Clinician Reviews

Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.

Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).

Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.

Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.

In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.

“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.

Other recent research has highlighted two promising non-peptide compounds, TTOAD2 and orforglipron. “These are synthetic, and we were interested in finding natural alternatives,” she added.
 

Natural Versions of Compounds That Activate GLP-1Rs

Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.

Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.

“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.

Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”

“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”

Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.

Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).

Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.

Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.

In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.

“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.

Other recent research has highlighted two promising non-peptide compounds, TTOAD2 and orforglipron. “These are synthetic, and we were interested in finding natural alternatives,” she added.
 

Natural Versions of Compounds That Activate GLP-1Rs

Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.

Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.

“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.

Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”

“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”

Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.

Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).

Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.

Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.

In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.

“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.

Other recent research has highlighted two promising non-peptide compounds, TTOAD2 and orforglipron. “These are synthetic, and we were interested in finding natural alternatives,” she added.
 

Natural Versions of Compounds That Activate GLP-1Rs

Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.

Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.

“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.

Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”

“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”

Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.

A version of this article appeared on Medscape.com.

As your patient’s scheduled bedtime is approaching, they begin to worry another restless night is looming. Could magnesium oil spray actually help them sleep? Some — even doctors — are sharing testimonials about how this simple tactic transformed their sleep quality. Experts suggest some sleep improvement is possible, though it does not negate the need for treatment, and should not be used in patients with cardiovascular disease.

Take Daniel Barrett, MD, a board-certified plastic surgeon and owner of Barrett Plastic Surgery in Beverly Hills, as an example. He decided to test whether magnesium oil could indeed give him a sleepy sensation and shared his experience. Dr. Barrett sprayed magnesium oil on his feet — until they felt “slippery and wet,” he said — and put his socks back on. (He said magnesium is absorbed more easily through the skin. Putting it on the skin helps this mineral get into the lymphatics and circulatory system, offering a way to get a higher concentration of magnesium in the bloodstream. The pores on the feet are also said to be the largest on the body, making them an ideal place for absorption.) 

“My central nervous system had calmed down a bit — it’s similar to what I feel when I take oral magnesium as well. It took about 15 minutes to feel the effect,” Dr. Barrett said.

Research shows that magnesium blocks N-methyl-D-aspartate (a receptor that can hinder sleep) and stimulates gamma-aminobutyric acid (a receptor that can promote good sleep), said Dennis Auckley, MD, director of MetroHealth’s Center for Sleep Medicine. And studies looking at the effects of oral magnesium have shown that taking it may be linked to better self-reported sleep quality and less daytime sleepiness, he said. But traditional magnesium supplements taken orally can sometimes come with side effects in your gut, so putting magnesium on the skin could help to avoid this. 

Magnesium oil on the feet could also help with certain sleep disturbances, such as nocturnal leg cramps and restless legs syndrome, said Sam Kashani, MD, a sleep medicine specialist and assistant clinical professor at UCLA Medical School. (Nocturnal leg cramps – one of the most common secondary factors of insomnia and sleep disturbances in older adults – includes sudden, painful contractions in the lower leg muscles while sleeping. Restless legs syndrome, on the other hand, is like nocturnal leg cramps, but minus the painful contractions, said Dr. Kashani.) 

“Magnesium is a mineral that does have some benefit with regard to reducing the muscle tightness and promoting a little bit more of relaxation of the muscles,” Dr. Kashani said. “This [magnesium oil on your soles] could be beneficial for these types of sleep problems.” 

Still, sleep medicine experts stressed that putting magnesium oil on your feet should not be viewed a cure-all for sleep troubles. 

“High-quality scientific evidence supporting magnesium as a sleep remedy is severely limited,” said Emerson Wickwire, PhD, an American Academy of Sleep Medicine spokesperson and section head of sleep medicine at the University of Maryland Medical School. “Certainly, magnesium is not supported as a treatment for sleep disorders.” 

If your patients plan to use magnesium oil on their feet to help them sleep, make sure they carefully follow the directions to make sure they are taking the proper dosage. Most importantly, patients with a history of cardiovascular complications, or issues with the heart and blood vessels should consult their doctor. 

“Magnesium is an electrolyte that has multiple roles and functions in the body, including within our cardiovascular system,” Dr. Kashani said. “So, if you are somebody who has heart troubles, you definitely want to talk to your primary doctor about any kind of supplements that you are taking, including magnesium.”
 

A version of this article appeared on WebMD.com.

As your patient’s scheduled bedtime is approaching, they begin to worry another restless night is looming. Could magnesium oil spray actually help them sleep? Some — even doctors — are sharing testimonials about how this simple tactic transformed their sleep quality. Experts suggest some sleep improvement is possible, though it does not negate the need for treatment, and should not be used in patients with cardiovascular disease.

Take Daniel Barrett, MD, a board-certified plastic surgeon and owner of Barrett Plastic Surgery in Beverly Hills, as an example. He decided to test whether magnesium oil could indeed give him a sleepy sensation and shared his experience. Dr. Barrett sprayed magnesium oil on his feet — until they felt “slippery and wet,” he said — and put his socks back on. (He said magnesium is absorbed more easily through the skin. Putting it on the skin helps this mineral get into the lymphatics and circulatory system, offering a way to get a higher concentration of magnesium in the bloodstream. The pores on the feet are also said to be the largest on the body, making them an ideal place for absorption.) 

“My central nervous system had calmed down a bit — it’s similar to what I feel when I take oral magnesium as well. It took about 15 minutes to feel the effect,” Dr. Barrett said.

Research shows that magnesium blocks N-methyl-D-aspartate (a receptor that can hinder sleep) and stimulates gamma-aminobutyric acid (a receptor that can promote good sleep), said Dennis Auckley, MD, director of MetroHealth’s Center for Sleep Medicine. And studies looking at the effects of oral magnesium have shown that taking it may be linked to better self-reported sleep quality and less daytime sleepiness, he said. But traditional magnesium supplements taken orally can sometimes come with side effects in your gut, so putting magnesium on the skin could help to avoid this. 

Magnesium oil on the feet could also help with certain sleep disturbances, such as nocturnal leg cramps and restless legs syndrome, said Sam Kashani, MD, a sleep medicine specialist and assistant clinical professor at UCLA Medical School. (Nocturnal leg cramps – one of the most common secondary factors of insomnia and sleep disturbances in older adults – includes sudden, painful contractions in the lower leg muscles while sleeping. Restless legs syndrome, on the other hand, is like nocturnal leg cramps, but minus the painful contractions, said Dr. Kashani.) 

“Magnesium is a mineral that does have some benefit with regard to reducing the muscle tightness and promoting a little bit more of relaxation of the muscles,” Dr. Kashani said. “This [magnesium oil on your soles] could be beneficial for these types of sleep problems.” 

Still, sleep medicine experts stressed that putting magnesium oil on your feet should not be viewed a cure-all for sleep troubles. 

“High-quality scientific evidence supporting magnesium as a sleep remedy is severely limited,” said Emerson Wickwire, PhD, an American Academy of Sleep Medicine spokesperson and section head of sleep medicine at the University of Maryland Medical School. “Certainly, magnesium is not supported as a treatment for sleep disorders.” 

If your patients plan to use magnesium oil on their feet to help them sleep, make sure they carefully follow the directions to make sure they are taking the proper dosage. Most importantly, patients with a history of cardiovascular complications, or issues with the heart and blood vessels should consult their doctor. 

“Magnesium is an electrolyte that has multiple roles and functions in the body, including within our cardiovascular system,” Dr. Kashani said. “So, if you are somebody who has heart troubles, you definitely want to talk to your primary doctor about any kind of supplements that you are taking, including magnesium.”
 

A version of this article appeared on WebMD.com.

As your patient’s scheduled bedtime is approaching, they begin to worry another restless night is looming. Could magnesium oil spray actually help them sleep? Some — even doctors — are sharing testimonials about how this simple tactic transformed their sleep quality. Experts suggest some sleep improvement is possible, though it does not negate the need for treatment, and should not be used in patients with cardiovascular disease.

Take Daniel Barrett, MD, a board-certified plastic surgeon and owner of Barrett Plastic Surgery in Beverly Hills, as an example. He decided to test whether magnesium oil could indeed give him a sleepy sensation and shared his experience. Dr. Barrett sprayed magnesium oil on his feet — until they felt “slippery and wet,” he said — and put his socks back on. (He said magnesium is absorbed more easily through the skin. Putting it on the skin helps this mineral get into the lymphatics and circulatory system, offering a way to get a higher concentration of magnesium in the bloodstream. The pores on the feet are also said to be the largest on the body, making them an ideal place for absorption.) 

“My central nervous system had calmed down a bit — it’s similar to what I feel when I take oral magnesium as well. It took about 15 minutes to feel the effect,” Dr. Barrett said.

Research shows that magnesium blocks N-methyl-D-aspartate (a receptor that can hinder sleep) and stimulates gamma-aminobutyric acid (a receptor that can promote good sleep), said Dennis Auckley, MD, director of MetroHealth’s Center for Sleep Medicine. And studies looking at the effects of oral magnesium have shown that taking it may be linked to better self-reported sleep quality and less daytime sleepiness, he said. But traditional magnesium supplements taken orally can sometimes come with side effects in your gut, so putting magnesium on the skin could help to avoid this. 

Magnesium oil on the feet could also help with certain sleep disturbances, such as nocturnal leg cramps and restless legs syndrome, said Sam Kashani, MD, a sleep medicine specialist and assistant clinical professor at UCLA Medical School. (Nocturnal leg cramps – one of the most common secondary factors of insomnia and sleep disturbances in older adults – includes sudden, painful contractions in the lower leg muscles while sleeping. Restless legs syndrome, on the other hand, is like nocturnal leg cramps, but minus the painful contractions, said Dr. Kashani.) 

“Magnesium is a mineral that does have some benefit with regard to reducing the muscle tightness and promoting a little bit more of relaxation of the muscles,” Dr. Kashani said. “This [magnesium oil on your soles] could be beneficial for these types of sleep problems.” 

Still, sleep medicine experts stressed that putting magnesium oil on your feet should not be viewed a cure-all for sleep troubles. 

“High-quality scientific evidence supporting magnesium as a sleep remedy is severely limited,” said Emerson Wickwire, PhD, an American Academy of Sleep Medicine spokesperson and section head of sleep medicine at the University of Maryland Medical School. “Certainly, magnesium is not supported as a treatment for sleep disorders.” 

If your patients plan to use magnesium oil on their feet to help them sleep, make sure they carefully follow the directions to make sure they are taking the proper dosage. Most importantly, patients with a history of cardiovascular complications, or issues with the heart and blood vessels should consult their doctor. 

“Magnesium is an electrolyte that has multiple roles and functions in the body, including within our cardiovascular system,” Dr. Kashani said. “So, if you are somebody who has heart troubles, you definitely want to talk to your primary doctor about any kind of supplements that you are taking, including magnesium.”
 

A version of this article appeared on WebMD.com.

TOPLINE:

Patients with sarcopenic obesity (SO) are at a greater risk for earlier death, but screening for muscle function could offer an opportunity for intervention.

METHODOLOGY:

• The proportion of older adults living with high body fat and/or low muscle function and mass has risen in recent years, but sarcopenia and SO are undiagnosed conditions.
• Researchers evaluated 5888 individuals who participated in a population-based cohort study in the Netherlands: Participants were largely of European descent (98%); the mean age of participants was 69.5 years, and 56.8% were female.
• Participants were included if they had available measurements of handgrip strength and had received a dual-energy x-ray absorptiometry scan.
• Sarcopenia was defined by researchers in JAMA Network Open as having low handgrip strength and was confirmed with a low appendicular skeletal muscle mass index; SO was defined as a body mass index (BMI) over 27, having low handgrip strength, a high fat percentage, and/or a low appendicular skeletal muscle index, which were defined as altered body composition (BC).

TAKEAWAY:

• Participants with probable and confirmed sarcopenia had a higher risk for all-cause mortality than those without during the 10-year follow-up period after adjusting for age, sex, and BMI (hazard ratios [HRs], 1.29, 1.93, respectively).
• Participants with SO and one BC component were at a higher risk for all-cause mortality (hazard ratio [HR], 1.94; 95% CI, 1.60-2.33).
• Participants with SO and both components of BC had almost three times the risk for mortality as those without (HR, 2.84; 95% CI, 1.97-4.11).

IN PRACTICE:

“These results suggest that screening for SO might be implemented in primary care. In addition, early nonpharmacologic interventions, such as nutrition and exercise training, should be included to delay the onset of and to treat sarcopenia, especially SO,” the researchers wrote.

SOURCE:

Yves Boirie, MD, PhD, of the Human Nutrition Unit at Université Clermont Auvergne in Clermont-Ferrand, France, is the corresponding author for this study. The study was funded by the Netherlands Organisation for Health Research and Development, the French National Research Agency, and the European Union’s Horizon 2020 research and innovation program, among others.

LIMITATIONS:

The researchers also did not consider specific causes of death. Because the most participants had European ancestry, the results cannot be generalized.

DISCLOSURES:

Various authors report receiving grants from the Agence Nationale de la Recherche and Agencia Estatal de Investigación. Other authors report being members of advisory board panels for Pfizer, Eli Lilly, Novo Nordisk, and Nutricia Research.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with sarcopenic obesity (SO) are at a greater risk for earlier death, but screening for muscle function could offer an opportunity for intervention.

METHODOLOGY:

• The proportion of older adults living with high body fat and/or low muscle function and mass has risen in recent years, but sarcopenia and SO are undiagnosed conditions.
• Researchers evaluated 5888 individuals who participated in a population-based cohort study in the Netherlands: Participants were largely of European descent (98%); the mean age of participants was 69.5 years, and 56.8% were female.
• Participants were included if they had available measurements of handgrip strength and had received a dual-energy x-ray absorptiometry scan.
• Sarcopenia was defined by researchers in JAMA Network Open as having low handgrip strength and was confirmed with a low appendicular skeletal muscle mass index; SO was defined as a body mass index (BMI) over 27, having low handgrip strength, a high fat percentage, and/or a low appendicular skeletal muscle index, which were defined as altered body composition (BC).

TAKEAWAY:

• Participants with probable and confirmed sarcopenia had a higher risk for all-cause mortality than those without during the 10-year follow-up period after adjusting for age, sex, and BMI (hazard ratios [HRs], 1.29, 1.93, respectively).
• Participants with SO and one BC component were at a higher risk for all-cause mortality (hazard ratio [HR], 1.94; 95% CI, 1.60-2.33).
• Participants with SO and both components of BC had almost three times the risk for mortality as those without (HR, 2.84; 95% CI, 1.97-4.11).

IN PRACTICE:

“These results suggest that screening for SO might be implemented in primary care. In addition, early nonpharmacologic interventions, such as nutrition and exercise training, should be included to delay the onset of and to treat sarcopenia, especially SO,” the researchers wrote.

SOURCE:

Yves Boirie, MD, PhD, of the Human Nutrition Unit at Université Clermont Auvergne in Clermont-Ferrand, France, is the corresponding author for this study. The study was funded by the Netherlands Organisation for Health Research and Development, the French National Research Agency, and the European Union’s Horizon 2020 research and innovation program, among others.

LIMITATIONS:

The researchers also did not consider specific causes of death. Because the most participants had European ancestry, the results cannot be generalized.

DISCLOSURES:

Various authors report receiving grants from the Agence Nationale de la Recherche and Agencia Estatal de Investigación. Other authors report being members of advisory board panels for Pfizer, Eli Lilly, Novo Nordisk, and Nutricia Research.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with sarcopenic obesity (SO) are at a greater risk for earlier death, but screening for muscle function could offer an opportunity for intervention.

METHODOLOGY:

• The proportion of older adults living with high body fat and/or low muscle function and mass has risen in recent years, but sarcopenia and SO are undiagnosed conditions.
• Researchers evaluated 5888 individuals who participated in a population-based cohort study in the Netherlands: Participants were largely of European descent (98%); the mean age of participants was 69.5 years, and 56.8% were female.
• Participants were included if they had available measurements of handgrip strength and had received a dual-energy x-ray absorptiometry scan.
• Sarcopenia was defined by researchers in JAMA Network Open as having low handgrip strength and was confirmed with a low appendicular skeletal muscle mass index; SO was defined as a body mass index (BMI) over 27, having low handgrip strength, a high fat percentage, and/or a low appendicular skeletal muscle index, which were defined as altered body composition (BC).

TAKEAWAY:

• Participants with probable and confirmed sarcopenia had a higher risk for all-cause mortality than those without during the 10-year follow-up period after adjusting for age, sex, and BMI (hazard ratios [HRs], 1.29, 1.93, respectively).
• Participants with SO and one BC component were at a higher risk for all-cause mortality (hazard ratio [HR], 1.94; 95% CI, 1.60-2.33).
• Participants with SO and both components of BC had almost three times the risk for mortality as those without (HR, 2.84; 95% CI, 1.97-4.11).

IN PRACTICE:

“These results suggest that screening for SO might be implemented in primary care. In addition, early nonpharmacologic interventions, such as nutrition and exercise training, should be included to delay the onset of and to treat sarcopenia, especially SO,” the researchers wrote.

SOURCE:

Yves Boirie, MD, PhD, of the Human Nutrition Unit at Université Clermont Auvergne in Clermont-Ferrand, France, is the corresponding author for this study. The study was funded by the Netherlands Organisation for Health Research and Development, the French National Research Agency, and the European Union’s Horizon 2020 research and innovation program, among others.

LIMITATIONS:

The researchers also did not consider specific causes of death. Because the most participants had European ancestry, the results cannot be generalized.

DISCLOSURES:

Various authors report receiving grants from the Agence Nationale de la Recherche and Agencia Estatal de Investigación. Other authors report being members of advisory board panels for Pfizer, Eli Lilly, Novo Nordisk, and Nutricia Research.

A version of this article appeared on Medscape.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Long naps of an hour or more, naps in the morning, or regular siestas may increase blood glucose levels in older people with type 2 diabetes (T2D).

METHODOLOGY:

• Napping is common in China and other cultures and may play a role in cardiometabolic health, but previous studies on the relationship between napping and glycemic control in T2D have reported conflicting results.
• In a cross-sectional study, the researchers assessed 226 individuals with T2D (median age, 67 years; about half women; mostly retired) from two community healthcare centers in China between May 2023 and July 2023.
• Using questionnaires, the participants were evaluated for A1c levels, as well as frequency, duration (shorter or longer than 1 hour), timing, and type of napping behavior (restorative for lack of sleep vs appetitive by habit or for enjoyment).
• Multivariate analysis controlled for age, sex, body mass index, T2D treatment regimen, diabetes duration, cognitive impairment, depression, night sleep duration, and insomnia symptoms.

TAKEAWAY:

• Among 180 participants who reported napping, 61 (33.9%) took long naps of 60 minutes and more, 162 (90%) reported afternoon napping, and 131 (72.8%) displayed appetitive napping.
• Restorative napping was linked to lower A1c levels than appetitive napping (β, −0.176; P = 0.028).
• Napping frequency was not associated with A1c levels.

IN PRACTICE:

“In clinical practice, healthcare professionals may offer tips about napping, eg, taking a nap less than an hour, taking a nap in the afternoon instead of in the morning, avoiding appetitive napping,” the authors concluded.

SOURCE:

The study, from corresponding author Bingqian Zhu, PhD, of the Shanghai Jiao Tong University School of Nursing, Shanghai, was published in Frontiers in Endocrinology.

LIMITATIONS:

The participants were older individuals, mostly retired, who may have had less need for restorative napping and more time for appetitive napping, limiting generalizability. The sample size may have been too small to find a link to napping frequency. Self-reported data could introduce recall bias. Only A1c levels were used as a measure of glycemic control.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and other sources. The authors declared no potential conflict of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Long naps of an hour or more, naps in the morning, or regular siestas may increase blood glucose levels in older people with type 2 diabetes (T2D).

METHODOLOGY:

• Napping is common in China and other cultures and may play a role in cardiometabolic health, but previous studies on the relationship between napping and glycemic control in T2D have reported conflicting results.
• In a cross-sectional study, the researchers assessed 226 individuals with T2D (median age, 67 years; about half women; mostly retired) from two community healthcare centers in China between May 2023 and July 2023.
• Using questionnaires, the participants were evaluated for A1c levels, as well as frequency, duration (shorter or longer than 1 hour), timing, and type of napping behavior (restorative for lack of sleep vs appetitive by habit or for enjoyment).
• Multivariate analysis controlled for age, sex, body mass index, T2D treatment regimen, diabetes duration, cognitive impairment, depression, night sleep duration, and insomnia symptoms.

TAKEAWAY:

• Among 180 participants who reported napping, 61 (33.9%) took long naps of 60 minutes and more, 162 (90%) reported afternoon napping, and 131 (72.8%) displayed appetitive napping.
• Restorative napping was linked to lower A1c levels than appetitive napping (β, −0.176; P = 0.028).
• Napping frequency was not associated with A1c levels.

IN PRACTICE:

“In clinical practice, healthcare professionals may offer tips about napping, eg, taking a nap less than an hour, taking a nap in the afternoon instead of in the morning, avoiding appetitive napping,” the authors concluded.

SOURCE:

The study, from corresponding author Bingqian Zhu, PhD, of the Shanghai Jiao Tong University School of Nursing, Shanghai, was published in Frontiers in Endocrinology.

LIMITATIONS:

The participants were older individuals, mostly retired, who may have had less need for restorative napping and more time for appetitive napping, limiting generalizability. The sample size may have been too small to find a link to napping frequency. Self-reported data could introduce recall bias. Only A1c levels were used as a measure of glycemic control.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and other sources. The authors declared no potential conflict of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Long naps of an hour or more, naps in the morning, or regular siestas may increase blood glucose levels in older people with type 2 diabetes (T2D).

METHODOLOGY:

• Napping is common in China and other cultures and may play a role in cardiometabolic health, but previous studies on the relationship between napping and glycemic control in T2D have reported conflicting results.
• In a cross-sectional study, the researchers assessed 226 individuals with T2D (median age, 67 years; about half women; mostly retired) from two community healthcare centers in China between May 2023 and July 2023.
• Using questionnaires, the participants were evaluated for A1c levels, as well as frequency, duration (shorter or longer than 1 hour), timing, and type of napping behavior (restorative for lack of sleep vs appetitive by habit or for enjoyment).
• Multivariate analysis controlled for age, sex, body mass index, T2D treatment regimen, diabetes duration, cognitive impairment, depression, night sleep duration, and insomnia symptoms.

TAKEAWAY:

• Among 180 participants who reported napping, 61 (33.9%) took long naps of 60 minutes and more, 162 (90%) reported afternoon napping, and 131 (72.8%) displayed appetitive napping.
• Restorative napping was linked to lower A1c levels than appetitive napping (β, −0.176; P = 0.028).
• Napping frequency was not associated with A1c levels.

IN PRACTICE:

“In clinical practice, healthcare professionals may offer tips about napping, eg, taking a nap less than an hour, taking a nap in the afternoon instead of in the morning, avoiding appetitive napping,” the authors concluded.

SOURCE:

The study, from corresponding author Bingqian Zhu, PhD, of the Shanghai Jiao Tong University School of Nursing, Shanghai, was published in Frontiers in Endocrinology.

LIMITATIONS:

The participants were older individuals, mostly retired, who may have had less need for restorative napping and more time for appetitive napping, limiting generalizability. The sample size may have been too small to find a link to napping frequency. Self-reported data could introduce recall bias. Only A1c levels were used as a measure of glycemic control.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and other sources. The authors declared no potential conflict of interest.

A version of this article appeared on Medscape.com.

By this summer, state employees in Florida covered by state group health insurance plans should have access to free annual skin cancer screenings.

On March 1, 2024, legislation was unanimously passed by both chambers of the state legislature that will provide for the free screenings for this group as of July 1. Some 321,000 state employees would be eligible, at a cost of about $357,000 per year, according to a legislative analysis. Gov. Ron DeSantis (R) has received and is expected to sign the bill.

The analysis concluded that the bill would have a “significant negative fiscal impact on the state employee group health plan,” as screenings will ultimately reduce cancer incidence and related morbidity and mortality.

The screenings aim to provide access to patients who may think they might not be able to afford a visit or who may have other perceived or real barriers to going for a skin check, said Sima Jain, MD, president of the Florida Academy of Dermatology. “It’s really meant to give patients access who need it,” said Dr. Jain, a dermatologist in private practice in Orlando.

The goal is early detection. “If I do a simple excision on a melanoma and we catch it early, it’s done, it’s cured,” Dr. Jain told this news organization. “It’s a win-win. We catch it early and insurance companies pay less money,” she said.

An effort to have all insurers in the state provide free screenings failed in 2023. 

From 2016 to 2020, Florida had a higher overall incidence of melanoma at 25.4 per 100,000 than the national average of 22.5, according to the National Cancer Institute. The state had some 7500 cases of melanoma each year during that period. The incidence rate in some Florida counties is as high as 32.7-45.6 per 100,000.

The Florida legislation will allow physician assistants and advanced practice nurses who operate under the supervision of a dermatologist to conduct the screenings.

It’s not clear how many state employees will access the free skin checks. “I don’t expect to see a flood of skin cancer screenings,” said Dr. Jain, noting that she hopes that it attracts primarily those at highest risk.

Once the bill is signed by the governor, Florida will be the second state to cover skin cancer screenings in some way. Illinois has required free skin cancer screening for all insured residents since 2020.

A version of this article appeared on Medscape.com .

By this summer, state employees in Florida covered by state group health insurance plans should have access to free annual skin cancer screenings.

On March 1, 2024, legislation was unanimously passed by both chambers of the state legislature that will provide for the free screenings for this group as of July 1. Some 321,000 state employees would be eligible, at a cost of about $357,000 per year, according to a legislative analysis. Gov. Ron DeSantis (R) has received and is expected to sign the bill.

The analysis concluded that the bill would have a “significant negative fiscal impact on the state employee group health plan,” as screenings will ultimately reduce cancer incidence and related morbidity and mortality.

The screenings aim to provide access to patients who may think they might not be able to afford a visit or who may have other perceived or real barriers to going for a skin check, said Sima Jain, MD, president of the Florida Academy of Dermatology. “It’s really meant to give patients access who need it,” said Dr. Jain, a dermatologist in private practice in Orlando.

The goal is early detection. “If I do a simple excision on a melanoma and we catch it early, it’s done, it’s cured,” Dr. Jain told this news organization. “It’s a win-win. We catch it early and insurance companies pay less money,” she said.

An effort to have all insurers in the state provide free screenings failed in 2023. 

From 2016 to 2020, Florida had a higher overall incidence of melanoma at 25.4 per 100,000 than the national average of 22.5, according to the National Cancer Institute. The state had some 7500 cases of melanoma each year during that period. The incidence rate in some Florida counties is as high as 32.7-45.6 per 100,000.

The Florida legislation will allow physician assistants and advanced practice nurses who operate under the supervision of a dermatologist to conduct the screenings.

It’s not clear how many state employees will access the free skin checks. “I don’t expect to see a flood of skin cancer screenings,” said Dr. Jain, noting that she hopes that it attracts primarily those at highest risk.

Once the bill is signed by the governor, Florida will be the second state to cover skin cancer screenings in some way. Illinois has required free skin cancer screening for all insured residents since 2020.

A version of this article appeared on Medscape.com .

By this summer, state employees in Florida covered by state group health insurance plans should have access to free annual skin cancer screenings.

On March 1, 2024, legislation was unanimously passed by both chambers of the state legislature that will provide for the free screenings for this group as of July 1. Some 321,000 state employees would be eligible, at a cost of about $357,000 per year, according to a legislative analysis. Gov. Ron DeSantis (R) has received and is expected to sign the bill.

The analysis concluded that the bill would have a “significant negative fiscal impact on the state employee group health plan,” as screenings will ultimately reduce cancer incidence and related morbidity and mortality.

The screenings aim to provide access to patients who may think they might not be able to afford a visit or who may have other perceived or real barriers to going for a skin check, said Sima Jain, MD, president of the Florida Academy of Dermatology. “It’s really meant to give patients access who need it,” said Dr. Jain, a dermatologist in private practice in Orlando.

The goal is early detection. “If I do a simple excision on a melanoma and we catch it early, it’s done, it’s cured,” Dr. Jain told this news organization. “It’s a win-win. We catch it early and insurance companies pay less money,” she said.

An effort to have all insurers in the state provide free screenings failed in 2023. 

From 2016 to 2020, Florida had a higher overall incidence of melanoma at 25.4 per 100,000 than the national average of 22.5, according to the National Cancer Institute. The state had some 7500 cases of melanoma each year during that period. The incidence rate in some Florida counties is as high as 32.7-45.6 per 100,000.

The Florida legislation will allow physician assistants and advanced practice nurses who operate under the supervision of a dermatologist to conduct the screenings.

It’s not clear how many state employees will access the free skin checks. “I don’t expect to see a flood of skin cancer screenings,” said Dr. Jain, noting that she hopes that it attracts primarily those at highest risk.

Once the bill is signed by the governor, Florida will be the second state to cover skin cancer screenings in some way. Illinois has required free skin cancer screening for all insured residents since 2020.

A version of this article appeared on Medscape.com .

The US Food and Drug Administration (FDA) has approved sotatercept (Winrevair, Merck), for the treatment of adults with pulmonary arterial hypertension (PAH), World Health Organization (WHO) Group 1, to increase exercise capacity, improve WHO functional class, and reduce the risk for clinical worsening events.

Sotatercept, which had breakthrough therapy designation, is a first-in-class activin signaling inhibitor that works by improving the balance between pro- and antiproliferative signaling to regulate the vascular cell proliferation that underlies PAH.

“Sotatercept added to background therapy has the potential to become a new standard-of-care option for patients with pulmonary arterial hypertension,” added coinvestigator Aaron B. Waxman, MD, PhD, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital, Boston.

The approval was based on results of the phase 3 STELLAR study, a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which, 323 patients with PAH (WHO Group 1, functional class II or III) were randomly assigned 1:1 to add sotatercept or placebo to stable background therapy.

The results showed that sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved average 6-minute walk distance from baseline by a significant and clinically meaningful 40.8 meters compared with placebo for the trial’s primary efficacy endpoint (P < .001).

Sotatercept also led to significant improvement in multiple secondary outcome measures, including:

• Reduction in the risk for death from any cause or PAH clinical worsening events by 84% vs background therapy alone (number of events: 9 vs 42; hazard ratio [HR], 0.16; P < .001) 
• Improvement in FC from baseline at 24 weeks in 29% of patients compared with 14% of patients treated with placebo (P < .001) 
• Improvement in pulmonary vascular resistance (PVR), with an average 235 dyn/sec/cm⁵ reduction in PVR from baseline (P < .001) 
• Improvement from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels. The median treatment difference in NT-proBNP between sotatercept and placebo was -442 pg/mL (P < .001) 

The results were reported last year at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, with simultaneous publication in The New England Journal of Medicine. 

Sotatercept injection may be administered by patients or caregivers with guidance, training, and follow-up from a healthcare provider. The recommended starting dose is 0.3 mg/kg. The recommended target dose is 0.7 mg/kg every 3 weeks.

Sotatercept may increase hemoglobin, may lead to erythrocytosis, and may decrease platelet count and lead to severe thrombocytopenia. Treatment should not be initiated if platelet count is < 50,000/mm³. 

Hemoglobin and platelets should be monitored before each dose of sotatercept for the first five doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required. 

Full prescribing information is available online. 

Merck estimates that sotatercept will be available for dispensing by select specialty pharmacies in the United States by the end of April 2024.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved sotatercept (Winrevair, Merck), for the treatment of adults with pulmonary arterial hypertension (PAH), World Health Organization (WHO) Group 1, to increase exercise capacity, improve WHO functional class, and reduce the risk for clinical worsening events.

Sotatercept, which had breakthrough therapy designation, is a first-in-class activin signaling inhibitor that works by improving the balance between pro- and antiproliferative signaling to regulate the vascular cell proliferation that underlies PAH.

“Sotatercept added to background therapy has the potential to become a new standard-of-care option for patients with pulmonary arterial hypertension,” added coinvestigator Aaron B. Waxman, MD, PhD, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital, Boston.

The approval was based on results of the phase 3 STELLAR study, a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which, 323 patients with PAH (WHO Group 1, functional class II or III) were randomly assigned 1:1 to add sotatercept or placebo to stable background therapy.

The results showed that sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved average 6-minute walk distance from baseline by a significant and clinically meaningful 40.8 meters compared with placebo for the trial’s primary efficacy endpoint (P < .001).

Sotatercept also led to significant improvement in multiple secondary outcome measures, including:

• Reduction in the risk for death from any cause or PAH clinical worsening events by 84% vs background therapy alone (number of events: 9 vs 42; hazard ratio [HR], 0.16; P < .001) 
• Improvement in FC from baseline at 24 weeks in 29% of patients compared with 14% of patients treated with placebo (P < .001) 
• Improvement in pulmonary vascular resistance (PVR), with an average 235 dyn/sec/cm⁵ reduction in PVR from baseline (P < .001) 
• Improvement from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels. The median treatment difference in NT-proBNP between sotatercept and placebo was -442 pg/mL (P < .001) 

The results were reported last year at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, with simultaneous publication in The New England Journal of Medicine. 

Sotatercept injection may be administered by patients or caregivers with guidance, training, and follow-up from a healthcare provider. The recommended starting dose is 0.3 mg/kg. The recommended target dose is 0.7 mg/kg every 3 weeks.

Sotatercept may increase hemoglobin, may lead to erythrocytosis, and may decrease platelet count and lead to severe thrombocytopenia. Treatment should not be initiated if platelet count is < 50,000/mm³. 

Hemoglobin and platelets should be monitored before each dose of sotatercept for the first five doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required. 

Full prescribing information is available online. 

Merck estimates that sotatercept will be available for dispensing by select specialty pharmacies in the United States by the end of April 2024.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved sotatercept (Winrevair, Merck), for the treatment of adults with pulmonary arterial hypertension (PAH), World Health Organization (WHO) Group 1, to increase exercise capacity, improve WHO functional class, and reduce the risk for clinical worsening events.

Sotatercept, which had breakthrough therapy designation, is a first-in-class activin signaling inhibitor that works by improving the balance between pro- and antiproliferative signaling to regulate the vascular cell proliferation that underlies PAH.

“Sotatercept added to background therapy has the potential to become a new standard-of-care option for patients with pulmonary arterial hypertension,” added coinvestigator Aaron B. Waxman, MD, PhD, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital, Boston.

The approval was based on results of the phase 3 STELLAR study, a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which, 323 patients with PAH (WHO Group 1, functional class II or III) were randomly assigned 1:1 to add sotatercept or placebo to stable background therapy.

The results showed that sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved average 6-minute walk distance from baseline by a significant and clinically meaningful 40.8 meters compared with placebo for the trial’s primary efficacy endpoint (P < .001).

Sotatercept also led to significant improvement in multiple secondary outcome measures, including:

• Reduction in the risk for death from any cause or PAH clinical worsening events by 84% vs background therapy alone (number of events: 9 vs 42; hazard ratio [HR], 0.16; P < .001) 
• Improvement in FC from baseline at 24 weeks in 29% of patients compared with 14% of patients treated with placebo (P < .001) 
• Improvement in pulmonary vascular resistance (PVR), with an average 235 dyn/sec/cm⁵ reduction in PVR from baseline (P < .001) 
• Improvement from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels. The median treatment difference in NT-proBNP between sotatercept and placebo was -442 pg/mL (P < .001) 

The results were reported last year at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, with simultaneous publication in The New England Journal of Medicine. 

Sotatercept injection may be administered by patients or caregivers with guidance, training, and follow-up from a healthcare provider. The recommended starting dose is 0.3 mg/kg. The recommended target dose is 0.7 mg/kg every 3 weeks.

Sotatercept may increase hemoglobin, may lead to erythrocytosis, and may decrease platelet count and lead to severe thrombocytopenia. Treatment should not be initiated if platelet count is < 50,000/mm³. 

Hemoglobin and platelets should be monitored before each dose of sotatercept for the first five doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required. 

Full prescribing information is available online. 

Merck estimates that sotatercept will be available for dispensing by select specialty pharmacies in the United States by the end of April 2024.

A version of this article appeared on Medscape.com.

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

Two classes of chemicals present in common household products may impair the development of oligodendrocytes, the myelinating cells of the central nervous system (CNS), which are critical to brain development and function. However, the researchers as well as outside experts agree more research is needed before any firm conclusions can be drawn. 

Quaternary ammonium compounds, ubiquitous in disinfecting agents and personal care products, and organophosphate flame retardants, which are commonly found in household items such as furniture and electronics had “surprising effects specifically on the non-nerve cells in the brain,” said lead researcher Paul Tesar, PhD, professor and director of the Institute for Glial Sciences, Case Western Reserve University School of Medicine, Cleveland. 

“Other studies have shown that our exposures to the chemicals in disinfecting agents nearly doubled during the pandemic,” Dr. Tesar noted. The finding that quaternary ammonium chemicals in disinfecting agents are harmful to specific brain cells suggests “we need to think about our increased utilization and exposure,” he added.

The results were published online on March 25 in Nature Neuroscience. 
 

Motor Dysfunction

Exposure to various chemicals in the environment has been shown to impair brain development. However, most of this research has focused on neurons. Less is known about effects on oligodendrocytes, which form the electrical insulation around the axons of CNS cells. Oligodendrocyte development continues from before birth into adulthood, thus these cells may be particularly vulnerable to damage from toxic chemicals.

The researchers analyzed the effects of 1823 chemicals on mouse oligodendrocyte development in cell cultures. They identified 292 chemicals that cause oligodendrocytes to die and 47 that inhibit oligodendrocyte generation. These chemicals belonged to two different classes.

They found that quaternary compounds were potently and selectively cytotoxic to developing oligodendrocytes and that organophosphate flame retardants prematurely arrested oligodendrocyte maturation. These effects were confirmed in mice and cultured human oligodendrocytes.

In addition, an analysis of epidemiologic data from the National Health and Nutrition Examination Survey (2013-2018) showed that one flame retardant metabolite, bis(1,3-dichloro-2-propy) phosphate (BDCIPP), was present in nearly all urine samples of children aged 3-11 years who were examined (1753 out of 1763 children).

After adjustment for multiple confounding factors, results showed that compared with children with urinary BDCIPP concentration in the lowest quartile, those with concentrations in the highest quartile were twice as likely to require special education (adjusted odds ratio [aOR], 2.0; 95% CI, 1.0-3.8) and were six times as likely to have gross motor dysfunction (aOR, 6.0; 95% CI, 1.7-21.9).

Children with urinary BDCIPP concentration within the third quartile also had significantly increased odds of motor dysfunction (aOR, 4.2; 95% CI, 1.1-16.2). 

“These results suggest that the identified chemicals are potentially hazardous to human health. However, we want to be clear that more studies are needed to make definitive connections between chemical exposure and human disease,” said Dr. Tesar.

“Future studies will need to deepen our understanding of the duration and timing of exposure required to initiate or exacerbate disease. This information is needed before specific recommendations, such as behavioral interventions, can be made to reduce exposure. Some of these chemicals have useful roles in our homes, but we need to consider how they’re being used and what level of exposure might be considered safe,” Dr. Tesar said. 

In his view, the results “provide a starting point to understand what exposure levels to these chemicals might be putting ourselves or kids at risk for toxicity.”
 

Too Soon to Tell

Commenting for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, who was not involved in the study, echoed the need for more research. 

“The biological mechanisms uncovered provide plausible pathways by which these chemicals could potentially impact human brain development related to oligodendrocytes and myelination. Oligodendrocytes play a critical role in plastic neurological processes throughout life, not just early neurodevelopment. So, disrupting their maturation and function theoretically could contribute to neurodevelopmental disorders as well as adult conditions like multiple sclerosis,” Dr. Lakhan said. 

“This study alone shouldn’t sound neurotoxicant alarms yet. We’ve seen many past chemical scares like saccharin and phthalates fizzle despite alarming lab results when real-world human brain impacts failed to materialize,” Dr. Lakhan cautioned. 

“Far more rigorous research directly linking household chemical exposures to cognitive deficits in people is still needed before drawing firm conclusions or prompting overreactions from the general public. Policymakers will eventually need to weigh potential risks vs benefits, but no definitive human health threat has currently been established,” Dr. Lakhan said. 

Sarah Evans, PhD, MPH, assistant professor in the Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York, also emphasized the need for further study.

“Given that most of the experiments in this study were conducted in isolated cells and a mouse model, further research is needed to determine whether exposure to these chemicals at levels experienced by the general population during critical windows of development impairs myelination and leads to adverse health outcomes like learning and behavior problems in humans,” said Dr. Evans, who was involved in the study.

“The authors’ finding of an association between higher urinary levels of the organophosphate flame-retardant metabolite BDCIPP and gross motor problems or need for special education in children aged 3-11 years in the CDC National Health and Nutrition Examination Survey strengthens their laboratory findings and warrants further investigation,” Dr. Evans added. 

The research was supported by grants from the National Institutes of Health, National Multiple Sclerosis Society, Howard Hughes Medical Institute and New York Stem Cell Foundation, and philanthropic support by sTF5 Care and the Long, Walter, Peterson, Goodman, and Geller families. Dr. Tesar, Dr. Lakhan, and Dr. Evans report no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

Two classes of chemicals present in common household products may impair the development of oligodendrocytes, the myelinating cells of the central nervous system (CNS), which are critical to brain development and function. However, the researchers as well as outside experts agree more research is needed before any firm conclusions can be drawn. 

Quaternary ammonium compounds, ubiquitous in disinfecting agents and personal care products, and organophosphate flame retardants, which are commonly found in household items such as furniture and electronics had “surprising effects specifically on the non-nerve cells in the brain,” said lead researcher Paul Tesar, PhD, professor and director of the Institute for Glial Sciences, Case Western Reserve University School of Medicine, Cleveland. 

“Other studies have shown that our exposures to the chemicals in disinfecting agents nearly doubled during the pandemic,” Dr. Tesar noted. The finding that quaternary ammonium chemicals in disinfecting agents are harmful to specific brain cells suggests “we need to think about our increased utilization and exposure,” he added.

The results were published online on March 25 in Nature Neuroscience. 
 

Motor Dysfunction

Exposure to various chemicals in the environment has been shown to impair brain development. However, most of this research has focused on neurons. Less is known about effects on oligodendrocytes, which form the electrical insulation around the axons of CNS cells. Oligodendrocyte development continues from before birth into adulthood, thus these cells may be particularly vulnerable to damage from toxic chemicals.

The researchers analyzed the effects of 1823 chemicals on mouse oligodendrocyte development in cell cultures. They identified 292 chemicals that cause oligodendrocytes to die and 47 that inhibit oligodendrocyte generation. These chemicals belonged to two different classes.

They found that quaternary compounds were potently and selectively cytotoxic to developing oligodendrocytes and that organophosphate flame retardants prematurely arrested oligodendrocyte maturation. These effects were confirmed in mice and cultured human oligodendrocytes.

In addition, an analysis of epidemiologic data from the National Health and Nutrition Examination Survey (2013-2018) showed that one flame retardant metabolite, bis(1,3-dichloro-2-propy) phosphate (BDCIPP), was present in nearly all urine samples of children aged 3-11 years who were examined (1753 out of 1763 children).

After adjustment for multiple confounding factors, results showed that compared with children with urinary BDCIPP concentration in the lowest quartile, those with concentrations in the highest quartile were twice as likely to require special education (adjusted odds ratio [aOR], 2.0; 95% CI, 1.0-3.8) and were six times as likely to have gross motor dysfunction (aOR, 6.0; 95% CI, 1.7-21.9).

Children with urinary BDCIPP concentration within the third quartile also had significantly increased odds of motor dysfunction (aOR, 4.2; 95% CI, 1.1-16.2). 

“These results suggest that the identified chemicals are potentially hazardous to human health. However, we want to be clear that more studies are needed to make definitive connections between chemical exposure and human disease,” said Dr. Tesar.

“Future studies will need to deepen our understanding of the duration and timing of exposure required to initiate or exacerbate disease. This information is needed before specific recommendations, such as behavioral interventions, can be made to reduce exposure. Some of these chemicals have useful roles in our homes, but we need to consider how they’re being used and what level of exposure might be considered safe,” Dr. Tesar said. 

In his view, the results “provide a starting point to understand what exposure levels to these chemicals might be putting ourselves or kids at risk for toxicity.”
 

Too Soon to Tell

Commenting for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, who was not involved in the study, echoed the need for more research. 

“The biological mechanisms uncovered provide plausible pathways by which these chemicals could potentially impact human brain development related to oligodendrocytes and myelination. Oligodendrocytes play a critical role in plastic neurological processes throughout life, not just early neurodevelopment. So, disrupting their maturation and function theoretically could contribute to neurodevelopmental disorders as well as adult conditions like multiple sclerosis,” Dr. Lakhan said. 

“This study alone shouldn’t sound neurotoxicant alarms yet. We’ve seen many past chemical scares like saccharin and phthalates fizzle despite alarming lab results when real-world human brain impacts failed to materialize,” Dr. Lakhan cautioned. 

“Far more rigorous research directly linking household chemical exposures to cognitive deficits in people is still needed before drawing firm conclusions or prompting overreactions from the general public. Policymakers will eventually need to weigh potential risks vs benefits, but no definitive human health threat has currently been established,” Dr. Lakhan said. 

Sarah Evans, PhD, MPH, assistant professor in the Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York, also emphasized the need for further study.

“Given that most of the experiments in this study were conducted in isolated cells and a mouse model, further research is needed to determine whether exposure to these chemicals at levels experienced by the general population during critical windows of development impairs myelination and leads to adverse health outcomes like learning and behavior problems in humans,” said Dr. Evans, who was involved in the study.

“The authors’ finding of an association between higher urinary levels of the organophosphate flame-retardant metabolite BDCIPP and gross motor problems or need for special education in children aged 3-11 years in the CDC National Health and Nutrition Examination Survey strengthens their laboratory findings and warrants further investigation,” Dr. Evans added. 

The research was supported by grants from the National Institutes of Health, National Multiple Sclerosis Society, Howard Hughes Medical Institute and New York Stem Cell Foundation, and philanthropic support by sTF5 Care and the Long, Walter, Peterson, Goodman, and Geller families. Dr. Tesar, Dr. Lakhan, and Dr. Evans report no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

Two classes of chemicals present in common household products may impair the development of oligodendrocytes, the myelinating cells of the central nervous system (CNS), which are critical to brain development and function. However, the researchers as well as outside experts agree more research is needed before any firm conclusions can be drawn. 

Quaternary ammonium compounds, ubiquitous in disinfecting agents and personal care products, and organophosphate flame retardants, which are commonly found in household items such as furniture and electronics had “surprising effects specifically on the non-nerve cells in the brain,” said lead researcher Paul Tesar, PhD, professor and director of the Institute for Glial Sciences, Case Western Reserve University School of Medicine, Cleveland. 

“Other studies have shown that our exposures to the chemicals in disinfecting agents nearly doubled during the pandemic,” Dr. Tesar noted. The finding that quaternary ammonium chemicals in disinfecting agents are harmful to specific brain cells suggests “we need to think about our increased utilization and exposure,” he added.

The results were published online on March 25 in Nature Neuroscience. 
 

Motor Dysfunction

Exposure to various chemicals in the environment has been shown to impair brain development. However, most of this research has focused on neurons. Less is known about effects on oligodendrocytes, which form the electrical insulation around the axons of CNS cells. Oligodendrocyte development continues from before birth into adulthood, thus these cells may be particularly vulnerable to damage from toxic chemicals.

The researchers analyzed the effects of 1823 chemicals on mouse oligodendrocyte development in cell cultures. They identified 292 chemicals that cause oligodendrocytes to die and 47 that inhibit oligodendrocyte generation. These chemicals belonged to two different classes.

They found that quaternary compounds were potently and selectively cytotoxic to developing oligodendrocytes and that organophosphate flame retardants prematurely arrested oligodendrocyte maturation. These effects were confirmed in mice and cultured human oligodendrocytes.

In addition, an analysis of epidemiologic data from the National Health and Nutrition Examination Survey (2013-2018) showed that one flame retardant metabolite, bis(1,3-dichloro-2-propy) phosphate (BDCIPP), was present in nearly all urine samples of children aged 3-11 years who were examined (1753 out of 1763 children).

After adjustment for multiple confounding factors, results showed that compared with children with urinary BDCIPP concentration in the lowest quartile, those with concentrations in the highest quartile were twice as likely to require special education (adjusted odds ratio [aOR], 2.0; 95% CI, 1.0-3.8) and were six times as likely to have gross motor dysfunction (aOR, 6.0; 95% CI, 1.7-21.9).

Children with urinary BDCIPP concentration within the third quartile also had significantly increased odds of motor dysfunction (aOR, 4.2; 95% CI, 1.1-16.2). 

“These results suggest that the identified chemicals are potentially hazardous to human health. However, we want to be clear that more studies are needed to make definitive connections between chemical exposure and human disease,” said Dr. Tesar.

“Future studies will need to deepen our understanding of the duration and timing of exposure required to initiate or exacerbate disease. This information is needed before specific recommendations, such as behavioral interventions, can be made to reduce exposure. Some of these chemicals have useful roles in our homes, but we need to consider how they’re being used and what level of exposure might be considered safe,” Dr. Tesar said. 

In his view, the results “provide a starting point to understand what exposure levels to these chemicals might be putting ourselves or kids at risk for toxicity.”
 

Too Soon to Tell

Commenting for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, who was not involved in the study, echoed the need for more research. 

“The biological mechanisms uncovered provide plausible pathways by which these chemicals could potentially impact human brain development related to oligodendrocytes and myelination. Oligodendrocytes play a critical role in plastic neurological processes throughout life, not just early neurodevelopment. So, disrupting their maturation and function theoretically could contribute to neurodevelopmental disorders as well as adult conditions like multiple sclerosis,” Dr. Lakhan said. 

“This study alone shouldn’t sound neurotoxicant alarms yet. We’ve seen many past chemical scares like saccharin and phthalates fizzle despite alarming lab results when real-world human brain impacts failed to materialize,” Dr. Lakhan cautioned. 

“Far more rigorous research directly linking household chemical exposures to cognitive deficits in people is still needed before drawing firm conclusions or prompting overreactions from the general public. Policymakers will eventually need to weigh potential risks vs benefits, but no definitive human health threat has currently been established,” Dr. Lakhan said. 

Sarah Evans, PhD, MPH, assistant professor in the Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York, also emphasized the need for further study.

“Given that most of the experiments in this study were conducted in isolated cells and a mouse model, further research is needed to determine whether exposure to these chemicals at levels experienced by the general population during critical windows of development impairs myelination and leads to adverse health outcomes like learning and behavior problems in humans,” said Dr. Evans, who was involved in the study.

“The authors’ finding of an association between higher urinary levels of the organophosphate flame-retardant metabolite BDCIPP and gross motor problems or need for special education in children aged 3-11 years in the CDC National Health and Nutrition Examination Survey strengthens their laboratory findings and warrants further investigation,” Dr. Evans added. 

The research was supported by grants from the National Institutes of Health, National Multiple Sclerosis Society, Howard Hughes Medical Institute and New York Stem Cell Foundation, and philanthropic support by sTF5 Care and the Long, Walter, Peterson, Goodman, and Geller families. Dr. Tesar, Dr. Lakhan, and Dr. Evans report no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Age-standardized stroke rates decreased in the United States between 1990 and 2019, while absolute stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates increased, a new study showed. Investigators noted the findings, which also show a significant increase in hemorrhagic stroke and an uptick in stroke among adults under 50 years in the South and Midwest, suggesting a significant shift in the US stroke burden.

METHODOLOGY:

• This in-depth, cross-sectional analysis of the 2019 Global Burden of Disease study included data on all-cause and ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs) between 1990 and 2019 in the United States.
• Researchers focused on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100,000 people.

TAKEAWAY:

• In 2019, the United States recorded 7.09 million prevalent strokes, 83% of which were ischemic and 57% of which occurred in women.
• The absolute numbers of stroke cases, mortality, and DALYs increased from 1990 to 2019, but the age-standardized rates either declined or remained steady.
• Overall incidence increased by 40% for ICH, 51% for SAH, and 13% for , and stroke mortality increased by 56% for ICH, 72% for SAH, and 5.4% for ischemic stroke.
• Age-adjusted analyses showed the results were not uniform across all geographical areas, with older adults (ages, 50-74 years) experiencing decreased incidence in coastal areas and younger individuals (ages, 15-49 years) experiencing an uptick in the South and Midwest United States.

IN PRACTICE:

“As the country prepares for an imminent swell in the aging population, coupled with a noticeable plateau in advancements against stroke mortality, it becomes evident that future directions must focus on a multipronged strategy,” the authors wrote. “This involves both embracing precision medicine’s potential and fortifying widespread public health campaigns.”

SOURCE:

Kevin N. Sheth, MD, of the Yale Center for Brain and Mind Health, Yale School of Medicine, New Haven, Connecticut, was the senior and corresponding author of the study. It was published online in JAMA Neurology.

LIMITATIONS:

The accuracy of stroke ascertainment was limited by the data source, which may be prone to misclassification. The data lacked detailed information on race, ethnicity, and stroke characteristics other than stroke type.

DISCLOSURES:

This work was funded by the Bill and Melinda Gates Foundation, the American Heart Association Medical Student Research Fellowship, grants from the National Institutes of Health, the American Heart Association, the Yale Pepper Scholar Award, and the Neurocritical Care Society Research fellowship. Sheth reported receiving grants from the National Institutes of Health, American Heart Association, and Hyperfine; personal fees/monitoring board fees/equity from Astrocyte, CSL Behring, Zoll, Sense, Bexorg, Rhaeos, and Alva and having a patent for Alva licensed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Age-standardized stroke rates decreased in the United States between 1990 and 2019, while absolute stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates increased, a new study showed. Investigators noted the findings, which also show a significant increase in hemorrhagic stroke and an uptick in stroke among adults under 50 years in the South and Midwest, suggesting a significant shift in the US stroke burden.

METHODOLOGY:

• This in-depth, cross-sectional analysis of the 2019 Global Burden of Disease study included data on all-cause and ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs) between 1990 and 2019 in the United States.
• Researchers focused on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100,000 people.

TAKEAWAY:

• In 2019, the United States recorded 7.09 million prevalent strokes, 83% of which were ischemic and 57% of which occurred in women.
• The absolute numbers of stroke cases, mortality, and DALYs increased from 1990 to 2019, but the age-standardized rates either declined or remained steady.
• Overall incidence increased by 40% for ICH, 51% for SAH, and 13% for , and stroke mortality increased by 56% for ICH, 72% for SAH, and 5.4% for ischemic stroke.
• Age-adjusted analyses showed the results were not uniform across all geographical areas, with older adults (ages, 50-74 years) experiencing decreased incidence in coastal areas and younger individuals (ages, 15-49 years) experiencing an uptick in the South and Midwest United States.

IN PRACTICE:

“As the country prepares for an imminent swell in the aging population, coupled with a noticeable plateau in advancements against stroke mortality, it becomes evident that future directions must focus on a multipronged strategy,” the authors wrote. “This involves both embracing precision medicine’s potential and fortifying widespread public health campaigns.”

SOURCE:

Kevin N. Sheth, MD, of the Yale Center for Brain and Mind Health, Yale School of Medicine, New Haven, Connecticut, was the senior and corresponding author of the study. It was published online in JAMA Neurology.

LIMITATIONS:

The accuracy of stroke ascertainment was limited by the data source, which may be prone to misclassification. The data lacked detailed information on race, ethnicity, and stroke characteristics other than stroke type.

DISCLOSURES:

This work was funded by the Bill and Melinda Gates Foundation, the American Heart Association Medical Student Research Fellowship, grants from the National Institutes of Health, the American Heart Association, the Yale Pepper Scholar Award, and the Neurocritical Care Society Research fellowship. Sheth reported receiving grants from the National Institutes of Health, American Heart Association, and Hyperfine; personal fees/monitoring board fees/equity from Astrocyte, CSL Behring, Zoll, Sense, Bexorg, Rhaeos, and Alva and having a patent for Alva licensed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Age-standardized stroke rates decreased in the United States between 1990 and 2019, while absolute stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates increased, a new study showed. Investigators noted the findings, which also show a significant increase in hemorrhagic stroke and an uptick in stroke among adults under 50 years in the South and Midwest, suggesting a significant shift in the US stroke burden.

METHODOLOGY:

• This in-depth, cross-sectional analysis of the 2019 Global Burden of Disease study included data on all-cause and ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs) between 1990 and 2019 in the United States.
• Researchers focused on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100,000 people.

TAKEAWAY:

• In 2019, the United States recorded 7.09 million prevalent strokes, 83% of which were ischemic and 57% of which occurred in women.
• The absolute numbers of stroke cases, mortality, and DALYs increased from 1990 to 2019, but the age-standardized rates either declined or remained steady.
• Overall incidence increased by 40% for ICH, 51% for SAH, and 13% for , and stroke mortality increased by 56% for ICH, 72% for SAH, and 5.4% for ischemic stroke.
• Age-adjusted analyses showed the results were not uniform across all geographical areas, with older adults (ages, 50-74 years) experiencing decreased incidence in coastal areas and younger individuals (ages, 15-49 years) experiencing an uptick in the South and Midwest United States.

IN PRACTICE:

“As the country prepares for an imminent swell in the aging population, coupled with a noticeable plateau in advancements against stroke mortality, it becomes evident that future directions must focus on a multipronged strategy,” the authors wrote. “This involves both embracing precision medicine’s potential and fortifying widespread public health campaigns.”

SOURCE:

Kevin N. Sheth, MD, of the Yale Center for Brain and Mind Health, Yale School of Medicine, New Haven, Connecticut, was the senior and corresponding author of the study. It was published online in JAMA Neurology.

LIMITATIONS:

The accuracy of stroke ascertainment was limited by the data source, which may be prone to misclassification. The data lacked detailed information on race, ethnicity, and stroke characteristics other than stroke type.

DISCLOSURES:

This work was funded by the Bill and Melinda Gates Foundation, the American Heart Association Medical Student Research Fellowship, grants from the National Institutes of Health, the American Heart Association, the Yale Pepper Scholar Award, and the Neurocritical Care Society Research fellowship. Sheth reported receiving grants from the National Institutes of Health, American Heart Association, and Hyperfine; personal fees/monitoring board fees/equity from Astrocyte, CSL Behring, Zoll, Sense, Bexorg, Rhaeos, and Alva and having a patent for Alva licensed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.