumab injections every other week for 1 year followed by initiation of an inclisiran regimen.

The primary outcome of ORION-3 was the change in LDL-C from baseline (the ORION-1 baseline) after 210 days of receiving inclisiran in ORION-3 (or a total of roughly 570 days after the start of ORION-1). The primary endpoint showed that, at day 210 of ORION-3 the average reduction in LDL-C from the original baseline level was 47.5%.

But a “more important” outcome, said Dr. Ray when he first reported the ORION-3 results during the American Heart Association scientific sessions in Chicago in November 2022, was that, overall, during 4 years on inclisiran this cohort showed an average cut in LDL-C from baseline of about 45% that consistently remained at this level throughout the 4 years of treatment.

“This provides us with an idea of what happens with chronic inclisiran dosing,” Dr. Ray explained. “There was no loss of biological efficacy, and we achieved these clinically meaningful, time-averaged reductions with a good safety profile. The great thing is that when patients get their injections [every 6 months] you see a consistent LDL-C reduction. A twice-annual injection is an opportunity to redesign” the way patients receive preventive cardiology care and treatment to lower LDL-C, Dr Ray said.

ORION-1 was sponsored by The Medicines Company. ORION-3 was sponsored by Novartis (which acquired The Medicines Company). Dr. Ray has received consulting fees, personal fees, and research grants from Novartis, as well as consulting fees and research grants from Amgen, the company that markets evolocumab (Repatha), and research grants from Regeneron, the company that markets alirocumab (Praluent). He has also received consulting fee, personal fees, and research grants from numerous other companies. Dr. Rosenson has been a consultant to and has received research funding from Amgen, Novartis, and Regeneron, and he has received speaking fees from Amgen and Regeneron, and has ties to several other pharmaceutical companies.
 

This article was updated on 1/26/2023.

Patients who received an injection of inclisiran (Leqvio), a small interfering RNA (siRNA) agent, every 6 months for as long as 4 years safely maintained about a 45% reduction from baseline in their level of low-density lipoprotein cholesterol (LDL-C) in an open-label extension study with 382 patients.

In addition to providing the longest reported treatment experience with inclisiran, which received Food and Drug Administration marketing approval a little over a year ago, the results also suggest with the most definitive evidence to date that inclisiran is less effective for lowering LDL-C, compared with a class of medications that reduce LDL-C by a related but distinct mechanism: antibodies that directly inhibit activity of the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, a drug class that includes alirocumab (Praluent) and evolocumab (Repatha). Inclisiran cuts PCSK9 activity by blocking this enzyme’s gene transcription in liver cells thereby interfering with PCSK9 production.

Mitchel L. Zoler/MDedge News

Results from this study, the ORION-3 trial, provide “the first prospective long-term evaluation of the durability and safety of an siRNA-based therapy to provide clinically meaningful reductions in LDL cholesterol with a convenient dosing schedule,” wrote Kausik K. Ray, MD, and coauthors in a report in The Lancet Diabetes & Endocrinology.

The findings “provide assurance that siRNA-based therapies are safe and have the potential to provide a convenient approach to managing” LDL-C, wrote Dr. Ray, a cardiologist and professor of public health at Imperial College London, and his associates.
 

Evolocumab surpasses inclisiran in crossover cohort

The new data from ORION-3 study included findings from 92 patients first treated with evolocumab injections every 2 weeks for a year, an intervention that lowered their LDL-C levels by an average of about 60%, compared with their pretreatment level. ORION-3’s study design then crossed these patients to treatment with injections of inclisiran twice a year during 3 further years of follow-up, during which their average LDL levels reset to a roughly 45% drop from baseline, a potentially clinically meaningful difference, commented Robert S. Rosenson, MD, a lipid management specialist who was not involved in the ORION-3 study.

“This is the first evidence that compared the two classes” within a single study, thereby avoiding a problematic cross-study comparison. “That’s why the data are important. They underscore that the monoclonal antibodies are more effective for lowering LDL-C,” compared with inclisiran, said Dr. Rosenson, professor and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai in New York.

The findings “confirm in a trial that the PCSK9 monoclonal antibodies are indeed more potent,” he said in an interview.

But Dr. Rosenson acknowledged that, while this analysis used data on patients treated with evolocumab and then switched to inclisiran collected prospectively in a single study, it has the limitation of involving a comparison that was not prespecified. The primary goal of the evolocumab-to-inclisiran switch included in ORION-3 was to assess the ease, safety, and efficacy of a switch to inclisiran from treatment with a PCSK9 antibody and was not intended to compare the two drug classes. 

The roughly 15% absolute difference in LDL-C lowering between the two tested drug classes can have substantial clinical implications for patients who start treatment with highly elevated levels of LDL-C, more than 190 mg/dL, because they have heterozygous familial hypercholesterolemia, are unable to take a statin because of intolerance, or both. The difference in LDL-C reduction with an antibody or with inclisiran could mean the difference between whether or not a patient like this achieves their LDL-C goal level, Dr. Rosenson explained.

Inclisiran’s upside

On the other hand, inclisiran has a couple of important advantages. First, its mechanism of action means that effective treatment involves one injection every 6 months following a patient’s first two injections at onset and after 90 days, with all injections administered in a clinician’s office. In contrast, both of the monoclonal antibodies require injections every other week, a schedule that depends on patient self-injections using prefilled syringes obtained from a pharmacy.

Mitchel L. Zoler/MDedge News

Twice-a-year dosing by a clinician can be a major attraction because it helps ensure treatment compliance, aids patients with physical or psychological limitations to self-injection, reduces the pill burden for patients who require multiple medications, and facilitates frequent travelers who would otherwise need to carry syringes with them on trips, Dr. Rosenson noted.

The second big advantage of office-based administration of inclisiran for U.S. Medicare patients is that the treatment is billed under a patient’s part B coverage, usually resulting in easier coverage and a significantly lower patient co-pay, compared with Medicare’s coverage for a pharmacy-dispensed agent, which is covered under Medicare part D. “Part B coverage is financially more doable” for most Medicare patients, said Dr. Rosenson.

The administration schedule for inclisiran as well as its superior Medicare coverage makes the agent “transformative” for LDL-C lowering in patients for whom treatment delivery, frequency, and payment are issues, he said.
 

Inclisiran uptake modest after FDA approval

Despite these pluses, uptake of inclisiran has been modest since it received U.S. marketing approval in December 2021. In its most recent quarterly financial filing, in October 2022, Novartis reported total worldwide income from inclisiran (Leqvio) of $70 million during the first 9 months of 2022, although a Novartis spokesperson noted that the company has seen “positive trends in uptake” over the course of 2022. Inclisiran is labeled as an “adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering” of LDL-C.

During 2022, inclisiran uptake lagged because of the usual problems that slow the introduction of new drugs and new drug classes, especially ones that require dosing by a clinician. Months were spent waiting for billing codes to roll out, for clinical staffs to incorporate inclisiran injections into their routines, and for commercial insurers to get up to speed on their coverage, Dr. Rosenson said.

Also, a key step for widespread uptake of a new medication for improving cardiovascular disease outcomes – results from phase 3 studies that document safety and efficacy for these outcomes – remains several years off. The ORION-4 trial and the VICTORION-2P trial, each assessing the impact of inclisiran on cardiovascular disease events in roughly 15,000 people, will need about another 3-4 years before their results become available.

Professional medical societies that issue cardiovascular-disease management guidelines “prefer agents with proven benefits in phase 3 trials,” Dr. Rosenson noted.

Hence, the most recent update to U.S. LDL-C–management guidelines, released in the second half of 2022 by the American College of Cardiology as an Expert Consensus Decision Pathway, said this about the current role for inclisiran: “At the present time, a PCSK9 monoclonal antibody is preferred as the initial PCSK9 inhibitor of choice in view of its demonstrated safety, efficacy, and benefits for cardiovascular outcomes in the FOURIER [for evolocumab] and ODYSSEY Outcomes [for alirocumab] trials. The ORION-4 and VICTORION-2P cardiovascular outcomes trials with inclisiran are currently underway, and their completion is anticipated in 2026 and 2027, respectively. In view of the twice-yearly dosing regimen, inclisiran may be considered in patients with demonstrated poor adherence to PCSK9 monoclonal antibodies. Patients with adverse effects from both PSCK9 monoclonal antibodies or those who may be unable to self-inject may also be considered for therapy with inclisiran.”
 

ORION-3 extended the ORION-1 trial

The ORION-1 study was a phase 2 placebo-controlled, dose-ranging safety and efficacy assessment of inclisiran that gave patients two injections of the drug, at day zero and 90 days, and followed them for an additional 120 days (210 days total follow-up duration), and in some cases for as long as 360 days total. Of the 370 patients who received inclisiran in ORION-1, 290 agreed to continue inclisiran in the open-label extension, ORION-3. ORION-1 also included 127 patients randomized to initial placebo treatment, and 92 of these patients agreed to continue in ORION-3 and became the patients initially treated with evolocumab injections every other week for 1 year followed by initiation of an inclisiran regimen.

The primary outcome of ORION-3 was the change in LDL-C from baseline (the ORION-1 baseline) after 210 days of receiving inclisiran in ORION-3 (or a total of roughly 570 days after the start of ORION-1). The primary endpoint showed that, at day 210 of ORION-3 the average reduction in LDL-C from the original baseline level was 47.5%.

But a “more important” outcome, said Dr. Ray when he first reported the ORION-3 results during the American Heart Association scientific sessions in Chicago in November 2022, was that, overall, during 4 years on inclisiran this cohort showed an average cut in LDL-C from baseline of about 45% that consistently remained at this level throughout the 4 years of treatment.

“This provides us with an idea of what happens with chronic inclisiran dosing,” Dr. Ray explained. “There was no loss of biological efficacy, and we achieved these clinically meaningful, time-averaged reductions with a good safety profile. The great thing is that when patients get their injections [every 6 months] you see a consistent LDL-C reduction. A twice-annual injection is an opportunity to redesign” the way patients receive preventive cardiology care and treatment to lower LDL-C, Dr Ray said.

ORION-1 was sponsored by The Medicines Company. ORION-3 was sponsored by Novartis (which acquired The Medicines Company). Dr. Ray has received consulting fees, personal fees, and research grants from Novartis, as well as consulting fees and research grants from Amgen, the company that markets evolocumab (Repatha), and research grants from Regeneron, the company that markets alirocumab (Praluent). He has also received consulting fee, personal fees, and research grants from numerous other companies. Dr. Rosenson has been a consultant to and has received research funding from Amgen, Novartis, and Regeneron, and he has received speaking fees from Amgen and Regeneron, and has ties to several other pharmaceutical companies.
 

This article was updated on 1/26/2023.

A new study that quantifies the harm to the liver of eating fast food might motivate people to eat less of it – especially those with obesity or diabetes.

The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.

Annbozhko/iStock/Getty Images

Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.

“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.

“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

More fast food, greater steatosis

The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.

Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).

Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.

Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).

“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.

For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.

The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
 

Diet coaching

The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.

“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.

For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.

Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.

“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.

“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.

The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.

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

A new study that quantifies the harm to the liver of eating fast food might motivate people to eat less of it – especially those with obesity or diabetes.

The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.

Annbozhko/iStock/Getty Images

Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.

“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.

“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

More fast food, greater steatosis

The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.

Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).

Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.

Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).

“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.

For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.

The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
 

Diet coaching

The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.

“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.

For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.

Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.

“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.

“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.

The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.

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

A new study that quantifies the harm to the liver of eating fast food might motivate people to eat less of it – especially those with obesity or diabetes.

The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.

Annbozhko/iStock/Getty Images

Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.

“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.

“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

More fast food, greater steatosis

The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.

Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).

Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.

Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).

“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.

For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.

The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
 

Diet coaching

The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.

“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.

For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.

Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.

“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.

“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.

The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.

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

Nearly 25% of hospital admissions included at least one adverse event, as indicated from data from 2,809 admissions at 11 hospitals.

The 1991 Harvard Medical Practice Study, which focused on medical injury and litigation, documented an adverse event rate of 3.7 events per 100 admissions; 28% of those events were attributed to negligence, write David W. Bates, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

Although patient safety has changed significantly since 1991, documenting improvements has been challenging, the researchers say. Several reports have shown a decrease in health care–associated infections. However, other aspects of safety – notably, adverse drug events, defined as injuries resulting from drugs taken – are not easily measured and tracked, the researchers say.

“We have not had good estimates of how much harm is being caused by care in hospitals in an ongoing way that looked across all types of adverse events,” and the current review is therefore important, Dr. Bates said in an interview.

In a study recently published in the New England Journal of Medicine, the researchers analyzed a random sample of 2,809 hospital admissions from 11 hospitals in Massachusetts during the 2018 calendar year. The hospitals ranged in size from fewer than 100 beds to more than 700 beds; all patients were aged 18 years and older. A panel of nine nurses reviewed the admissions records to identify potential adverse events, and eight physicians reviewed the adverse event summaries and either agreed or disagreed with the adverse event type. The severity of each event was ranked using a general severity scale into categories of significant, serious, life-threatening, or fatal.

Overall, at least one adverse event was identified in 23.6% of the hospital admissions. A total of 978 adverse events were deemed to have occurred during the index admission, and 222 of these (22.7%) were deemed preventable. Among the preventable adverse events, 19.7% were classified as serious, 3.3% as life-threatening, and 0.5% as fatal.

A total of 523 admissions (18.6%) involved at least one significant adverse event, defined as an event that caused unnecessary harm but from which recovery was rapid. A total of 211 admissions involved a serious adverse event, defined as harm resulting in substantial intervention or prolonged recovery; 34 included at least one life-threatening event; and seven admissions involved a fatal adverse event.

A total of 191 admissions involved at least one adverse event deemed preventable. Of those, 29 involved at least one preventable adverse event that was serious, life-threatening, or fatal, the researchers write. Of the seven deaths in the study population, one was deemed preventable.

The most common adverse events were adverse drug events, which accounted for 39.0% of the adverse events; surgical or other procedural events accounted for 30.4%; patient care events (including falls and pressure ulcers) accounted for 15.0%; and health care–associated infections accounted for 11.9%.
 

Overcoming barriers to better safety

“The overall level of harm, with nearly 1 in 4 patients suffering an adverse event, was higher than I expected it might be,” Dr. Bates told this news organization. However, techniques for identifying adverse events have improved, and “it is easier to find them in electronic records than in paper records,” he noted.

“Hospitals have many issues they are currently dealing with since COVID, and one issue is simply prioritization,” Dr. Bates said. “But it is now possible to measure harm for all patients using electronic tools, and if hospitals know how much harm they are having in specific areas, they can make choices about which ones to focus on.”

“We now have effective prevention strategies for most of the main kinds of harm,” he said. Generally, rates of harm are high because these strategies are not being used effectively, he said. “In addition, there are new tools that can be used – for example, to identify patients who are decompensating earlier,” he noted.

As for additional research, some specific types of harm that have been resistant to interventions, such as pressure ulcers, deserve more attention, said Dr. Bates. “In addition, diagnostic errors appear to cause a great deal of harm, but we don’t yet have good strategies for preventing these,” he said.

The study findings were limited by several factors, including the use of data from hospitals that might not represent hospitals at large and by the inclusion mainly of patients with private insurance, the researchers write. Other limitations include the likelihood that some adverse events were missed and the level of agreement on adverse events between adjudicators was only fair.

However, the findings serve as a reminder to health care professionals of the need for continued attention to improving patient safety, and measuring adverse events remains a critical part of guiding these improvements, the researchers conclude.
 

Timely reassessment and opportunities to improve

In the decades since the publication of the report, “To Err Is Human,” by the National Academies in 2000, significant attention has been paid to improving patient safety during hospitalizations, and health care systems have increased in both system and disease complexity, Said Suman Pal, MBBS, a specialist in hospital medicine at the University of New Mexico, Albuquerque, said in an interview. “Therefore, this study is important in reassessing the safety of inpatient care at the current time,” he said.

“The findings of this study showing preventable adverse events in approximately 7% of all admissions; while concerning, is not surprising, as it is consistent with other studies over time, as the authors have also noted in their discussion,” said Dr. Pal. The current findings “underscore the importance of continuous quality improvement efforts to increase the safety of patient care for hospitalized patients,” he noted.

“The increasing complexity of medical care, fragmentation of health care, structural inequities of health systems, and more recent widespread public health challenges such as the COVID-19 pandemic have been, in my opinion, barriers to improving patient safety,” Dr. Pal said. “The use of innovation and an interdisciplinary approach to patient safety and quality improvement in hospital-based care, such as the use of machine learning to monitor trends and predict the individualized risk of harm, could be a potential way out” to help reduce barriers and improve safety, he said.

“Additional research is needed to understand the key drivers of preventable harm for hospitalized patients in the United States,” said Dr. Pal. “When planning for change, keen attention must be paid to understanding how these [drivers] may differ for patients who have been historically marginalized or are otherwise underserved so as to not exacerbate health care inequities,” he added.

The study was funded by the Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions. Dr. Bates owns stock options with AESOP, Clew, FeelBetter, Guided Clinical Solutions, MDClone, and ValeraHealth and has grants/contracts from IBM Watson and EarlySense. He has also served as a consultant for CDI Negev. Dr. Pal has disclosed no relevant financial relationships.

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

Nearly 25% of hospital admissions included at least one adverse event, as indicated from data from 2,809 admissions at 11 hospitals.

The 1991 Harvard Medical Practice Study, which focused on medical injury and litigation, documented an adverse event rate of 3.7 events per 100 admissions; 28% of those events were attributed to negligence, write David W. Bates, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

Although patient safety has changed significantly since 1991, documenting improvements has been challenging, the researchers say. Several reports have shown a decrease in health care–associated infections. However, other aspects of safety – notably, adverse drug events, defined as injuries resulting from drugs taken – are not easily measured and tracked, the researchers say.

“We have not had good estimates of how much harm is being caused by care in hospitals in an ongoing way that looked across all types of adverse events,” and the current review is therefore important, Dr. Bates said in an interview.

In a study recently published in the New England Journal of Medicine, the researchers analyzed a random sample of 2,809 hospital admissions from 11 hospitals in Massachusetts during the 2018 calendar year. The hospitals ranged in size from fewer than 100 beds to more than 700 beds; all patients were aged 18 years and older. A panel of nine nurses reviewed the admissions records to identify potential adverse events, and eight physicians reviewed the adverse event summaries and either agreed or disagreed with the adverse event type. The severity of each event was ranked using a general severity scale into categories of significant, serious, life-threatening, or fatal.

Overall, at least one adverse event was identified in 23.6% of the hospital admissions. A total of 978 adverse events were deemed to have occurred during the index admission, and 222 of these (22.7%) were deemed preventable. Among the preventable adverse events, 19.7% were classified as serious, 3.3% as life-threatening, and 0.5% as fatal.

A total of 523 admissions (18.6%) involved at least one significant adverse event, defined as an event that caused unnecessary harm but from which recovery was rapid. A total of 211 admissions involved a serious adverse event, defined as harm resulting in substantial intervention or prolonged recovery; 34 included at least one life-threatening event; and seven admissions involved a fatal adverse event.

A total of 191 admissions involved at least one adverse event deemed preventable. Of those, 29 involved at least one preventable adverse event that was serious, life-threatening, or fatal, the researchers write. Of the seven deaths in the study population, one was deemed preventable.

The most common adverse events were adverse drug events, which accounted for 39.0% of the adverse events; surgical or other procedural events accounted for 30.4%; patient care events (including falls and pressure ulcers) accounted for 15.0%; and health care–associated infections accounted for 11.9%.
 

Overcoming barriers to better safety

“The overall level of harm, with nearly 1 in 4 patients suffering an adverse event, was higher than I expected it might be,” Dr. Bates told this news organization. However, techniques for identifying adverse events have improved, and “it is easier to find them in electronic records than in paper records,” he noted.

“Hospitals have many issues they are currently dealing with since COVID, and one issue is simply prioritization,” Dr. Bates said. “But it is now possible to measure harm for all patients using electronic tools, and if hospitals know how much harm they are having in specific areas, they can make choices about which ones to focus on.”

“We now have effective prevention strategies for most of the main kinds of harm,” he said. Generally, rates of harm are high because these strategies are not being used effectively, he said. “In addition, there are new tools that can be used – for example, to identify patients who are decompensating earlier,” he noted.

As for additional research, some specific types of harm that have been resistant to interventions, such as pressure ulcers, deserve more attention, said Dr. Bates. “In addition, diagnostic errors appear to cause a great deal of harm, but we don’t yet have good strategies for preventing these,” he said.

The study findings were limited by several factors, including the use of data from hospitals that might not represent hospitals at large and by the inclusion mainly of patients with private insurance, the researchers write. Other limitations include the likelihood that some adverse events were missed and the level of agreement on adverse events between adjudicators was only fair.

However, the findings serve as a reminder to health care professionals of the need for continued attention to improving patient safety, and measuring adverse events remains a critical part of guiding these improvements, the researchers conclude.
 

Timely reassessment and opportunities to improve

In the decades since the publication of the report, “To Err Is Human,” by the National Academies in 2000, significant attention has been paid to improving patient safety during hospitalizations, and health care systems have increased in both system and disease complexity, Said Suman Pal, MBBS, a specialist in hospital medicine at the University of New Mexico, Albuquerque, said in an interview. “Therefore, this study is important in reassessing the safety of inpatient care at the current time,” he said.

“The findings of this study showing preventable adverse events in approximately 7% of all admissions; while concerning, is not surprising, as it is consistent with other studies over time, as the authors have also noted in their discussion,” said Dr. Pal. The current findings “underscore the importance of continuous quality improvement efforts to increase the safety of patient care for hospitalized patients,” he noted.

“The increasing complexity of medical care, fragmentation of health care, structural inequities of health systems, and more recent widespread public health challenges such as the COVID-19 pandemic have been, in my opinion, barriers to improving patient safety,” Dr. Pal said. “The use of innovation and an interdisciplinary approach to patient safety and quality improvement in hospital-based care, such as the use of machine learning to monitor trends and predict the individualized risk of harm, could be a potential way out” to help reduce barriers and improve safety, he said.

“Additional research is needed to understand the key drivers of preventable harm for hospitalized patients in the United States,” said Dr. Pal. “When planning for change, keen attention must be paid to understanding how these [drivers] may differ for patients who have been historically marginalized or are otherwise underserved so as to not exacerbate health care inequities,” he added.

The study was funded by the Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions. Dr. Bates owns stock options with AESOP, Clew, FeelBetter, Guided Clinical Solutions, MDClone, and ValeraHealth and has grants/contracts from IBM Watson and EarlySense. He has also served as a consultant for CDI Negev. Dr. Pal has disclosed no relevant financial relationships.

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

Nearly 25% of hospital admissions included at least one adverse event, as indicated from data from 2,809 admissions at 11 hospitals.

The 1991 Harvard Medical Practice Study, which focused on medical injury and litigation, documented an adverse event rate of 3.7 events per 100 admissions; 28% of those events were attributed to negligence, write David W. Bates, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

Although patient safety has changed significantly since 1991, documenting improvements has been challenging, the researchers say. Several reports have shown a decrease in health care–associated infections. However, other aspects of safety – notably, adverse drug events, defined as injuries resulting from drugs taken – are not easily measured and tracked, the researchers say.

“We have not had good estimates of how much harm is being caused by care in hospitals in an ongoing way that looked across all types of adverse events,” and the current review is therefore important, Dr. Bates said in an interview.

In a study recently published in the New England Journal of Medicine, the researchers analyzed a random sample of 2,809 hospital admissions from 11 hospitals in Massachusetts during the 2018 calendar year. The hospitals ranged in size from fewer than 100 beds to more than 700 beds; all patients were aged 18 years and older. A panel of nine nurses reviewed the admissions records to identify potential adverse events, and eight physicians reviewed the adverse event summaries and either agreed or disagreed with the adverse event type. The severity of each event was ranked using a general severity scale into categories of significant, serious, life-threatening, or fatal.

Overall, at least one adverse event was identified in 23.6% of the hospital admissions. A total of 978 adverse events were deemed to have occurred during the index admission, and 222 of these (22.7%) were deemed preventable. Among the preventable adverse events, 19.7% were classified as serious, 3.3% as life-threatening, and 0.5% as fatal.

A total of 523 admissions (18.6%) involved at least one significant adverse event, defined as an event that caused unnecessary harm but from which recovery was rapid. A total of 211 admissions involved a serious adverse event, defined as harm resulting in substantial intervention or prolonged recovery; 34 included at least one life-threatening event; and seven admissions involved a fatal adverse event.

A total of 191 admissions involved at least one adverse event deemed preventable. Of those, 29 involved at least one preventable adverse event that was serious, life-threatening, or fatal, the researchers write. Of the seven deaths in the study population, one was deemed preventable.

The most common adverse events were adverse drug events, which accounted for 39.0% of the adverse events; surgical or other procedural events accounted for 30.4%; patient care events (including falls and pressure ulcers) accounted for 15.0%; and health care–associated infections accounted for 11.9%.
 

Overcoming barriers to better safety

“The overall level of harm, with nearly 1 in 4 patients suffering an adverse event, was higher than I expected it might be,” Dr. Bates told this news organization. However, techniques for identifying adverse events have improved, and “it is easier to find them in electronic records than in paper records,” he noted.

“Hospitals have many issues they are currently dealing with since COVID, and one issue is simply prioritization,” Dr. Bates said. “But it is now possible to measure harm for all patients using electronic tools, and if hospitals know how much harm they are having in specific areas, they can make choices about which ones to focus on.”

“We now have effective prevention strategies for most of the main kinds of harm,” he said. Generally, rates of harm are high because these strategies are not being used effectively, he said. “In addition, there are new tools that can be used – for example, to identify patients who are decompensating earlier,” he noted.

As for additional research, some specific types of harm that have been resistant to interventions, such as pressure ulcers, deserve more attention, said Dr. Bates. “In addition, diagnostic errors appear to cause a great deal of harm, but we don’t yet have good strategies for preventing these,” he said.

The study findings were limited by several factors, including the use of data from hospitals that might not represent hospitals at large and by the inclusion mainly of patients with private insurance, the researchers write. Other limitations include the likelihood that some adverse events were missed and the level of agreement on adverse events between adjudicators was only fair.

However, the findings serve as a reminder to health care professionals of the need for continued attention to improving patient safety, and measuring adverse events remains a critical part of guiding these improvements, the researchers conclude.
 

Timely reassessment and opportunities to improve

In the decades since the publication of the report, “To Err Is Human,” by the National Academies in 2000, significant attention has been paid to improving patient safety during hospitalizations, and health care systems have increased in both system and disease complexity, Said Suman Pal, MBBS, a specialist in hospital medicine at the University of New Mexico, Albuquerque, said in an interview. “Therefore, this study is important in reassessing the safety of inpatient care at the current time,” he said.

“The findings of this study showing preventable adverse events in approximately 7% of all admissions; while concerning, is not surprising, as it is consistent with other studies over time, as the authors have also noted in their discussion,” said Dr. Pal. The current findings “underscore the importance of continuous quality improvement efforts to increase the safety of patient care for hospitalized patients,” he noted.

“The increasing complexity of medical care, fragmentation of health care, structural inequities of health systems, and more recent widespread public health challenges such as the COVID-19 pandemic have been, in my opinion, barriers to improving patient safety,” Dr. Pal said. “The use of innovation and an interdisciplinary approach to patient safety and quality improvement in hospital-based care, such as the use of machine learning to monitor trends and predict the individualized risk of harm, could be a potential way out” to help reduce barriers and improve safety, he said.

“Additional research is needed to understand the key drivers of preventable harm for hospitalized patients in the United States,” said Dr. Pal. “When planning for change, keen attention must be paid to understanding how these [drivers] may differ for patients who have been historically marginalized or are otherwise underserved so as to not exacerbate health care inequities,” he added.

The study was funded by the Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions. Dr. Bates owns stock options with AESOP, Clew, FeelBetter, Guided Clinical Solutions, MDClone, and ValeraHealth and has grants/contracts from IBM Watson and EarlySense. He has also served as a consultant for CDI Negev. Dr. Pal has disclosed no relevant financial relationships.

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

A new study likely makes the best estimate yet of the degree of retinopathy risk that patients who take the antimalarial drug hydroxychloroquine (HCQ) can expect, deriving mainly from the cumulative dose taken during the first 5 years of use, according to a study published in Annals of Internal Medicine.

HCQ works to decrease activity in a patient’s immune system, which is effective in many cases of systemic lupus erythematosus, one of the most common indications for the drug. However, an adverse outcome of treatment can be HCQ retinopathy, a progressive form of vision loss in patients taking HCQ over an extended period (mostly for longer than 5 years). The disease is often asymptomatic, although some patients do present a paracentral scotoma and a decrease in color vision. Patients may also notice flashing shapes in their vision and find that they have difficulty reading. Eventually, HCQ retinopathy can lead to loss of visual acuity, loss of peripheral vision, and loss of night vision.

Researchers from Kaiser Permanente Northern California and Harvard Medical School analyzed 3,325 persons who received HCQ for 5 or more years between 2004 and 2020. Their goal was to both characterize the long-term risk for incident HCQ retinopathy and examine the degree to which average HCQ dose within the first 5 years of treatment serves as a prediction of the risk.

The researchers then estimated the risk for developing retinopathy after 15 years, according to patients’ average dosing levels during the first 5 years of therapy. Overall, 81 participants developed HCQ retinopathy with overall cumulative incidences of 2.5% after 10 years and 8.6% after 15 years; the risk was greater for those given a higher dose during the first 5 years of treatment.

The mechanism of how HCQ toxicity may occur is still not completely known. There is evidence that toxicity happens because HCQ binds to melanin in both the retinal pigment epithelium and uvea in high concentrations. HCQ can interfere with lysosomal function, leading to oxidation and accumulation of lysosomes, which can cause dysfunction of the retinal pigment epithelium.

Progressive retinopathy can continue even after the drug is stopped. “It’s thought to be a very mild but important risk,” said Nilanjana Bose, MD, MBA, a rheumatologist with Memorial Hermann Health System in Houston. “Patients taking HCQ must be screened for retinal issues, most certainly elderly patients and patients with any kind of comorbidities.”

“Examination alone is not sufficient to evaluate early changes, and specialized testing must be done. These include color photos, visual field tests, optical coherence tomography, fundus autofluorescence and in some cases, multifocal electroretinogram. Also, the AAO [American Academy of Ophthalmology] has specific recommendations related to Asian patients as they may have a different pattern of retinopathy that must also be considered.”
 

More accurate risk measurements

This news organization asked study coauthor April Jorge, MD, assistant professor of medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, Boston, to discuss the study, how it correlates to past research, and what it adds that’s new and useful to rheumatologists and ophthalmologists:

Question: Your research found that a higher dose of HCQ in the first 5 years of treatment led to a greater risk of retinopathy. Is there any indication that a lower dose given more frequently, either within that 5-year period or longer, would pose a similar risk?

Answer: In our study, we assessed the HCQ dose in the first 5 years of use but followed patients who continued the medication longer than 5 years, through up to 15 years of use. Therefore, we compared the risk of HCQ retinopathy associated with different HCQ dosages but for the same duration of use. We found that for any dose of HCQ, the risk of retinopathy increases the longer the medication is used. However, patients who used a higher dose of HCQ had a higher risk of developing retinopathy over time.

Also unique to our study, we graded the severity of HCQ retinopathy outcomes. This was important, as we found that the majority of retinopathy cases detected through routine screening are mild and presumed to be asymptomatic. This will likely be reassuring news for patients that we can screen for this adverse event to detect it early and prevent vision loss.

Another important difference was that we assessed the risk of retinopathy associated with using over 6 mg/kg per day, between 5 and 6 mg/kg per day, and less than 5 mg/kg per day, whereas the highest dosing group assessed in the 2014 study included all patients using over 5 mg/kg per day. The risk was considerably higher in the > 6 mg/kg per day group than in the 5-6 mg/kg per day group.

Q: How can rheumatologists and ophthalmologists use this new information specifically to better treat their patients?

A: Our study provides more accurate estimates of the risk of HCQ retinopathy than in prior studies. These risk estimates can be used when rheumatologists (and other clinicians who prescribe HCQ) consider the risks and benefits of this otherwise important and well-tolerated medication. The risk associated with different dose ranges could also inform dosing decisions, since dosing over 6 mg/kg per day may be more of a concern than using doses in the 5-6 mg/kg range. Ophthalmologists can also use these new risk estimates to counsel patients of the importance of HCQ retinopathy screening and can also hopefully provide some reassurance to patients that the risk of severe retinopathy is low as long as they are being monitored.

The study authors were supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rheumatology Research Foundation. The authors report no relevant financial relationships. Dr. Bose and Dr. Mirza had no relevant disclosures.

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

A new study likely makes the best estimate yet of the degree of retinopathy risk that patients who take the antimalarial drug hydroxychloroquine (HCQ) can expect, deriving mainly from the cumulative dose taken during the first 5 years of use, according to a study published in Annals of Internal Medicine.

HCQ works to decrease activity in a patient’s immune system, which is effective in many cases of systemic lupus erythematosus, one of the most common indications for the drug. However, an adverse outcome of treatment can be HCQ retinopathy, a progressive form of vision loss in patients taking HCQ over an extended period (mostly for longer than 5 years). The disease is often asymptomatic, although some patients do present a paracentral scotoma and a decrease in color vision. Patients may also notice flashing shapes in their vision and find that they have difficulty reading. Eventually, HCQ retinopathy can lead to loss of visual acuity, loss of peripheral vision, and loss of night vision.

Researchers from Kaiser Permanente Northern California and Harvard Medical School analyzed 3,325 persons who received HCQ for 5 or more years between 2004 and 2020. Their goal was to both characterize the long-term risk for incident HCQ retinopathy and examine the degree to which average HCQ dose within the first 5 years of treatment serves as a prediction of the risk.

The researchers then estimated the risk for developing retinopathy after 15 years, according to patients’ average dosing levels during the first 5 years of therapy. Overall, 81 participants developed HCQ retinopathy with overall cumulative incidences of 2.5% after 10 years and 8.6% after 15 years; the risk was greater for those given a higher dose during the first 5 years of treatment.

The mechanism of how HCQ toxicity may occur is still not completely known. There is evidence that toxicity happens because HCQ binds to melanin in both the retinal pigment epithelium and uvea in high concentrations. HCQ can interfere with lysosomal function, leading to oxidation and accumulation of lysosomes, which can cause dysfunction of the retinal pigment epithelium.

Progressive retinopathy can continue even after the drug is stopped. “It’s thought to be a very mild but important risk,” said Nilanjana Bose, MD, MBA, a rheumatologist with Memorial Hermann Health System in Houston. “Patients taking HCQ must be screened for retinal issues, most certainly elderly patients and patients with any kind of comorbidities.”

“Examination alone is not sufficient to evaluate early changes, and specialized testing must be done. These include color photos, visual field tests, optical coherence tomography, fundus autofluorescence and in some cases, multifocal electroretinogram. Also, the AAO [American Academy of Ophthalmology] has specific recommendations related to Asian patients as they may have a different pattern of retinopathy that must also be considered.”
 

More accurate risk measurements

This news organization asked study coauthor April Jorge, MD, assistant professor of medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, Boston, to discuss the study, how it correlates to past research, and what it adds that’s new and useful to rheumatologists and ophthalmologists:

Question: Your research found that a higher dose of HCQ in the first 5 years of treatment led to a greater risk of retinopathy. Is there any indication that a lower dose given more frequently, either within that 5-year period or longer, would pose a similar risk?

Answer: In our study, we assessed the HCQ dose in the first 5 years of use but followed patients who continued the medication longer than 5 years, through up to 15 years of use. Therefore, we compared the risk of HCQ retinopathy associated with different HCQ dosages but for the same duration of use. We found that for any dose of HCQ, the risk of retinopathy increases the longer the medication is used. However, patients who used a higher dose of HCQ had a higher risk of developing retinopathy over time.

Also unique to our study, we graded the severity of HCQ retinopathy outcomes. This was important, as we found that the majority of retinopathy cases detected through routine screening are mild and presumed to be asymptomatic. This will likely be reassuring news for patients that we can screen for this adverse event to detect it early and prevent vision loss.

Another important difference was that we assessed the risk of retinopathy associated with using over 6 mg/kg per day, between 5 and 6 mg/kg per day, and less than 5 mg/kg per day, whereas the highest dosing group assessed in the 2014 study included all patients using over 5 mg/kg per day. The risk was considerably higher in the > 6 mg/kg per day group than in the 5-6 mg/kg per day group.

Q: How can rheumatologists and ophthalmologists use this new information specifically to better treat their patients?

A: Our study provides more accurate estimates of the risk of HCQ retinopathy than in prior studies. These risk estimates can be used when rheumatologists (and other clinicians who prescribe HCQ) consider the risks and benefits of this otherwise important and well-tolerated medication. The risk associated with different dose ranges could also inform dosing decisions, since dosing over 6 mg/kg per day may be more of a concern than using doses in the 5-6 mg/kg range. Ophthalmologists can also use these new risk estimates to counsel patients of the importance of HCQ retinopathy screening and can also hopefully provide some reassurance to patients that the risk of severe retinopathy is low as long as they are being monitored.

The study authors were supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rheumatology Research Foundation. The authors report no relevant financial relationships. Dr. Bose and Dr. Mirza had no relevant disclosures.

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

A new study likely makes the best estimate yet of the degree of retinopathy risk that patients who take the antimalarial drug hydroxychloroquine (HCQ) can expect, deriving mainly from the cumulative dose taken during the first 5 years of use, according to a study published in Annals of Internal Medicine.

HCQ works to decrease activity in a patient’s immune system, which is effective in many cases of systemic lupus erythematosus, one of the most common indications for the drug. However, an adverse outcome of treatment can be HCQ retinopathy, a progressive form of vision loss in patients taking HCQ over an extended period (mostly for longer than 5 years). The disease is often asymptomatic, although some patients do present a paracentral scotoma and a decrease in color vision. Patients may also notice flashing shapes in their vision and find that they have difficulty reading. Eventually, HCQ retinopathy can lead to loss of visual acuity, loss of peripheral vision, and loss of night vision.

Researchers from Kaiser Permanente Northern California and Harvard Medical School analyzed 3,325 persons who received HCQ for 5 or more years between 2004 and 2020. Their goal was to both characterize the long-term risk for incident HCQ retinopathy and examine the degree to which average HCQ dose within the first 5 years of treatment serves as a prediction of the risk.

The researchers then estimated the risk for developing retinopathy after 15 years, according to patients’ average dosing levels during the first 5 years of therapy. Overall, 81 participants developed HCQ retinopathy with overall cumulative incidences of 2.5% after 10 years and 8.6% after 15 years; the risk was greater for those given a higher dose during the first 5 years of treatment.

The mechanism of how HCQ toxicity may occur is still not completely known. There is evidence that toxicity happens because HCQ binds to melanin in both the retinal pigment epithelium and uvea in high concentrations. HCQ can interfere with lysosomal function, leading to oxidation and accumulation of lysosomes, which can cause dysfunction of the retinal pigment epithelium.

Progressive retinopathy can continue even after the drug is stopped. “It’s thought to be a very mild but important risk,” said Nilanjana Bose, MD, MBA, a rheumatologist with Memorial Hermann Health System in Houston. “Patients taking HCQ must be screened for retinal issues, most certainly elderly patients and patients with any kind of comorbidities.”

“Examination alone is not sufficient to evaluate early changes, and specialized testing must be done. These include color photos, visual field tests, optical coherence tomography, fundus autofluorescence and in some cases, multifocal electroretinogram. Also, the AAO [American Academy of Ophthalmology] has specific recommendations related to Asian patients as they may have a different pattern of retinopathy that must also be considered.”
 

More accurate risk measurements

This news organization asked study coauthor April Jorge, MD, assistant professor of medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, Boston, to discuss the study, how it correlates to past research, and what it adds that’s new and useful to rheumatologists and ophthalmologists:

Question: Your research found that a higher dose of HCQ in the first 5 years of treatment led to a greater risk of retinopathy. Is there any indication that a lower dose given more frequently, either within that 5-year period or longer, would pose a similar risk?

Answer: In our study, we assessed the HCQ dose in the first 5 years of use but followed patients who continued the medication longer than 5 years, through up to 15 years of use. Therefore, we compared the risk of HCQ retinopathy associated with different HCQ dosages but for the same duration of use. We found that for any dose of HCQ, the risk of retinopathy increases the longer the medication is used. However, patients who used a higher dose of HCQ had a higher risk of developing retinopathy over time.

Also unique to our study, we graded the severity of HCQ retinopathy outcomes. This was important, as we found that the majority of retinopathy cases detected through routine screening are mild and presumed to be asymptomatic. This will likely be reassuring news for patients that we can screen for this adverse event to detect it early and prevent vision loss.

Another important difference was that we assessed the risk of retinopathy associated with using over 6 mg/kg per day, between 5 and 6 mg/kg per day, and less than 5 mg/kg per day, whereas the highest dosing group assessed in the 2014 study included all patients using over 5 mg/kg per day. The risk was considerably higher in the > 6 mg/kg per day group than in the 5-6 mg/kg per day group.

Q: How can rheumatologists and ophthalmologists use this new information specifically to better treat their patients?

A: Our study provides more accurate estimates of the risk of HCQ retinopathy than in prior studies. These risk estimates can be used when rheumatologists (and other clinicians who prescribe HCQ) consider the risks and benefits of this otherwise important and well-tolerated medication. The risk associated with different dose ranges could also inform dosing decisions, since dosing over 6 mg/kg per day may be more of a concern than using doses in the 5-6 mg/kg range. Ophthalmologists can also use these new risk estimates to counsel patients of the importance of HCQ retinopathy screening and can also hopefully provide some reassurance to patients that the risk of severe retinopathy is low as long as they are being monitored.

The study authors were supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rheumatology Research Foundation. The authors report no relevant financial relationships. Dr. Bose and Dr. Mirza had no relevant disclosures.

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