Measures of fetal breathing movement were lower in fetuses of pregnant patients who received buprenorphine, compared with controls, based on data from 177 individuals.

The findings were presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists by Caroline Bulger, MD, of East Tennessee State University, Johnson City.

Pregnant patients with opioid-use disorder in the community surrounding Johnson City receive medication-assisted therapy with buprenorphine during the prenatal period, Dr. Bulger and colleagues wrote in their abstract. The current prenatal program for substance use disorder was established in 2016 based on patient requests for assistance in lowering their buprenorphine dosages during pregnancy, said senior author Martin E. Olsen, MD, also of East Tennessee State University, in an interview.

“Buprenorphine medication–assisted treatment in pregnancy is associated with long-term effects on childhood development such as smaller neonatal brains, decreased school performance, and low birth weight;” however, data on the fetal effects of buprenorphine are limited, said Dr. Olsen.

The current study was conducted to evaluate a short-term finding of the fetal effects of buprenorphine, Dr. Olsen said.

“This study was performed after obstetric sonographers at our institution noted that biophysical profile [BPP] ultrasound assessments of the fetuses of mothers on buprenorphine took longer than for other patients,” said Dr. Olsen.

The researchers conducted a retrospective chart review of 131 patients who received buprenorphine and 46 who were followed for chronic hypertension and served as high-risk controls. Patients were seen at a single institution between July 1, 2016, and June 30, 2020.

The researchers hypothesized that BPP of fetuses in patients receiving buprenorphine might be different from controls because of the effects of buprenorphine.

Overall, patients who received buprenorphine were more likely to have a fetal breathing score of zero than those who underwent a BPP for hypertension. A significant relationship emerged between buprenorphine dosage and breathing motion assessment; patients on high-dose buprenorphine were more likely than patients on low doses to have values of zero on fetal breathing motion assessment, and a chi-squared test yielded a P value of .04269.

The takeaway for clinical practice is that clinicians performing BPP ultrasounds on buprenorphine-exposed fetuses can expect that these assessments may take longer on average than assessments of other high-risk patients, said Dr. Olsen. “Additional assessment after a low BPP score is still indicated for these fetuses just as in other high-risk pregnancies,” he said.

The study was limited primarily by the retrospective design, Dr. Olsen said.

Although current treatment guidelines do not emphasize the effects of maternal buprenorphine use on fetal development, these findings support previous research showing effects of buprenorphine on fetal brain structure, the researchers wrote in their abstract. Looking ahead, “We recommend additional study on the maternal buprenorphine medication–assisted treatment dose effects for fetal and neonatal development with attention to such factors as head circumference, birth weight, achievement of developmental milestones, and school performance,” Dr. Olsen said.

“We and others have shown that the lowest effective dose of buprenorphine can lower neonatal abstinence syndrome/neonatal opioid withdrawal syndrome rates,” but data showing an impact of lowest effective dose management on long-term complications of fetal buprenorphine exposure are lacking, he noted.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Measures of fetal breathing movement were lower in fetuses of pregnant patients who received buprenorphine, compared with controls, based on data from 177 individuals.

The findings were presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists by Caroline Bulger, MD, of East Tennessee State University, Johnson City.

Pregnant patients with opioid-use disorder in the community surrounding Johnson City receive medication-assisted therapy with buprenorphine during the prenatal period, Dr. Bulger and colleagues wrote in their abstract. The current prenatal program for substance use disorder was established in 2016 based on patient requests for assistance in lowering their buprenorphine dosages during pregnancy, said senior author Martin E. Olsen, MD, also of East Tennessee State University, in an interview.

“Buprenorphine medication–assisted treatment in pregnancy is associated with long-term effects on childhood development such as smaller neonatal brains, decreased school performance, and low birth weight;” however, data on the fetal effects of buprenorphine are limited, said Dr. Olsen.

The current study was conducted to evaluate a short-term finding of the fetal effects of buprenorphine, Dr. Olsen said.

“This study was performed after obstetric sonographers at our institution noted that biophysical profile [BPP] ultrasound assessments of the fetuses of mothers on buprenorphine took longer than for other patients,” said Dr. Olsen.

The researchers conducted a retrospective chart review of 131 patients who received buprenorphine and 46 who were followed for chronic hypertension and served as high-risk controls. Patients were seen at a single institution between July 1, 2016, and June 30, 2020.

The researchers hypothesized that BPP of fetuses in patients receiving buprenorphine might be different from controls because of the effects of buprenorphine.

Overall, patients who received buprenorphine were more likely to have a fetal breathing score of zero than those who underwent a BPP for hypertension. A significant relationship emerged between buprenorphine dosage and breathing motion assessment; patients on high-dose buprenorphine were more likely than patients on low doses to have values of zero on fetal breathing motion assessment, and a chi-squared test yielded a P value of .04269.

The takeaway for clinical practice is that clinicians performing BPP ultrasounds on buprenorphine-exposed fetuses can expect that these assessments may take longer on average than assessments of other high-risk patients, said Dr. Olsen. “Additional assessment after a low BPP score is still indicated for these fetuses just as in other high-risk pregnancies,” he said.

The study was limited primarily by the retrospective design, Dr. Olsen said.

Although current treatment guidelines do not emphasize the effects of maternal buprenorphine use on fetal development, these findings support previous research showing effects of buprenorphine on fetal brain structure, the researchers wrote in their abstract. Looking ahead, “We recommend additional study on the maternal buprenorphine medication–assisted treatment dose effects for fetal and neonatal development with attention to such factors as head circumference, birth weight, achievement of developmental milestones, and school performance,” Dr. Olsen said.

“We and others have shown that the lowest effective dose of buprenorphine can lower neonatal abstinence syndrome/neonatal opioid withdrawal syndrome rates,” but data showing an impact of lowest effective dose management on long-term complications of fetal buprenorphine exposure are lacking, he noted.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Measures of fetal breathing movement were lower in fetuses of pregnant patients who received buprenorphine, compared with controls, based on data from 177 individuals.

The findings were presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists by Caroline Bulger, MD, of East Tennessee State University, Johnson City.

Pregnant patients with opioid-use disorder in the community surrounding Johnson City receive medication-assisted therapy with buprenorphine during the prenatal period, Dr. Bulger and colleagues wrote in their abstract. The current prenatal program for substance use disorder was established in 2016 based on patient requests for assistance in lowering their buprenorphine dosages during pregnancy, said senior author Martin E. Olsen, MD, also of East Tennessee State University, in an interview.

“Buprenorphine medication–assisted treatment in pregnancy is associated with long-term effects on childhood development such as smaller neonatal brains, decreased school performance, and low birth weight;” however, data on the fetal effects of buprenorphine are limited, said Dr. Olsen.

The current study was conducted to evaluate a short-term finding of the fetal effects of buprenorphine, Dr. Olsen said.

“This study was performed after obstetric sonographers at our institution noted that biophysical profile [BPP] ultrasound assessments of the fetuses of mothers on buprenorphine took longer than for other patients,” said Dr. Olsen.

The researchers conducted a retrospective chart review of 131 patients who received buprenorphine and 46 who were followed for chronic hypertension and served as high-risk controls. Patients were seen at a single institution between July 1, 2016, and June 30, 2020.

The researchers hypothesized that BPP of fetuses in patients receiving buprenorphine might be different from controls because of the effects of buprenorphine.

Overall, patients who received buprenorphine were more likely to have a fetal breathing score of zero than those who underwent a BPP for hypertension. A significant relationship emerged between buprenorphine dosage and breathing motion assessment; patients on high-dose buprenorphine were more likely than patients on low doses to have values of zero on fetal breathing motion assessment, and a chi-squared test yielded a P value of .04269.

The takeaway for clinical practice is that clinicians performing BPP ultrasounds on buprenorphine-exposed fetuses can expect that these assessments may take longer on average than assessments of other high-risk patients, said Dr. Olsen. “Additional assessment after a low BPP score is still indicated for these fetuses just as in other high-risk pregnancies,” he said.

The study was limited primarily by the retrospective design, Dr. Olsen said.

Although current treatment guidelines do not emphasize the effects of maternal buprenorphine use on fetal development, these findings support previous research showing effects of buprenorphine on fetal brain structure, the researchers wrote in their abstract. Looking ahead, “We recommend additional study on the maternal buprenorphine medication–assisted treatment dose effects for fetal and neonatal development with attention to such factors as head circumference, birth weight, achievement of developmental milestones, and school performance,” Dr. Olsen said.

“We and others have shown that the lowest effective dose of buprenorphine can lower neonatal abstinence syndrome/neonatal opioid withdrawal syndrome rates,” but data showing an impact of lowest effective dose management on long-term complications of fetal buprenorphine exposure are lacking, he noted.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Welcome everyone. I’m Dr. John White. I’m the chief medical officer at WebMD. Does your biologic sex impact your health? Does it have any play in how you’re diagnosed, how you’re treated in terms of what symptoms you have? Of course it does. We all know that. But that’s not something that many people believed 5, 10 years ago, certainly not 20 years ago. And it was only because of leaders like my guest today, Phyllis Greenberger, who really championed the need for research on women’s health. She has a new book out, which I love. It’s called Sex Cells: the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Please welcome my very good friend, Phyllis Greenberger.

Thank you.

Phyllis, It’s great to see you today.

It’s great to see you as well.

Now, you and I have been talking about this for easily 2 decades.

At least.

And some people think, oh, of course it makes sense. Although I saw you disagreeing that not everyone still believes that. But what has been that journey? Why has it been so hard to make people understand, as you point out early on in your book, women are not smaller men?

I think the basic reason was that it was just believed that men and women were the same except for their reproductive organs. So minus the reproductive organs, whether it was a device, a diagnostic, or therapeutic, if it was used and successful on a male, that it would be successful on a female. We’re really very far from understanding the differences, and there’s still a lot of distrust and disbelief and ignorance about it. And so there’s still a long way to go.

But you talk about that in the book, that there’s still a long way to go. Why is that? What’s the biggest obstacle? Is it just misinformation, lack of information? People don’t understand the science? There’s still resistance in some areas. Why is that?

I think it’s misinformation, and I gave a presentation, I don’t know how many years ago, at least 20 years ago, about the curriculum. And at the time, there was no women’s health in the curriculum. It was health. So if it was on cardiovascular issues or on osteoporosis, it was sort of the basic. And at the time, there would maybe be one woman whose job was women’s health, and she’d have an office, and otherwise there was nothing. And maybe they talked about breast cancer, who knows. But I spoke to someone just the other day, in view of all the attention that the book is getting now, whether that’s changed, whether it’s necessary and required. And she said it’s not. So, it’s not necessarily on the curriculum of all research and medical institutions, and even if women’s health, quote unquote, is on the curriculum, it doesn’t mean that they’re really looking at sex differences. And the difference is obvious. I mean, gender is really, it’s a social construct, but biological sex is how disease occurs and develops. And so if you’re not looking, and because there’s so little research now on sex differences that I don’t even know, I mean, how much you could actually teach.

So what needs to change? This book is a manifesto in many ways in how we need to include women; we need to make research more inclusive of everyone. But we’re not there yet. So what needs to change, Phyllis?

During this whole saga of trying to get people to listen to me and to the society, we really started out just looking at clinical trials and that, as you mentioned, I mean, there are issues in rural communities. There’s travel issues for women and child care. There’s a lot of disbelief or fear of clinical trials in some ethnicities. I do think, going to the future, that technology can help that. I mean, if people have broadband, which of course is also an issue in rural areas.

What could women do today? What should women listeners hear and then be doing? Should they be saying something to their doctor? Should they be asking specific questions? When they interact with the health care system, how can they make sure they’re getting the best care that’s appropriate for them when we know that sex cells matter?

Well, that’s a good question. It depends on, frankly, if your doctor is aware of this, if he or she has learned anything about this in school, which, I had already said, we’re not sure about that because research is still ongoing and there’s so much we don’t know. So I mean, you used to think, or I used to think, that you go to, you want a physician who’s older and more experienced. But now I think you should be going to a physician who’s younger and hopefully has learned about this, because the physicians that were educated years ago and have been practicing for 20, 30 years, I don’t know how much they know about this, whether they’re even aware of it.

Phyllis, you are a woman of action. You’ve lived in the DC area. You have championed legislative reforms, executive agendas. What do you want done now? What needs to be changed today? The curriculum is going to take time, but what else needs to change?

That’s a good question. I mean, if curriculum is going to take a while and you can ask your doctor if he prescribes the medication, whether it’s been tested on women, but then if it hasn’t been tested on women, but it’s the only thing that there is for your condition, I mean, so it’s very difficult. The Biden administration, as you know, just allocated a hundred million dollars for women’s health research.

What do you hope to accomplish with this book?

Well, what I’m hoping is that I spoke to someone at AMWA and I’m hoping — and AMWA is an association for women medical students. And I’m hoping that’s the audience. The audience needs to be. I mean, obviously everybody that I know that’s not a doctor that’s read it, found it fascinating and didn’t know a lot of the stuff that was in it. So I think it’s an interesting book anyway, and I think women should be aware of it. But really I think it needs to be for medical students.

And to your credit, you built the Society for Women’s Health Research into a powerful force in Washington under your tenure in really promoting the need for Office of Women’s Health and Research in general. The book is entitled Sex Cells, the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Phyllis Greenberger, thank you so much for all that you’ve done for women’s health, for women’s research. We wouldn’t be where we are today if it wasn’t for you. So thanks.

Thank you very much, John. Thank you. I appreciate the opportunity.

Dr. Whyte, is chief medical officer, WebMD, New York, NY. He has disclosed no relevant financial relationships. Ms. Greenberger is a women’s health advocate and author of “Sex Cells: The Fight to Overcome Bias and Discrimination in Women’s Healthcare”

This interview originally appeared on WebMD on May 23, 2024. A version of this article appeared on Medscape.com .

Welcome everyone. I’m Dr. John White. I’m the chief medical officer at WebMD. Does your biologic sex impact your health? Does it have any play in how you’re diagnosed, how you’re treated in terms of what symptoms you have? Of course it does. We all know that. But that’s not something that many people believed 5, 10 years ago, certainly not 20 years ago. And it was only because of leaders like my guest today, Phyllis Greenberger, who really championed the need for research on women’s health. She has a new book out, which I love. It’s called Sex Cells: the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Please welcome my very good friend, Phyllis Greenberger.

Thank you.

Phyllis, It’s great to see you today.

It’s great to see you as well.

Now, you and I have been talking about this for easily 2 decades.

At least.

And some people think, oh, of course it makes sense. Although I saw you disagreeing that not everyone still believes that. But what has been that journey? Why has it been so hard to make people understand, as you point out early on in your book, women are not smaller men?

I think the basic reason was that it was just believed that men and women were the same except for their reproductive organs. So minus the reproductive organs, whether it was a device, a diagnostic, or therapeutic, if it was used and successful on a male, that it would be successful on a female. We’re really very far from understanding the differences, and there’s still a lot of distrust and disbelief and ignorance about it. And so there’s still a long way to go.

But you talk about that in the book, that there’s still a long way to go. Why is that? What’s the biggest obstacle? Is it just misinformation, lack of information? People don’t understand the science? There’s still resistance in some areas. Why is that?

I think it’s misinformation, and I gave a presentation, I don’t know how many years ago, at least 20 years ago, about the curriculum. And at the time, there was no women’s health in the curriculum. It was health. So if it was on cardiovascular issues or on osteoporosis, it was sort of the basic. And at the time, there would maybe be one woman whose job was women’s health, and she’d have an office, and otherwise there was nothing. And maybe they talked about breast cancer, who knows. But I spoke to someone just the other day, in view of all the attention that the book is getting now, whether that’s changed, whether it’s necessary and required. And she said it’s not. So, it’s not necessarily on the curriculum of all research and medical institutions, and even if women’s health, quote unquote, is on the curriculum, it doesn’t mean that they’re really looking at sex differences. And the difference is obvious. I mean, gender is really, it’s a social construct, but biological sex is how disease occurs and develops. And so if you’re not looking, and because there’s so little research now on sex differences that I don’t even know, I mean, how much you could actually teach.

So what needs to change? This book is a manifesto in many ways in how we need to include women; we need to make research more inclusive of everyone. But we’re not there yet. So what needs to change, Phyllis?

During this whole saga of trying to get people to listen to me and to the society, we really started out just looking at clinical trials and that, as you mentioned, I mean, there are issues in rural communities. There’s travel issues for women and child care. There’s a lot of disbelief or fear of clinical trials in some ethnicities. I do think, going to the future, that technology can help that. I mean, if people have broadband, which of course is also an issue in rural areas.

What could women do today? What should women listeners hear and then be doing? Should they be saying something to their doctor? Should they be asking specific questions? When they interact with the health care system, how can they make sure they’re getting the best care that’s appropriate for them when we know that sex cells matter?

Well, that’s a good question. It depends on, frankly, if your doctor is aware of this, if he or she has learned anything about this in school, which, I had already said, we’re not sure about that because research is still ongoing and there’s so much we don’t know. So I mean, you used to think, or I used to think, that you go to, you want a physician who’s older and more experienced. But now I think you should be going to a physician who’s younger and hopefully has learned about this, because the physicians that were educated years ago and have been practicing for 20, 30 years, I don’t know how much they know about this, whether they’re even aware of it.

Phyllis, you are a woman of action. You’ve lived in the DC area. You have championed legislative reforms, executive agendas. What do you want done now? What needs to be changed today? The curriculum is going to take time, but what else needs to change?

That’s a good question. I mean, if curriculum is going to take a while and you can ask your doctor if he prescribes the medication, whether it’s been tested on women, but then if it hasn’t been tested on women, but it’s the only thing that there is for your condition, I mean, so it’s very difficult. The Biden administration, as you know, just allocated a hundred million dollars for women’s health research.

What do you hope to accomplish with this book?

Well, what I’m hoping is that I spoke to someone at AMWA and I’m hoping — and AMWA is an association for women medical students. And I’m hoping that’s the audience. The audience needs to be. I mean, obviously everybody that I know that’s not a doctor that’s read it, found it fascinating and didn’t know a lot of the stuff that was in it. So I think it’s an interesting book anyway, and I think women should be aware of it. But really I think it needs to be for medical students.

And to your credit, you built the Society for Women’s Health Research into a powerful force in Washington under your tenure in really promoting the need for Office of Women’s Health and Research in general. The book is entitled Sex Cells, the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Phyllis Greenberger, thank you so much for all that you’ve done for women’s health, for women’s research. We wouldn’t be where we are today if it wasn’t for you. So thanks.

Thank you very much, John. Thank you. I appreciate the opportunity.

Dr. Whyte, is chief medical officer, WebMD, New York, NY. He has disclosed no relevant financial relationships. Ms. Greenberger is a women’s health advocate and author of “Sex Cells: The Fight to Overcome Bias and Discrimination in Women’s Healthcare”

This interview originally appeared on WebMD on May 23, 2024. A version of this article appeared on Medscape.com .

Welcome everyone. I’m Dr. John White. I’m the chief medical officer at WebMD. Does your biologic sex impact your health? Does it have any play in how you’re diagnosed, how you’re treated in terms of what symptoms you have? Of course it does. We all know that. But that’s not something that many people believed 5, 10 years ago, certainly not 20 years ago. And it was only because of leaders like my guest today, Phyllis Greenberger, who really championed the need for research on women’s health. She has a new book out, which I love. It’s called Sex Cells: the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Please welcome my very good friend, Phyllis Greenberger.

Thank you.

Phyllis, It’s great to see you today.

It’s great to see you as well.

Now, you and I have been talking about this for easily 2 decades.

At least.

And some people think, oh, of course it makes sense. Although I saw you disagreeing that not everyone still believes that. But what has been that journey? Why has it been so hard to make people understand, as you point out early on in your book, women are not smaller men?

I think the basic reason was that it was just believed that men and women were the same except for their reproductive organs. So minus the reproductive organs, whether it was a device, a diagnostic, or therapeutic, if it was used and successful on a male, that it would be successful on a female. We’re really very far from understanding the differences, and there’s still a lot of distrust and disbelief and ignorance about it. And so there’s still a long way to go.

But you talk about that in the book, that there’s still a long way to go. Why is that? What’s the biggest obstacle? Is it just misinformation, lack of information? People don’t understand the science? There’s still resistance in some areas. Why is that?

I think it’s misinformation, and I gave a presentation, I don’t know how many years ago, at least 20 years ago, about the curriculum. And at the time, there was no women’s health in the curriculum. It was health. So if it was on cardiovascular issues or on osteoporosis, it was sort of the basic. And at the time, there would maybe be one woman whose job was women’s health, and she’d have an office, and otherwise there was nothing. And maybe they talked about breast cancer, who knows. But I spoke to someone just the other day, in view of all the attention that the book is getting now, whether that’s changed, whether it’s necessary and required. And she said it’s not. So, it’s not necessarily on the curriculum of all research and medical institutions, and even if women’s health, quote unquote, is on the curriculum, it doesn’t mean that they’re really looking at sex differences. And the difference is obvious. I mean, gender is really, it’s a social construct, but biological sex is how disease occurs and develops. And so if you’re not looking, and because there’s so little research now on sex differences that I don’t even know, I mean, how much you could actually teach.

So what needs to change? This book is a manifesto in many ways in how we need to include women; we need to make research more inclusive of everyone. But we’re not there yet. So what needs to change, Phyllis?

During this whole saga of trying to get people to listen to me and to the society, we really started out just looking at clinical trials and that, as you mentioned, I mean, there are issues in rural communities. There’s travel issues for women and child care. There’s a lot of disbelief or fear of clinical trials in some ethnicities. I do think, going to the future, that technology can help that. I mean, if people have broadband, which of course is also an issue in rural areas.

What could women do today? What should women listeners hear and then be doing? Should they be saying something to their doctor? Should they be asking specific questions? When they interact with the health care system, how can they make sure they’re getting the best care that’s appropriate for them when we know that sex cells matter?

Well, that’s a good question. It depends on, frankly, if your doctor is aware of this, if he or she has learned anything about this in school, which, I had already said, we’re not sure about that because research is still ongoing and there’s so much we don’t know. So I mean, you used to think, or I used to think, that you go to, you want a physician who’s older and more experienced. But now I think you should be going to a physician who’s younger and hopefully has learned about this, because the physicians that were educated years ago and have been practicing for 20, 30 years, I don’t know how much they know about this, whether they’re even aware of it.

Phyllis, you are a woman of action. You’ve lived in the DC area. You have championed legislative reforms, executive agendas. What do you want done now? What needs to be changed today? The curriculum is going to take time, but what else needs to change?

That’s a good question. I mean, if curriculum is going to take a while and you can ask your doctor if he prescribes the medication, whether it’s been tested on women, but then if it hasn’t been tested on women, but it’s the only thing that there is for your condition, I mean, so it’s very difficult. The Biden administration, as you know, just allocated a hundred million dollars for women’s health research.

What do you hope to accomplish with this book?

Well, what I’m hoping is that I spoke to someone at AMWA and I’m hoping — and AMWA is an association for women medical students. And I’m hoping that’s the audience. The audience needs to be. I mean, obviously everybody that I know that’s not a doctor that’s read it, found it fascinating and didn’t know a lot of the stuff that was in it. So I think it’s an interesting book anyway, and I think women should be aware of it. But really I think it needs to be for medical students.

And to your credit, you built the Society for Women’s Health Research into a powerful force in Washington under your tenure in really promoting the need for Office of Women’s Health and Research in general. The book is entitled Sex Cells, the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Phyllis Greenberger, thank you so much for all that you’ve done for women’s health, for women’s research. We wouldn’t be where we are today if it wasn’t for you. So thanks.

Thank you very much, John. Thank you. I appreciate the opportunity.

Dr. Whyte, is chief medical officer, WebMD, New York, NY. He has disclosed no relevant financial relationships. Ms. Greenberger is a women’s health advocate and author of “Sex Cells: The Fight to Overcome Bias and Discrimination in Women’s Healthcare”

This interview originally appeared on WebMD on May 23, 2024. A version of this article appeared on Medscape.com .

TOPLINE:

Healthier sleep is associated with lower odds of developing a wide range of gastrointestinal conditions, regardless of genetic susceptibility, new research revealed.

METHODOLOGY:

• Due to the widespread prevalence of sleep issues and a growing burden of digestive diseases globally, researchers investigated the association between sleep quality and digestive disorders in a prospective cohort study of 410,586 people in the UK Biobank.
• Five individual sleep behaviors were assessed: sleep duration, insomnia, snoring, daytime sleepiness, and chronotype.
• A healthy sleep was defined as a morning chronotype, 7-8 hours of sleep duration, no self-reported snoring, never or rare insomnia, and a low frequency of daytime sleepiness, for a score of 5/5.
• The study investigators tracked the development of 16 digestive diseases over a mean period of 13.2 years.
• As well as looking at healthy sleep scores, researchers considered genetic susceptibility to gastrointestinal conditions.

TAKEAWAY:

• Participants with a healthy sleep score had 28% lower odds of developing any digestive disease (hazard ratio [HR], 0.72; 95% CI, 0.69-0.75) than those with a sleep score of 0/1.
• Of the 16 digestive diseases looked at, the reduction of risk was highest for irritable bowel syndrome at 50% (HR, 0.50; 95% CI, 0.45-0.57).
• A healthy sleep score was also associated with 37% reduced odds for metabolic dysfunction–associated steatotic liver disease (formerly known as nonalcoholic fatty liver disease; HR, 0.63; 95% CI, 0.55-0.71), 35% lower chance for peptic ulcer (HR, 0.65; 95% CI, 0.058-0.74), 34% reduced chance for dyspepsia (HR, 0.66; 95% CI, 0.58-0.75), and a 25% lower risk for diverticulosis (HR, 0.75; 95% CI, 0.71-0.80).
• High genetic risk and poor sleep scores were also associated with increased odds (53% to > 200%) of developing digestive diseases.
• However, healthy sleep reduced the risk for digestive diseases regardless of genetic susceptibility.

IN PRACTICE:

“Our findings underscore the potential holistic impact of different sleep behaviors in mitigating the risk of digestive diseases in clinical practice,” wrote Shiyi Yu, MD, of Guangdong Provincial People’s Hospital, Guangzhou, Guangdong, China, and colleagues.

Poor sleep can also change our gut microbiome, Dr. Yu told this news organization. If you don’t sleep well, the repair of the gut lining cannot be finished during the night.

SOURCE:

The study was presented at the Digestive Disease Week® (DDW), 2024, annual meeting.

DISCLOSURES:

Dr. Yu had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Healthier sleep is associated with lower odds of developing a wide range of gastrointestinal conditions, regardless of genetic susceptibility, new research revealed.

METHODOLOGY:

• Due to the widespread prevalence of sleep issues and a growing burden of digestive diseases globally, researchers investigated the association between sleep quality and digestive disorders in a prospective cohort study of 410,586 people in the UK Biobank.
• Five individual sleep behaviors were assessed: sleep duration, insomnia, snoring, daytime sleepiness, and chronotype.
• A healthy sleep was defined as a morning chronotype, 7-8 hours of sleep duration, no self-reported snoring, never or rare insomnia, and a low frequency of daytime sleepiness, for a score of 5/5.
• The study investigators tracked the development of 16 digestive diseases over a mean period of 13.2 years.
• As well as looking at healthy sleep scores, researchers considered genetic susceptibility to gastrointestinal conditions.

TAKEAWAY:

• Participants with a healthy sleep score had 28% lower odds of developing any digestive disease (hazard ratio [HR], 0.72; 95% CI, 0.69-0.75) than those with a sleep score of 0/1.
• Of the 16 digestive diseases looked at, the reduction of risk was highest for irritable bowel syndrome at 50% (HR, 0.50; 95% CI, 0.45-0.57).
• A healthy sleep score was also associated with 37% reduced odds for metabolic dysfunction–associated steatotic liver disease (formerly known as nonalcoholic fatty liver disease; HR, 0.63; 95% CI, 0.55-0.71), 35% lower chance for peptic ulcer (HR, 0.65; 95% CI, 0.058-0.74), 34% reduced chance for dyspepsia (HR, 0.66; 95% CI, 0.58-0.75), and a 25% lower risk for diverticulosis (HR, 0.75; 95% CI, 0.71-0.80).
• High genetic risk and poor sleep scores were also associated with increased odds (53% to > 200%) of developing digestive diseases.
• However, healthy sleep reduced the risk for digestive diseases regardless of genetic susceptibility.

IN PRACTICE:

“Our findings underscore the potential holistic impact of different sleep behaviors in mitigating the risk of digestive diseases in clinical practice,” wrote Shiyi Yu, MD, of Guangdong Provincial People’s Hospital, Guangzhou, Guangdong, China, and colleagues.

Poor sleep can also change our gut microbiome, Dr. Yu told this news organization. If you don’t sleep well, the repair of the gut lining cannot be finished during the night.

SOURCE:

The study was presented at the Digestive Disease Week® (DDW), 2024, annual meeting.

DISCLOSURES:

Dr. Yu had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Healthier sleep is associated with lower odds of developing a wide range of gastrointestinal conditions, regardless of genetic susceptibility, new research revealed.

METHODOLOGY:

• Due to the widespread prevalence of sleep issues and a growing burden of digestive diseases globally, researchers investigated the association between sleep quality and digestive disorders in a prospective cohort study of 410,586 people in the UK Biobank.
• Five individual sleep behaviors were assessed: sleep duration, insomnia, snoring, daytime sleepiness, and chronotype.
• A healthy sleep was defined as a morning chronotype, 7-8 hours of sleep duration, no self-reported snoring, never or rare insomnia, and a low frequency of daytime sleepiness, for a score of 5/5.
• The study investigators tracked the development of 16 digestive diseases over a mean period of 13.2 years.
• As well as looking at healthy sleep scores, researchers considered genetic susceptibility to gastrointestinal conditions.

TAKEAWAY:

• Participants with a healthy sleep score had 28% lower odds of developing any digestive disease (hazard ratio [HR], 0.72; 95% CI, 0.69-0.75) than those with a sleep score of 0/1.
• Of the 16 digestive diseases looked at, the reduction of risk was highest for irritable bowel syndrome at 50% (HR, 0.50; 95% CI, 0.45-0.57).
• A healthy sleep score was also associated with 37% reduced odds for metabolic dysfunction–associated steatotic liver disease (formerly known as nonalcoholic fatty liver disease; HR, 0.63; 95% CI, 0.55-0.71), 35% lower chance for peptic ulcer (HR, 0.65; 95% CI, 0.058-0.74), 34% reduced chance for dyspepsia (HR, 0.66; 95% CI, 0.58-0.75), and a 25% lower risk for diverticulosis (HR, 0.75; 95% CI, 0.71-0.80).
• High genetic risk and poor sleep scores were also associated with increased odds (53% to > 200%) of developing digestive diseases.
• However, healthy sleep reduced the risk for digestive diseases regardless of genetic susceptibility.

IN PRACTICE:

“Our findings underscore the potential holistic impact of different sleep behaviors in mitigating the risk of digestive diseases in clinical practice,” wrote Shiyi Yu, MD, of Guangdong Provincial People’s Hospital, Guangzhou, Guangdong, China, and colleagues.

Poor sleep can also change our gut microbiome, Dr. Yu told this news organization. If you don’t sleep well, the repair of the gut lining cannot be finished during the night.

SOURCE:

The study was presented at the Digestive Disease Week® (DDW), 2024, annual meeting.

DISCLOSURES:

Dr. Yu had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Guselkumab (Tremfya, Janssen/Johnson & Johnson) was superior to placebo for maintenance therapy in people with moderately to severely active ulcerative colitis (UC), according to the results of the phase 3 Quasar Maintenance Study.

The primary outcome of clinical remission at 44 weeks was greater with either of two dose regimens of guselkumab than with placebo, David Rubin, MD, AGAF, reported as part of his presentation (Abstract 759) at the annual Digestive Disease Week® (DDW).

Guselkumab is not the only biologic approved or in development for UC, but it is unique because of its dual action. It is an interleukin (IL)-23p19 subunit inhibitor that blocks IL-23 and also binds to the CD64 receptor on cells that produce IL-23.

Dr. Rubin, who is chief of the Section of Gastroenterology, Hepatology and Nutrition at University of Chicago Medicine, Chicago, said he was unsure at the beginning of the trial if this dual activity “might have any value.”

Targeting both the IL-23 circulating in the tissue and the receptor remains to be proven, “but nonetheless seems reasonable,” he said.

The study included 568 people, about 42% of whom had an inadequate response or were intolerant to prior advanced therapy, and 42.5% of whom had failed two or more advanced therapy classes.

Clinical responders from two prior guselkumab induction studies were enrolled in this randomized withdrawal, double-blind maintenance trial. At either 12 weeks or 24 weeks of induction, patients were randomly assigned to subcutaneous 200-mg guselkumab every 4 weeks (n = 190), 100-mg guselkumab every 8 weeks (n = 188), or placebo (n = 190). The placebo group served as a guselkumab withdrawal group.

Participants had a mean age of 41 years and a mean disease duration of 7.8 years. The 40% using oral corticosteroids were tapered off during the study.

A total of 45.2% of the 100-mg guselkumab group and 50.0% of the 200-mg guselkumab group met the primary outcome of clinical remission at week 44 compared with 18.9% with placebo.

“It was interesting to note that the 200 mg every 4 weeks was similar in efficacy at week 44 to the 100 mg every 8 weeks. It’s much less medicine, but you get similar results,” Dr. Rubin said.
 

Secondary Outcomes Also Superior

“The bottom line is not only did it work, but it worked when you look at some secondary endpoints, including endoscopic remission, where the bowel is completely healed,” Dr. Rubin said in an interview.

Overall, 34% of all participants who received guselkumab achieved this outcome, “which is a very high rate,” he said. “We haven’t seen a Mayo score of zero — meaning endoscopic remission — at that rate with any of our other therapies currently.”

Among the participants who achieved clinical remission, 69% of them also showed complete remission on endoscopy.

Other secondary outcomes significantly better at week 44 vs placebo included corticosteroid-free clinical remission, maintenance of clinical remission, clinical response, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, endoscopic normalization, Inflammatory Bowel Disease Questionnaire remission, and fatigue response.

“It was a great study. I think it’s very promising data,” said session co-moderator Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston.

“As we get more data from these more selective interleukins, we’ll get a better sense of how that plays out” vs other similar agents in development, he added.
 

IL-23 Target Seems Safe

One or more adverse events were reported by 70% of the higher-dose guselkumab group, 65% of the lower-dose guselkumab group, and 68% of the placebo group.

The most common adverse events in a combined 200-mg and 100-mg guselkumab group were lower than in the placebo group: 11.2% vs 14.1% reported COVID-19, 11.2% vs 29.7% reported exacerbation of UC, and 6.1% vs 6.8% experienced arthralgia, respectively.

No cases of active tuberculosis, opportunistic infection, anaphylaxis, serum sickness, Hy’s law, or serious hepatic issues were reported. One patient had clear cell renal carcinoma, another had rectal adenocarcinoma, and one hemorrhagic stroke was reported in the treatment groups. No patients died during the trial.

A higher proportion of people in the placebo group (13.7%) discontinued the study than those in the 100-mg guselkumab group (10.6%) and the 200-mg guselkumab group (11.6%).

“In general, we have accepted that the IL-23 target seems to be a very safe one,” Dr. Rubin said.

A leading theory is that unlike some interleukins, IL-23 is only expressed where the body has inflammation; therefore, targeting IL-23 does not affect other areas, he explained.

If approved by the Food and Drug Administration, it would expand the official indications for guselkumab, which was approved in 2020 for psoriatic arthritis and in 2017 for plaque psoriasis.

The study was supported by Janssen Research & Development, LLC. Dr. Rubin is a consultant for Janssen. Dr. Ananthakrishnan had no relevant disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Guselkumab (Tremfya, Janssen/Johnson & Johnson) was superior to placebo for maintenance therapy in people with moderately to severely active ulcerative colitis (UC), according to the results of the phase 3 Quasar Maintenance Study.

The primary outcome of clinical remission at 44 weeks was greater with either of two dose regimens of guselkumab than with placebo, David Rubin, MD, AGAF, reported as part of his presentation (Abstract 759) at the annual Digestive Disease Week® (DDW).

Guselkumab is not the only biologic approved or in development for UC, but it is unique because of its dual action. It is an interleukin (IL)-23p19 subunit inhibitor that blocks IL-23 and also binds to the CD64 receptor on cells that produce IL-23.

Dr. Rubin, who is chief of the Section of Gastroenterology, Hepatology and Nutrition at University of Chicago Medicine, Chicago, said he was unsure at the beginning of the trial if this dual activity “might have any value.”

Targeting both the IL-23 circulating in the tissue and the receptor remains to be proven, “but nonetheless seems reasonable,” he said.

The study included 568 people, about 42% of whom had an inadequate response or were intolerant to prior advanced therapy, and 42.5% of whom had failed two or more advanced therapy classes.

Clinical responders from two prior guselkumab induction studies were enrolled in this randomized withdrawal, double-blind maintenance trial. At either 12 weeks or 24 weeks of induction, patients were randomly assigned to subcutaneous 200-mg guselkumab every 4 weeks (n = 190), 100-mg guselkumab every 8 weeks (n = 188), or placebo (n = 190). The placebo group served as a guselkumab withdrawal group.

Participants had a mean age of 41 years and a mean disease duration of 7.8 years. The 40% using oral corticosteroids were tapered off during the study.

A total of 45.2% of the 100-mg guselkumab group and 50.0% of the 200-mg guselkumab group met the primary outcome of clinical remission at week 44 compared with 18.9% with placebo.

“It was interesting to note that the 200 mg every 4 weeks was similar in efficacy at week 44 to the 100 mg every 8 weeks. It’s much less medicine, but you get similar results,” Dr. Rubin said.
 

Secondary Outcomes Also Superior

“The bottom line is not only did it work, but it worked when you look at some secondary endpoints, including endoscopic remission, where the bowel is completely healed,” Dr. Rubin said in an interview.

Overall, 34% of all participants who received guselkumab achieved this outcome, “which is a very high rate,” he said. “We haven’t seen a Mayo score of zero — meaning endoscopic remission — at that rate with any of our other therapies currently.”

Among the participants who achieved clinical remission, 69% of them also showed complete remission on endoscopy.

Other secondary outcomes significantly better at week 44 vs placebo included corticosteroid-free clinical remission, maintenance of clinical remission, clinical response, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, endoscopic normalization, Inflammatory Bowel Disease Questionnaire remission, and fatigue response.

“It was a great study. I think it’s very promising data,” said session co-moderator Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston.

“As we get more data from these more selective interleukins, we’ll get a better sense of how that plays out” vs other similar agents in development, he added.
 

IL-23 Target Seems Safe

One or more adverse events were reported by 70% of the higher-dose guselkumab group, 65% of the lower-dose guselkumab group, and 68% of the placebo group.

The most common adverse events in a combined 200-mg and 100-mg guselkumab group were lower than in the placebo group: 11.2% vs 14.1% reported COVID-19, 11.2% vs 29.7% reported exacerbation of UC, and 6.1% vs 6.8% experienced arthralgia, respectively.

No cases of active tuberculosis, opportunistic infection, anaphylaxis, serum sickness, Hy’s law, or serious hepatic issues were reported. One patient had clear cell renal carcinoma, another had rectal adenocarcinoma, and one hemorrhagic stroke was reported in the treatment groups. No patients died during the trial.

A higher proportion of people in the placebo group (13.7%) discontinued the study than those in the 100-mg guselkumab group (10.6%) and the 200-mg guselkumab group (11.6%).

“In general, we have accepted that the IL-23 target seems to be a very safe one,” Dr. Rubin said.

A leading theory is that unlike some interleukins, IL-23 is only expressed where the body has inflammation; therefore, targeting IL-23 does not affect other areas, he explained.

If approved by the Food and Drug Administration, it would expand the official indications for guselkumab, which was approved in 2020 for psoriatic arthritis and in 2017 for plaque psoriasis.

The study was supported by Janssen Research & Development, LLC. Dr. Rubin is a consultant for Janssen. Dr. Ananthakrishnan had no relevant disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Guselkumab (Tremfya, Janssen/Johnson & Johnson) was superior to placebo for maintenance therapy in people with moderately to severely active ulcerative colitis (UC), according to the results of the phase 3 Quasar Maintenance Study.

The primary outcome of clinical remission at 44 weeks was greater with either of two dose regimens of guselkumab than with placebo, David Rubin, MD, AGAF, reported as part of his presentation (Abstract 759) at the annual Digestive Disease Week® (DDW).

Guselkumab is not the only biologic approved or in development for UC, but it is unique because of its dual action. It is an interleukin (IL)-23p19 subunit inhibitor that blocks IL-23 and also binds to the CD64 receptor on cells that produce IL-23.

Dr. Rubin, who is chief of the Section of Gastroenterology, Hepatology and Nutrition at University of Chicago Medicine, Chicago, said he was unsure at the beginning of the trial if this dual activity “might have any value.”

Targeting both the IL-23 circulating in the tissue and the receptor remains to be proven, “but nonetheless seems reasonable,” he said.

The study included 568 people, about 42% of whom had an inadequate response or were intolerant to prior advanced therapy, and 42.5% of whom had failed two or more advanced therapy classes.

Clinical responders from two prior guselkumab induction studies were enrolled in this randomized withdrawal, double-blind maintenance trial. At either 12 weeks or 24 weeks of induction, patients were randomly assigned to subcutaneous 200-mg guselkumab every 4 weeks (n = 190), 100-mg guselkumab every 8 weeks (n = 188), or placebo (n = 190). The placebo group served as a guselkumab withdrawal group.

Participants had a mean age of 41 years and a mean disease duration of 7.8 years. The 40% using oral corticosteroids were tapered off during the study.

A total of 45.2% of the 100-mg guselkumab group and 50.0% of the 200-mg guselkumab group met the primary outcome of clinical remission at week 44 compared with 18.9% with placebo.

“It was interesting to note that the 200 mg every 4 weeks was similar in efficacy at week 44 to the 100 mg every 8 weeks. It’s much less medicine, but you get similar results,” Dr. Rubin said.
 

Secondary Outcomes Also Superior

“The bottom line is not only did it work, but it worked when you look at some secondary endpoints, including endoscopic remission, where the bowel is completely healed,” Dr. Rubin said in an interview.

Overall, 34% of all participants who received guselkumab achieved this outcome, “which is a very high rate,” he said. “We haven’t seen a Mayo score of zero — meaning endoscopic remission — at that rate with any of our other therapies currently.”

Among the participants who achieved clinical remission, 69% of them also showed complete remission on endoscopy.

Other secondary outcomes significantly better at week 44 vs placebo included corticosteroid-free clinical remission, maintenance of clinical remission, clinical response, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, endoscopic normalization, Inflammatory Bowel Disease Questionnaire remission, and fatigue response.

“It was a great study. I think it’s very promising data,” said session co-moderator Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston.

“As we get more data from these more selective interleukins, we’ll get a better sense of how that plays out” vs other similar agents in development, he added.
 

IL-23 Target Seems Safe

One or more adverse events were reported by 70% of the higher-dose guselkumab group, 65% of the lower-dose guselkumab group, and 68% of the placebo group.

The most common adverse events in a combined 200-mg and 100-mg guselkumab group were lower than in the placebo group: 11.2% vs 14.1% reported COVID-19, 11.2% vs 29.7% reported exacerbation of UC, and 6.1% vs 6.8% experienced arthralgia, respectively.

No cases of active tuberculosis, opportunistic infection, anaphylaxis, serum sickness, Hy’s law, or serious hepatic issues were reported. One patient had clear cell renal carcinoma, another had rectal adenocarcinoma, and one hemorrhagic stroke was reported in the treatment groups. No patients died during the trial.

A higher proportion of people in the placebo group (13.7%) discontinued the study than those in the 100-mg guselkumab group (10.6%) and the 200-mg guselkumab group (11.6%).

“In general, we have accepted that the IL-23 target seems to be a very safe one,” Dr. Rubin said.

A leading theory is that unlike some interleukins, IL-23 is only expressed where the body has inflammation; therefore, targeting IL-23 does not affect other areas, he explained.

If approved by the Food and Drug Administration, it would expand the official indications for guselkumab, which was approved in 2020 for psoriatic arthritis and in 2017 for plaque psoriasis.

The study was supported by Janssen Research & Development, LLC. Dr. Rubin is a consultant for Janssen. Dr. Ananthakrishnan had no relevant disclosures.

A version of this article appeared on Medscape.com.

To date, men undergoing screening through the measurement of prostate-specific antigen (PSA) levels have had a significant reduction in neoplastic mortality. Because of its low specificity, however, this practice often leads to frequent, unnecessary, invasive biopsies and the diagnosis of low-grade, indolent cancer. While guided biopsies with multiparametric MRI can improve the diagnosis of grade 2 prostate cancers, widespread implementation remains challenging. The use of noninvasive biomarkers to stratify the risk for prostate cancer may be a more practical option.

The National Comprehensive Cancer Network proposes a test consisting of six blood and urine biomarkers for all grades of prostate cancer, and it outperforms PSA testing. However, current practice focuses on detecting high-grade cancers. It has been hypothesized that increasing the number of biomarkers by including molecules specifically expressed in aggressive high-grade prostate cancers could improve test accuracy. Based on the identification of new genes that are overexpressed in high-grade cancers, a polymerase chain reaction (PCR) technique targeting 54 candidate markers was used to develop an optimal 18-gene test that could be used before imaging (with MRI) and biopsy and to assess whether the latter procedures are warranted.
 

Development Cohort

In the development cohort (n = 815; median age, 63 years), quantitative PCR (qPCR) analysis of the 54 candidate genes was performed on urine samples that had been prospectively collected before biopsy following a digital rectal examination. Patients with previously diagnosed prostate cancer, abnormal MRI results, and those who had already undergone a prostate biopsy were excluded. Participants’ PSA levels ranged from 3 to 10 ng/mL (median interquartile range [IQR], 5.6 [4.6-7.2] ng/mL). Valid qPCR results were obtained from 761 participants (93.4%). Subsequently, prostate biopsy revealed grade 2 or higher cancer in 293 participants (38.5%).

Thus, a urine test called MyProstateScore 2.0 (MPSA) was developed, with two formulations: MPSA2 and MPSA2+, depending on whether a prostate volume was considered. The final MPSA2 development model included clinical data and 17 of the most informative markers, including nine specific to cancer, which were associated with the KLK3 reference gene.
 

Validation and Analyses

The external validation cohort (n = 813) consisted of participants in the NCI EDRN PCA3 Evaluation trial. Valid qPCR results were obtained from 743 participants, of whom 151 (20.3%) were found to have high-grade prostate cancer.

The median MPS2 score was higher in patients with grade 2 or higher prostate cancer (0.44; IQR, 0.23-0.69) than in those with noncontributory biopsies (0.08; IQR, 0.03-0.19; P < .001) or grade 1 cancer (0.25; IQR, 0.09-0.48; P < .01).

Comparative analyses included PSA, the Prostate Cancer Prevention Trial risk calculator, the Prostate Health Index (PHI), and various previous genetic models. Decision curve analyses quantified the benefit of each biomarker studied. The 151 participants with high-grade prostate cancer had operating curve values ranging from 0.60 for PSA alone to 0.77 for PHI and 0.76 for a two-gene multiplex model. The MPSA model had values of 0.81 and 0.82 for MPSA2+. For a required sensitivity of 95%, the MPS2 model could reduce the rate of unnecessary initial biopsies in the population by 35%-42%, with an impact of 15%-30% for other tests. Among the subgroups analyzed, MPS2 models showed negative predictive values of 95%-99% for grade 2 or higher prostate cancers and 99% for grade 3 or higher tumors.
 

MPS2 and Competitors

Existing biomarkers have reduced selectivity in detecting high-grade prostate tumors. This lower performance has led to the development of a new urine test including, for the first time, markers specifically overexpressed in high-grade prostate cancer. This new MPS2 test has a sensitivity of 95% for high-grade prostate cancer and a specificity ranging from 35% to 51%, depending on the subgroups. For clinicians, widespread use of MPS2 could greatly reduce the number of unnecessary biopsies while maintaining a high detection rate of grade 2 or higher prostate cancer.

Among patients who have had a negative first biopsy, MPS2 would have a sensitivity of 94.4% and a specificity of 51%, which is much higher than other tests like prostate cancer antigen 3 gene, three-gene model, and MPS. In addition, in patients with grade 1 prostate cancer, urinary markers for high-grade cancer could indicate the existence of a more aggressive tumor requiring increased monitoring.

This study has limitations, however. The ethnic diversity of its population was limited. A few Black men were included, for example. Second, a systematic biopsy was used as the reference, which can increase negative predictive value and decrease positive predictive value. Classification errors may have occurred. Therefore, further studies are needed to confirm these initial results and the long-term positive impact of using MPS2.

In conclusion, an 18-gene urine test seems to be more relevant for diagnosing high-grade prostate cancer than existing tests. It could prevent additional imaging or biopsy examinations in 35%-41% of patients. Therefore, the use of such tests in patients with high PSA levels could reduce the potential risks associated with prostate cancer screening while preserving its long-term benefits.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

To date, men undergoing screening through the measurement of prostate-specific antigen (PSA) levels have had a significant reduction in neoplastic mortality. Because of its low specificity, however, this practice often leads to frequent, unnecessary, invasive biopsies and the diagnosis of low-grade, indolent cancer. While guided biopsies with multiparametric MRI can improve the diagnosis of grade 2 prostate cancers, widespread implementation remains challenging. The use of noninvasive biomarkers to stratify the risk for prostate cancer may be a more practical option.

The National Comprehensive Cancer Network proposes a test consisting of six blood and urine biomarkers for all grades of prostate cancer, and it outperforms PSA testing. However, current practice focuses on detecting high-grade cancers. It has been hypothesized that increasing the number of biomarkers by including molecules specifically expressed in aggressive high-grade prostate cancers could improve test accuracy. Based on the identification of new genes that are overexpressed in high-grade cancers, a polymerase chain reaction (PCR) technique targeting 54 candidate markers was used to develop an optimal 18-gene test that could be used before imaging (with MRI) and biopsy and to assess whether the latter procedures are warranted.
 

Development Cohort

In the development cohort (n = 815; median age, 63 years), quantitative PCR (qPCR) analysis of the 54 candidate genes was performed on urine samples that had been prospectively collected before biopsy following a digital rectal examination. Patients with previously diagnosed prostate cancer, abnormal MRI results, and those who had already undergone a prostate biopsy were excluded. Participants’ PSA levels ranged from 3 to 10 ng/mL (median interquartile range [IQR], 5.6 [4.6-7.2] ng/mL). Valid qPCR results were obtained from 761 participants (93.4%). Subsequently, prostate biopsy revealed grade 2 or higher cancer in 293 participants (38.5%).

Thus, a urine test called MyProstateScore 2.0 (MPSA) was developed, with two formulations: MPSA2 and MPSA2+, depending on whether a prostate volume was considered. The final MPSA2 development model included clinical data and 17 of the most informative markers, including nine specific to cancer, which were associated with the KLK3 reference gene.
 

Validation and Analyses

The external validation cohort (n = 813) consisted of participants in the NCI EDRN PCA3 Evaluation trial. Valid qPCR results were obtained from 743 participants, of whom 151 (20.3%) were found to have high-grade prostate cancer.

The median MPS2 score was higher in patients with grade 2 or higher prostate cancer (0.44; IQR, 0.23-0.69) than in those with noncontributory biopsies (0.08; IQR, 0.03-0.19; P < .001) or grade 1 cancer (0.25; IQR, 0.09-0.48; P < .01).

Comparative analyses included PSA, the Prostate Cancer Prevention Trial risk calculator, the Prostate Health Index (PHI), and various previous genetic models. Decision curve analyses quantified the benefit of each biomarker studied. The 151 participants with high-grade prostate cancer had operating curve values ranging from 0.60 for PSA alone to 0.77 for PHI and 0.76 for a two-gene multiplex model. The MPSA model had values of 0.81 and 0.82 for MPSA2+. For a required sensitivity of 95%, the MPS2 model could reduce the rate of unnecessary initial biopsies in the population by 35%-42%, with an impact of 15%-30% for other tests. Among the subgroups analyzed, MPS2 models showed negative predictive values of 95%-99% for grade 2 or higher prostate cancers and 99% for grade 3 or higher tumors.
 

MPS2 and Competitors

Existing biomarkers have reduced selectivity in detecting high-grade prostate tumors. This lower performance has led to the development of a new urine test including, for the first time, markers specifically overexpressed in high-grade prostate cancer. This new MPS2 test has a sensitivity of 95% for high-grade prostate cancer and a specificity ranging from 35% to 51%, depending on the subgroups. For clinicians, widespread use of MPS2 could greatly reduce the number of unnecessary biopsies while maintaining a high detection rate of grade 2 or higher prostate cancer.

Among patients who have had a negative first biopsy, MPS2 would have a sensitivity of 94.4% and a specificity of 51%, which is much higher than other tests like prostate cancer antigen 3 gene, three-gene model, and MPS. In addition, in patients with grade 1 prostate cancer, urinary markers for high-grade cancer could indicate the existence of a more aggressive tumor requiring increased monitoring.

This study has limitations, however. The ethnic diversity of its population was limited. A few Black men were included, for example. Second, a systematic biopsy was used as the reference, which can increase negative predictive value and decrease positive predictive value. Classification errors may have occurred. Therefore, further studies are needed to confirm these initial results and the long-term positive impact of using MPS2.

In conclusion, an 18-gene urine test seems to be more relevant for diagnosing high-grade prostate cancer than existing tests. It could prevent additional imaging or biopsy examinations in 35%-41% of patients. Therefore, the use of such tests in patients with high PSA levels could reduce the potential risks associated with prostate cancer screening while preserving its long-term benefits.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

To date, men undergoing screening through the measurement of prostate-specific antigen (PSA) levels have had a significant reduction in neoplastic mortality. Because of its low specificity, however, this practice often leads to frequent, unnecessary, invasive biopsies and the diagnosis of low-grade, indolent cancer. While guided biopsies with multiparametric MRI can improve the diagnosis of grade 2 prostate cancers, widespread implementation remains challenging. The use of noninvasive biomarkers to stratify the risk for prostate cancer may be a more practical option.

The National Comprehensive Cancer Network proposes a test consisting of six blood and urine biomarkers for all grades of prostate cancer, and it outperforms PSA testing. However, current practice focuses on detecting high-grade cancers. It has been hypothesized that increasing the number of biomarkers by including molecules specifically expressed in aggressive high-grade prostate cancers could improve test accuracy. Based on the identification of new genes that are overexpressed in high-grade cancers, a polymerase chain reaction (PCR) technique targeting 54 candidate markers was used to develop an optimal 18-gene test that could be used before imaging (with MRI) and biopsy and to assess whether the latter procedures are warranted.
 

Development Cohort

In the development cohort (n = 815; median age, 63 years), quantitative PCR (qPCR) analysis of the 54 candidate genes was performed on urine samples that had been prospectively collected before biopsy following a digital rectal examination. Patients with previously diagnosed prostate cancer, abnormal MRI results, and those who had already undergone a prostate biopsy were excluded. Participants’ PSA levels ranged from 3 to 10 ng/mL (median interquartile range [IQR], 5.6 [4.6-7.2] ng/mL). Valid qPCR results were obtained from 761 participants (93.4%). Subsequently, prostate biopsy revealed grade 2 or higher cancer in 293 participants (38.5%).

Thus, a urine test called MyProstateScore 2.0 (MPSA) was developed, with two formulations: MPSA2 and MPSA2+, depending on whether a prostate volume was considered. The final MPSA2 development model included clinical data and 17 of the most informative markers, including nine specific to cancer, which were associated with the KLK3 reference gene.
 

Validation and Analyses

The external validation cohort (n = 813) consisted of participants in the NCI EDRN PCA3 Evaluation trial. Valid qPCR results were obtained from 743 participants, of whom 151 (20.3%) were found to have high-grade prostate cancer.

The median MPS2 score was higher in patients with grade 2 or higher prostate cancer (0.44; IQR, 0.23-0.69) than in those with noncontributory biopsies (0.08; IQR, 0.03-0.19; P < .001) or grade 1 cancer (0.25; IQR, 0.09-0.48; P < .01).

Comparative analyses included PSA, the Prostate Cancer Prevention Trial risk calculator, the Prostate Health Index (PHI), and various previous genetic models. Decision curve analyses quantified the benefit of each biomarker studied. The 151 participants with high-grade prostate cancer had operating curve values ranging from 0.60 for PSA alone to 0.77 for PHI and 0.76 for a two-gene multiplex model. The MPSA model had values of 0.81 and 0.82 for MPSA2+. For a required sensitivity of 95%, the MPS2 model could reduce the rate of unnecessary initial biopsies in the population by 35%-42%, with an impact of 15%-30% for other tests. Among the subgroups analyzed, MPS2 models showed negative predictive values of 95%-99% for grade 2 or higher prostate cancers and 99% for grade 3 or higher tumors.
 

MPS2 and Competitors

Existing biomarkers have reduced selectivity in detecting high-grade prostate tumors. This lower performance has led to the development of a new urine test including, for the first time, markers specifically overexpressed in high-grade prostate cancer. This new MPS2 test has a sensitivity of 95% for high-grade prostate cancer and a specificity ranging from 35% to 51%, depending on the subgroups. For clinicians, widespread use of MPS2 could greatly reduce the number of unnecessary biopsies while maintaining a high detection rate of grade 2 or higher prostate cancer.

Among patients who have had a negative first biopsy, MPS2 would have a sensitivity of 94.4% and a specificity of 51%, which is much higher than other tests like prostate cancer antigen 3 gene, three-gene model, and MPS. In addition, in patients with grade 1 prostate cancer, urinary markers for high-grade cancer could indicate the existence of a more aggressive tumor requiring increased monitoring.

This study has limitations, however. The ethnic diversity of its population was limited. A few Black men were included, for example. Second, a systematic biopsy was used as the reference, which can increase negative predictive value and decrease positive predictive value. Classification errors may have occurred. Therefore, further studies are needed to confirm these initial results and the long-term positive impact of using MPS2.

In conclusion, an 18-gene urine test seems to be more relevant for diagnosing high-grade prostate cancer than existing tests. It could prevent additional imaging or biopsy examinations in 35%-41% of patients. Therefore, the use of such tests in patients with high PSA levels could reduce the potential risks associated with prostate cancer screening while preserving its long-term benefits.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Avoiding the use of antianaerobic antibiotics for empiric treatment of patients with sepsis can prevent depletion of beneficial bacteria in the gut microbiome and reduce both organ dysfunction and in-hospital mortality, a critical care specialists contends.

“You may not be personally moved by a 2- to 5-percent absolute difference in mortality, but sepsis is so common and so lethal that even small differences in outcomes can actually translate into enormous public health implications,” said Robert P. Dickson, MD a pulmonary and critical care specialist at the University of Michigan in Ann Arbor.

Neil Osterweil/MDedge News

If instead of prescribing piperacillin-tazobactam (Zosyn; pip-tazo) for sepsis critical care specialists were to switch to cefepime “even if you make very conservative assumptions like a modest effect size, you’re still talking about [saving] thousands of lives a year,” he said in a scientific symposium at the American Thoracic Society’s international conference.

“This is why I say this isn’t really over the horizon; this is microbiome modulation that’s happening all the time,” he said.

Most patients with sepsis in a medical ICU with respiratory, urinary or bloodstream sources of infection do not have indications for antianaerobic antibiotics, and there are no head-to-head clinical trials demonstrating a benefit for one anti-sepsis antibiotic strategy over another he said.

“In contrast, every observational study between antianaerobic and non-antianaerobic shows benefits to the anaerobe-sparing [drugs], and it’s been shown with animal models too. So to my mind, it’s already practice changing. I need to be talked into giving antianaerobic antibiotics for septic patients” he said.
 

Targeting gut microbiota

There are three basic approaches to focusing on the gut microbiome as a therapeutic target. The hardest is attempting to engineer an ecosystem — a fiendishly complex task with unpredictable results that has never been shown to work in either the gut or in the ICU, Dr. Dickson said.

A second approach, the use of probiotics to repopulate the gut with beneficial bacteria, is largely futile in the ICU, as the large majority of patients are on antibiotics and can’t be safely weaned off of them while in critical care. In this situation, giving probiotics would be akin to try to repopulate a forest while a forest fire is raging, he said.

The third and easiest approach is to minimize dysbiosis — imbalance of organisms in the gut — in the first place.

Anaerobic bacteria in the gut have been shown in several different disease states and animals models to be protective against pneumonia, organ failure, and death.

To see whether antianaerobic antibiotics could increase risk for adverse outcomes in the ICU, Dr. Dickson and colleagues previously conducted a retrospective study of 3032 mechanically ventilated patients in their center who received antibiotics either with or without anaerobic coverage in the first 72 hours.

They found that patients treated with early antianaerobic antibiotics had decreased ventilator-associated pneumonia-free survival (hazard ratio [HR] 1.24), infection-free survival (HR 1.22), and overall survival (HR 1.14) compared with patients who received antibiotics without anaerobic cover (all comparisons statistically significant by confidence intervals).

In a subcohort of 116 patients for whom gut microbiota data compositions were available, those who received antianaerobic antibiotics had decreased initial gut bacterial density (P = .00038), increased microbiome expansion during hospitalization (P = .011), and domination of the microbiome by Enterobacteriaceae species (P = .045). They also found that Enterobacteriaceae were enriched among respiratory pathogens in antianaerobic treated patients, and that in murine models, treatment with antianaerobic antibiotics increased susceptibility to Enterobacteriaceae pneumonia and increased the risk of death from non-infectious injuries.
 

Pip-tazo vs. cefepime

In the ACORN (Antibiotic Choice on Renal Outcomes) trial, results of which were reported by this news organization in November 2023, there were no differences in the highest stage of acute kidney injury or death in the first 14 days between piperacillin-tazobactam and cefepime. Remarking on the results, lead investigator Edward T. Qian, MD, MSc from Vanderbilt University in Nashville, Tennessee, said “I think the big takeaway is that you should feel comfortable starting or using pip-tazo for your patients who are coming into the hospital and receiving empiric antibiotics for acute infection.”

But as Dr. Dickson’s group reported more recently in JAMA Internal Medicine, a 15-month pip-tazo shortage allowed the investigators to conduct a natural experiment comparing 90-day outcomes among 7569 patients with sepsis who received vancomycin plus either pip-tazo or cefepime.

They found in an instrumental variable analysis that piperacillin-tazobactam was associated with an absolute increase in mortality at 90 days of 5.0%, and that patients who received this antianaerobic antibiotic had 2.1 fewer organ failure–free days, 1.1 fewer ventilator-free days, and 1.5 fewer vasopressor-free days.

“Our study reveals the potential risks associated with empirical piperacillin-tazobactam in patients with sepsis without a specific indication for antianaerobic therapy. These findings should prompt reconsideration and further study of the widespread use of empirical antianaerobic antibiotics in sepsis,” the investigators concluded.
 

Who gets what?

In the question-and-answer at the end of the session, comoderator Christina Sarah Thornton, MD, PhD, FRCPC from the University of Calgary, Alberta, asked Dr. Dickson whether the question of antianaerobic overuse in the ICU “is a function that we aren’t able yet from a diagnostic perspective to identify the group that may need antianaerobes? Because we often don’t get culture data back in time for a critically ill patient. Do you think there could maybe be a more rapid diagnostic for these patients?”

He replied that “a lot of our problems would be solved if we had really good, reliable rapid diagnostics for infection,” but noted that most of the patients in the study mentioned above did not have indications for antianaerobics.

Asked by this reporter whether Dr. Dickson’s presentation changed her mind about the use of piperacillin-tazobactam in her patients, Dr. Thornton replied “Yes! It did for me.”

She noted that although in Canada respirologists don’t work in intensive care units, “it makes me wonder about just giving pip-tazo to patients that are really sick. It definitely changed my mind.”

The work of Dr. Dickson and colleagues is supported by National Institute of Health and Agency for Healthcare Research and Quality grants. He reported no other relevant disclosures. Dr. Thornton had no relevant disclosures.

SAN DIEGO — Avoiding the use of antianaerobic antibiotics for empiric treatment of patients with sepsis can prevent depletion of beneficial bacteria in the gut microbiome and reduce both organ dysfunction and in-hospital mortality, a critical care specialists contends.

“You may not be personally moved by a 2- to 5-percent absolute difference in mortality, but sepsis is so common and so lethal that even small differences in outcomes can actually translate into enormous public health implications,” said Robert P. Dickson, MD a pulmonary and critical care specialist at the University of Michigan in Ann Arbor.

Neil Osterweil/MDedge News

If instead of prescribing piperacillin-tazobactam (Zosyn; pip-tazo) for sepsis critical care specialists were to switch to cefepime “even if you make very conservative assumptions like a modest effect size, you’re still talking about [saving] thousands of lives a year,” he said in a scientific symposium at the American Thoracic Society’s international conference.

“This is why I say this isn’t really over the horizon; this is microbiome modulation that’s happening all the time,” he said.

Most patients with sepsis in a medical ICU with respiratory, urinary or bloodstream sources of infection do not have indications for antianaerobic antibiotics, and there are no head-to-head clinical trials demonstrating a benefit for one anti-sepsis antibiotic strategy over another he said.

“In contrast, every observational study between antianaerobic and non-antianaerobic shows benefits to the anaerobe-sparing [drugs], and it’s been shown with animal models too. So to my mind, it’s already practice changing. I need to be talked into giving antianaerobic antibiotics for septic patients” he said.
 

Targeting gut microbiota

There are three basic approaches to focusing on the gut microbiome as a therapeutic target. The hardest is attempting to engineer an ecosystem — a fiendishly complex task with unpredictable results that has never been shown to work in either the gut or in the ICU, Dr. Dickson said.

A second approach, the use of probiotics to repopulate the gut with beneficial bacteria, is largely futile in the ICU, as the large majority of patients are on antibiotics and can’t be safely weaned off of them while in critical care. In this situation, giving probiotics would be akin to try to repopulate a forest while a forest fire is raging, he said.

The third and easiest approach is to minimize dysbiosis — imbalance of organisms in the gut — in the first place.

Anaerobic bacteria in the gut have been shown in several different disease states and animals models to be protective against pneumonia, organ failure, and death.

To see whether antianaerobic antibiotics could increase risk for adverse outcomes in the ICU, Dr. Dickson and colleagues previously conducted a retrospective study of 3032 mechanically ventilated patients in their center who received antibiotics either with or without anaerobic coverage in the first 72 hours.

They found that patients treated with early antianaerobic antibiotics had decreased ventilator-associated pneumonia-free survival (hazard ratio [HR] 1.24), infection-free survival (HR 1.22), and overall survival (HR 1.14) compared with patients who received antibiotics without anaerobic cover (all comparisons statistically significant by confidence intervals).

In a subcohort of 116 patients for whom gut microbiota data compositions were available, those who received antianaerobic antibiotics had decreased initial gut bacterial density (P = .00038), increased microbiome expansion during hospitalization (P = .011), and domination of the microbiome by Enterobacteriaceae species (P = .045). They also found that Enterobacteriaceae were enriched among respiratory pathogens in antianaerobic treated patients, and that in murine models, treatment with antianaerobic antibiotics increased susceptibility to Enterobacteriaceae pneumonia and increased the risk of death from non-infectious injuries.
 

Pip-tazo vs. cefepime

In the ACORN (Antibiotic Choice on Renal Outcomes) trial, results of which were reported by this news organization in November 2023, there were no differences in the highest stage of acute kidney injury or death in the first 14 days between piperacillin-tazobactam and cefepime. Remarking on the results, lead investigator Edward T. Qian, MD, MSc from Vanderbilt University in Nashville, Tennessee, said “I think the big takeaway is that you should feel comfortable starting or using pip-tazo for your patients who are coming into the hospital and receiving empiric antibiotics for acute infection.”

But as Dr. Dickson’s group reported more recently in JAMA Internal Medicine, a 15-month pip-tazo shortage allowed the investigators to conduct a natural experiment comparing 90-day outcomes among 7569 patients with sepsis who received vancomycin plus either pip-tazo or cefepime.

They found in an instrumental variable analysis that piperacillin-tazobactam was associated with an absolute increase in mortality at 90 days of 5.0%, and that patients who received this antianaerobic antibiotic had 2.1 fewer organ failure–free days, 1.1 fewer ventilator-free days, and 1.5 fewer vasopressor-free days.

“Our study reveals the potential risks associated with empirical piperacillin-tazobactam in patients with sepsis without a specific indication for antianaerobic therapy. These findings should prompt reconsideration and further study of the widespread use of empirical antianaerobic antibiotics in sepsis,” the investigators concluded.
 

Who gets what?

In the question-and-answer at the end of the session, comoderator Christina Sarah Thornton, MD, PhD, FRCPC from the University of Calgary, Alberta, asked Dr. Dickson whether the question of antianaerobic overuse in the ICU “is a function that we aren’t able yet from a diagnostic perspective to identify the group that may need antianaerobes? Because we often don’t get culture data back in time for a critically ill patient. Do you think there could maybe be a more rapid diagnostic for these patients?”

He replied that “a lot of our problems would be solved if we had really good, reliable rapid diagnostics for infection,” but noted that most of the patients in the study mentioned above did not have indications for antianaerobics.

Asked by this reporter whether Dr. Dickson’s presentation changed her mind about the use of piperacillin-tazobactam in her patients, Dr. Thornton replied “Yes! It did for me.”

She noted that although in Canada respirologists don’t work in intensive care units, “it makes me wonder about just giving pip-tazo to patients that are really sick. It definitely changed my mind.”

The work of Dr. Dickson and colleagues is supported by National Institute of Health and Agency for Healthcare Research and Quality grants. He reported no other relevant disclosures. Dr. Thornton had no relevant disclosures.

SAN DIEGO — Avoiding the use of antianaerobic antibiotics for empiric treatment of patients with sepsis can prevent depletion of beneficial bacteria in the gut microbiome and reduce both organ dysfunction and in-hospital mortality, a critical care specialists contends.

“You may not be personally moved by a 2- to 5-percent absolute difference in mortality, but sepsis is so common and so lethal that even small differences in outcomes can actually translate into enormous public health implications,” said Robert P. Dickson, MD a pulmonary and critical care specialist at the University of Michigan in Ann Arbor.

Neil Osterweil/MDedge News

If instead of prescribing piperacillin-tazobactam (Zosyn; pip-tazo) for sepsis critical care specialists were to switch to cefepime “even if you make very conservative assumptions like a modest effect size, you’re still talking about [saving] thousands of lives a year,” he said in a scientific symposium at the American Thoracic Society’s international conference.

“This is why I say this isn’t really over the horizon; this is microbiome modulation that’s happening all the time,” he said.

Most patients with sepsis in a medical ICU with respiratory, urinary or bloodstream sources of infection do not have indications for antianaerobic antibiotics, and there are no head-to-head clinical trials demonstrating a benefit for one anti-sepsis antibiotic strategy over another he said.

“In contrast, every observational study between antianaerobic and non-antianaerobic shows benefits to the anaerobe-sparing [drugs], and it’s been shown with animal models too. So to my mind, it’s already practice changing. I need to be talked into giving antianaerobic antibiotics for septic patients” he said.
 

Targeting gut microbiota

There are three basic approaches to focusing on the gut microbiome as a therapeutic target. The hardest is attempting to engineer an ecosystem — a fiendishly complex task with unpredictable results that has never been shown to work in either the gut or in the ICU, Dr. Dickson said.

A second approach, the use of probiotics to repopulate the gut with beneficial bacteria, is largely futile in the ICU, as the large majority of patients are on antibiotics and can’t be safely weaned off of them while in critical care. In this situation, giving probiotics would be akin to try to repopulate a forest while a forest fire is raging, he said.

The third and easiest approach is to minimize dysbiosis — imbalance of organisms in the gut — in the first place.

Anaerobic bacteria in the gut have been shown in several different disease states and animals models to be protective against pneumonia, organ failure, and death.

To see whether antianaerobic antibiotics could increase risk for adverse outcomes in the ICU, Dr. Dickson and colleagues previously conducted a retrospective study of 3032 mechanically ventilated patients in their center who received antibiotics either with or without anaerobic coverage in the first 72 hours.

They found that patients treated with early antianaerobic antibiotics had decreased ventilator-associated pneumonia-free survival (hazard ratio [HR] 1.24), infection-free survival (HR 1.22), and overall survival (HR 1.14) compared with patients who received antibiotics without anaerobic cover (all comparisons statistically significant by confidence intervals).

In a subcohort of 116 patients for whom gut microbiota data compositions were available, those who received antianaerobic antibiotics had decreased initial gut bacterial density (P = .00038), increased microbiome expansion during hospitalization (P = .011), and domination of the microbiome by Enterobacteriaceae species (P = .045). They also found that Enterobacteriaceae were enriched among respiratory pathogens in antianaerobic treated patients, and that in murine models, treatment with antianaerobic antibiotics increased susceptibility to Enterobacteriaceae pneumonia and increased the risk of death from non-infectious injuries.
 

Pip-tazo vs. cefepime

In the ACORN (Antibiotic Choice on Renal Outcomes) trial, results of which were reported by this news organization in November 2023, there were no differences in the highest stage of acute kidney injury or death in the first 14 days between piperacillin-tazobactam and cefepime. Remarking on the results, lead investigator Edward T. Qian, MD, MSc from Vanderbilt University in Nashville, Tennessee, said “I think the big takeaway is that you should feel comfortable starting or using pip-tazo for your patients who are coming into the hospital and receiving empiric antibiotics for acute infection.”

But as Dr. Dickson’s group reported more recently in JAMA Internal Medicine, a 15-month pip-tazo shortage allowed the investigators to conduct a natural experiment comparing 90-day outcomes among 7569 patients with sepsis who received vancomycin plus either pip-tazo or cefepime.

They found in an instrumental variable analysis that piperacillin-tazobactam was associated with an absolute increase in mortality at 90 days of 5.0%, and that patients who received this antianaerobic antibiotic had 2.1 fewer organ failure–free days, 1.1 fewer ventilator-free days, and 1.5 fewer vasopressor-free days.

“Our study reveals the potential risks associated with empirical piperacillin-tazobactam in patients with sepsis without a specific indication for antianaerobic therapy. These findings should prompt reconsideration and further study of the widespread use of empirical antianaerobic antibiotics in sepsis,” the investigators concluded.
 

Who gets what?

In the question-and-answer at the end of the session, comoderator Christina Sarah Thornton, MD, PhD, FRCPC from the University of Calgary, Alberta, asked Dr. Dickson whether the question of antianaerobic overuse in the ICU “is a function that we aren’t able yet from a diagnostic perspective to identify the group that may need antianaerobes? Because we often don’t get culture data back in time for a critically ill patient. Do you think there could maybe be a more rapid diagnostic for these patients?”

He replied that “a lot of our problems would be solved if we had really good, reliable rapid diagnostics for infection,” but noted that most of the patients in the study mentioned above did not have indications for antianaerobics.

Asked by this reporter whether Dr. Dickson’s presentation changed her mind about the use of piperacillin-tazobactam in her patients, Dr. Thornton replied “Yes! It did for me.”

She noted that although in Canada respirologists don’t work in intensive care units, “it makes me wonder about just giving pip-tazo to patients that are really sick. It definitely changed my mind.”

The work of Dr. Dickson and colleagues is supported by National Institute of Health and Agency for Healthcare Research and Quality grants. He reported no other relevant disclosures. Dr. Thornton had no relevant disclosures.

About one in six children (17%) between 3 and 17 years have a disability, which may affect their ability to make decisions when they transition to adulthood.

Typically, at age 18, a young adult assumes rights such as the legal right to make medical decisions (including reproductive decisions), and mental health, financial, and education decisions.

The American Academy of Pediatrics (AAP) recently issued a policy statement in Pediatrics to help pediatricians help young people with Intellectual and/or Developmental Disabilities (IDD) and their families with alternative ways to make those decisions if necessary .
 

Several Options in the Continuum

The AAP describes a continuum of decision-making for youth with IDD from fully autonomous decisions to decisions made by an appointed guardian.

Highlighting an array of options is one way this paper is helpful, said Matthew Siegel, MD, chief of clinical enterprise with the Department of Psychiatry & Behavioral Sciences at Boston Children’s Hospital in Massachusetts. “I suspect that for a lot of practitioners what they’re aware of is guardianship or no guardianship.” These authors highlight that the options are more nuanced, he said.

Pediatricians have widely different ideas about what their role should be in facilitating decision-making in the transition period, he said, so this paper helps clarify what advocacy and discussion are needed.

The paper, written by first author Renee M. Turchi, MD, MPH, and colleagues on behalf of the Council on Children with Disabilities’ Committee on Medical Liability and Risk Management, states that, “The goal should always be the least restrictive decision-making that balances autonomy with safety and supports.”
 

One Alternative Is Supported Decision-Making

Supported decision-making is one alternative to guardianship. Authors explain that under that framework, a patient can choose a trusted support person and create an agreement with that person on what kinds of decisions the person needs help with and how much assistance is needed. The individual makes the final decision, not the support person.

Authors explain the benefits of that approach: “Individuals with IDD who use supported decision-making report increased confidence in themselves and their decision-making, improved decision-making skills, increased engagement with their community, and perceived more control of their lives,” the authors wrote.

Another option for people with IDD might be, rather than formally naming a substitute decision-maker, allowing a parent or caregiver access to their electronic health record or allowing that person to have independent discussions with their physician.

With guardianship, also called conservatorship in some states, a court requires clear and convincing evidence that the youth is not competent to make his or her own decisions. The court may order evaluations by many professionals, including pediatricians.
 

State-Specific Legal Information Is Available

Many states have recently enacted laws surrounding supported decision-making and guardianship. The authors reference a national resource center website that details the legislation for each state and points to resources and tools for pediatricians, families, and patients.

“Historically, pediatricians have rarely discussed the legal aspects of transition to adult-oriented services with the youth with IDD and subsequently, their families,” the authors wrote.
 

Discussions Should Start Early

Ideally, the authors wrote, the discussions about what level of supports might be necessary in the transition to adulthood should start at age 12-14 and include the youth, teachers, parents, and the medical team.

That’s earlier than some of the previous guidance, Dr. Siegel said, and it will be important to evaluate future evidence on the best age to start planning “both from a cognitive development standpoint and from a practicality standpoint.”

The authors point out that the needs for level of support may change and “pediatricians can reevaluate the decision-making arrangement as part of the annual physical/mental examinations to align with the youth’s desires, needs, and decision-making abilities over time.”

The authors and Dr. Siegel report no relevant financial relationships.

About one in six children (17%) between 3 and 17 years have a disability, which may affect their ability to make decisions when they transition to adulthood.

Typically, at age 18, a young adult assumes rights such as the legal right to make medical decisions (including reproductive decisions), and mental health, financial, and education decisions.

The American Academy of Pediatrics (AAP) recently issued a policy statement in Pediatrics to help pediatricians help young people with Intellectual and/or Developmental Disabilities (IDD) and their families with alternative ways to make those decisions if necessary .
 

Several Options in the Continuum

The AAP describes a continuum of decision-making for youth with IDD from fully autonomous decisions to decisions made by an appointed guardian.

Highlighting an array of options is one way this paper is helpful, said Matthew Siegel, MD, chief of clinical enterprise with the Department of Psychiatry & Behavioral Sciences at Boston Children’s Hospital in Massachusetts. “I suspect that for a lot of practitioners what they’re aware of is guardianship or no guardianship.” These authors highlight that the options are more nuanced, he said.

Pediatricians have widely different ideas about what their role should be in facilitating decision-making in the transition period, he said, so this paper helps clarify what advocacy and discussion are needed.

The paper, written by first author Renee M. Turchi, MD, MPH, and colleagues on behalf of the Council on Children with Disabilities’ Committee on Medical Liability and Risk Management, states that, “The goal should always be the least restrictive decision-making that balances autonomy with safety and supports.”
 

One Alternative Is Supported Decision-Making

Supported decision-making is one alternative to guardianship. Authors explain that under that framework, a patient can choose a trusted support person and create an agreement with that person on what kinds of decisions the person needs help with and how much assistance is needed. The individual makes the final decision, not the support person.

Authors explain the benefits of that approach: “Individuals with IDD who use supported decision-making report increased confidence in themselves and their decision-making, improved decision-making skills, increased engagement with their community, and perceived more control of their lives,” the authors wrote.

Another option for people with IDD might be, rather than formally naming a substitute decision-maker, allowing a parent or caregiver access to their electronic health record or allowing that person to have independent discussions with their physician.

With guardianship, also called conservatorship in some states, a court requires clear and convincing evidence that the youth is not competent to make his or her own decisions. The court may order evaluations by many professionals, including pediatricians.
 

State-Specific Legal Information Is Available

Many states have recently enacted laws surrounding supported decision-making and guardianship. The authors reference a national resource center website that details the legislation for each state and points to resources and tools for pediatricians, families, and patients.

“Historically, pediatricians have rarely discussed the legal aspects of transition to adult-oriented services with the youth with IDD and subsequently, their families,” the authors wrote.
 

Discussions Should Start Early

Ideally, the authors wrote, the discussions about what level of supports might be necessary in the transition to adulthood should start at age 12-14 and include the youth, teachers, parents, and the medical team.

That’s earlier than some of the previous guidance, Dr. Siegel said, and it will be important to evaluate future evidence on the best age to start planning “both from a cognitive development standpoint and from a practicality standpoint.”

The authors point out that the needs for level of support may change and “pediatricians can reevaluate the decision-making arrangement as part of the annual physical/mental examinations to align with the youth’s desires, needs, and decision-making abilities over time.”

The authors and Dr. Siegel report no relevant financial relationships.

About one in six children (17%) between 3 and 17 years have a disability, which may affect their ability to make decisions when they transition to adulthood.

Typically, at age 18, a young adult assumes rights such as the legal right to make medical decisions (including reproductive decisions), and mental health, financial, and education decisions.

The American Academy of Pediatrics (AAP) recently issued a policy statement in Pediatrics to help pediatricians help young people with Intellectual and/or Developmental Disabilities (IDD) and their families with alternative ways to make those decisions if necessary .
 

Several Options in the Continuum

The AAP describes a continuum of decision-making for youth with IDD from fully autonomous decisions to decisions made by an appointed guardian.

Highlighting an array of options is one way this paper is helpful, said Matthew Siegel, MD, chief of clinical enterprise with the Department of Psychiatry & Behavioral Sciences at Boston Children’s Hospital in Massachusetts. “I suspect that for a lot of practitioners what they’re aware of is guardianship or no guardianship.” These authors highlight that the options are more nuanced, he said.

Pediatricians have widely different ideas about what their role should be in facilitating decision-making in the transition period, he said, so this paper helps clarify what advocacy and discussion are needed.

The paper, written by first author Renee M. Turchi, MD, MPH, and colleagues on behalf of the Council on Children with Disabilities’ Committee on Medical Liability and Risk Management, states that, “The goal should always be the least restrictive decision-making that balances autonomy with safety and supports.”
 

One Alternative Is Supported Decision-Making

Supported decision-making is one alternative to guardianship. Authors explain that under that framework, a patient can choose a trusted support person and create an agreement with that person on what kinds of decisions the person needs help with and how much assistance is needed. The individual makes the final decision, not the support person.

Authors explain the benefits of that approach: “Individuals with IDD who use supported decision-making report increased confidence in themselves and their decision-making, improved decision-making skills, increased engagement with their community, and perceived more control of their lives,” the authors wrote.

Another option for people with IDD might be, rather than formally naming a substitute decision-maker, allowing a parent or caregiver access to their electronic health record or allowing that person to have independent discussions with their physician.

With guardianship, also called conservatorship in some states, a court requires clear and convincing evidence that the youth is not competent to make his or her own decisions. The court may order evaluations by many professionals, including pediatricians.
 

State-Specific Legal Information Is Available

Many states have recently enacted laws surrounding supported decision-making and guardianship. The authors reference a national resource center website that details the legislation for each state and points to resources and tools for pediatricians, families, and patients.

“Historically, pediatricians have rarely discussed the legal aspects of transition to adult-oriented services with the youth with IDD and subsequently, their families,” the authors wrote.
 

Discussions Should Start Early

Ideally, the authors wrote, the discussions about what level of supports might be necessary in the transition to adulthood should start at age 12-14 and include the youth, teachers, parents, and the medical team.

That’s earlier than some of the previous guidance, Dr. Siegel said, and it will be important to evaluate future evidence on the best age to start planning “both from a cognitive development standpoint and from a practicality standpoint.”

The authors point out that the needs for level of support may change and “pediatricians can reevaluate the decision-making arrangement as part of the annual physical/mental examinations to align with the youth’s desires, needs, and decision-making abilities over time.”

The authors and Dr. Siegel report no relevant financial relationships.

Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.

“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.

Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
 

Little Consensus on Statins for This Age Group

Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.

Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.

Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.

Risk Reduction Seen in Both Senior Groups

Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.

In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.

Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.

One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.

Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”

Numbers Needed to Treat Are Strikingly Low

He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.

The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”

For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”

Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.

He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.

Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.

“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.

“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”

The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.

Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.

“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.

Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
 

Little Consensus on Statins for This Age Group

Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.

Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.

Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.

Risk Reduction Seen in Both Senior Groups

Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.

In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.

Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.

One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.

Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”

Numbers Needed to Treat Are Strikingly Low

He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.

The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”

For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”

Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.

He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.

Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.

“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.

“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”

The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.

Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.

“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.

Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
 

Little Consensus on Statins for This Age Group

Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.

Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.

Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.

Risk Reduction Seen in Both Senior Groups

Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.

In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.

Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.

One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.

Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”

Numbers Needed to Treat Are Strikingly Low

He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.

The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”

For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”

Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.

He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.

Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.

“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.

“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”

The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.

Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.

A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.

This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.¹

A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.

A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:

• •diphenhydramine (intravenous);
• •trimethobenzamide (intramuscular);
• •granisetron (intravenous);
• •valproate (intravenous);
• •neuroleptics (intravenous):
  • ◦prochlorperazine,
  • ◦chlorpromazine,
  • ◦haloperidol,
  • ◦droperidol,
  • ◦methotrimeprazine; and
• •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
• •ketorolac (intravenous); and
• •magnesium sulfate (intravenous).

Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.

According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.² With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.

Additional References

1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source

2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source

Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.

A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.

This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.¹

A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.

A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:

• •diphenhydramine (intravenous);
• •trimethobenzamide (intramuscular);
• •granisetron (intravenous);
• •valproate (intravenous);
• •neuroleptics (intravenous):
  • ◦prochlorperazine,
  • ◦chlorpromazine,
  • ◦haloperidol,
  • ◦droperidol,
  • ◦methotrimeprazine; and
• •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
• •ketorolac (intravenous); and
• •magnesium sulfate (intravenous).

Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.

According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.² With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.

Additional References

1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source

2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source

Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.

A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.

This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.¹

A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.

A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:

• •diphenhydramine (intravenous);
• •trimethobenzamide (intramuscular);
• •granisetron (intravenous);
• •valproate (intravenous);
• •neuroleptics (intravenous):
  • ◦prochlorperazine,
  • ◦chlorpromazine,
  • ◦haloperidol,
  • ◦droperidol,
  • ◦methotrimeprazine; and
• •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
• •ketorolac (intravenous); and
• •magnesium sulfate (intravenous).

Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.

According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.² With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.

Additional References

1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source

2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source