TOPLINE:

Cognitive function in children aged 18 months to 10 years is associated with the enrichment or depletion of specific species of gut microbes, new research reveals.

METHODOLOGY: 

• Researchers analyzed the relationship between the microbiome, neuroanatomy, and cognition (ie, the microbiome-gut-brain axis) in stool samples from 381 neurotypically developing children aged 40 days to 10 years (mean age, 2 years and 2 months).
• Stool samples were taken within a week of age-appropriate cognitive and behavioral assessments.
• Shotgun metagenomic sequencing was used to analyze the DNA of the organisms present in each sample.
• MRI data were obtained, with machine models then used to predict whether participants’ brain region volume was influenced by microbial profiles.

TAKEAWAY: 

• Researchers found increasing variation in microbial species and microbial gene functions in children older than 18 months, and the overall variation was significantly associated with variation in cognitive function scores.
• Several microbial species were significantly enriched in children with higher cognitive function scores (eg, Alistipes obesi, Asaccharobacter celatus, Eubacterium eligens, and Faecalibacterium prausnitzii), with Sutterella wadsworthensis being the only species significantly negatively associated with these scores.
• Machine models indicated that taxa key in predicting cognitive function were similarly important for predicting individual brain regions and subscales of cognitive function.

IN PRACTICE:

“Understanding the gut-brain-microbiome axis in early life is particularly important since differences or interventions in early life can have outsized and longer-term consequences than those at later ages,” the authors wrote.

SOURCE:

The study, led by Kevin S. Bonham, PhD, Wellesley College, Wellesley, Massachusetts, was published online on December 22, 2023, in Science Advances.

LIMITATIONS:

Use of multiple age-appropriate cognitive assessments enabled analysis across multiple developmental periods, but test-retest reliability and differences between test administrators may have introduced noise into these observations, particularly in the youngest children. The study period overlapped with the beginning of the pandemic, and score reductions due to the lockdowns were more pronounced in some age groups than during the recruitment period. 

DISCLOSURES:

The study was funded by the US National Institutes of Health and Wellcome: LEAP 1kD. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Cognitive function in children aged 18 months to 10 years is associated with the enrichment or depletion of specific species of gut microbes, new research reveals.

METHODOLOGY: 

• Researchers analyzed the relationship between the microbiome, neuroanatomy, and cognition (ie, the microbiome-gut-brain axis) in stool samples from 381 neurotypically developing children aged 40 days to 10 years (mean age, 2 years and 2 months).
• Stool samples were taken within a week of age-appropriate cognitive and behavioral assessments.
• Shotgun metagenomic sequencing was used to analyze the DNA of the organisms present in each sample.
• MRI data were obtained, with machine models then used to predict whether participants’ brain region volume was influenced by microbial profiles.

TAKEAWAY: 

• Researchers found increasing variation in microbial species and microbial gene functions in children older than 18 months, and the overall variation was significantly associated with variation in cognitive function scores.
• Several microbial species were significantly enriched in children with higher cognitive function scores (eg, Alistipes obesi, Asaccharobacter celatus, Eubacterium eligens, and Faecalibacterium prausnitzii), with Sutterella wadsworthensis being the only species significantly negatively associated with these scores.
• Machine models indicated that taxa key in predicting cognitive function were similarly important for predicting individual brain regions and subscales of cognitive function.

IN PRACTICE:

“Understanding the gut-brain-microbiome axis in early life is particularly important since differences or interventions in early life can have outsized and longer-term consequences than those at later ages,” the authors wrote.

SOURCE:

The study, led by Kevin S. Bonham, PhD, Wellesley College, Wellesley, Massachusetts, was published online on December 22, 2023, in Science Advances.

LIMITATIONS:

Use of multiple age-appropriate cognitive assessments enabled analysis across multiple developmental periods, but test-retest reliability and differences between test administrators may have introduced noise into these observations, particularly in the youngest children. The study period overlapped with the beginning of the pandemic, and score reductions due to the lockdowns were more pronounced in some age groups than during the recruitment period. 

DISCLOSURES:

The study was funded by the US National Institutes of Health and Wellcome: LEAP 1kD. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Cognitive function in children aged 18 months to 10 years is associated with the enrichment or depletion of specific species of gut microbes, new research reveals.

METHODOLOGY: 

• Researchers analyzed the relationship between the microbiome, neuroanatomy, and cognition (ie, the microbiome-gut-brain axis) in stool samples from 381 neurotypically developing children aged 40 days to 10 years (mean age, 2 years and 2 months).
• Stool samples were taken within a week of age-appropriate cognitive and behavioral assessments.
• Shotgun metagenomic sequencing was used to analyze the DNA of the organisms present in each sample.
• MRI data were obtained, with machine models then used to predict whether participants’ brain region volume was influenced by microbial profiles.

TAKEAWAY: 

• Researchers found increasing variation in microbial species and microbial gene functions in children older than 18 months, and the overall variation was significantly associated with variation in cognitive function scores.
• Several microbial species were significantly enriched in children with higher cognitive function scores (eg, Alistipes obesi, Asaccharobacter celatus, Eubacterium eligens, and Faecalibacterium prausnitzii), with Sutterella wadsworthensis being the only species significantly negatively associated with these scores.
• Machine models indicated that taxa key in predicting cognitive function were similarly important for predicting individual brain regions and subscales of cognitive function.

IN PRACTICE:

“Understanding the gut-brain-microbiome axis in early life is particularly important since differences or interventions in early life can have outsized and longer-term consequences than those at later ages,” the authors wrote.

SOURCE:

The study, led by Kevin S. Bonham, PhD, Wellesley College, Wellesley, Massachusetts, was published online on December 22, 2023, in Science Advances.

LIMITATIONS:

Use of multiple age-appropriate cognitive assessments enabled analysis across multiple developmental periods, but test-retest reliability and differences between test administrators may have introduced noise into these observations, particularly in the youngest children. The study period overlapped with the beginning of the pandemic, and score reductions due to the lockdowns were more pronounced in some age groups than during the recruitment period. 

DISCLOSURES:

The study was funded by the US National Institutes of Health and Wellcome: LEAP 1kD. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

This interview was recorded Dec. 8, 2023. The transcript has been edited for clarity.

Kathrin LaFaver, MD: I have the pleasure of talking with Dr. Elizabeth Loder today. Dr. Loder is the vice chair of academic affairs in the department of neurology and a staff physician at Graham Headache Center at Brigham and Women’s Hospital in Boston. She’s also a professor of neurology at Harvard Medical School and has been a mentor to many headache specialists in the field.

We’ll be talking about the topic of sexism in medicine.

Elizabeth W. Loder, MD, MPH: Thank you so much, Dr. LaFaver. I’m very pleased to be here to talk about something that I think is very important.

Dr. LaFaver: Dr. Loder, you were a speaker at our Women in Neurology third annual conference in Florida, giving a talk on this very topic, sexism in medicine. It was very helpful, especially for many younger women entering the field of neurology, to hear that some of the experiences they’re having are not unique to them, but unfortunately remain a more systemic issue.

To get us started, could you define sexism in medicine for us, and how you got interested in this topic?
 

Sexism Can Be Subtle

Dr. Loder: You’re absolutely right. Sexism is still there. It might be a bit more subtle than it used to be at the beginning of my career, but it’s definitely still there. It’s nice for women, particularly those entering the field, to know that they’re not alone.

What is sexism? Well, it’s generally considered to be prejudice or discrimination against someone based on their sex or gender. One thing that’s important to remember is it’s not always extremely obvious. It’s not always intentional. I think most of us, I’d include myself in that, have sexist views. We may not always be aware of them. This is part of the unconscious bias that many of us have been trained to think.

As one example, we’re socialized — or I certainly was — to think of doctors as male. When a patient says, “I saw a cardiologist,” in my mind, I think that that person might have been male. Sometimes, I will ask, “What did he say?” That’s an example of sexism.

Sexism can be internalized. It can come from any source. We’re all implicated in it. I think that’s very important to remember. This is not a case of them doing something to us. This is something that is much more widespread and engendered in the society that we live in.

Dr. LaFaver: I think that’s really important to realize. Could you mention some other examples, specifically in the field of neurology, that you have encountered?

Dr. Loder: Certainly, looking over my own career — and I’m at a point now where I can look at early, mid, and late career — things were, of course, very different when I began. I would say that sexism was much more overt.

Very early in my career, I experienced a large amount of hostility from a boss. I ended up having to leave. This was, I believe, based on my sex. It turned out that leaving was a good thing for me, but it was a very unpleasant experience.

I also became a leader in my professional society. During my path to leadership and seeing other women attempt to make progress within the organization, I certainly saw behavior that I would characterize as rooted in sexism. To its credit, though, the professional society to which I belong, I think, has become one of the most progressive societies out there. The women within have been able to affect quite a bit of change in that professional organization.

I dealt with a case of sexual harassment in my own division when I was a division chief, which gave me insight into institutional policies and procedures meant to deal with situations like that, which, I think, leave something to be desired. That’s changing.

Now, I work in academic affairs, and I see how likely or unlikely people, based on their sex, are to put themselves forward for promotion, how likely they are to believe in their own capabilities. I also work as a medical journal editor, and I see generally that women are more hesitant to proclaim themselves experts and to accept invitations to provide or write editorial commentary. Sometimes, they do not perceive themselves as being expert enough to do so. I have seen many of these things over my career.

Dr. LaFaver: Thank you for sharing. I think it’s important to realize that it›s not just unidirectional but sometimes affects women and kind of goes both ways.

As you mentioned, these issues are not always overt. In recent years, microaggressions has become more of a term that has been used. Could you talk a bit about that? What are the microaggressions and how do they affect women?
 

Microaggressions and Migraine Mavens

Dr. Loder: The term microaggression has become very popular, and I think many people find it somewhat irritating. That, to me, is inherent in what a microaggression is. Microaggressions, by definition, are small things. It’s hard to prove that they were rooted in sexism. Sometimes, there’s a large amount of ambiguity about it. It can be as simple as inviting a pregnant woman to sit down because you perceive that she needs to sit, commenting on somebody’s shoes, or things like that.

Often, they’re unintentional. Sometimes, they come from a place of what we might term benevolent sexism, people trying to be helpful to a woman because they perceive that she’s weaker or she might not be able to do something, or maybe she has family responsibilities. They think that they’re being helpful. These things happen when we perceive people to be different in some way, as women are perceived to be different in terms of their responsibilities in the home or different in terms of what we expect from them in the workplace.

The problem with microaggressions is because they’re small, each one of them, I think the temptation is often to say, “Oh you know, they didn’t mean it. It’s not that big a deal. It was just a comment on your shoes.” If a woman brings that up, she’s often made to feel, sometimes by other women, that she should just chill out. This isn’t a big deal.

The problem is that they may not be a big deal in and of themselves, but when they are repeated over a long period of time, they can really sap somebody’s confidence in herself, make her question her own competence, and can have a cumulative effect that is very negative.

Although I think many people are skeptical about microaggressions as an important contribution to how women do in the workplace and in other settings, they are, in my opinion, important. I’ll just emphasize again that they come from everywhere, including other women and colleagues who mean to be helpful.

Dr. LaFaver: I know you have led a team of headache specialists and wrote a fantastic article about navigating sexism at work and what not to say to your female colleagues. Could you share some tips for them to navigate sexism at work and, specifically, as it applies to our careers in medicine.

Dr. Loder: Thank you for calling out that article. It actually grew organically out of a Facebook group that I started called Migraine Mavens. I’ve worked in the headache field throughout my career, and I experienced something that, to me, was kind of discouraging that I felt was sexist within our field. I just thought, What can I do? I thought, Well, maybe there’s some strength to be had in sharing this with other women, and maybe we should have our own social media community, so I formed this group.

After I gave a talk at the American Headache Society about sexism in the headache field, one of the members sent me a message saying, “Your talk was very timely. Immediately after you gave this talk, somebody stopped me in the hall and said, ‘Congratulations on your leadership position in the society, but are you really sure you can do this because you’ve got young children at home?’ Your talk was very needed.”

People started just discussing within the group, “Oh, this happened to me,” “That happened to me.” We began to brainstorm what we could have done differently. When these things happen, people are not necessarily prepared for them, and later on, you lie awake thinking of what you could have said.

We decided to write a paper. It ended up being published in The Journal of Head and Face Pain, and it was based on real vignettes from people in the group. We anonymized them so that people would not recognize themselves necessarily, but they’re all real. They’re things that really happened to women in the group.

We first describe the vignette — what happened. Then we explain, for those who need the explanation, what’s wrong with it. Why is it wrong to tell somebody to smile, for example. What could you do differently? What could somebody who sees this happen do, the so-called bystander or upstander? If you witness something like that, can you help the person toward whom this problematic behavior is directed? We came up with some examples. The all-purpose thing is to say, “What did you just say?” Make them repeat it, which often helps people to realize how inappropriate it is.

This got published as an article. It became quite the subject of attention on X [formerly Twitter] and elsewhere. I guess the term going viral would apply to this. It included a large amount of real-world advice. The thing I really loved about it was that it was written by the women in the group who had experienced these things. I would characterize it as having been somewhat therapeutic. We got many messages from women in other disciplines, outside medicine, saying that this happens in oceanography, for example. I think what we described really resonated beyond the field of headache medicine and neurology.
 

Institutional Sexism

Dr. LaFaver: Looking beyond the individual person, do you have any recommendations for medical institutions to share in order to do better and maybe create an environment that is less sexist?

Dr. Loder: Yes. I think many institutions try to deal with the problem of lack of diversity, whether it›s women or other underrepresented groups, by hiring. That’s one way to go about it, but I think retention strategies are also very important, and they need to pay attention to the work environment.

Every institution now has guidelines about harassment, bullying, sexism, racism, and so on. In general though — and I’m not speaking about any particular institution — these policies and procedures are often crafted with an eye toward protecting the institution. I would advise institutions to be a bit more genuine about this, and not to think so quickly about what can we do to prevent the institution from facing a charge of sexism, or what can we do to deny or dismiss these allegations, toward thinking, what can we do to really and truly be helpful to these women? In other words, approach it from the point of view of trying to help the people involved instead of trying to help the institution. That will make a very big difference.

I also think that citizenship activities, serving on committees, doing thankless tasks behind the scenes, and clinical work, seeing patients ... Women are overrepresented among clinicians. Of course, we know that research and bringing in big grants is often prioritized over clinical care, despite what institutions may say about that in public. I think those activities should be valued more highly, both in terms of pay and in terms of academic recognition.

In regard to the issue of salary, I would encourage institutions to publish salaries or at least make them easily findable by people within the institution. I think there should be objective criteria for salary determinations. The most important thing is that I do not think that women should be expected to negotiate their salaries. Women are judged differently than men when they attempt to negotiate salaries. It often backfires for them. It also is something that many women do not feel comfortable doing.

Waiting until somebody tries to negotiate a higher salary really guarantees, embeds, and operationalizes sex differences in salaries. We need to move away from the idea that you have to be a go-getter and that you have to ask for this raise. There should be objective criteria, salaries should be revisited on a regular basis, and the kinds of activities that women do that are undervalued should be more recognized in terms of money and advancement within academia.

Dr. LaFaver: I couldn’t agree more. One of the other topics discussed at the Women in Neurology conference was mid-career development, retention, and career paths. I think it’s known that many women leave academic medicine mid-career. I think these are excellent suggestions and hopefully will help to make careers successful for men and women, without needing to worry about being treated differently or unfairly.

Thank you so much. This was a wonderful overview of this topic.

Dr. Loder: You’re welcome, Dr. LaFaver. Thank you so much for asking me to speak on this topic. I really appreciate it.

Dr. LaFaver: Thanks, everyone.

 

Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, New York. Dr. LaFaver and Dr. Loder disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This interview was recorded Dec. 8, 2023. The transcript has been edited for clarity.

Kathrin LaFaver, MD: I have the pleasure of talking with Dr. Elizabeth Loder today. Dr. Loder is the vice chair of academic affairs in the department of neurology and a staff physician at Graham Headache Center at Brigham and Women’s Hospital in Boston. She’s also a professor of neurology at Harvard Medical School and has been a mentor to many headache specialists in the field.

We’ll be talking about the topic of sexism in medicine.

Elizabeth W. Loder, MD, MPH: Thank you so much, Dr. LaFaver. I’m very pleased to be here to talk about something that I think is very important.

Dr. LaFaver: Dr. Loder, you were a speaker at our Women in Neurology third annual conference in Florida, giving a talk on this very topic, sexism in medicine. It was very helpful, especially for many younger women entering the field of neurology, to hear that some of the experiences they’re having are not unique to them, but unfortunately remain a more systemic issue.

To get us started, could you define sexism in medicine for us, and how you got interested in this topic?
 

Sexism Can Be Subtle

Dr. Loder: You’re absolutely right. Sexism is still there. It might be a bit more subtle than it used to be at the beginning of my career, but it’s definitely still there. It’s nice for women, particularly those entering the field, to know that they’re not alone.

What is sexism? Well, it’s generally considered to be prejudice or discrimination against someone based on their sex or gender. One thing that’s important to remember is it’s not always extremely obvious. It’s not always intentional. I think most of us, I’d include myself in that, have sexist views. We may not always be aware of them. This is part of the unconscious bias that many of us have been trained to think.

As one example, we’re socialized — or I certainly was — to think of doctors as male. When a patient says, “I saw a cardiologist,” in my mind, I think that that person might have been male. Sometimes, I will ask, “What did he say?” That’s an example of sexism.

Sexism can be internalized. It can come from any source. We’re all implicated in it. I think that’s very important to remember. This is not a case of them doing something to us. This is something that is much more widespread and engendered in the society that we live in.

Dr. LaFaver: I think that’s really important to realize. Could you mention some other examples, specifically in the field of neurology, that you have encountered?

Dr. Loder: Certainly, looking over my own career — and I’m at a point now where I can look at early, mid, and late career — things were, of course, very different when I began. I would say that sexism was much more overt.

Very early in my career, I experienced a large amount of hostility from a boss. I ended up having to leave. This was, I believe, based on my sex. It turned out that leaving was a good thing for me, but it was a very unpleasant experience.

I also became a leader in my professional society. During my path to leadership and seeing other women attempt to make progress within the organization, I certainly saw behavior that I would characterize as rooted in sexism. To its credit, though, the professional society to which I belong, I think, has become one of the most progressive societies out there. The women within have been able to affect quite a bit of change in that professional organization.

I dealt with a case of sexual harassment in my own division when I was a division chief, which gave me insight into institutional policies and procedures meant to deal with situations like that, which, I think, leave something to be desired. That’s changing.

Now, I work in academic affairs, and I see how likely or unlikely people, based on their sex, are to put themselves forward for promotion, how likely they are to believe in their own capabilities. I also work as a medical journal editor, and I see generally that women are more hesitant to proclaim themselves experts and to accept invitations to provide or write editorial commentary. Sometimes, they do not perceive themselves as being expert enough to do so. I have seen many of these things over my career.

Dr. LaFaver: Thank you for sharing. I think it’s important to realize that it›s not just unidirectional but sometimes affects women and kind of goes both ways.

As you mentioned, these issues are not always overt. In recent years, microaggressions has become more of a term that has been used. Could you talk a bit about that? What are the microaggressions and how do they affect women?
 

Microaggressions and Migraine Mavens

Dr. Loder: The term microaggression has become very popular, and I think many people find it somewhat irritating. That, to me, is inherent in what a microaggression is. Microaggressions, by definition, are small things. It’s hard to prove that they were rooted in sexism. Sometimes, there’s a large amount of ambiguity about it. It can be as simple as inviting a pregnant woman to sit down because you perceive that she needs to sit, commenting on somebody’s shoes, or things like that.

Often, they’re unintentional. Sometimes, they come from a place of what we might term benevolent sexism, people trying to be helpful to a woman because they perceive that she’s weaker or she might not be able to do something, or maybe she has family responsibilities. They think that they’re being helpful. These things happen when we perceive people to be different in some way, as women are perceived to be different in terms of their responsibilities in the home or different in terms of what we expect from them in the workplace.

The problem with microaggressions is because they’re small, each one of them, I think the temptation is often to say, “Oh you know, they didn’t mean it. It’s not that big a deal. It was just a comment on your shoes.” If a woman brings that up, she’s often made to feel, sometimes by other women, that she should just chill out. This isn’t a big deal.

The problem is that they may not be a big deal in and of themselves, but when they are repeated over a long period of time, they can really sap somebody’s confidence in herself, make her question her own competence, and can have a cumulative effect that is very negative.

Although I think many people are skeptical about microaggressions as an important contribution to how women do in the workplace and in other settings, they are, in my opinion, important. I’ll just emphasize again that they come from everywhere, including other women and colleagues who mean to be helpful.

Dr. LaFaver: I know you have led a team of headache specialists and wrote a fantastic article about navigating sexism at work and what not to say to your female colleagues. Could you share some tips for them to navigate sexism at work and, specifically, as it applies to our careers in medicine.

Dr. Loder: Thank you for calling out that article. It actually grew organically out of a Facebook group that I started called Migraine Mavens. I’ve worked in the headache field throughout my career, and I experienced something that, to me, was kind of discouraging that I felt was sexist within our field. I just thought, What can I do? I thought, Well, maybe there’s some strength to be had in sharing this with other women, and maybe we should have our own social media community, so I formed this group.

After I gave a talk at the American Headache Society about sexism in the headache field, one of the members sent me a message saying, “Your talk was very timely. Immediately after you gave this talk, somebody stopped me in the hall and said, ‘Congratulations on your leadership position in the society, but are you really sure you can do this because you’ve got young children at home?’ Your talk was very needed.”

People started just discussing within the group, “Oh, this happened to me,” “That happened to me.” We began to brainstorm what we could have done differently. When these things happen, people are not necessarily prepared for them, and later on, you lie awake thinking of what you could have said.

We decided to write a paper. It ended up being published in The Journal of Head and Face Pain, and it was based on real vignettes from people in the group. We anonymized them so that people would not recognize themselves necessarily, but they’re all real. They’re things that really happened to women in the group.

We first describe the vignette — what happened. Then we explain, for those who need the explanation, what’s wrong with it. Why is it wrong to tell somebody to smile, for example. What could you do differently? What could somebody who sees this happen do, the so-called bystander or upstander? If you witness something like that, can you help the person toward whom this problematic behavior is directed? We came up with some examples. The all-purpose thing is to say, “What did you just say?” Make them repeat it, which often helps people to realize how inappropriate it is.

This got published as an article. It became quite the subject of attention on X [formerly Twitter] and elsewhere. I guess the term going viral would apply to this. It included a large amount of real-world advice. The thing I really loved about it was that it was written by the women in the group who had experienced these things. I would characterize it as having been somewhat therapeutic. We got many messages from women in other disciplines, outside medicine, saying that this happens in oceanography, for example. I think what we described really resonated beyond the field of headache medicine and neurology.
 

Institutional Sexism

Dr. LaFaver: Looking beyond the individual person, do you have any recommendations for medical institutions to share in order to do better and maybe create an environment that is less sexist?

Dr. Loder: Yes. I think many institutions try to deal with the problem of lack of diversity, whether it›s women or other underrepresented groups, by hiring. That’s one way to go about it, but I think retention strategies are also very important, and they need to pay attention to the work environment.

Every institution now has guidelines about harassment, bullying, sexism, racism, and so on. In general though — and I’m not speaking about any particular institution — these policies and procedures are often crafted with an eye toward protecting the institution. I would advise institutions to be a bit more genuine about this, and not to think so quickly about what can we do to prevent the institution from facing a charge of sexism, or what can we do to deny or dismiss these allegations, toward thinking, what can we do to really and truly be helpful to these women? In other words, approach it from the point of view of trying to help the people involved instead of trying to help the institution. That will make a very big difference.

I also think that citizenship activities, serving on committees, doing thankless tasks behind the scenes, and clinical work, seeing patients ... Women are overrepresented among clinicians. Of course, we know that research and bringing in big grants is often prioritized over clinical care, despite what institutions may say about that in public. I think those activities should be valued more highly, both in terms of pay and in terms of academic recognition.

In regard to the issue of salary, I would encourage institutions to publish salaries or at least make them easily findable by people within the institution. I think there should be objective criteria for salary determinations. The most important thing is that I do not think that women should be expected to negotiate their salaries. Women are judged differently than men when they attempt to negotiate salaries. It often backfires for them. It also is something that many women do not feel comfortable doing.

Waiting until somebody tries to negotiate a higher salary really guarantees, embeds, and operationalizes sex differences in salaries. We need to move away from the idea that you have to be a go-getter and that you have to ask for this raise. There should be objective criteria, salaries should be revisited on a regular basis, and the kinds of activities that women do that are undervalued should be more recognized in terms of money and advancement within academia.

Dr. LaFaver: I couldn’t agree more. One of the other topics discussed at the Women in Neurology conference was mid-career development, retention, and career paths. I think it’s known that many women leave academic medicine mid-career. I think these are excellent suggestions and hopefully will help to make careers successful for men and women, without needing to worry about being treated differently or unfairly.

Thank you so much. This was a wonderful overview of this topic.

Dr. Loder: You’re welcome, Dr. LaFaver. Thank you so much for asking me to speak on this topic. I really appreciate it.

Dr. LaFaver: Thanks, everyone.

 

Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, New York. Dr. LaFaver and Dr. Loder disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This interview was recorded Dec. 8, 2023. The transcript has been edited for clarity.

Kathrin LaFaver, MD: I have the pleasure of talking with Dr. Elizabeth Loder today. Dr. Loder is the vice chair of academic affairs in the department of neurology and a staff physician at Graham Headache Center at Brigham and Women’s Hospital in Boston. She’s also a professor of neurology at Harvard Medical School and has been a mentor to many headache specialists in the field.

We’ll be talking about the topic of sexism in medicine.

Elizabeth W. Loder, MD, MPH: Thank you so much, Dr. LaFaver. I’m very pleased to be here to talk about something that I think is very important.

Dr. LaFaver: Dr. Loder, you were a speaker at our Women in Neurology third annual conference in Florida, giving a talk on this very topic, sexism in medicine. It was very helpful, especially for many younger women entering the field of neurology, to hear that some of the experiences they’re having are not unique to them, but unfortunately remain a more systemic issue.

To get us started, could you define sexism in medicine for us, and how you got interested in this topic?
 

Sexism Can Be Subtle

Dr. Loder: You’re absolutely right. Sexism is still there. It might be a bit more subtle than it used to be at the beginning of my career, but it’s definitely still there. It’s nice for women, particularly those entering the field, to know that they’re not alone.

What is sexism? Well, it’s generally considered to be prejudice or discrimination against someone based on their sex or gender. One thing that’s important to remember is it’s not always extremely obvious. It’s not always intentional. I think most of us, I’d include myself in that, have sexist views. We may not always be aware of them. This is part of the unconscious bias that many of us have been trained to think.

As one example, we’re socialized — or I certainly was — to think of doctors as male. When a patient says, “I saw a cardiologist,” in my mind, I think that that person might have been male. Sometimes, I will ask, “What did he say?” That’s an example of sexism.

Sexism can be internalized. It can come from any source. We’re all implicated in it. I think that’s very important to remember. This is not a case of them doing something to us. This is something that is much more widespread and engendered in the society that we live in.

Dr. LaFaver: I think that’s really important to realize. Could you mention some other examples, specifically in the field of neurology, that you have encountered?

Dr. Loder: Certainly, looking over my own career — and I’m at a point now where I can look at early, mid, and late career — things were, of course, very different when I began. I would say that sexism was much more overt.

Very early in my career, I experienced a large amount of hostility from a boss. I ended up having to leave. This was, I believe, based on my sex. It turned out that leaving was a good thing for me, but it was a very unpleasant experience.

I also became a leader in my professional society. During my path to leadership and seeing other women attempt to make progress within the organization, I certainly saw behavior that I would characterize as rooted in sexism. To its credit, though, the professional society to which I belong, I think, has become one of the most progressive societies out there. The women within have been able to affect quite a bit of change in that professional organization.

I dealt with a case of sexual harassment in my own division when I was a division chief, which gave me insight into institutional policies and procedures meant to deal with situations like that, which, I think, leave something to be desired. That’s changing.

Now, I work in academic affairs, and I see how likely or unlikely people, based on their sex, are to put themselves forward for promotion, how likely they are to believe in their own capabilities. I also work as a medical journal editor, and I see generally that women are more hesitant to proclaim themselves experts and to accept invitations to provide or write editorial commentary. Sometimes, they do not perceive themselves as being expert enough to do so. I have seen many of these things over my career.

Dr. LaFaver: Thank you for sharing. I think it’s important to realize that it›s not just unidirectional but sometimes affects women and kind of goes both ways.

As you mentioned, these issues are not always overt. In recent years, microaggressions has become more of a term that has been used. Could you talk a bit about that? What are the microaggressions and how do they affect women?
 

Microaggressions and Migraine Mavens

Dr. Loder: The term microaggression has become very popular, and I think many people find it somewhat irritating. That, to me, is inherent in what a microaggression is. Microaggressions, by definition, are small things. It’s hard to prove that they were rooted in sexism. Sometimes, there’s a large amount of ambiguity about it. It can be as simple as inviting a pregnant woman to sit down because you perceive that she needs to sit, commenting on somebody’s shoes, or things like that.

Often, they’re unintentional. Sometimes, they come from a place of what we might term benevolent sexism, people trying to be helpful to a woman because they perceive that she’s weaker or she might not be able to do something, or maybe she has family responsibilities. They think that they’re being helpful. These things happen when we perceive people to be different in some way, as women are perceived to be different in terms of their responsibilities in the home or different in terms of what we expect from them in the workplace.

The problem with microaggressions is because they’re small, each one of them, I think the temptation is often to say, “Oh you know, they didn’t mean it. It’s not that big a deal. It was just a comment on your shoes.” If a woman brings that up, she’s often made to feel, sometimes by other women, that she should just chill out. This isn’t a big deal.

The problem is that they may not be a big deal in and of themselves, but when they are repeated over a long period of time, they can really sap somebody’s confidence in herself, make her question her own competence, and can have a cumulative effect that is very negative.

Although I think many people are skeptical about microaggressions as an important contribution to how women do in the workplace and in other settings, they are, in my opinion, important. I’ll just emphasize again that they come from everywhere, including other women and colleagues who mean to be helpful.

Dr. LaFaver: I know you have led a team of headache specialists and wrote a fantastic article about navigating sexism at work and what not to say to your female colleagues. Could you share some tips for them to navigate sexism at work and, specifically, as it applies to our careers in medicine.

Dr. Loder: Thank you for calling out that article. It actually grew organically out of a Facebook group that I started called Migraine Mavens. I’ve worked in the headache field throughout my career, and I experienced something that, to me, was kind of discouraging that I felt was sexist within our field. I just thought, What can I do? I thought, Well, maybe there’s some strength to be had in sharing this with other women, and maybe we should have our own social media community, so I formed this group.

After I gave a talk at the American Headache Society about sexism in the headache field, one of the members sent me a message saying, “Your talk was very timely. Immediately after you gave this talk, somebody stopped me in the hall and said, ‘Congratulations on your leadership position in the society, but are you really sure you can do this because you’ve got young children at home?’ Your talk was very needed.”

People started just discussing within the group, “Oh, this happened to me,” “That happened to me.” We began to brainstorm what we could have done differently. When these things happen, people are not necessarily prepared for them, and later on, you lie awake thinking of what you could have said.

We decided to write a paper. It ended up being published in The Journal of Head and Face Pain, and it was based on real vignettes from people in the group. We anonymized them so that people would not recognize themselves necessarily, but they’re all real. They’re things that really happened to women in the group.

We first describe the vignette — what happened. Then we explain, for those who need the explanation, what’s wrong with it. Why is it wrong to tell somebody to smile, for example. What could you do differently? What could somebody who sees this happen do, the so-called bystander or upstander? If you witness something like that, can you help the person toward whom this problematic behavior is directed? We came up with some examples. The all-purpose thing is to say, “What did you just say?” Make them repeat it, which often helps people to realize how inappropriate it is.

This got published as an article. It became quite the subject of attention on X [formerly Twitter] and elsewhere. I guess the term going viral would apply to this. It included a large amount of real-world advice. The thing I really loved about it was that it was written by the women in the group who had experienced these things. I would characterize it as having been somewhat therapeutic. We got many messages from women in other disciplines, outside medicine, saying that this happens in oceanography, for example. I think what we described really resonated beyond the field of headache medicine and neurology.
 

Institutional Sexism

Dr. LaFaver: Looking beyond the individual person, do you have any recommendations for medical institutions to share in order to do better and maybe create an environment that is less sexist?

Dr. Loder: Yes. I think many institutions try to deal with the problem of lack of diversity, whether it›s women or other underrepresented groups, by hiring. That’s one way to go about it, but I think retention strategies are also very important, and they need to pay attention to the work environment.

Every institution now has guidelines about harassment, bullying, sexism, racism, and so on. In general though — and I’m not speaking about any particular institution — these policies and procedures are often crafted with an eye toward protecting the institution. I would advise institutions to be a bit more genuine about this, and not to think so quickly about what can we do to prevent the institution from facing a charge of sexism, or what can we do to deny or dismiss these allegations, toward thinking, what can we do to really and truly be helpful to these women? In other words, approach it from the point of view of trying to help the people involved instead of trying to help the institution. That will make a very big difference.

I also think that citizenship activities, serving on committees, doing thankless tasks behind the scenes, and clinical work, seeing patients ... Women are overrepresented among clinicians. Of course, we know that research and bringing in big grants is often prioritized over clinical care, despite what institutions may say about that in public. I think those activities should be valued more highly, both in terms of pay and in terms of academic recognition.

In regard to the issue of salary, I would encourage institutions to publish salaries or at least make them easily findable by people within the institution. I think there should be objective criteria for salary determinations. The most important thing is that I do not think that women should be expected to negotiate their salaries. Women are judged differently than men when they attempt to negotiate salaries. It often backfires for them. It also is something that many women do not feel comfortable doing.

Waiting until somebody tries to negotiate a higher salary really guarantees, embeds, and operationalizes sex differences in salaries. We need to move away from the idea that you have to be a go-getter and that you have to ask for this raise. There should be objective criteria, salaries should be revisited on a regular basis, and the kinds of activities that women do that are undervalued should be more recognized in terms of money and advancement within academia.

Dr. LaFaver: I couldn’t agree more. One of the other topics discussed at the Women in Neurology conference was mid-career development, retention, and career paths. I think it’s known that many women leave academic medicine mid-career. I think these are excellent suggestions and hopefully will help to make careers successful for men and women, without needing to worry about being treated differently or unfairly.

Thank you so much. This was a wonderful overview of this topic.

Dr. Loder: You’re welcome, Dr. LaFaver. Thank you so much for asking me to speak on this topic. I really appreciate it.

Dr. LaFaver: Thanks, everyone.

 

Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, New York. Dr. LaFaver and Dr. Loder disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

A meta-analysis showed that all doses of tirzepatide, a novel twincretin molecule, reduced albuminuria levels without affecting renal function in patients with type 2 diabetes (T2D).

METHODOLOGY:

• A meta-analysis of eight randomized controlled trials compared the effects of tirzepatide and control treatment (placebo or any active comparator) on albuminuria levels and renal function in patients with T2D.
• The pooled data included 6226 patients with T2D who received tirzepatide (5, 10, or 15 mg) and 3307 participants in the control group who received placebo, semaglutide, or insulin.
• The primary outcome was the difference in absolute change in urinary albumin-creatinine ratio (UACR) from baseline between the tirzepatide and control groups.
• The secondary efficacy endpoint was the comparative change in estimated glomerular filtration rate (eGFR) between the two groups.

TAKEAWAY:

• Overall, tirzepatide reduced UACR by ~27% (mean difference [MD], −26.9%; P < .001) compared with controls.
• The reduction in UACR was consistent across all tirzepatide doses (5 mg: MD, −23.12%; 10 mg: MD, −27.87%; 15 mg: MD, −27.15).
• Benefits of tirzepatide were even more pronounced in patients with increased albuminuria levels (UACR ≥ 30 mg/g) at baseline (MD, −41.42%; P < .001) than in controls.
• However, tirzepatide vs control treatment did not have a significant effect on eGFR levels (P = .46), which indicated no negative effect of tirzepatide on renal function.

IN PRACTICE:

“Tirzepatide seems to be a ‘rising star’ for the prevention and delaying of chronic kidney disease and related, surrogate renal outcomes in patients with T2DM,” the authors wrote.

SOURCE:

Paschalis Karakasis, MD, Aristotle University of Thessaloniki, Thessaloniki, Greece, led this study, which was published online December 20, 2023, in the journal Diabetes, Obesity and Metabolism.

LIMITATIONS:

There was significant heterogeneity between the studies. Bias may have come from the open-label design in the included randomized controlled trials. The pathophysiological mechanisms underlying the effect of tirzepatide on chronic kidney disease pathogenesis are speculative.

DISCLOSURES:

The paper did not receive any specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A meta-analysis showed that all doses of tirzepatide, a novel twincretin molecule, reduced albuminuria levels without affecting renal function in patients with type 2 diabetes (T2D).

METHODOLOGY:

• A meta-analysis of eight randomized controlled trials compared the effects of tirzepatide and control treatment (placebo or any active comparator) on albuminuria levels and renal function in patients with T2D.
• The pooled data included 6226 patients with T2D who received tirzepatide (5, 10, or 15 mg) and 3307 participants in the control group who received placebo, semaglutide, or insulin.
• The primary outcome was the difference in absolute change in urinary albumin-creatinine ratio (UACR) from baseline between the tirzepatide and control groups.
• The secondary efficacy endpoint was the comparative change in estimated glomerular filtration rate (eGFR) between the two groups.

TAKEAWAY:

• Overall, tirzepatide reduced UACR by ~27% (mean difference [MD], −26.9%; P < .001) compared with controls.
• The reduction in UACR was consistent across all tirzepatide doses (5 mg: MD, −23.12%; 10 mg: MD, −27.87%; 15 mg: MD, −27.15).
• Benefits of tirzepatide were even more pronounced in patients with increased albuminuria levels (UACR ≥ 30 mg/g) at baseline (MD, −41.42%; P < .001) than in controls.
• However, tirzepatide vs control treatment did not have a significant effect on eGFR levels (P = .46), which indicated no negative effect of tirzepatide on renal function.

IN PRACTICE:

“Tirzepatide seems to be a ‘rising star’ for the prevention and delaying of chronic kidney disease and related, surrogate renal outcomes in patients with T2DM,” the authors wrote.

SOURCE:

Paschalis Karakasis, MD, Aristotle University of Thessaloniki, Thessaloniki, Greece, led this study, which was published online December 20, 2023, in the journal Diabetes, Obesity and Metabolism.

LIMITATIONS:

There was significant heterogeneity between the studies. Bias may have come from the open-label design in the included randomized controlled trials. The pathophysiological mechanisms underlying the effect of tirzepatide on chronic kidney disease pathogenesis are speculative.

DISCLOSURES:

The paper did not receive any specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A meta-analysis showed that all doses of tirzepatide, a novel twincretin molecule, reduced albuminuria levels without affecting renal function in patients with type 2 diabetes (T2D).

METHODOLOGY:

• A meta-analysis of eight randomized controlled trials compared the effects of tirzepatide and control treatment (placebo or any active comparator) on albuminuria levels and renal function in patients with T2D.
• The pooled data included 6226 patients with T2D who received tirzepatide (5, 10, or 15 mg) and 3307 participants in the control group who received placebo, semaglutide, or insulin.
• The primary outcome was the difference in absolute change in urinary albumin-creatinine ratio (UACR) from baseline between the tirzepatide and control groups.
• The secondary efficacy endpoint was the comparative change in estimated glomerular filtration rate (eGFR) between the two groups.

TAKEAWAY:

• Overall, tirzepatide reduced UACR by ~27% (mean difference [MD], −26.9%; P < .001) compared with controls.
• The reduction in UACR was consistent across all tirzepatide doses (5 mg: MD, −23.12%; 10 mg: MD, −27.87%; 15 mg: MD, −27.15).
• Benefits of tirzepatide were even more pronounced in patients with increased albuminuria levels (UACR ≥ 30 mg/g) at baseline (MD, −41.42%; P < .001) than in controls.
• However, tirzepatide vs control treatment did not have a significant effect on eGFR levels (P = .46), which indicated no negative effect of tirzepatide on renal function.

IN PRACTICE:

“Tirzepatide seems to be a ‘rising star’ for the prevention and delaying of chronic kidney disease and related, surrogate renal outcomes in patients with T2DM,” the authors wrote.

SOURCE:

Paschalis Karakasis, MD, Aristotle University of Thessaloniki, Thessaloniki, Greece, led this study, which was published online December 20, 2023, in the journal Diabetes, Obesity and Metabolism.

LIMITATIONS:

There was significant heterogeneity between the studies. Bias may have come from the open-label design in the included randomized controlled trials. The pathophysiological mechanisms underlying the effect of tirzepatide on chronic kidney disease pathogenesis are speculative.

DISCLOSURES:

The paper did not receive any specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — There are subtleties and nuances to diagnosing, treating, and monitoring the progress of treatment of hair loss in children. Moreover, hair loss in children can be challenging because it can be caused by a range of conditions, some common and others relatively rare.

Michelle Oboite, MD, shared tips on how to distinguish types of hair loss, when to treat with medications such as topical corticosteroids or Janus kinase (JAK) inhibitors, and why shared decision-making is important, at the ODAC Dermatology, Aesthetic & Surgical Conference.

What these conditions share is that they can negatively affect the quality of life for a child or teenager when the condition leads to anxiety, teasing, or bullying. “It is very isolating to have this condition that everyone in the world can see that you have and judge you for it,” said Dr. Oboite, an attending physician in the dermatology section of Children’s Hospital of Philadelphia.

While alopecia areata, tinea capitis, and trichotillomania are more common, other causes of hair loss in children include androgenetic alopecia, primary scarring alopecias, such as central centrifugal cicatricial alopecia, and dissecting cellulitis. Others are lichen planopilaris and genetic conditions, including loose anagen syndrome, uncombable hair syndrome, and “something so rare” — it has no acronym — autosomal recessive hypotrichosis with recurrent skin vesicles, Dr. Oboite said.
 

Alopecia Areata

Alopecia areata can differ from child to child and can appear in different stages: A localized patch stage, a diffuse patchy stage, or alopecia universalis. In this last stage, the child has already lost most or all the hair on the scalp and eyebrows, as well as the eyelashes.

The decision to treat or not to treat, particularly in younger children, should be on the basis of shared decision-making between a healthcare provider and caregiver, said Dr. Oboite, who is also an assistant professor of clinical dermatology at the University of Pennsylvania, Philadelphia.

Some younger children may not experience any negative impact from the condition, so waiting until they are older is an option.

Also, consider the impact of treatment on a child. Some therapies require frequent blood draws for monitoring, and some topical therapies that are applied multiple times a day “can be very overwhelming” for young children, Dr. Oboite said.

Most children with alopecia areata are healthy and do not need extensive screening laboratory testing. However, one exception is if thyroid dysfunction, commonly associated with alopecia areata, is suspected.

For alopecia areata, Dr. Oboite recommends starting with topical therapies, either topical corticosteroids (as first line) or topical JAK inhibitors (either topical ruxolitinib or compounded topical tofacitinib, both off-label for this indication).

Topical corticosteroids can be effective, but “you want to be thoughtful of the strength you’re using, the application frequency, and then the total amount of surface area that you’re treating,” Dr. Oboite said. Too potent or too much of a topical corticosteroid increases the risk for atrophy and systemic absorption, respectively. To reduce the risk, she reserves the use of ultrahigh-potency topical corticosteroids, such as clobetasol, for children ages 10 years or older. For children younger than 10 years, she recommends using mid-high-potency topical corticosteroids instead.

She recommends once-a-day application around bedtime 5 days a week, generally Monday through Friday to make it easier to remember.

“For children who have over 50% of the scalp involved, I do consider systemic therapy,” Dr. Oboite said. This can include oral steroids such as dexamethasone, prednisone, or prednisolone. For children with recalcitrant disease, she is more likely to use the oral JAK inhibitor ritlecitinib because it was recently approved by the Food and Drug Administration for treating severe alopecia areata in children 12 years and older and in adults.

Another strategy Dr. Oboite uses is to add low-dose oral minoxidil as an adjuvant to other systemic therapy. “I find that it helps with faster hair regrowth,” she said.
 

Tinea Capitis

Oral treatment is indicated for tinea capitis. “Topicals just don’t really clear this,” Dr. Oboite said. Also, talk to patients and families about preventing reinfection with the dermatophyte that causes this condition. “Make sure we’re cleaning hats, combs, brushes, and pillowcases. That is really important.”

Some patients can develop a widespread rash while on treatment. But in most cases, it’s not an adverse reaction to the medication but rather an indication that the body’s response is revving up, she noted.

Griseofulvin 20 mg/kg/d is one treatment option. Another is terbinafine (using weight-based dosing). A tip with terbinafine is that because the tablet needs to be crushed for a young child, “you can put it in anything, besides applesauce or yogurt with fruit on the bottom, which can be acidic and reduce the effectiveness of the medication,” Dr. Oboite said.

For cases of severe, inflammatory tinea capitis such as a kerion, “I will say you have to hold the hands of these patients, the journey can be long,” she added.
 

Trichotillomania

Trichotillomania occurs when someone cannot stop pulling their own hair, and in the early phases, it can be confused with alopecia areata. A thorough history and examination of the patient can help distinguish the two conditions. Sometimes a child or teen has a history of anxiety-related behaviors like nail biting that points to trichotillomania. Another tip is to use a dermatoscope to help distinguish hair loss conditions because it avoids having to do as many biopsies in children.

Redirection therapy can work for younger children, and cognitive behavioral therapy (CBT) can help older children with trichotillomania. In response to a question during the Q&A period, Dr. Oboite said psychiatrists or psychologists can perform CBT. If it takes time to get an appointment, there are some CBT apps that can help in the meantime, she said.

“One thing really important is to not blame the child,” Dr. Oboite said. “Most children don’t even know that they’re doing this. This is often not a behavior that is being done on purpose.”

Androgenetic Alopecia

Rarely, children and teenagers can also present with androgenetic alopecia, which Dr. Oboite has successfully treated with topical minoxidil, applied once a day before increasing to twice a day if tolerated. “I will tell them that when they pick it up, it will say ‘you should not use in children.’ But it actually can be used in children safely.”

Low-dose oral minoxidil is another option. Both treatments require a commitment by patients and parents because they are “taking this for a long time.”
 

Loose Anagen and Uncombable Hair Syndromes

A rare genetic form of hair loss is called loose anagen syndrome. Children with this disorder will have thin hair that is easily pulled out without a lot of force. Their hair appears to typically only grow to a certain length (such as to the nape of the neck) and then stops.

Another genetic hair loss condition is uncombable hair syndrome. It can cause hair to grow out of the scalp in all directions, and as the name suggests, it is almost impossible to comb or brush down. Along with loose anagen syndrome, uncombable hair syndrome tends to improve as the child gets older. “The key point here is telling parents that it can get better with time,” Dr. Oboite said.
 

A Condition With No Well-Known Acronym

She described a child she treated who had hair that never grew and was easily broken. The patient’s skin was prone to bruising, and her fingernails would easily fall off after trauma; her dentist noted that she had no buds for adult teeth on x-rays. These different presentations are important because hair, teeth, and nails all come from the same ectoderm germ line in embryo development, Dr. Oboite said.

Exome sequencing revealed the girl had a very rare diagnosis called autosomal recessive hypotrichosis with recurrent skin vesicles. “So, it is really important to recognize that children who are presenting with hair issues can have a genetic, underlying condition,” she said. Examining the skin, nails, and teeth, in addition to the hair, can be clues to these very rare diagnoses.

Some of these hair loss conditions in children can be challenging to diagnose and manage, Dr. Oboite said. “So don’t be afraid to ask for help on complex or rare cases.” Pediatric dermatologists “are always happy to help you. Hair loss is daunting, and hair loss in children can be even more daunting,” but the rewards of accurate diagnosis and successful treatment can be great, she said.

Dr. Oboite reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — There are subtleties and nuances to diagnosing, treating, and monitoring the progress of treatment of hair loss in children. Moreover, hair loss in children can be challenging because it can be caused by a range of conditions, some common and others relatively rare.

Michelle Oboite, MD, shared tips on how to distinguish types of hair loss, when to treat with medications such as topical corticosteroids or Janus kinase (JAK) inhibitors, and why shared decision-making is important, at the ODAC Dermatology, Aesthetic & Surgical Conference.

What these conditions share is that they can negatively affect the quality of life for a child or teenager when the condition leads to anxiety, teasing, or bullying. “It is very isolating to have this condition that everyone in the world can see that you have and judge you for it,” said Dr. Oboite, an attending physician in the dermatology section of Children’s Hospital of Philadelphia.

While alopecia areata, tinea capitis, and trichotillomania are more common, other causes of hair loss in children include androgenetic alopecia, primary scarring alopecias, such as central centrifugal cicatricial alopecia, and dissecting cellulitis. Others are lichen planopilaris and genetic conditions, including loose anagen syndrome, uncombable hair syndrome, and “something so rare” — it has no acronym — autosomal recessive hypotrichosis with recurrent skin vesicles, Dr. Oboite said.
 

Alopecia Areata

Alopecia areata can differ from child to child and can appear in different stages: A localized patch stage, a diffuse patchy stage, or alopecia universalis. In this last stage, the child has already lost most or all the hair on the scalp and eyebrows, as well as the eyelashes.

The decision to treat or not to treat, particularly in younger children, should be on the basis of shared decision-making between a healthcare provider and caregiver, said Dr. Oboite, who is also an assistant professor of clinical dermatology at the University of Pennsylvania, Philadelphia.

Some younger children may not experience any negative impact from the condition, so waiting until they are older is an option.

Also, consider the impact of treatment on a child. Some therapies require frequent blood draws for monitoring, and some topical therapies that are applied multiple times a day “can be very overwhelming” for young children, Dr. Oboite said.

Most children with alopecia areata are healthy and do not need extensive screening laboratory testing. However, one exception is if thyroid dysfunction, commonly associated with alopecia areata, is suspected.

For alopecia areata, Dr. Oboite recommends starting with topical therapies, either topical corticosteroids (as first line) or topical JAK inhibitors (either topical ruxolitinib or compounded topical tofacitinib, both off-label for this indication).

Topical corticosteroids can be effective, but “you want to be thoughtful of the strength you’re using, the application frequency, and then the total amount of surface area that you’re treating,” Dr. Oboite said. Too potent or too much of a topical corticosteroid increases the risk for atrophy and systemic absorption, respectively. To reduce the risk, she reserves the use of ultrahigh-potency topical corticosteroids, such as clobetasol, for children ages 10 years or older. For children younger than 10 years, she recommends using mid-high-potency topical corticosteroids instead.

She recommends once-a-day application around bedtime 5 days a week, generally Monday through Friday to make it easier to remember.

“For children who have over 50% of the scalp involved, I do consider systemic therapy,” Dr. Oboite said. This can include oral steroids such as dexamethasone, prednisone, or prednisolone. For children with recalcitrant disease, she is more likely to use the oral JAK inhibitor ritlecitinib because it was recently approved by the Food and Drug Administration for treating severe alopecia areata in children 12 years and older and in adults.

Another strategy Dr. Oboite uses is to add low-dose oral minoxidil as an adjuvant to other systemic therapy. “I find that it helps with faster hair regrowth,” she said.
 

Tinea Capitis

Oral treatment is indicated for tinea capitis. “Topicals just don’t really clear this,” Dr. Oboite said. Also, talk to patients and families about preventing reinfection with the dermatophyte that causes this condition. “Make sure we’re cleaning hats, combs, brushes, and pillowcases. That is really important.”

Some patients can develop a widespread rash while on treatment. But in most cases, it’s not an adverse reaction to the medication but rather an indication that the body’s response is revving up, she noted.

Griseofulvin 20 mg/kg/d is one treatment option. Another is terbinafine (using weight-based dosing). A tip with terbinafine is that because the tablet needs to be crushed for a young child, “you can put it in anything, besides applesauce or yogurt with fruit on the bottom, which can be acidic and reduce the effectiveness of the medication,” Dr. Oboite said.

For cases of severe, inflammatory tinea capitis such as a kerion, “I will say you have to hold the hands of these patients, the journey can be long,” she added.
 

Trichotillomania

Trichotillomania occurs when someone cannot stop pulling their own hair, and in the early phases, it can be confused with alopecia areata. A thorough history and examination of the patient can help distinguish the two conditions. Sometimes a child or teen has a history of anxiety-related behaviors like nail biting that points to trichotillomania. Another tip is to use a dermatoscope to help distinguish hair loss conditions because it avoids having to do as many biopsies in children.

Redirection therapy can work for younger children, and cognitive behavioral therapy (CBT) can help older children with trichotillomania. In response to a question during the Q&A period, Dr. Oboite said psychiatrists or psychologists can perform CBT. If it takes time to get an appointment, there are some CBT apps that can help in the meantime, she said.

“One thing really important is to not blame the child,” Dr. Oboite said. “Most children don’t even know that they’re doing this. This is often not a behavior that is being done on purpose.”

Androgenetic Alopecia

Rarely, children and teenagers can also present with androgenetic alopecia, which Dr. Oboite has successfully treated with topical minoxidil, applied once a day before increasing to twice a day if tolerated. “I will tell them that when they pick it up, it will say ‘you should not use in children.’ But it actually can be used in children safely.”

Low-dose oral minoxidil is another option. Both treatments require a commitment by patients and parents because they are “taking this for a long time.”
 

Loose Anagen and Uncombable Hair Syndromes

A rare genetic form of hair loss is called loose anagen syndrome. Children with this disorder will have thin hair that is easily pulled out without a lot of force. Their hair appears to typically only grow to a certain length (such as to the nape of the neck) and then stops.

Another genetic hair loss condition is uncombable hair syndrome. It can cause hair to grow out of the scalp in all directions, and as the name suggests, it is almost impossible to comb or brush down. Along with loose anagen syndrome, uncombable hair syndrome tends to improve as the child gets older. “The key point here is telling parents that it can get better with time,” Dr. Oboite said.
 

A Condition With No Well-Known Acronym

She described a child she treated who had hair that never grew and was easily broken. The patient’s skin was prone to bruising, and her fingernails would easily fall off after trauma; her dentist noted that she had no buds for adult teeth on x-rays. These different presentations are important because hair, teeth, and nails all come from the same ectoderm germ line in embryo development, Dr. Oboite said.

Exome sequencing revealed the girl had a very rare diagnosis called autosomal recessive hypotrichosis with recurrent skin vesicles. “So, it is really important to recognize that children who are presenting with hair issues can have a genetic, underlying condition,” she said. Examining the skin, nails, and teeth, in addition to the hair, can be clues to these very rare diagnoses.

Some of these hair loss conditions in children can be challenging to diagnose and manage, Dr. Oboite said. “So don’t be afraid to ask for help on complex or rare cases.” Pediatric dermatologists “are always happy to help you. Hair loss is daunting, and hair loss in children can be even more daunting,” but the rewards of accurate diagnosis and successful treatment can be great, she said.

Dr. Oboite reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — There are subtleties and nuances to diagnosing, treating, and monitoring the progress of treatment of hair loss in children. Moreover, hair loss in children can be challenging because it can be caused by a range of conditions, some common and others relatively rare.

Michelle Oboite, MD, shared tips on how to distinguish types of hair loss, when to treat with medications such as topical corticosteroids or Janus kinase (JAK) inhibitors, and why shared decision-making is important, at the ODAC Dermatology, Aesthetic & Surgical Conference.

What these conditions share is that they can negatively affect the quality of life for a child or teenager when the condition leads to anxiety, teasing, or bullying. “It is very isolating to have this condition that everyone in the world can see that you have and judge you for it,” said Dr. Oboite, an attending physician in the dermatology section of Children’s Hospital of Philadelphia.

While alopecia areata, tinea capitis, and trichotillomania are more common, other causes of hair loss in children include androgenetic alopecia, primary scarring alopecias, such as central centrifugal cicatricial alopecia, and dissecting cellulitis. Others are lichen planopilaris and genetic conditions, including loose anagen syndrome, uncombable hair syndrome, and “something so rare” — it has no acronym — autosomal recessive hypotrichosis with recurrent skin vesicles, Dr. Oboite said.
 

Alopecia Areata

Alopecia areata can differ from child to child and can appear in different stages: A localized patch stage, a diffuse patchy stage, or alopecia universalis. In this last stage, the child has already lost most or all the hair on the scalp and eyebrows, as well as the eyelashes.

The decision to treat or not to treat, particularly in younger children, should be on the basis of shared decision-making between a healthcare provider and caregiver, said Dr. Oboite, who is also an assistant professor of clinical dermatology at the University of Pennsylvania, Philadelphia.

Some younger children may not experience any negative impact from the condition, so waiting until they are older is an option.

Also, consider the impact of treatment on a child. Some therapies require frequent blood draws for monitoring, and some topical therapies that are applied multiple times a day “can be very overwhelming” for young children, Dr. Oboite said.

Most children with alopecia areata are healthy and do not need extensive screening laboratory testing. However, one exception is if thyroid dysfunction, commonly associated with alopecia areata, is suspected.

For alopecia areata, Dr. Oboite recommends starting with topical therapies, either topical corticosteroids (as first line) or topical JAK inhibitors (either topical ruxolitinib or compounded topical tofacitinib, both off-label for this indication).

Topical corticosteroids can be effective, but “you want to be thoughtful of the strength you’re using, the application frequency, and then the total amount of surface area that you’re treating,” Dr. Oboite said. Too potent or too much of a topical corticosteroid increases the risk for atrophy and systemic absorption, respectively. To reduce the risk, she reserves the use of ultrahigh-potency topical corticosteroids, such as clobetasol, for children ages 10 years or older. For children younger than 10 years, she recommends using mid-high-potency topical corticosteroids instead.

She recommends once-a-day application around bedtime 5 days a week, generally Monday through Friday to make it easier to remember.

“For children who have over 50% of the scalp involved, I do consider systemic therapy,” Dr. Oboite said. This can include oral steroids such as dexamethasone, prednisone, or prednisolone. For children with recalcitrant disease, she is more likely to use the oral JAK inhibitor ritlecitinib because it was recently approved by the Food and Drug Administration for treating severe alopecia areata in children 12 years and older and in adults.

Another strategy Dr. Oboite uses is to add low-dose oral minoxidil as an adjuvant to other systemic therapy. “I find that it helps with faster hair regrowth,” she said.
 

Tinea Capitis

Oral treatment is indicated for tinea capitis. “Topicals just don’t really clear this,” Dr. Oboite said. Also, talk to patients and families about preventing reinfection with the dermatophyte that causes this condition. “Make sure we’re cleaning hats, combs, brushes, and pillowcases. That is really important.”

Some patients can develop a widespread rash while on treatment. But in most cases, it’s not an adverse reaction to the medication but rather an indication that the body’s response is revving up, she noted.

Griseofulvin 20 mg/kg/d is one treatment option. Another is terbinafine (using weight-based dosing). A tip with terbinafine is that because the tablet needs to be crushed for a young child, “you can put it in anything, besides applesauce or yogurt with fruit on the bottom, which can be acidic and reduce the effectiveness of the medication,” Dr. Oboite said.

For cases of severe, inflammatory tinea capitis such as a kerion, “I will say you have to hold the hands of these patients, the journey can be long,” she added.
 

Trichotillomania

Trichotillomania occurs when someone cannot stop pulling their own hair, and in the early phases, it can be confused with alopecia areata. A thorough history and examination of the patient can help distinguish the two conditions. Sometimes a child or teen has a history of anxiety-related behaviors like nail biting that points to trichotillomania. Another tip is to use a dermatoscope to help distinguish hair loss conditions because it avoids having to do as many biopsies in children.

Redirection therapy can work for younger children, and cognitive behavioral therapy (CBT) can help older children with trichotillomania. In response to a question during the Q&A period, Dr. Oboite said psychiatrists or psychologists can perform CBT. If it takes time to get an appointment, there are some CBT apps that can help in the meantime, she said.

“One thing really important is to not blame the child,” Dr. Oboite said. “Most children don’t even know that they’re doing this. This is often not a behavior that is being done on purpose.”

Androgenetic Alopecia

Rarely, children and teenagers can also present with androgenetic alopecia, which Dr. Oboite has successfully treated with topical minoxidil, applied once a day before increasing to twice a day if tolerated. “I will tell them that when they pick it up, it will say ‘you should not use in children.’ But it actually can be used in children safely.”

Low-dose oral minoxidil is another option. Both treatments require a commitment by patients and parents because they are “taking this for a long time.”
 

Loose Anagen and Uncombable Hair Syndromes

A rare genetic form of hair loss is called loose anagen syndrome. Children with this disorder will have thin hair that is easily pulled out without a lot of force. Their hair appears to typically only grow to a certain length (such as to the nape of the neck) and then stops.

Another genetic hair loss condition is uncombable hair syndrome. It can cause hair to grow out of the scalp in all directions, and as the name suggests, it is almost impossible to comb or brush down. Along with loose anagen syndrome, uncombable hair syndrome tends to improve as the child gets older. “The key point here is telling parents that it can get better with time,” Dr. Oboite said.
 

A Condition With No Well-Known Acronym

She described a child she treated who had hair that never grew and was easily broken. The patient’s skin was prone to bruising, and her fingernails would easily fall off after trauma; her dentist noted that she had no buds for adult teeth on x-rays. These different presentations are important because hair, teeth, and nails all come from the same ectoderm germ line in embryo development, Dr. Oboite said.

Exome sequencing revealed the girl had a very rare diagnosis called autosomal recessive hypotrichosis with recurrent skin vesicles. “So, it is really important to recognize that children who are presenting with hair issues can have a genetic, underlying condition,” she said. Examining the skin, nails, and teeth, in addition to the hair, can be clues to these very rare diagnoses.

Some of these hair loss conditions in children can be challenging to diagnose and manage, Dr. Oboite said. “So don’t be afraid to ask for help on complex or rare cases.” Pediatric dermatologists “are always happy to help you. Hair loss is daunting, and hair loss in children can be even more daunting,” but the rewards of accurate diagnosis and successful treatment can be great, she said.

Dr. Oboite reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Using an advanced microscopic technique, American researchers have detected 100,000 nanoplastic molecules per liter of water in plastic bottles. Because of their small size, these particles can enter the bloodstream, cells, and the brain, thus posing potential health risks. The study, recently published in the Proceedings of the National Academy of Sciences, raises concerns about the impact of these nanoparticles.

An Unknown Realm

In recent years, the global presence of tiny particles known as microplastics has raised concerns. The particles are found in polar ice, soil, drinking water, and food. Formed as plastics break down into increasingly small pieces, these particles are consumed by humans and other organisms, with unknown effects on health and ecosystems. Whereas macroplastics have been found in various organs, including the lungs and liver, the study marks a unique exploration into the world of nanoplastics.

Concerns about nanoplastic presence in humans intensified when a 2018 study revealed contamination signs in 93% of 259 examined bottles from nine countries.

The novelty of this research lies in its focus, using a refined spectrometry method, on the poorly understood world of nanoplastics, which derive from the decomposition of microplastics. For the first time, American researchers, including biophysicists and chemists, counted and identified these tiny particles in bottled water. On average, they found around 240,000 detectable plastic fragments per liter, which is 10-100 times more than previous estimates based on larger sizes.

Microplastics are defined as fragments ranging from 5 mm to 1 µm, whereas nanoplastics, particles < 1 µm, are measured in billionths of a meter.

In contrast to microplastics, nanoplastics are so small that they can traverse the intestines and lungs and move directly into the bloodstream, reaching organs such as the heart or brain or even the fetus via the placenta.

“This was previously an obscure, unexplored area. Toxicity studies could only speculate about what was in there,” said Beizhan Yan, PhD, coauthor of the study and environmental chemist at the Lamont–Doherty Earth Observatory of Columbia University, New York. “This study opens a window for us to observe a world we were not exposed to before.”
 

90% Nanoplastics Found

The new study employed a technique called stimulated Raman scattering microscopy, which was invented by study coauthor Wei Min, a biophysicist at Columbia. This method involves probing samples simultaneously with two lasers tuned to resonate specific molecules.

Researchers tested three bottled water brands that are popular in the United States, analyzing plastic particles up to 100 nm in size. They identified 110,000-370,000 plastic particles per liter. About 90% were nanoplastics — which are invisible by standard imaging techniques — and the rest were microplastics. The study also identified the seven plastics involved.

The most common is polyamide, a type of nylon, likely from plastic filters purportedly used to purify water before bottling. Next is polyethylene terephthalate, which is commonly used for water bottles and other food containers. Researchers also found other common plastics, including polystyrene, polyvinyl chloride, and methyl methacrylate, used in various industrial processes.
 

Not Size But Quantity

What’s more concerning is that the seven types of plastics accounted for only about 10% of all nanoparticles found in the samples. Researchers have no idea about the composition of the remaining 90%. If these are all nanoparticles, their number could reach tens of millions per liter, representing the complex composition of seemingly simple water samples, as noted by the authors.

Researchers now plan to expand beyond bottled water, exploring the vast realm of nanoplastics. They emphasize that, in terms of mass, nanoplastics are far smaller than microplastics, but “it’s not about size. It’s about the numbers as smaller things can easily penetrate us.”

The team aims to study tap water, which also contains microplastics but in much smaller proportions than bottled water.

This article was translated from the Medscape French edition. 

Using an advanced microscopic technique, American researchers have detected 100,000 nanoplastic molecules per liter of water in plastic bottles. Because of their small size, these particles can enter the bloodstream, cells, and the brain, thus posing potential health risks. The study, recently published in the Proceedings of the National Academy of Sciences, raises concerns about the impact of these nanoparticles.

An Unknown Realm

In recent years, the global presence of tiny particles known as microplastics has raised concerns. The particles are found in polar ice, soil, drinking water, and food. Formed as plastics break down into increasingly small pieces, these particles are consumed by humans and other organisms, with unknown effects on health and ecosystems. Whereas macroplastics have been found in various organs, including the lungs and liver, the study marks a unique exploration into the world of nanoplastics.

Concerns about nanoplastic presence in humans intensified when a 2018 study revealed contamination signs in 93% of 259 examined bottles from nine countries.

The novelty of this research lies in its focus, using a refined spectrometry method, on the poorly understood world of nanoplastics, which derive from the decomposition of microplastics. For the first time, American researchers, including biophysicists and chemists, counted and identified these tiny particles in bottled water. On average, they found around 240,000 detectable plastic fragments per liter, which is 10-100 times more than previous estimates based on larger sizes.

Microplastics are defined as fragments ranging from 5 mm to 1 µm, whereas nanoplastics, particles < 1 µm, are measured in billionths of a meter.

In contrast to microplastics, nanoplastics are so small that they can traverse the intestines and lungs and move directly into the bloodstream, reaching organs such as the heart or brain or even the fetus via the placenta.

“This was previously an obscure, unexplored area. Toxicity studies could only speculate about what was in there,” said Beizhan Yan, PhD, coauthor of the study and environmental chemist at the Lamont–Doherty Earth Observatory of Columbia University, New York. “This study opens a window for us to observe a world we were not exposed to before.”
 

90% Nanoplastics Found

The new study employed a technique called stimulated Raman scattering microscopy, which was invented by study coauthor Wei Min, a biophysicist at Columbia. This method involves probing samples simultaneously with two lasers tuned to resonate specific molecules.

Researchers tested three bottled water brands that are popular in the United States, analyzing plastic particles up to 100 nm in size. They identified 110,000-370,000 plastic particles per liter. About 90% were nanoplastics — which are invisible by standard imaging techniques — and the rest were microplastics. The study also identified the seven plastics involved.

The most common is polyamide, a type of nylon, likely from plastic filters purportedly used to purify water before bottling. Next is polyethylene terephthalate, which is commonly used for water bottles and other food containers. Researchers also found other common plastics, including polystyrene, polyvinyl chloride, and methyl methacrylate, used in various industrial processes.
 

Not Size But Quantity

What’s more concerning is that the seven types of plastics accounted for only about 10% of all nanoparticles found in the samples. Researchers have no idea about the composition of the remaining 90%. If these are all nanoparticles, their number could reach tens of millions per liter, representing the complex composition of seemingly simple water samples, as noted by the authors.

Researchers now plan to expand beyond bottled water, exploring the vast realm of nanoplastics. They emphasize that, in terms of mass, nanoplastics are far smaller than microplastics, but “it’s not about size. It’s about the numbers as smaller things can easily penetrate us.”

The team aims to study tap water, which also contains microplastics but in much smaller proportions than bottled water.

This article was translated from the Medscape French edition. 

Using an advanced microscopic technique, American researchers have detected 100,000 nanoplastic molecules per liter of water in plastic bottles. Because of their small size, these particles can enter the bloodstream, cells, and the brain, thus posing potential health risks. The study, recently published in the Proceedings of the National Academy of Sciences, raises concerns about the impact of these nanoparticles.

An Unknown Realm

In recent years, the global presence of tiny particles known as microplastics has raised concerns. The particles are found in polar ice, soil, drinking water, and food. Formed as plastics break down into increasingly small pieces, these particles are consumed by humans and other organisms, with unknown effects on health and ecosystems. Whereas macroplastics have been found in various organs, including the lungs and liver, the study marks a unique exploration into the world of nanoplastics.

Concerns about nanoplastic presence in humans intensified when a 2018 study revealed contamination signs in 93% of 259 examined bottles from nine countries.

The novelty of this research lies in its focus, using a refined spectrometry method, on the poorly understood world of nanoplastics, which derive from the decomposition of microplastics. For the first time, American researchers, including biophysicists and chemists, counted and identified these tiny particles in bottled water. On average, they found around 240,000 detectable plastic fragments per liter, which is 10-100 times more than previous estimates based on larger sizes.

Microplastics are defined as fragments ranging from 5 mm to 1 µm, whereas nanoplastics, particles < 1 µm, are measured in billionths of a meter.

In contrast to microplastics, nanoplastics are so small that they can traverse the intestines and lungs and move directly into the bloodstream, reaching organs such as the heart or brain or even the fetus via the placenta.

“This was previously an obscure, unexplored area. Toxicity studies could only speculate about what was in there,” said Beizhan Yan, PhD, coauthor of the study and environmental chemist at the Lamont–Doherty Earth Observatory of Columbia University, New York. “This study opens a window for us to observe a world we were not exposed to before.”
 

90% Nanoplastics Found

The new study employed a technique called stimulated Raman scattering microscopy, which was invented by study coauthor Wei Min, a biophysicist at Columbia. This method involves probing samples simultaneously with two lasers tuned to resonate specific molecules.

Researchers tested three bottled water brands that are popular in the United States, analyzing plastic particles up to 100 nm in size. They identified 110,000-370,000 plastic particles per liter. About 90% were nanoplastics — which are invisible by standard imaging techniques — and the rest were microplastics. The study also identified the seven plastics involved.

The most common is polyamide, a type of nylon, likely from plastic filters purportedly used to purify water before bottling. Next is polyethylene terephthalate, which is commonly used for water bottles and other food containers. Researchers also found other common plastics, including polystyrene, polyvinyl chloride, and methyl methacrylate, used in various industrial processes.
 

Not Size But Quantity

What’s more concerning is that the seven types of plastics accounted for only about 10% of all nanoparticles found in the samples. Researchers have no idea about the composition of the remaining 90%. If these are all nanoparticles, their number could reach tens of millions per liter, representing the complex composition of seemingly simple water samples, as noted by the authors.

Researchers now plan to expand beyond bottled water, exploring the vast realm of nanoplastics. They emphasize that, in terms of mass, nanoplastics are far smaller than microplastics, but “it’s not about size. It’s about the numbers as smaller things can easily penetrate us.”

The team aims to study tap water, which also contains microplastics but in much smaller proportions than bottled water.

This article was translated from the Medscape French edition. 

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?

Acne

One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes. 
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added. 
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.

Psoriasis

A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis. 
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said. 
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.

Atopic Dermatitis

Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up. 

Rosacea

Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said. 
Dr. Shi reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?

Acne

One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes. 
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added. 
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.

Psoriasis

A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis. 
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said. 
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.

Atopic Dermatitis

Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up. 

Rosacea

Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said. 
Dr. Shi reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?

Acne

One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes. 
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added. 
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.

Psoriasis

A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis. 
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said. 
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.

Atopic Dermatitis

Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up. 

Rosacea

Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said. 
Dr. Shi reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

New data from the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) suggest that a daily multivitamin may help protect the aging brain. However, at least one expert has concerns about the study’s methodology and, as a result, the interpretation of its findings. 

The meta-analysis of three separate cognition studies provides “strong and consistent evidence that taking a daily multivitamin, containing more than 20 essential micronutrients, can help prevent memory loss and slow down cognitive aging,” study investigator Chirag Vyas, MBBS, MPH, with Massachusetts General Hospital and Harvard Medical School, Boston, told this news organization. 

“We are not now recommending multivitamin use, but the evidence is compelling that supports the promise of multivitamins to help prevent cognitive decline,” Dr. Vyas said. 

The new data, from the cognitive substudies of COSMOS, were published online in the American Journal of Clinical Nutrition.
 

Clinically Meaningful Benefit?

To recap, COSMOS was a 2 x 2 factorial trial of coca extract (500 mg/d flavanols) and/or a daily commercial multivitamin-mineral (MVM) supplement for cardiovascular disease and cancer prevention among more than 21,000 US adults aged 60 years or older. 

Neither the cocoa extract nor the MVM supplement had a significant impact on cancer or cardiovascular disease events.

COMOS-Mind was a substudy of 2262 participants aged 65 or older without dementia who completed telephone-based cognitive assessments at baseline and annually for 3 years. 

As previously reported by this news organization in COSMOS-Mind, there was no cognitive benefit of daily cocoa extract, but daily MVM supplementation was associated with improved global cognition, episodic memory, and executive function. However, the difference in global cognitive function between MVM and placebo was small, with a mean 0.07-point improvement on the z-score at 3 years. 

COSMOS-Web was a substudy of 3562 original participants who were evaluated annually for 3 years using an internet-based battery of neuropsychological tests. 

In this analysis, those taking the MVM supplement performed better on a test for immediate memory recall (remembering a list of 20 words); they were able to remember an additional 0.71 word on average compared with 0.44 word in the placebo group. However, they did not improve on tests of memory retention, executive function, or novel object recognition.

The new data are from COSMOS-Clinic, an analysis of 573 participants who completed in-person cognitive assessments. 

COSMOS-Clinic showed a modest benefit of MVM, compared with placebo, on global cognition over 2 years (mean difference, 0.06 SD units [SU]), with a significantly more favorable change in episodic memory (mean difference, 0.12 SU) but not in executive function/attention (mean difference, 0.04 SU), the researchers reported. 

They also conducted a meta-analysis based on the three separate cognitive substudies, with 5200 nonoverlapping COSMOS participants. 

The results showed “clear evidence” of MVM benefits on global cognition (mean difference, 0.07 SU; P = .0009) and episodic memory (mean difference, 0.06 SU; P =.0007), they reported, with the magnitude of effect on global cognition equivalent to reducing cognitive aging by 2 years.

In a statement, JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, who led the overall COSMOS trial, said that “the finding that a daily multivitamin improved memory and slowed cognitive aging in three separate placebo-controlled studies in COSMOS is exciting and further supports the promise of multivitamins as a safe, accessible, and affordable approach to protecting cognitive health in older adults.”
 

Not a Meta-analysis?

In an interview with this news organization, Christopher Labos, MD CM, MSc, a cardiologist and epidemiologist based in Montreal, Canada, who wasn’t involved in COSMOS, cautioned that the evidence to date on multivitamins for memory and brain health are “not all that impressive.”

Dr. Labos is a columnist for this news organization and previously has written about the COSMOS trial. 

He said it is important to note that this “meta-analysis of COSMOS data, strictly speaking, is not a meta-analysis” because the patients were all from the original COSMOS study without including any additional patients, “so you don’t have any more data than what you started with.

“The fact that the results are consistent with the original trial is not surprising. In fact, it would be concerning if they were not consistent because they’re the same population. They were just assessed differently — by phone, online, or in person,” Dr. Labos explained. 

“It is hard to tell what the benefit with multivitamins actually means in terms of hard clinical endpoints that matter to patients. Scoring a little bit better on a standardized test — I guess that’s a good thing, but does that mean you’re less likely to get dementia? I’m not sure we’re there yet,” he told this news organization. 

The bottom line, said Dr. Labos, is that “at this point, the evidence does not support recommending multivitamins purely for brain health. There is also a cost and potential downside associated with their use.”

Also weighing in on the new analyses from COSMOS, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, said while there are now “positive, large-scale, long-term studies that show that multivitamin-mineral supplementation for older adults may slow cognitive aging, the Alzheimer’s Association is not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults.

“Independent confirmatory studies are needed in larger, more diverse, and representative study populations. COSMOS-Clinic, for example, had less than 2% non-White in the multivitamin group and 5% non-White in the placebo group. It is critical that future treatments and preventions are effective in all populations,” Dr. Sexton told this news organization.

She noted that multivitamin supplements are “generally easy to find and relatively affordable. With confirmation, these promising findings have the potential to significantly impact public health — improving brain health, lowering healthcare costs, reducing caregiver burden — especially among older adults.”

The Alzheimer’s Association, Dr. Sexton said, “envisions a future where there are multiple treatments available that address the disease in multiple ways — like heart disease and cancer — and that can be combined into powerful combination therapies, in conjunction with brain-healthy guidelines for lifestyle, like diet and physical activity.”

The Alzheimer’s Association is leading a 2-year clinical trial known as US POINTER to evaluate whether lifestyle interventions that target multiple risk factors can protect cognition in older adults at increased risk for cognitive decline.

COSMOS-Clinic and the cognition studies in the meta-analysis were supported by investigator-initiated grants from Mars Edge, a segment of Mars Inc., and the National Institutes of Health. Multivitamin and placebo tablets and packaging were donated by Pfizer, Inc Consumer Healthcare (now Haleon). Disclosures for the COSMOS investigators are available with the original article. Dr. Labos and Dr. Sexton have no relevant disclosures. 

A version of this article appeared on Medscape.com.

New data from the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) suggest that a daily multivitamin may help protect the aging brain. However, at least one expert has concerns about the study’s methodology and, as a result, the interpretation of its findings. 

The meta-analysis of three separate cognition studies provides “strong and consistent evidence that taking a daily multivitamin, containing more than 20 essential micronutrients, can help prevent memory loss and slow down cognitive aging,” study investigator Chirag Vyas, MBBS, MPH, with Massachusetts General Hospital and Harvard Medical School, Boston, told this news organization. 

“We are not now recommending multivitamin use, but the evidence is compelling that supports the promise of multivitamins to help prevent cognitive decline,” Dr. Vyas said. 

The new data, from the cognitive substudies of COSMOS, were published online in the American Journal of Clinical Nutrition.
 

Clinically Meaningful Benefit?

To recap, COSMOS was a 2 x 2 factorial trial of coca extract (500 mg/d flavanols) and/or a daily commercial multivitamin-mineral (MVM) supplement for cardiovascular disease and cancer prevention among more than 21,000 US adults aged 60 years or older. 

Neither the cocoa extract nor the MVM supplement had a significant impact on cancer or cardiovascular disease events.

COMOS-Mind was a substudy of 2262 participants aged 65 or older without dementia who completed telephone-based cognitive assessments at baseline and annually for 3 years. 

As previously reported by this news organization in COSMOS-Mind, there was no cognitive benefit of daily cocoa extract, but daily MVM supplementation was associated with improved global cognition, episodic memory, and executive function. However, the difference in global cognitive function between MVM and placebo was small, with a mean 0.07-point improvement on the z-score at 3 years. 

COSMOS-Web was a substudy of 3562 original participants who were evaluated annually for 3 years using an internet-based battery of neuropsychological tests. 

In this analysis, those taking the MVM supplement performed better on a test for immediate memory recall (remembering a list of 20 words); they were able to remember an additional 0.71 word on average compared with 0.44 word in the placebo group. However, they did not improve on tests of memory retention, executive function, or novel object recognition.

The new data are from COSMOS-Clinic, an analysis of 573 participants who completed in-person cognitive assessments. 

COSMOS-Clinic showed a modest benefit of MVM, compared with placebo, on global cognition over 2 years (mean difference, 0.06 SD units [SU]), with a significantly more favorable change in episodic memory (mean difference, 0.12 SU) but not in executive function/attention (mean difference, 0.04 SU), the researchers reported. 

They also conducted a meta-analysis based on the three separate cognitive substudies, with 5200 nonoverlapping COSMOS participants. 

The results showed “clear evidence” of MVM benefits on global cognition (mean difference, 0.07 SU; P = .0009) and episodic memory (mean difference, 0.06 SU; P =.0007), they reported, with the magnitude of effect on global cognition equivalent to reducing cognitive aging by 2 years.

In a statement, JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, who led the overall COSMOS trial, said that “the finding that a daily multivitamin improved memory and slowed cognitive aging in three separate placebo-controlled studies in COSMOS is exciting and further supports the promise of multivitamins as a safe, accessible, and affordable approach to protecting cognitive health in older adults.”
 

Not a Meta-analysis?

In an interview with this news organization, Christopher Labos, MD CM, MSc, a cardiologist and epidemiologist based in Montreal, Canada, who wasn’t involved in COSMOS, cautioned that the evidence to date on multivitamins for memory and brain health are “not all that impressive.”

Dr. Labos is a columnist for this news organization and previously has written about the COSMOS trial. 

He said it is important to note that this “meta-analysis of COSMOS data, strictly speaking, is not a meta-analysis” because the patients were all from the original COSMOS study without including any additional patients, “so you don’t have any more data than what you started with.

“The fact that the results are consistent with the original trial is not surprising. In fact, it would be concerning if they were not consistent because they’re the same population. They were just assessed differently — by phone, online, or in person,” Dr. Labos explained. 

“It is hard to tell what the benefit with multivitamins actually means in terms of hard clinical endpoints that matter to patients. Scoring a little bit better on a standardized test — I guess that’s a good thing, but does that mean you’re less likely to get dementia? I’m not sure we’re there yet,” he told this news organization. 

The bottom line, said Dr. Labos, is that “at this point, the evidence does not support recommending multivitamins purely for brain health. There is also a cost and potential downside associated with their use.”

Also weighing in on the new analyses from COSMOS, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, said while there are now “positive, large-scale, long-term studies that show that multivitamin-mineral supplementation for older adults may slow cognitive aging, the Alzheimer’s Association is not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults.

“Independent confirmatory studies are needed in larger, more diverse, and representative study populations. COSMOS-Clinic, for example, had less than 2% non-White in the multivitamin group and 5% non-White in the placebo group. It is critical that future treatments and preventions are effective in all populations,” Dr. Sexton told this news organization.

She noted that multivitamin supplements are “generally easy to find and relatively affordable. With confirmation, these promising findings have the potential to significantly impact public health — improving brain health, lowering healthcare costs, reducing caregiver burden — especially among older adults.”

The Alzheimer’s Association, Dr. Sexton said, “envisions a future where there are multiple treatments available that address the disease in multiple ways — like heart disease and cancer — and that can be combined into powerful combination therapies, in conjunction with brain-healthy guidelines for lifestyle, like diet and physical activity.”

The Alzheimer’s Association is leading a 2-year clinical trial known as US POINTER to evaluate whether lifestyle interventions that target multiple risk factors can protect cognition in older adults at increased risk for cognitive decline.

COSMOS-Clinic and the cognition studies in the meta-analysis were supported by investigator-initiated grants from Mars Edge, a segment of Mars Inc., and the National Institutes of Health. Multivitamin and placebo tablets and packaging were donated by Pfizer, Inc Consumer Healthcare (now Haleon). Disclosures for the COSMOS investigators are available with the original article. Dr. Labos and Dr. Sexton have no relevant disclosures. 

A version of this article appeared on Medscape.com.

New data from the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) suggest that a daily multivitamin may help protect the aging brain. However, at least one expert has concerns about the study’s methodology and, as a result, the interpretation of its findings. 

The meta-analysis of three separate cognition studies provides “strong and consistent evidence that taking a daily multivitamin, containing more than 20 essential micronutrients, can help prevent memory loss and slow down cognitive aging,” study investigator Chirag Vyas, MBBS, MPH, with Massachusetts General Hospital and Harvard Medical School, Boston, told this news organization. 

“We are not now recommending multivitamin use, but the evidence is compelling that supports the promise of multivitamins to help prevent cognitive decline,” Dr. Vyas said. 

The new data, from the cognitive substudies of COSMOS, were published online in the American Journal of Clinical Nutrition.
 

Clinically Meaningful Benefit?

To recap, COSMOS was a 2 x 2 factorial trial of coca extract (500 mg/d flavanols) and/or a daily commercial multivitamin-mineral (MVM) supplement for cardiovascular disease and cancer prevention among more than 21,000 US adults aged 60 years or older. 

Neither the cocoa extract nor the MVM supplement had a significant impact on cancer or cardiovascular disease events.

COMOS-Mind was a substudy of 2262 participants aged 65 or older without dementia who completed telephone-based cognitive assessments at baseline and annually for 3 years. 

As previously reported by this news organization in COSMOS-Mind, there was no cognitive benefit of daily cocoa extract, but daily MVM supplementation was associated with improved global cognition, episodic memory, and executive function. However, the difference in global cognitive function between MVM and placebo was small, with a mean 0.07-point improvement on the z-score at 3 years. 

COSMOS-Web was a substudy of 3562 original participants who were evaluated annually for 3 years using an internet-based battery of neuropsychological tests. 

In this analysis, those taking the MVM supplement performed better on a test for immediate memory recall (remembering a list of 20 words); they were able to remember an additional 0.71 word on average compared with 0.44 word in the placebo group. However, they did not improve on tests of memory retention, executive function, or novel object recognition.

The new data are from COSMOS-Clinic, an analysis of 573 participants who completed in-person cognitive assessments. 

COSMOS-Clinic showed a modest benefit of MVM, compared with placebo, on global cognition over 2 years (mean difference, 0.06 SD units [SU]), with a significantly more favorable change in episodic memory (mean difference, 0.12 SU) but not in executive function/attention (mean difference, 0.04 SU), the researchers reported. 

They also conducted a meta-analysis based on the three separate cognitive substudies, with 5200 nonoverlapping COSMOS participants. 

The results showed “clear evidence” of MVM benefits on global cognition (mean difference, 0.07 SU; P = .0009) and episodic memory (mean difference, 0.06 SU; P =.0007), they reported, with the magnitude of effect on global cognition equivalent to reducing cognitive aging by 2 years.

In a statement, JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, who led the overall COSMOS trial, said that “the finding that a daily multivitamin improved memory and slowed cognitive aging in three separate placebo-controlled studies in COSMOS is exciting and further supports the promise of multivitamins as a safe, accessible, and affordable approach to protecting cognitive health in older adults.”
 

Not a Meta-analysis?

In an interview with this news organization, Christopher Labos, MD CM, MSc, a cardiologist and epidemiologist based in Montreal, Canada, who wasn’t involved in COSMOS, cautioned that the evidence to date on multivitamins for memory and brain health are “not all that impressive.”

Dr. Labos is a columnist for this news organization and previously has written about the COSMOS trial. 

He said it is important to note that this “meta-analysis of COSMOS data, strictly speaking, is not a meta-analysis” because the patients were all from the original COSMOS study without including any additional patients, “so you don’t have any more data than what you started with.

“The fact that the results are consistent with the original trial is not surprising. In fact, it would be concerning if they were not consistent because they’re the same population. They were just assessed differently — by phone, online, or in person,” Dr. Labos explained. 

“It is hard to tell what the benefit with multivitamins actually means in terms of hard clinical endpoints that matter to patients. Scoring a little bit better on a standardized test — I guess that’s a good thing, but does that mean you’re less likely to get dementia? I’m not sure we’re there yet,” he told this news organization. 

The bottom line, said Dr. Labos, is that “at this point, the evidence does not support recommending multivitamins purely for brain health. There is also a cost and potential downside associated with their use.”

Also weighing in on the new analyses from COSMOS, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, said while there are now “positive, large-scale, long-term studies that show that multivitamin-mineral supplementation for older adults may slow cognitive aging, the Alzheimer’s Association is not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults.

“Independent confirmatory studies are needed in larger, more diverse, and representative study populations. COSMOS-Clinic, for example, had less than 2% non-White in the multivitamin group and 5% non-White in the placebo group. It is critical that future treatments and preventions are effective in all populations,” Dr. Sexton told this news organization.

She noted that multivitamin supplements are “generally easy to find and relatively affordable. With confirmation, these promising findings have the potential to significantly impact public health — improving brain health, lowering healthcare costs, reducing caregiver burden — especially among older adults.”

The Alzheimer’s Association, Dr. Sexton said, “envisions a future where there are multiple treatments available that address the disease in multiple ways — like heart disease and cancer — and that can be combined into powerful combination therapies, in conjunction with brain-healthy guidelines for lifestyle, like diet and physical activity.”

The Alzheimer’s Association is leading a 2-year clinical trial known as US POINTER to evaluate whether lifestyle interventions that target multiple risk factors can protect cognition in older adults at increased risk for cognitive decline.

COSMOS-Clinic and the cognition studies in the meta-analysis were supported by investigator-initiated grants from Mars Edge, a segment of Mars Inc., and the National Institutes of Health. Multivitamin and placebo tablets and packaging were donated by Pfizer, Inc Consumer Healthcare (now Haleon). Disclosures for the COSMOS investigators are available with the original article. Dr. Labos and Dr. Sexton have no relevant disclosures. 

A version of this article appeared on Medscape.com.

Buprenorphine use, compared with methadone use, in pregnancy has been linked with a slightly lower risk of major congenital malformations in a new study of medications for opioid use disorder (OUD).

Elizabeth A. Suarez, PhD, MPH, with the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues published the findings in JAMA Internal Medicine.

The lower risk for buprenorphine was small (risk ratio, 0.82; 95% confidence interval [CI], 0.69-0.97), and methadone use should not be ruled out on that basis, the authors wrote. For some women, particularly those on stable treatment before pregnancy or women who do not respond well to buprenorphine, methadone may be the better choice, they explained.
 

Either Medication Better Than Not Treating

The authors noted that either medication “is strongly recommended over untreated OUD during pregnancy.”

JAMA Internal Medicine Deputy Editor Deborah Grady, MD, MPH, with the Department of Medicine, University of California, San Francisco, emphasized that recommendation in an editor’s note, highlighting that treatment for OUD is critical to prevent infections, overdose, and death in pregnant women as well as neonatal opioid withdrawal syndrome and fetal death.

She stressed that internists and other primary care physicians have a key role in ensuring pregnant women with OUD receive appropriate treatment.

Given the importance of the issue, she wrote, “we have taken the unusual step of publishing two accompanying invited commentaries.”

Two developments may help increase use of buprenorphine, the study authors wrote. One is a recent study showing lower risk of adverse neonatal outcomes when buprenorphine is used during pregnancy compared with methadone. Another is the removal last year of the prescribing waiver for buprenorphine.
 

Study Included Medicaid Data Over 18 Years

The population-based cohort study used data from publicly insured Medicaid beneficiaries from 2000 to 2018. Pregnancies with enrollment from 90 days before pregnancy through 1 month after delivery and first-trimester use of buprenorphine or methadone were included (n = 13,360). The data were linked with infants’ health data.

The study group included 9,514 pregnancies with first-trimester buprenorphine exposure and 3,846 with methadone exposure. The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone.

Major malformations were any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, oral clefts, and clubfoot.
 

Two Invited Commentaries Urge Caution in Interpretation

The two invited commentaries Dr. Grady mentioned in her editor’s note point both to the importance of the team’s findings and the need for better understanding of factors that may affect the choice of which OUD medication to use.

A commentary by Max Jordan Nguemeni Tiako, MD, MS, with the Department of Medicine, Brigham and Women’s Hospital, and colleagues, said that while the Suarez et al. data are important to share with patients, “the ultimate treatment decision must be the result of shared decision-making between a knowledgeable clinician and the patient, rather than promoting one medication over another.”

They urge putting the findings in context given the study population, which comprises a relatively stable group of women with OUD, most of whom were taking OUD medications before they got pregnant. The study sample excludes a substantial number of women who are chronically underinsured or uninsured, Dr. Tiako’s team wrote, because those included were enrolled in Medicaid for 3 consecutive months before pregnancy.

“We urge caution when extrapolating these findings to newly pregnant individuals with untreated OUD,” they wrote.
 

Both Medications are Safe

Cara Poland, MD, MEd, with the Henry Ford Health + Michigan State University Health Sciences in Grand Rapids, and coauthors, added in another commentary that Suarez et al. didn’t include a comparison between the population-level congenital defect rate and the defect rate for people using medications for OUD in pregnancy.

That comparison, they wrote, would have better illustrated the safety of medications for OUD “instead of simply comparing two medications with long-standing safety data.”

When a clinician starts a woman on medication for OUD in pregnancy, it’s important to understand several factors, including individual access to and comfort with different treatment approaches, they noted. It’s also important to weigh whether changing medications is worth the potential drawbacks of disrupting their well-managed care.

They wrote that the paper by Suarez et al. does not make the case for switching medications based on their findings.

Internists, they added, are ideal experts to explain risk of fetal abnormalities in the wider context of supporting engagement with continuous medication for OUD.

“In the absence of other concerns, switching medications (methadone to buprenorphine) or — worse — discontinuing [medication for] OUD because of this study runs counter to the substantial evidence regarding the safety of these medications during pregnancy,” Dr. Poland’s team wrote. “No treatment is without risk in pregnancy.”

This study was supported by the National Institute on Drug Abuse. In the Suarez et al. study, coauthors Dr. Hernández-Díaz, Dr. Gray, Dr. Connery, Dr. Zhu, and Dr. Huybrechts reported grants, personal fees and consulting payments from several pharmaceutical companies. Dr. Grady reports no relevant financial relationships in her editor’s note. No relevant financial relationships were reported by authors of the Tiako et al. commentary.

Regarding the commentary by Poland et al., grants were reported from the Michigan Health Endowment Fund, the Michigan Department of Health and Human Services, the National Institute on Drug Abuse and Blue Cross Blue Shield of Michigan outside the submitted work. No other disclosures were reported.

Buprenorphine use, compared with methadone use, in pregnancy has been linked with a slightly lower risk of major congenital malformations in a new study of medications for opioid use disorder (OUD).

Elizabeth A. Suarez, PhD, MPH, with the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues published the findings in JAMA Internal Medicine.

The lower risk for buprenorphine was small (risk ratio, 0.82; 95% confidence interval [CI], 0.69-0.97), and methadone use should not be ruled out on that basis, the authors wrote. For some women, particularly those on stable treatment before pregnancy or women who do not respond well to buprenorphine, methadone may be the better choice, they explained.
 

Either Medication Better Than Not Treating

The authors noted that either medication “is strongly recommended over untreated OUD during pregnancy.”

JAMA Internal Medicine Deputy Editor Deborah Grady, MD, MPH, with the Department of Medicine, University of California, San Francisco, emphasized that recommendation in an editor’s note, highlighting that treatment for OUD is critical to prevent infections, overdose, and death in pregnant women as well as neonatal opioid withdrawal syndrome and fetal death.

She stressed that internists and other primary care physicians have a key role in ensuring pregnant women with OUD receive appropriate treatment.

Given the importance of the issue, she wrote, “we have taken the unusual step of publishing two accompanying invited commentaries.”

Two developments may help increase use of buprenorphine, the study authors wrote. One is a recent study showing lower risk of adverse neonatal outcomes when buprenorphine is used during pregnancy compared with methadone. Another is the removal last year of the prescribing waiver for buprenorphine.
 

Study Included Medicaid Data Over 18 Years

The population-based cohort study used data from publicly insured Medicaid beneficiaries from 2000 to 2018. Pregnancies with enrollment from 90 days before pregnancy through 1 month after delivery and first-trimester use of buprenorphine or methadone were included (n = 13,360). The data were linked with infants’ health data.

The study group included 9,514 pregnancies with first-trimester buprenorphine exposure and 3,846 with methadone exposure. The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone.

Major malformations were any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, oral clefts, and clubfoot.
 

Two Invited Commentaries Urge Caution in Interpretation

The two invited commentaries Dr. Grady mentioned in her editor’s note point both to the importance of the team’s findings and the need for better understanding of factors that may affect the choice of which OUD medication to use.

A commentary by Max Jordan Nguemeni Tiako, MD, MS, with the Department of Medicine, Brigham and Women’s Hospital, and colleagues, said that while the Suarez et al. data are important to share with patients, “the ultimate treatment decision must be the result of shared decision-making between a knowledgeable clinician and the patient, rather than promoting one medication over another.”

They urge putting the findings in context given the study population, which comprises a relatively stable group of women with OUD, most of whom were taking OUD medications before they got pregnant. The study sample excludes a substantial number of women who are chronically underinsured or uninsured, Dr. Tiako’s team wrote, because those included were enrolled in Medicaid for 3 consecutive months before pregnancy.

“We urge caution when extrapolating these findings to newly pregnant individuals with untreated OUD,” they wrote.
 

Both Medications are Safe

Cara Poland, MD, MEd, with the Henry Ford Health + Michigan State University Health Sciences in Grand Rapids, and coauthors, added in another commentary that Suarez et al. didn’t include a comparison between the population-level congenital defect rate and the defect rate for people using medications for OUD in pregnancy.

That comparison, they wrote, would have better illustrated the safety of medications for OUD “instead of simply comparing two medications with long-standing safety data.”

When a clinician starts a woman on medication for OUD in pregnancy, it’s important to understand several factors, including individual access to and comfort with different treatment approaches, they noted. It’s also important to weigh whether changing medications is worth the potential drawbacks of disrupting their well-managed care.

They wrote that the paper by Suarez et al. does not make the case for switching medications based on their findings.

Internists, they added, are ideal experts to explain risk of fetal abnormalities in the wider context of supporting engagement with continuous medication for OUD.

“In the absence of other concerns, switching medications (methadone to buprenorphine) or — worse — discontinuing [medication for] OUD because of this study runs counter to the substantial evidence regarding the safety of these medications during pregnancy,” Dr. Poland’s team wrote. “No treatment is without risk in pregnancy.”

This study was supported by the National Institute on Drug Abuse. In the Suarez et al. study, coauthors Dr. Hernández-Díaz, Dr. Gray, Dr. Connery, Dr. Zhu, and Dr. Huybrechts reported grants, personal fees and consulting payments from several pharmaceutical companies. Dr. Grady reports no relevant financial relationships in her editor’s note. No relevant financial relationships were reported by authors of the Tiako et al. commentary.

Regarding the commentary by Poland et al., grants were reported from the Michigan Health Endowment Fund, the Michigan Department of Health and Human Services, the National Institute on Drug Abuse and Blue Cross Blue Shield of Michigan outside the submitted work. No other disclosures were reported.

Buprenorphine use, compared with methadone use, in pregnancy has been linked with a slightly lower risk of major congenital malformations in a new study of medications for opioid use disorder (OUD).

Elizabeth A. Suarez, PhD, MPH, with the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues published the findings in JAMA Internal Medicine.

The lower risk for buprenorphine was small (risk ratio, 0.82; 95% confidence interval [CI], 0.69-0.97), and methadone use should not be ruled out on that basis, the authors wrote. For some women, particularly those on stable treatment before pregnancy or women who do not respond well to buprenorphine, methadone may be the better choice, they explained.
 

Either Medication Better Than Not Treating

The authors noted that either medication “is strongly recommended over untreated OUD during pregnancy.”

JAMA Internal Medicine Deputy Editor Deborah Grady, MD, MPH, with the Department of Medicine, University of California, San Francisco, emphasized that recommendation in an editor’s note, highlighting that treatment for OUD is critical to prevent infections, overdose, and death in pregnant women as well as neonatal opioid withdrawal syndrome and fetal death.

She stressed that internists and other primary care physicians have a key role in ensuring pregnant women with OUD receive appropriate treatment.

Given the importance of the issue, she wrote, “we have taken the unusual step of publishing two accompanying invited commentaries.”

Two developments may help increase use of buprenorphine, the study authors wrote. One is a recent study showing lower risk of adverse neonatal outcomes when buprenorphine is used during pregnancy compared with methadone. Another is the removal last year of the prescribing waiver for buprenorphine.
 

Study Included Medicaid Data Over 18 Years

The population-based cohort study used data from publicly insured Medicaid beneficiaries from 2000 to 2018. Pregnancies with enrollment from 90 days before pregnancy through 1 month after delivery and first-trimester use of buprenorphine or methadone were included (n = 13,360). The data were linked with infants’ health data.

The study group included 9,514 pregnancies with first-trimester buprenorphine exposure and 3,846 with methadone exposure. The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone.

Major malformations were any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, oral clefts, and clubfoot.
 

Two Invited Commentaries Urge Caution in Interpretation

The two invited commentaries Dr. Grady mentioned in her editor’s note point both to the importance of the team’s findings and the need for better understanding of factors that may affect the choice of which OUD medication to use.

A commentary by Max Jordan Nguemeni Tiako, MD, MS, with the Department of Medicine, Brigham and Women’s Hospital, and colleagues, said that while the Suarez et al. data are important to share with patients, “the ultimate treatment decision must be the result of shared decision-making between a knowledgeable clinician and the patient, rather than promoting one medication over another.”

They urge putting the findings in context given the study population, which comprises a relatively stable group of women with OUD, most of whom were taking OUD medications before they got pregnant. The study sample excludes a substantial number of women who are chronically underinsured or uninsured, Dr. Tiako’s team wrote, because those included were enrolled in Medicaid for 3 consecutive months before pregnancy.

“We urge caution when extrapolating these findings to newly pregnant individuals with untreated OUD,” they wrote.
 

Both Medications are Safe

Cara Poland, MD, MEd, with the Henry Ford Health + Michigan State University Health Sciences in Grand Rapids, and coauthors, added in another commentary that Suarez et al. didn’t include a comparison between the population-level congenital defect rate and the defect rate for people using medications for OUD in pregnancy.

That comparison, they wrote, would have better illustrated the safety of medications for OUD “instead of simply comparing two medications with long-standing safety data.”

When a clinician starts a woman on medication for OUD in pregnancy, it’s important to understand several factors, including individual access to and comfort with different treatment approaches, they noted. It’s also important to weigh whether changing medications is worth the potential drawbacks of disrupting their well-managed care.

They wrote that the paper by Suarez et al. does not make the case for switching medications based on their findings.

Internists, they added, are ideal experts to explain risk of fetal abnormalities in the wider context of supporting engagement with continuous medication for OUD.

“In the absence of other concerns, switching medications (methadone to buprenorphine) or — worse — discontinuing [medication for] OUD because of this study runs counter to the substantial evidence regarding the safety of these medications during pregnancy,” Dr. Poland’s team wrote. “No treatment is without risk in pregnancy.”

This study was supported by the National Institute on Drug Abuse. In the Suarez et al. study, coauthors Dr. Hernández-Díaz, Dr. Gray, Dr. Connery, Dr. Zhu, and Dr. Huybrechts reported grants, personal fees and consulting payments from several pharmaceutical companies. Dr. Grady reports no relevant financial relationships in her editor’s note. No relevant financial relationships were reported by authors of the Tiako et al. commentary.

Regarding the commentary by Poland et al., grants were reported from the Michigan Health Endowment Fund, the Michigan Department of Health and Human Services, the National Institute on Drug Abuse and Blue Cross Blue Shield of Michigan outside the submitted work. No other disclosures were reported.

A clinic aimed at managing patients with difficult-to-control atopic dermatitis (AD) by involving assessments from a team of clinicians from different disciplines led to significant improvements in severity of the disease, results from a single-center study showed.

“A significant challenge in caring for patients with atopic dermatitis is lack of collaboration between healthcare providers, leading to disjointed care, inconsistent treatment plans, and conflicting dialogue with patients,” first author Alexis Tracy, MD, a combined allergy and dermatology research fellow at Rady Children’s Hospital, San Diego, and colleagues wrote in the study, which was published online January 14, 2024, in Pediatric Dermatology.

Launched in 2019, the clinic, which is called the Multidisciplinary Atopic Dermatitis Program (MADP), is a collaborative effort between with Rady Children’s Hospital and the University of California San Diego Health division of dermatology, division of allergy & immunology, and the hospital’s clinical pharmacy. Patients referred to the MADP undergo a concurrent, comprehensive evaluation by a dermatologist, allergist, clinical pharmacist, and others who help to assess AD severity, provide family education about the disease, and form a care plan using the model of shared decision-making (SDM). Visits take about two hours, and the frequency of follow-up visits varies.

Courtesy Rady Children&#039;s Hospital

In the dermatology realm, tools used to compare the extent and severity of AD between visits include the Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), the Children’s Dermatology Life Quality Index (CDLQI), Validated Investigator Global Assessment (vIGA), Body Surface Area (BSA), and the Numerical Rating Scale (NRS).To investigate the MADP’s success to date, Dr. Tracy and colleagues evaluated 44 patients with a history of moderate to severe, persistent AD who were referred to the clinic between April 3, 2019, and October 22, 2022, and had between one and three follow-up visits. The patients ranged from age 4 months to 18 years (mean, 7.74 years).

Compared with baseline, EASI scores of patients decreased significantly, with an average mean improvement of 9.61 by the second visit, 15.12 by the third visit, and 17.42 by the fourth visit (P <.001 for all three). These represent an average decreases of 44.20%, 63.26%, 74.35%, respectively.

At the seventh visit, the EASI score decreased by a mean of 33.48 (P = .008), which represents an average decrease of 91.52% from baseline. Of the 44 patients, 32 achieved an EASI 50 and 21 achieved an EASI 75.

In other findings, the mean vIGA improved with each visit, with the largest observed improvement at the seventh visit (a mean of 2.25 points; P = .009) and the greatest mean improvement in the POEM score was seen at the sixth visit (a mean of 11.13 points; P < .001). The mean difference in CDLQI scores also increased with each visit, with the largest improvement seen at the sixth visit (an increase of 12 points; P < .001).

Similarly, BSA progressively improved at each clinic visit, from a mean decrease of 16.02% at the second visit to a mean decrease of 56.04% at the seventh visit (P < .001 for both). Meanwhile, the largest mean improvement in pruritus was seen at the sixth visit (a mean of 4.10 points; P = .001).

In an interview, MADP’s codirector, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, said that the consistency of data showing rapid, consistent improvement with a varied set of physician assessed scores and patient-reported outcomes “was very impressive, especially given the variation in severity, extent and difficult course of many of the patients we saw, and spectrum of interventions – from topical regimens to advanced systemic therapies,” he said. “As clinicians we tend to remember the ‘tough cases,’ and it was tremendous to see the impact and utility of the clinic.”

Courtesy University of California, San Diego

Important model of care

Asked to comment on the results, pediatric dermatologist Moise L. Levy, MD, professor of internal medicine and pediatrics at the University of Texas at Austin, who was not involved with the study, characterized the MADP as an important model of care. “Multi-interdisciplinary care of such conditions is well-known to be of great help for patients and their families,” he told this news organization.

“A key part of the ‘team’ is the family/patient engagement and shared decision-making. The use of visual aides to highlight components of care was likely of great use, as well,” he said. “All such interventions impact the disease, as well as associated problems, such as itch, sleep, and mental health. Importantly, such interventions, while known to be useful as demonstrated by the authors, take time, and relate to improved outcomes as noted by the date outlined by the authors.”

The study authors acknowledged certain limitations of the study, including the lack of a control group with single-specialty visits. “The real take-away is that taking the time to do more holistic assessments of health — with skin and allergy issues being discussed, and consistent education and messaging — helps make our medical interventions more successful, with both objective disease improvement and patient/family satisfaction,” Dr. Eichenfield said in the interview.

Pfizer and Sanofi provided financial support to MADP, and for the study. Dr. Eichenfield disclosed that he serves as a scientific adviser, consultant, and/or clinical trial investigator for AbbVie, Amgen, Aslan, Castle Biosciences, Dermavant, Eli Lilly and Company, Forté, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron Pharmaceuticals, Sanofi-Genzyme, Trialspark, and UCB. Dr. Geng disclosed ties with Sanofi, Regeneron, Pfizer, and AbbVie, and is an adviser to Incyte, Galderma, Eli-Lilly, and LEO. The other authors reported having no disclosures. Dr. Levy disclosed ties with Abeona, Amgen, Arcutis, Castle Creek, Dusa Pharma, Krystal Bio, Novan, Regeneron, and Sanofi Genzyme. He is also an investigator for Janssen.

A clinic aimed at managing patients with difficult-to-control atopic dermatitis (AD) by involving assessments from a team of clinicians from different disciplines led to significant improvements in severity of the disease, results from a single-center study showed.

“A significant challenge in caring for patients with atopic dermatitis is lack of collaboration between healthcare providers, leading to disjointed care, inconsistent treatment plans, and conflicting dialogue with patients,” first author Alexis Tracy, MD, a combined allergy and dermatology research fellow at Rady Children’s Hospital, San Diego, and colleagues wrote in the study, which was published online January 14, 2024, in Pediatric Dermatology.

Launched in 2019, the clinic, which is called the Multidisciplinary Atopic Dermatitis Program (MADP), is a collaborative effort between with Rady Children’s Hospital and the University of California San Diego Health division of dermatology, division of allergy & immunology, and the hospital’s clinical pharmacy. Patients referred to the MADP undergo a concurrent, comprehensive evaluation by a dermatologist, allergist, clinical pharmacist, and others who help to assess AD severity, provide family education about the disease, and form a care plan using the model of shared decision-making (SDM). Visits take about two hours, and the frequency of follow-up visits varies.

Courtesy Rady Children&#039;s Hospital

In the dermatology realm, tools used to compare the extent and severity of AD between visits include the Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), the Children’s Dermatology Life Quality Index (CDLQI), Validated Investigator Global Assessment (vIGA), Body Surface Area (BSA), and the Numerical Rating Scale (NRS).To investigate the MADP’s success to date, Dr. Tracy and colleagues evaluated 44 patients with a history of moderate to severe, persistent AD who were referred to the clinic between April 3, 2019, and October 22, 2022, and had between one and three follow-up visits. The patients ranged from age 4 months to 18 years (mean, 7.74 years).

Compared with baseline, EASI scores of patients decreased significantly, with an average mean improvement of 9.61 by the second visit, 15.12 by the third visit, and 17.42 by the fourth visit (P <.001 for all three). These represent an average decreases of 44.20%, 63.26%, 74.35%, respectively.

At the seventh visit, the EASI score decreased by a mean of 33.48 (P = .008), which represents an average decrease of 91.52% from baseline. Of the 44 patients, 32 achieved an EASI 50 and 21 achieved an EASI 75.

In other findings, the mean vIGA improved with each visit, with the largest observed improvement at the seventh visit (a mean of 2.25 points; P = .009) and the greatest mean improvement in the POEM score was seen at the sixth visit (a mean of 11.13 points; P < .001). The mean difference in CDLQI scores also increased with each visit, with the largest improvement seen at the sixth visit (an increase of 12 points; P < .001).

Similarly, BSA progressively improved at each clinic visit, from a mean decrease of 16.02% at the second visit to a mean decrease of 56.04% at the seventh visit (P < .001 for both). Meanwhile, the largest mean improvement in pruritus was seen at the sixth visit (a mean of 4.10 points; P = .001).

In an interview, MADP’s codirector, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, said that the consistency of data showing rapid, consistent improvement with a varied set of physician assessed scores and patient-reported outcomes “was very impressive, especially given the variation in severity, extent and difficult course of many of the patients we saw, and spectrum of interventions – from topical regimens to advanced systemic therapies,” he said. “As clinicians we tend to remember the ‘tough cases,’ and it was tremendous to see the impact and utility of the clinic.”

Courtesy University of California, San Diego

Important model of care

Asked to comment on the results, pediatric dermatologist Moise L. Levy, MD, professor of internal medicine and pediatrics at the University of Texas at Austin, who was not involved with the study, characterized the MADP as an important model of care. “Multi-interdisciplinary care of such conditions is well-known to be of great help for patients and their families,” he told this news organization.

“A key part of the ‘team’ is the family/patient engagement and shared decision-making. The use of visual aides to highlight components of care was likely of great use, as well,” he said. “All such interventions impact the disease, as well as associated problems, such as itch, sleep, and mental health. Importantly, such interventions, while known to be useful as demonstrated by the authors, take time, and relate to improved outcomes as noted by the date outlined by the authors.”

The study authors acknowledged certain limitations of the study, including the lack of a control group with single-specialty visits. “The real take-away is that taking the time to do more holistic assessments of health — with skin and allergy issues being discussed, and consistent education and messaging — helps make our medical interventions more successful, with both objective disease improvement and patient/family satisfaction,” Dr. Eichenfield said in the interview.

Pfizer and Sanofi provided financial support to MADP, and for the study. Dr. Eichenfield disclosed that he serves as a scientific adviser, consultant, and/or clinical trial investigator for AbbVie, Amgen, Aslan, Castle Biosciences, Dermavant, Eli Lilly and Company, Forté, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron Pharmaceuticals, Sanofi-Genzyme, Trialspark, and UCB. Dr. Geng disclosed ties with Sanofi, Regeneron, Pfizer, and AbbVie, and is an adviser to Incyte, Galderma, Eli-Lilly, and LEO. The other authors reported having no disclosures. Dr. Levy disclosed ties with Abeona, Amgen, Arcutis, Castle Creek, Dusa Pharma, Krystal Bio, Novan, Regeneron, and Sanofi Genzyme. He is also an investigator for Janssen.

A clinic aimed at managing patients with difficult-to-control atopic dermatitis (AD) by involving assessments from a team of clinicians from different disciplines led to significant improvements in severity of the disease, results from a single-center study showed.

“A significant challenge in caring for patients with atopic dermatitis is lack of collaboration between healthcare providers, leading to disjointed care, inconsistent treatment plans, and conflicting dialogue with patients,” first author Alexis Tracy, MD, a combined allergy and dermatology research fellow at Rady Children’s Hospital, San Diego, and colleagues wrote in the study, which was published online January 14, 2024, in Pediatric Dermatology.

Launched in 2019, the clinic, which is called the Multidisciplinary Atopic Dermatitis Program (MADP), is a collaborative effort between with Rady Children’s Hospital and the University of California San Diego Health division of dermatology, division of allergy & immunology, and the hospital’s clinical pharmacy. Patients referred to the MADP undergo a concurrent, comprehensive evaluation by a dermatologist, allergist, clinical pharmacist, and others who help to assess AD severity, provide family education about the disease, and form a care plan using the model of shared decision-making (SDM). Visits take about two hours, and the frequency of follow-up visits varies.

Courtesy Rady Children&#039;s Hospital

In the dermatology realm, tools used to compare the extent and severity of AD between visits include the Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), the Children’s Dermatology Life Quality Index (CDLQI), Validated Investigator Global Assessment (vIGA), Body Surface Area (BSA), and the Numerical Rating Scale (NRS).To investigate the MADP’s success to date, Dr. Tracy and colleagues evaluated 44 patients with a history of moderate to severe, persistent AD who were referred to the clinic between April 3, 2019, and October 22, 2022, and had between one and three follow-up visits. The patients ranged from age 4 months to 18 years (mean, 7.74 years).

Compared with baseline, EASI scores of patients decreased significantly, with an average mean improvement of 9.61 by the second visit, 15.12 by the third visit, and 17.42 by the fourth visit (P <.001 for all three). These represent an average decreases of 44.20%, 63.26%, 74.35%, respectively.

At the seventh visit, the EASI score decreased by a mean of 33.48 (P = .008), which represents an average decrease of 91.52% from baseline. Of the 44 patients, 32 achieved an EASI 50 and 21 achieved an EASI 75.

In other findings, the mean vIGA improved with each visit, with the largest observed improvement at the seventh visit (a mean of 2.25 points; P = .009) and the greatest mean improvement in the POEM score was seen at the sixth visit (a mean of 11.13 points; P < .001). The mean difference in CDLQI scores also increased with each visit, with the largest improvement seen at the sixth visit (an increase of 12 points; P < .001).

Similarly, BSA progressively improved at each clinic visit, from a mean decrease of 16.02% at the second visit to a mean decrease of 56.04% at the seventh visit (P < .001 for both). Meanwhile, the largest mean improvement in pruritus was seen at the sixth visit (a mean of 4.10 points; P = .001).

In an interview, MADP’s codirector, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, said that the consistency of data showing rapid, consistent improvement with a varied set of physician assessed scores and patient-reported outcomes “was very impressive, especially given the variation in severity, extent and difficult course of many of the patients we saw, and spectrum of interventions – from topical regimens to advanced systemic therapies,” he said. “As clinicians we tend to remember the ‘tough cases,’ and it was tremendous to see the impact and utility of the clinic.”

Courtesy University of California, San Diego

Important model of care

Asked to comment on the results, pediatric dermatologist Moise L. Levy, MD, professor of internal medicine and pediatrics at the University of Texas at Austin, who was not involved with the study, characterized the MADP as an important model of care. “Multi-interdisciplinary care of such conditions is well-known to be of great help for patients and their families,” he told this news organization.

“A key part of the ‘team’ is the family/patient engagement and shared decision-making. The use of visual aides to highlight components of care was likely of great use, as well,” he said. “All such interventions impact the disease, as well as associated problems, such as itch, sleep, and mental health. Importantly, such interventions, while known to be useful as demonstrated by the authors, take time, and relate to improved outcomes as noted by the date outlined by the authors.”

The study authors acknowledged certain limitations of the study, including the lack of a control group with single-specialty visits. “The real take-away is that taking the time to do more holistic assessments of health — with skin and allergy issues being discussed, and consistent education and messaging — helps make our medical interventions more successful, with both objective disease improvement and patient/family satisfaction,” Dr. Eichenfield said in the interview.

Pfizer and Sanofi provided financial support to MADP, and for the study. Dr. Eichenfield disclosed that he serves as a scientific adviser, consultant, and/or clinical trial investigator for AbbVie, Amgen, Aslan, Castle Biosciences, Dermavant, Eli Lilly and Company, Forté, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron Pharmaceuticals, Sanofi-Genzyme, Trialspark, and UCB. Dr. Geng disclosed ties with Sanofi, Regeneron, Pfizer, and AbbVie, and is an adviser to Incyte, Galderma, Eli-Lilly, and LEO. The other authors reported having no disclosures. Dr. Levy disclosed ties with Abeona, Amgen, Arcutis, Castle Creek, Dusa Pharma, Krystal Bio, Novan, Regeneron, and Sanofi Genzyme. He is also an investigator for Janssen.