MDedge Pediatrics

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.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.

Data from the Minnesota Department of Health (MDH) underscore the often poor reliability of a clinical diagnosis of varicella (chickenpox) in children without laboratory test confirmation, according to a report featured in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

Only about half of clinically diagnosed varicella cases — cases diagnosed by examining rashes without laboratory testing — were positive for the varicella-zoster virus (VZV), suggesting lab testing is important to avoid consequences such as children being kept out of school longer than necessary.

Clinical diagnosis continues to be the primary method for diagnosing varicella, said authors of the report, led by Alison Ruprecht, MPH, a state epidemiologist with the MDH. But the signs and symptoms of those who have received the varicella vaccine (including fewer skin lesions, mostly maculopapular) make it difficult to diagnose.
 

Minnesota Offers Free Tests

In December 2016, the MDH expanded polymerase chain reaction (PCR) laboratory testing for varicella in the state. The program reached out to clinicians through newsletters, webinars, advisories, and conferences describing the importance of lab testing when clinicians suspect a patient’s rash is varicella. The department also offered free testing at MDH Public Health Laboratory (PHL) through an agreement with the CDC and follow-up, if needed, with clinicians on testing practices.

MDH also provided specimen collection kits (containing a collection swab for vesicular fluid and slides for collection of scabs or scraping of maculopapular lesions) to clinics. Free testing was available for people with suspected varicella, including those who had been clinically diagnosed, or people who self-reported suspected varicella or whose school or child care reported the suspected cases. In addition to testing for varicella, MDH-PHL performed PCR testing for herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and enterovirus on all samples.

The state then saw lab-confirmed varicella cases double from 17% (235 of 1,426) during January 2013–November 2016 to 36% (619 of 1,717) during December 2016–March 2023 (P < .001).

During December 2016–March 2023, MDH-PHL tested specimens for 420 patients with suspected varicella; the median patient age was 5 years (range = 0-68 years). Of those, 23% provided specimens collected at home.
 

Clinical Diagnosis Versus Lab Test Confirmation

The researchers found that among 208 patients receiving a clinical diagnosis of varicella after only examination at a medical facility, fewer than half (45%) had positive varicella-zoster virus (VZV) lab test results. VZV detection was 66% lower in those who received varicella vaccine compared with those who did not.

The researchers acknowledged that outreach, at-home specimen collection, and free testing likely increased lab testing numbers.

They added that, “This increase in varicella testing likely also contributed to an increase in appropriate clinical management and school exclusion recommendations for suspect varicella cases.

“Clinicians should incorporate routine laboratory testing whenever varicella is suspected,” the researchers wrote. “Public health and school health professionals should emphasize the importance of laboratory confirmation in their recommendations to clinicians and parents.”
 

Presentation May Also Be Different in Immunocompromised

Sam Dominguez, MD, infectious disease specialist at Children’s Colorado in Aurora, who was not part of the research, said in addition to presentation being harder to recognize in those who are vaccinated, varicella is harder to diagnose in the immunocompromised population, where the rash may not be as prominent or more localized or appear in any number of atypical presentations.

In addition, he said, clinicians don’t see many cases these days. “Providers aren’t as familiar with what varicella looks like, especially younger providers who weren’t trained in the prevaccination era,” he said.

Cost is often an issue with lab testing as well as turn-around time and access, he said, and those factors can be barriers.

Dr. Dominguez said some classic presentations are easily diagnosed as varicella. “If you have a normal, healthy kid, who you’re seeing in the outpatient world who presents with a very classic rash for chickenpox, I don’t think laboratory testing is necessarily warranted in that scenario.”

But when clinicians aren’t confident in their diagnosis, “I think in those scenarios, testing can be very helpful in terms of management from a treatment standpoint as well as a potential infection control standpoint,” he said.

The authors reported no relevant financial relationships. Dr. Dominguez is a consultant for diagnostic companies Karius and BioFire. He has grant support from Pfizer and BioFire.

Data from the Minnesota Department of Health (MDH) underscore the often poor reliability of a clinical diagnosis of varicella (chickenpox) in children without laboratory test confirmation, according to a report featured in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

Only about half of clinically diagnosed varicella cases — cases diagnosed by examining rashes without laboratory testing — were positive for the varicella-zoster virus (VZV), suggesting lab testing is important to avoid consequences such as children being kept out of school longer than necessary.

Clinical diagnosis continues to be the primary method for diagnosing varicella, said authors of the report, led by Alison Ruprecht, MPH, a state epidemiologist with the MDH. But the signs and symptoms of those who have received the varicella vaccine (including fewer skin lesions, mostly maculopapular) make it difficult to diagnose.
 

Minnesota Offers Free Tests

In December 2016, the MDH expanded polymerase chain reaction (PCR) laboratory testing for varicella in the state. The program reached out to clinicians through newsletters, webinars, advisories, and conferences describing the importance of lab testing when clinicians suspect a patient’s rash is varicella. The department also offered free testing at MDH Public Health Laboratory (PHL) through an agreement with the CDC and follow-up, if needed, with clinicians on testing practices.

MDH also provided specimen collection kits (containing a collection swab for vesicular fluid and slides for collection of scabs or scraping of maculopapular lesions) to clinics. Free testing was available for people with suspected varicella, including those who had been clinically diagnosed, or people who self-reported suspected varicella or whose school or child care reported the suspected cases. In addition to testing for varicella, MDH-PHL performed PCR testing for herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and enterovirus on all samples.

The state then saw lab-confirmed varicella cases double from 17% (235 of 1,426) during January 2013–November 2016 to 36% (619 of 1,717) during December 2016–March 2023 (P < .001).

During December 2016–March 2023, MDH-PHL tested specimens for 420 patients with suspected varicella; the median patient age was 5 years (range = 0-68 years). Of those, 23% provided specimens collected at home.
 

Clinical Diagnosis Versus Lab Test Confirmation

The researchers found that among 208 patients receiving a clinical diagnosis of varicella after only examination at a medical facility, fewer than half (45%) had positive varicella-zoster virus (VZV) lab test results. VZV detection was 66% lower in those who received varicella vaccine compared with those who did not.

The researchers acknowledged that outreach, at-home specimen collection, and free testing likely increased lab testing numbers.

They added that, “This increase in varicella testing likely also contributed to an increase in appropriate clinical management and school exclusion recommendations for suspect varicella cases.

“Clinicians should incorporate routine laboratory testing whenever varicella is suspected,” the researchers wrote. “Public health and school health professionals should emphasize the importance of laboratory confirmation in their recommendations to clinicians and parents.”
 

Presentation May Also Be Different in Immunocompromised

Sam Dominguez, MD, infectious disease specialist at Children’s Colorado in Aurora, who was not part of the research, said in addition to presentation being harder to recognize in those who are vaccinated, varicella is harder to diagnose in the immunocompromised population, where the rash may not be as prominent or more localized or appear in any number of atypical presentations.

In addition, he said, clinicians don’t see many cases these days. “Providers aren’t as familiar with what varicella looks like, especially younger providers who weren’t trained in the prevaccination era,” he said.

Cost is often an issue with lab testing as well as turn-around time and access, he said, and those factors can be barriers.

Dr. Dominguez said some classic presentations are easily diagnosed as varicella. “If you have a normal, healthy kid, who you’re seeing in the outpatient world who presents with a very classic rash for chickenpox, I don’t think laboratory testing is necessarily warranted in that scenario.”

But when clinicians aren’t confident in their diagnosis, “I think in those scenarios, testing can be very helpful in terms of management from a treatment standpoint as well as a potential infection control standpoint,” he said.

The authors reported no relevant financial relationships. Dr. Dominguez is a consultant for diagnostic companies Karius and BioFire. He has grant support from Pfizer and BioFire.

Data from the Minnesota Department of Health (MDH) underscore the often poor reliability of a clinical diagnosis of varicella (chickenpox) in children without laboratory test confirmation, according to a report featured in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

Only about half of clinically diagnosed varicella cases — cases diagnosed by examining rashes without laboratory testing — were positive for the varicella-zoster virus (VZV), suggesting lab testing is important to avoid consequences such as children being kept out of school longer than necessary.

Clinical diagnosis continues to be the primary method for diagnosing varicella, said authors of the report, led by Alison Ruprecht, MPH, a state epidemiologist with the MDH. But the signs and symptoms of those who have received the varicella vaccine (including fewer skin lesions, mostly maculopapular) make it difficult to diagnose.
 

Minnesota Offers Free Tests

In December 2016, the MDH expanded polymerase chain reaction (PCR) laboratory testing for varicella in the state. The program reached out to clinicians through newsletters, webinars, advisories, and conferences describing the importance of lab testing when clinicians suspect a patient’s rash is varicella. The department also offered free testing at MDH Public Health Laboratory (PHL) through an agreement with the CDC and follow-up, if needed, with clinicians on testing practices.

MDH also provided specimen collection kits (containing a collection swab for vesicular fluid and slides for collection of scabs or scraping of maculopapular lesions) to clinics. Free testing was available for people with suspected varicella, including those who had been clinically diagnosed, or people who self-reported suspected varicella or whose school or child care reported the suspected cases. In addition to testing for varicella, MDH-PHL performed PCR testing for herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), and enterovirus on all samples.

The state then saw lab-confirmed varicella cases double from 17% (235 of 1,426) during January 2013–November 2016 to 36% (619 of 1,717) during December 2016–March 2023 (P < .001).

During December 2016–March 2023, MDH-PHL tested specimens for 420 patients with suspected varicella; the median patient age was 5 years (range = 0-68 years). Of those, 23% provided specimens collected at home.
 

Clinical Diagnosis Versus Lab Test Confirmation

The researchers found that among 208 patients receiving a clinical diagnosis of varicella after only examination at a medical facility, fewer than half (45%) had positive varicella-zoster virus (VZV) lab test results. VZV detection was 66% lower in those who received varicella vaccine compared with those who did not.

The researchers acknowledged that outreach, at-home specimen collection, and free testing likely increased lab testing numbers.

They added that, “This increase in varicella testing likely also contributed to an increase in appropriate clinical management and school exclusion recommendations for suspect varicella cases.

“Clinicians should incorporate routine laboratory testing whenever varicella is suspected,” the researchers wrote. “Public health and school health professionals should emphasize the importance of laboratory confirmation in their recommendations to clinicians and parents.”
 

Presentation May Also Be Different in Immunocompromised

Sam Dominguez, MD, infectious disease specialist at Children’s Colorado in Aurora, who was not part of the research, said in addition to presentation being harder to recognize in those who are vaccinated, varicella is harder to diagnose in the immunocompromised population, where the rash may not be as prominent or more localized or appear in any number of atypical presentations.

In addition, he said, clinicians don’t see many cases these days. “Providers aren’t as familiar with what varicella looks like, especially younger providers who weren’t trained in the prevaccination era,” he said.

Cost is often an issue with lab testing as well as turn-around time and access, he said, and those factors can be barriers.

Dr. Dominguez said some classic presentations are easily diagnosed as varicella. “If you have a normal, healthy kid, who you’re seeing in the outpatient world who presents with a very classic rash for chickenpox, I don’t think laboratory testing is necessarily warranted in that scenario.”

But when clinicians aren’t confident in their diagnosis, “I think in those scenarios, testing can be very helpful in terms of management from a treatment standpoint as well as a potential infection control standpoint,” he said.

The authors reported no relevant financial relationships. Dr. Dominguez is a consultant for diagnostic companies Karius and BioFire. He has grant support from Pfizer and BioFire.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.

Primary care physicians play a critical role in identifying patients at risk for serious mental health issues, including suicidality. But the ever-increasing demands on their clinical time can hinder the ability to identify emotional distress in time to intervene. Can artificial intelligence (AI) help?

This news organization spoke with Tom Zaubler, MD, a psychiatrist and chief medical officer of NeuroFlow, about how AI can improve the ability of primary care physicians and other clinicians to screen their patients for suicidal ideation and boost rates of treatment for mental health issues in their patients. This interview has been edited for clarity and length.

Question: How can AI help in suicide prevention and mental health screening in primary care?

Answer: Recent studies have demonstrated the potential of AI in mental health screening and suicide prevention. One method is natural language processing (NLP), which can analyze patients› journal entries for signs of suicidal thoughts or behaviors. This technology has shown promise in detecting suicidal ideation in patients who may not report such thoughts on traditional screening tools like the Patient Health Questionnaire-9 (PHQ-9). AI can be part of an integrated approach to identify and provide support to individuals at risk for suicide or those without a psychiatric history but who may still be at risk.

Q: A recent study by [Maria] Oquendo and colleagues found that one fifth of patients who attempt suicide do not meet the criteria for a mental health disorder.

Improved screening is obviously important, but in some ways it’s not the most important part of the problem. The lack of accessibility to specialized mental health care is a critical obstacle to treating patients with acute psychiatric needs.

How can primary care doctors effectively connect patients with mental health support, given the scarcity of mental health professionals?

A: Primary care doctors can leverage technology to extend mental health support. This includes using platforms for safety screening and providing patients with immediate access to local and national resources and digital interventions. Alerts can be sent to professionals within the practice or employed by technology companies to offer immediate support, including suicide safety planning and counseling. Users can hit a button to “Find a Therapist.” Also, if they acknowledge feelings of self-harm, these keywords are detected within the app by NLP. “Urgent alerts” are then sent to clinicians who are overseeing patient care. If someone is flagged, a social worker or member of a response services team intervenes and calls the person at risk to tailor care. These interventions do not always require a psychiatrist or masters-prepared clinician but can be effectively managed by trained paraprofessionals. These staff members can provide suicide safety planning and lethal-means-restriction counseling, and can assess the need for escalation of care.

Q: How is technology likely to manifest in physician practices in the near future to support mental health care?

A: Automated screening platforms for depression and anxiety, alerts for physicians when patients screen positively, and integration with collaborative care models are a few of the ways technology will become part of clinical practice. Additionally, advanced data analytics and predictive modeling using electronic health records and claims data will help identify high-risk patients. Technologies like voice recognition and machine learning can analyze patient journals and possibly, in the future, social media feeds to detect mental health issues. These technologies aim to extend and augment the capabilities of healthcare practices, improving the identification and management of patients at risk for mental health issues.

Q: Are these technologies as effective in pediatric populations, and are there any specific challenges?

A: Technologies for mental health screening and support are effective in pediatric populations, with certain age-specific considerations and legal restrictions on technology use. For adolescents and older children comfortable with technology, digital tools can significantly impact mental health care. For younger children, technology must facilitate information-gathering from various sources, including parents and teachers. Despite challenges, technology is crucial for early identification and intervention in pediatric mental health, potentially shortening the time to diagnosis and improving outcomes.

The statistics are horrifying. One third of adolescent girls have seriously thought about suicide over the past year; 13% attempt suicide. So there’s a need in the adolescent population and in the preadolescent population, too, because there’s an 8- to 10-year lag between onset of symptoms and diagnosis of mental illness. If we can shorten that lag, you see improved performance in schools; you see decreased truancy; you see greater economic achievement and so on. It makes such a profound difference. Not to mention it saves lives. So, yes, technology is critical in a pediatric population. It exists and it’s happening right now. There are challenges, but the goal can be met.

Q: A 2014 study found that 45% of people who completed suicide visited a primary care physician in the preceding month. And only 23% of people who attempt suicide have not seen a primary care physician within the past year. What does that say about the importance of screening at the primary care level?

A: The fact that a significant percentage of individuals who die by suicide have visited a primary care physician within a month or year prior to their death underscores the critical role of primary care in suicide prevention. This highlights the potential for primary care settings to identify and intervene with individuals at risk for suicide, making the case for the importance of integrating effective mental health screenings and support technologies in primary care practices.

Q: In other words, we’re not talking about a marginal benefit.

A: No, the potential benefit is huge. The United States Preventive Services Task Force did not endorse universal screening for suicide in its 2023 recommendations; they felt — and I accept that conclusion — there wasn›t enough evidence [at the time] to really support that recommendation. I think when you talk to a lot of suicide researchers, what you will hear is that providing suicide assessments as far upstream as possible is critical, especially when you start seeing more and more research showing that 20% of the population who die by suicide are not likely to have any psychiatric pathology at all. I believe the evidence base will soon support a recommendation for universal screening for adults. I believe it is especially important to screen for suicidal ideation in kids, given the high rates of suicide in this population.

Dr. Zaubler has disclosed the following relevant financial relationships: chief medical officer, NeuroFlow.

A version of this article appeared on Medscape.com.

Primary care physicians play a critical role in identifying patients at risk for serious mental health issues, including suicidality. But the ever-increasing demands on their clinical time can hinder the ability to identify emotional distress in time to intervene. Can artificial intelligence (AI) help?

This news organization spoke with Tom Zaubler, MD, a psychiatrist and chief medical officer of NeuroFlow, about how AI can improve the ability of primary care physicians and other clinicians to screen their patients for suicidal ideation and boost rates of treatment for mental health issues in their patients. This interview has been edited for clarity and length.

Question: How can AI help in suicide prevention and mental health screening in primary care?

Answer: Recent studies have demonstrated the potential of AI in mental health screening and suicide prevention. One method is natural language processing (NLP), which can analyze patients› journal entries for signs of suicidal thoughts or behaviors. This technology has shown promise in detecting suicidal ideation in patients who may not report such thoughts on traditional screening tools like the Patient Health Questionnaire-9 (PHQ-9). AI can be part of an integrated approach to identify and provide support to individuals at risk for suicide or those without a psychiatric history but who may still be at risk.

Q: A recent study by [Maria] Oquendo and colleagues found that one fifth of patients who attempt suicide do not meet the criteria for a mental health disorder.

Improved screening is obviously important, but in some ways it’s not the most important part of the problem. The lack of accessibility to specialized mental health care is a critical obstacle to treating patients with acute psychiatric needs.

How can primary care doctors effectively connect patients with mental health support, given the scarcity of mental health professionals?

A: Primary care doctors can leverage technology to extend mental health support. This includes using platforms for safety screening and providing patients with immediate access to local and national resources and digital interventions. Alerts can be sent to professionals within the practice or employed by technology companies to offer immediate support, including suicide safety planning and counseling. Users can hit a button to “Find a Therapist.” Also, if they acknowledge feelings of self-harm, these keywords are detected within the app by NLP. “Urgent alerts” are then sent to clinicians who are overseeing patient care. If someone is flagged, a social worker or member of a response services team intervenes and calls the person at risk to tailor care. These interventions do not always require a psychiatrist or masters-prepared clinician but can be effectively managed by trained paraprofessionals. These staff members can provide suicide safety planning and lethal-means-restriction counseling, and can assess the need for escalation of care.

Q: How is technology likely to manifest in physician practices in the near future to support mental health care?

A: Automated screening platforms for depression and anxiety, alerts for physicians when patients screen positively, and integration with collaborative care models are a few of the ways technology will become part of clinical practice. Additionally, advanced data analytics and predictive modeling using electronic health records and claims data will help identify high-risk patients. Technologies like voice recognition and machine learning can analyze patient journals and possibly, in the future, social media feeds to detect mental health issues. These technologies aim to extend and augment the capabilities of healthcare practices, improving the identification and management of patients at risk for mental health issues.

Q: Are these technologies as effective in pediatric populations, and are there any specific challenges?

A: Technologies for mental health screening and support are effective in pediatric populations, with certain age-specific considerations and legal restrictions on technology use. For adolescents and older children comfortable with technology, digital tools can significantly impact mental health care. For younger children, technology must facilitate information-gathering from various sources, including parents and teachers. Despite challenges, technology is crucial for early identification and intervention in pediatric mental health, potentially shortening the time to diagnosis and improving outcomes.

The statistics are horrifying. One third of adolescent girls have seriously thought about suicide over the past year; 13% attempt suicide. So there’s a need in the adolescent population and in the preadolescent population, too, because there’s an 8- to 10-year lag between onset of symptoms and diagnosis of mental illness. If we can shorten that lag, you see improved performance in schools; you see decreased truancy; you see greater economic achievement and so on. It makes such a profound difference. Not to mention it saves lives. So, yes, technology is critical in a pediatric population. It exists and it’s happening right now. There are challenges, but the goal can be met.

Q: A 2014 study found that 45% of people who completed suicide visited a primary care physician in the preceding month. And only 23% of people who attempt suicide have not seen a primary care physician within the past year. What does that say about the importance of screening at the primary care level?

A: The fact that a significant percentage of individuals who die by suicide have visited a primary care physician within a month or year prior to their death underscores the critical role of primary care in suicide prevention. This highlights the potential for primary care settings to identify and intervene with individuals at risk for suicide, making the case for the importance of integrating effective mental health screenings and support technologies in primary care practices.

Q: In other words, we’re not talking about a marginal benefit.

A: No, the potential benefit is huge. The United States Preventive Services Task Force did not endorse universal screening for suicide in its 2023 recommendations; they felt — and I accept that conclusion — there wasn›t enough evidence [at the time] to really support that recommendation. I think when you talk to a lot of suicide researchers, what you will hear is that providing suicide assessments as far upstream as possible is critical, especially when you start seeing more and more research showing that 20% of the population who die by suicide are not likely to have any psychiatric pathology at all. I believe the evidence base will soon support a recommendation for universal screening for adults. I believe it is especially important to screen for suicidal ideation in kids, given the high rates of suicide in this population.

Dr. Zaubler has disclosed the following relevant financial relationships: chief medical officer, NeuroFlow.

A version of this article appeared on Medscape.com.

Primary care physicians play a critical role in identifying patients at risk for serious mental health issues, including suicidality. But the ever-increasing demands on their clinical time can hinder the ability to identify emotional distress in time to intervene. Can artificial intelligence (AI) help?

This news organization spoke with Tom Zaubler, MD, a psychiatrist and chief medical officer of NeuroFlow, about how AI can improve the ability of primary care physicians and other clinicians to screen their patients for suicidal ideation and boost rates of treatment for mental health issues in their patients. This interview has been edited for clarity and length.

Question: How can AI help in suicide prevention and mental health screening in primary care?

Answer: Recent studies have demonstrated the potential of AI in mental health screening and suicide prevention. One method is natural language processing (NLP), which can analyze patients› journal entries for signs of suicidal thoughts or behaviors. This technology has shown promise in detecting suicidal ideation in patients who may not report such thoughts on traditional screening tools like the Patient Health Questionnaire-9 (PHQ-9). AI can be part of an integrated approach to identify and provide support to individuals at risk for suicide or those without a psychiatric history but who may still be at risk.

Q: A recent study by [Maria] Oquendo and colleagues found that one fifth of patients who attempt suicide do not meet the criteria for a mental health disorder.

Improved screening is obviously important, but in some ways it’s not the most important part of the problem. The lack of accessibility to specialized mental health care is a critical obstacle to treating patients with acute psychiatric needs.

How can primary care doctors effectively connect patients with mental health support, given the scarcity of mental health professionals?

A: Primary care doctors can leverage technology to extend mental health support. This includes using platforms for safety screening and providing patients with immediate access to local and national resources and digital interventions. Alerts can be sent to professionals within the practice or employed by technology companies to offer immediate support, including suicide safety planning and counseling. Users can hit a button to “Find a Therapist.” Also, if they acknowledge feelings of self-harm, these keywords are detected within the app by NLP. “Urgent alerts” are then sent to clinicians who are overseeing patient care. If someone is flagged, a social worker or member of a response services team intervenes and calls the person at risk to tailor care. These interventions do not always require a psychiatrist or masters-prepared clinician but can be effectively managed by trained paraprofessionals. These staff members can provide suicide safety planning and lethal-means-restriction counseling, and can assess the need for escalation of care.

Q: How is technology likely to manifest in physician practices in the near future to support mental health care?

A: Automated screening platforms for depression and anxiety, alerts for physicians when patients screen positively, and integration with collaborative care models are a few of the ways technology will become part of clinical practice. Additionally, advanced data analytics and predictive modeling using electronic health records and claims data will help identify high-risk patients. Technologies like voice recognition and machine learning can analyze patient journals and possibly, in the future, social media feeds to detect mental health issues. These technologies aim to extend and augment the capabilities of healthcare practices, improving the identification and management of patients at risk for mental health issues.

Q: Are these technologies as effective in pediatric populations, and are there any specific challenges?

A: Technologies for mental health screening and support are effective in pediatric populations, with certain age-specific considerations and legal restrictions on technology use. For adolescents and older children comfortable with technology, digital tools can significantly impact mental health care. For younger children, technology must facilitate information-gathering from various sources, including parents and teachers. Despite challenges, technology is crucial for early identification and intervention in pediatric mental health, potentially shortening the time to diagnosis and improving outcomes.

The statistics are horrifying. One third of adolescent girls have seriously thought about suicide over the past year; 13% attempt suicide. So there’s a need in the adolescent population and in the preadolescent population, too, because there’s an 8- to 10-year lag between onset of symptoms and diagnosis of mental illness. If we can shorten that lag, you see improved performance in schools; you see decreased truancy; you see greater economic achievement and so on. It makes such a profound difference. Not to mention it saves lives. So, yes, technology is critical in a pediatric population. It exists and it’s happening right now. There are challenges, but the goal can be met.

Q: A 2014 study found that 45% of people who completed suicide visited a primary care physician in the preceding month. And only 23% of people who attempt suicide have not seen a primary care physician within the past year. What does that say about the importance of screening at the primary care level?

A: The fact that a significant percentage of individuals who die by suicide have visited a primary care physician within a month or year prior to their death underscores the critical role of primary care in suicide prevention. This highlights the potential for primary care settings to identify and intervene with individuals at risk for suicide, making the case for the importance of integrating effective mental health screenings and support technologies in primary care practices.

Q: In other words, we’re not talking about a marginal benefit.

A: No, the potential benefit is huge. The United States Preventive Services Task Force did not endorse universal screening for suicide in its 2023 recommendations; they felt — and I accept that conclusion — there wasn›t enough evidence [at the time] to really support that recommendation. I think when you talk to a lot of suicide researchers, what you will hear is that providing suicide assessments as far upstream as possible is critical, especially when you start seeing more and more research showing that 20% of the population who die by suicide are not likely to have any psychiatric pathology at all. I believe the evidence base will soon support a recommendation for universal screening for adults. I believe it is especially important to screen for suicidal ideation in kids, given the high rates of suicide in this population.

Dr. Zaubler has disclosed the following relevant financial relationships: chief medical officer, NeuroFlow.

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.

I don’t recommend ice baths. Perhaps I should. On my podcast-filled commute, I am reminded for miles of the mental and physical benefits of this revolutionary wellness routine: Cold exposure causes a spike in adrenaline and raises your baseline dopamine, thereby giving you superhuman focus and energy. Goodbye procrastination! Eliminate your ADHD in one icy step! I’m trying to be the fashionable mustached-columnist here so maybe I should get on board.

In fact, a heavyset, similarly-mustached 32-year-old patient just asked if I do ice baths. It was meant as a compliment, I believe. Displaying poise wearing my Chief of Dermatology embroidered white coat in my toddler-art-adorned office, I could hear him thinking: “This doc is legit. On fleek.” (Note, this is an approximation and the patient’s actual thoughts may have varied). We were talking podcasts and he was curious about my daily routine.

Kaiser Permanente

Now, ice baths probably do have the benefits that Andrew Huberman, Joe Rogan, and the others have described, I don’t argue. And the experience is oft described as invigorating with a runner’s high-like euphoria that follows a good dunk. I’ve tried it. I would describe it as “very uncomfortable.” To boot, following icy-cold morning showers, I wasn’t any better able to stave off opening my New York Times app on a newsy day. No, cold water isn’t my jams. But then again, I don’t journal like Marcus Aurelius or sleep on a mattress that keeps my body a chill 97 degrees like an inverse sous vide. If I were asked by Huberman in an interview what I do to be mentally strong, I’d answer, “I clean the pool.”

“Here’s how I do it, Dr. Huberman,” I’d say. “First, open the pool cover. Then with a cup with pool water from about 12 inches down, fill these little beakers with water and add a few drops of chemical reagents. Then calculate the ounces of calcium hypochlorite, muriatic acid, and other chemicals to make your pools sparkle. After skimming, take your pool brush and brush the bottom and sides of your pool. Rack your equipment when done and close the cover back up. This exercise takes about 15 minutes.” It’s a mundane task, but ah, there’s the point. Like folding the laundry, weeding the garden, emptying the dishwasher, they can be oh, so gratifying. Each of these has a crisp beginning and end and offer a lovely spot to be present. Let the thoughts flow with each stroke of the brush. Watch the water ripple the surface as you slowly pull the long pole out, dripping 7.4 pH water as you glide it in for the next pass. This is the Benabio secret to success.

Dr. Benabio

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

I don’t recommend ice baths. Perhaps I should. On my podcast-filled commute, I am reminded for miles of the mental and physical benefits of this revolutionary wellness routine: Cold exposure causes a spike in adrenaline and raises your baseline dopamine, thereby giving you superhuman focus and energy. Goodbye procrastination! Eliminate your ADHD in one icy step! I’m trying to be the fashionable mustached-columnist here so maybe I should get on board.

In fact, a heavyset, similarly-mustached 32-year-old patient just asked if I do ice baths. It was meant as a compliment, I believe. Displaying poise wearing my Chief of Dermatology embroidered white coat in my toddler-art-adorned office, I could hear him thinking: “This doc is legit. On fleek.” (Note, this is an approximation and the patient’s actual thoughts may have varied). We were talking podcasts and he was curious about my daily routine.

Kaiser Permanente

Now, ice baths probably do have the benefits that Andrew Huberman, Joe Rogan, and the others have described, I don’t argue. And the experience is oft described as invigorating with a runner’s high-like euphoria that follows a good dunk. I’ve tried it. I would describe it as “very uncomfortable.” To boot, following icy-cold morning showers, I wasn’t any better able to stave off opening my New York Times app on a newsy day. No, cold water isn’t my jams. But then again, I don’t journal like Marcus Aurelius or sleep on a mattress that keeps my body a chill 97 degrees like an inverse sous vide. If I were asked by Huberman in an interview what I do to be mentally strong, I’d answer, “I clean the pool.”

“Here’s how I do it, Dr. Huberman,” I’d say. “First, open the pool cover. Then with a cup with pool water from about 12 inches down, fill these little beakers with water and add a few drops of chemical reagents. Then calculate the ounces of calcium hypochlorite, muriatic acid, and other chemicals to make your pools sparkle. After skimming, take your pool brush and brush the bottom and sides of your pool. Rack your equipment when done and close the cover back up. This exercise takes about 15 minutes.” It’s a mundane task, but ah, there’s the point. Like folding the laundry, weeding the garden, emptying the dishwasher, they can be oh, so gratifying. Each of these has a crisp beginning and end and offer a lovely spot to be present. Let the thoughts flow with each stroke of the brush. Watch the water ripple the surface as you slowly pull the long pole out, dripping 7.4 pH water as you glide it in for the next pass. This is the Benabio secret to success.

Dr. Benabio

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

I don’t recommend ice baths. Perhaps I should. On my podcast-filled commute, I am reminded for miles of the mental and physical benefits of this revolutionary wellness routine: Cold exposure causes a spike in adrenaline and raises your baseline dopamine, thereby giving you superhuman focus and energy. Goodbye procrastination! Eliminate your ADHD in one icy step! I’m trying to be the fashionable mustached-columnist here so maybe I should get on board.

In fact, a heavyset, similarly-mustached 32-year-old patient just asked if I do ice baths. It was meant as a compliment, I believe. Displaying poise wearing my Chief of Dermatology embroidered white coat in my toddler-art-adorned office, I could hear him thinking: “This doc is legit. On fleek.” (Note, this is an approximation and the patient’s actual thoughts may have varied). We were talking podcasts and he was curious about my daily routine.

Kaiser Permanente

Now, ice baths probably do have the benefits that Andrew Huberman, Joe Rogan, and the others have described, I don’t argue. And the experience is oft described as invigorating with a runner’s high-like euphoria that follows a good dunk. I’ve tried it. I would describe it as “very uncomfortable.” To boot, following icy-cold morning showers, I wasn’t any better able to stave off opening my New York Times app on a newsy day. No, cold water isn’t my jams. But then again, I don’t journal like Marcus Aurelius or sleep on a mattress that keeps my body a chill 97 degrees like an inverse sous vide. If I were asked by Huberman in an interview what I do to be mentally strong, I’d answer, “I clean the pool.”

“Here’s how I do it, Dr. Huberman,” I’d say. “First, open the pool cover. Then with a cup with pool water from about 12 inches down, fill these little beakers with water and add a few drops of chemical reagents. Then calculate the ounces of calcium hypochlorite, muriatic acid, and other chemicals to make your pools sparkle. After skimming, take your pool brush and brush the bottom and sides of your pool. Rack your equipment when done and close the cover back up. This exercise takes about 15 minutes.” It’s a mundane task, but ah, there’s the point. Like folding the laundry, weeding the garden, emptying the dishwasher, they can be oh, so gratifying. Each of these has a crisp beginning and end and offer a lovely spot to be present. Let the thoughts flow with each stroke of the brush. Watch the water ripple the surface as you slowly pull the long pole out, dripping 7.4 pH water as you glide it in for the next pass. This is the Benabio secret to success.

Dr. Benabio

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

Please note that this is a commentary, an opinion piece: my opinion. The statements here do not necessarily represent those of this news organization or any of the myriad people or institutions that comprise this corner of the human universe.

Some days, speaking as a long-time physician and editor, I wish that there were no such things as race or ethnicity or even geographic origin for that matter. We can’t get away from sex, gender, disability, age, or culture. I’m not sure about religion. I wish people were just people.

But race is deeply embedded in the American experience — an almost invisible but inevitable presence in all of our thoughts and expressions about human activities.

In medical education (for eons it seems) the student has been taught to mention race in the first sentence of a given patient presentation, along with age and sex. In human epidemiologic research, race is almost always a studied variable. In clinical and basic medical research, looking at the impact of race on this, that, or the other is commonplace. “Mixed race not otherwise specified” is ubiquitous in the United States yet blithely ignored by most who tally these statistics. Race is rarely gene-specific. It is more of a social and cultural construct but with plainly visible overt phenotypic markers — an almost infinite mix of daily reality.

Our country, and much of Western civilization in 2024, is based on the principle that all men are created equal, although the originators of that notion were unaware of their own “equity-challenged” situation.

Many organizations, in and out of government, are now understanding, developing, and implementing programs (and thought/language patterns) to socialize diversity, equity, and inclusion (known as DEI) into their culture. It should not be surprising that many who prefer the status quo are not happy with the pressure from this movement and are using whatever methods are available to them to prevent full DEI. Such it always is.

The trusty Copilot from Bing provides these definitions:

• Diversity refers to the presence of variety within the organizational workforce. This includes aspects such as gender, culture, ethnicity, religion, disability, age, and opinion.
• Equity encompasses concepts of fairness and justice. It involves fair compensation, substantive equality, and addressing societal disparities. Equity also considers unique circumstances and adjusts treatment to achieve equal outcomes.
• Inclusion focuses on creating an organizational culture where all employees feel heard, fostering a sense of belonging and integration.

I am more than proud that my old domain of peer-reviewed, primary source, medical (and science) journals is taking a leading role in this noble, necessary, and long overdue movement for medicine.

As the central repository and transmitter of new medical information, including scientific studies, clinical medicine reports, ethics measures, and education, medical journals (including those deemed prestigious) have historically been among the worst offenders in perpetuating non-DEI objectives in their leadership, staffing, focus, instructions for authors, style manuals, and published materials.

This issue came to a head in March 2021 when a JAMA podcast about racism in American medicine was followed by this promotional tweet: “No physician is racist, so how can there be structural racism in health care?”

Reactions and actions were rapid, strong, and decisive. After an interregnum at JAMA, a new editor in chief, Kirsten Bibbins-Domingo, PhD, MD, MAS, was named. She and her large staff of editors and editorial board members from the multijournal JAMA Network joined a worldwide movement of (currently) 56 publishing organizations representing 15,000 journals called the Joint Commitment for Action on Inclusion and Diversity in Publishing.

A recent JAMA editorial with 29 authors describes the entire commitment initiative of publishers-editors. It reports JAMA Network data from 2023 and 2024 from surveys of 455 editors (a 91% response rate) about their own gender (five choices), ethnic origins or geographic ancestry (13 choices), and race (eight choices), demonstrating considerable progress toward DEI goals. The survey’s complex multinational classifications may not jibe with the categorizations used in some countries (too bad that “mixed” is not “mixed in” — a missed opportunity).

This encouraging movement will not fix it all. But when people of certain groups are represented at the table, that point of view is far more likely to make it into the lexicon, language, and omnipresent work products, potentially changing cultural norms. Even the measurement of movement related to disparity in healthcare is marred by frequent variations of data accuracy. More consistency in what to measure can help a lot, and the medical literature can be very influential.

A personal anecdote: When I was a professor at UC Davis in 1978, Allan Bakke, MD, was my student. Some of you will remember the saga of affirmative action on admissions, which was just revisited in the light of a recent decision by the US Supreme Court.

Back in 1978, the dean at UC Davis told me that he kept two file folders on the admission processes in different desk drawers. One categorized all applicants and enrollees by race, and the other did not. Depending on who came to visit and ask questions, he would choose one or the other file to share once he figured out what they were looking for (this is not a joke).

The strength of the current active political pushback against the entire DEI movement has deep roots and should not be underestimated. There will be a lot of to-ing and fro-ing.

French writer Victor Hugo is credited with stating, “There is nothing as powerful as an idea whose time has come.” A majority of Americans, physicians, and other healthcare professionals believe in basic fairness. The time for DEI in all aspects of medicine is now.

Dr. Lundberg, editor in chief of Cancer Commons, disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.

Please note that this is a commentary, an opinion piece: my opinion. The statements here do not necessarily represent those of this news organization or any of the myriad people or institutions that comprise this corner of the human universe.

Some days, speaking as a long-time physician and editor, I wish that there were no such things as race or ethnicity or even geographic origin for that matter. We can’t get away from sex, gender, disability, age, or culture. I’m not sure about religion. I wish people were just people.

But race is deeply embedded in the American experience — an almost invisible but inevitable presence in all of our thoughts and expressions about human activities.

In medical education (for eons it seems) the student has been taught to mention race in the first sentence of a given patient presentation, along with age and sex. In human epidemiologic research, race is almost always a studied variable. In clinical and basic medical research, looking at the impact of race on this, that, or the other is commonplace. “Mixed race not otherwise specified” is ubiquitous in the United States yet blithely ignored by most who tally these statistics. Race is rarely gene-specific. It is more of a social and cultural construct but with plainly visible overt phenotypic markers — an almost infinite mix of daily reality.

Our country, and much of Western civilization in 2024, is based on the principle that all men are created equal, although the originators of that notion were unaware of their own “equity-challenged” situation.

Many organizations, in and out of government, are now understanding, developing, and implementing programs (and thought/language patterns) to socialize diversity, equity, and inclusion (known as DEI) into their culture. It should not be surprising that many who prefer the status quo are not happy with the pressure from this movement and are using whatever methods are available to them to prevent full DEI. Such it always is.

The trusty Copilot from Bing provides these definitions:

• Diversity refers to the presence of variety within the organizational workforce. This includes aspects such as gender, culture, ethnicity, religion, disability, age, and opinion.
• Equity encompasses concepts of fairness and justice. It involves fair compensation, substantive equality, and addressing societal disparities. Equity also considers unique circumstances and adjusts treatment to achieve equal outcomes.
• Inclusion focuses on creating an organizational culture where all employees feel heard, fostering a sense of belonging and integration.

I am more than proud that my old domain of peer-reviewed, primary source, medical (and science) journals is taking a leading role in this noble, necessary, and long overdue movement for medicine.

As the central repository and transmitter of new medical information, including scientific studies, clinical medicine reports, ethics measures, and education, medical journals (including those deemed prestigious) have historically been among the worst offenders in perpetuating non-DEI objectives in their leadership, staffing, focus, instructions for authors, style manuals, and published materials.

This issue came to a head in March 2021 when a JAMA podcast about racism in American medicine was followed by this promotional tweet: “No physician is racist, so how can there be structural racism in health care?”

Reactions and actions were rapid, strong, and decisive. After an interregnum at JAMA, a new editor in chief, Kirsten Bibbins-Domingo, PhD, MD, MAS, was named. She and her large staff of editors and editorial board members from the multijournal JAMA Network joined a worldwide movement of (currently) 56 publishing organizations representing 15,000 journals called the Joint Commitment for Action on Inclusion and Diversity in Publishing.

A recent JAMA editorial with 29 authors describes the entire commitment initiative of publishers-editors. It reports JAMA Network data from 2023 and 2024 from surveys of 455 editors (a 91% response rate) about their own gender (five choices), ethnic origins or geographic ancestry (13 choices), and race (eight choices), demonstrating considerable progress toward DEI goals. The survey’s complex multinational classifications may not jibe with the categorizations used in some countries (too bad that “mixed” is not “mixed in” — a missed opportunity).

This encouraging movement will not fix it all. But when people of certain groups are represented at the table, that point of view is far more likely to make it into the lexicon, language, and omnipresent work products, potentially changing cultural norms. Even the measurement of movement related to disparity in healthcare is marred by frequent variations of data accuracy. More consistency in what to measure can help a lot, and the medical literature can be very influential.

A personal anecdote: When I was a professor at UC Davis in 1978, Allan Bakke, MD, was my student. Some of you will remember the saga of affirmative action on admissions, which was just revisited in the light of a recent decision by the US Supreme Court.

Back in 1978, the dean at UC Davis told me that he kept two file folders on the admission processes in different desk drawers. One categorized all applicants and enrollees by race, and the other did not. Depending on who came to visit and ask questions, he would choose one or the other file to share once he figured out what they were looking for (this is not a joke).

The strength of the current active political pushback against the entire DEI movement has deep roots and should not be underestimated. There will be a lot of to-ing and fro-ing.

French writer Victor Hugo is credited with stating, “There is nothing as powerful as an idea whose time has come.” A majority of Americans, physicians, and other healthcare professionals believe in basic fairness. The time for DEI in all aspects of medicine is now.

Dr. Lundberg, editor in chief of Cancer Commons, disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.

Please note that this is a commentary, an opinion piece: my opinion. The statements here do not necessarily represent those of this news organization or any of the myriad people or institutions that comprise this corner of the human universe.

Some days, speaking as a long-time physician and editor, I wish that there were no such things as race or ethnicity or even geographic origin for that matter. We can’t get away from sex, gender, disability, age, or culture. I’m not sure about religion. I wish people were just people.

But race is deeply embedded in the American experience — an almost invisible but inevitable presence in all of our thoughts and expressions about human activities.

In medical education (for eons it seems) the student has been taught to mention race in the first sentence of a given patient presentation, along with age and sex. In human epidemiologic research, race is almost always a studied variable. In clinical and basic medical research, looking at the impact of race on this, that, or the other is commonplace. “Mixed race not otherwise specified” is ubiquitous in the United States yet blithely ignored by most who tally these statistics. Race is rarely gene-specific. It is more of a social and cultural construct but with plainly visible overt phenotypic markers — an almost infinite mix of daily reality.

Our country, and much of Western civilization in 2024, is based on the principle that all men are created equal, although the originators of that notion were unaware of their own “equity-challenged” situation.

Many organizations, in and out of government, are now understanding, developing, and implementing programs (and thought/language patterns) to socialize diversity, equity, and inclusion (known as DEI) into their culture. It should not be surprising that many who prefer the status quo are not happy with the pressure from this movement and are using whatever methods are available to them to prevent full DEI. Such it always is.

The trusty Copilot from Bing provides these definitions:

• Diversity refers to the presence of variety within the organizational workforce. This includes aspects such as gender, culture, ethnicity, religion, disability, age, and opinion.
• Equity encompasses concepts of fairness and justice. It involves fair compensation, substantive equality, and addressing societal disparities. Equity also considers unique circumstances and adjusts treatment to achieve equal outcomes.
• Inclusion focuses on creating an organizational culture where all employees feel heard, fostering a sense of belonging and integration.

I am more than proud that my old domain of peer-reviewed, primary source, medical (and science) journals is taking a leading role in this noble, necessary, and long overdue movement for medicine.

As the central repository and transmitter of new medical information, including scientific studies, clinical medicine reports, ethics measures, and education, medical journals (including those deemed prestigious) have historically been among the worst offenders in perpetuating non-DEI objectives in their leadership, staffing, focus, instructions for authors, style manuals, and published materials.

This issue came to a head in March 2021 when a JAMA podcast about racism in American medicine was followed by this promotional tweet: “No physician is racist, so how can there be structural racism in health care?”

Reactions and actions were rapid, strong, and decisive. After an interregnum at JAMA, a new editor in chief, Kirsten Bibbins-Domingo, PhD, MD, MAS, was named. She and her large staff of editors and editorial board members from the multijournal JAMA Network joined a worldwide movement of (currently) 56 publishing organizations representing 15,000 journals called the Joint Commitment for Action on Inclusion and Diversity in Publishing.

A recent JAMA editorial with 29 authors describes the entire commitment initiative of publishers-editors. It reports JAMA Network data from 2023 and 2024 from surveys of 455 editors (a 91% response rate) about their own gender (five choices), ethnic origins or geographic ancestry (13 choices), and race (eight choices), demonstrating considerable progress toward DEI goals. The survey’s complex multinational classifications may not jibe with the categorizations used in some countries (too bad that “mixed” is not “mixed in” — a missed opportunity).

This encouraging movement will not fix it all. But when people of certain groups are represented at the table, that point of view is far more likely to make it into the lexicon, language, and omnipresent work products, potentially changing cultural norms. Even the measurement of movement related to disparity in healthcare is marred by frequent variations of data accuracy. More consistency in what to measure can help a lot, and the medical literature can be very influential.

A personal anecdote: When I was a professor at UC Davis in 1978, Allan Bakke, MD, was my student. Some of you will remember the saga of affirmative action on admissions, which was just revisited in the light of a recent decision by the US Supreme Court.

Back in 1978, the dean at UC Davis told me that he kept two file folders on the admission processes in different desk drawers. One categorized all applicants and enrollees by race, and the other did not. Depending on who came to visit and ask questions, he would choose one or the other file to share once he figured out what they were looking for (this is not a joke).

The strength of the current active political pushback against the entire DEI movement has deep roots and should not be underestimated. There will be a lot of to-ing and fro-ing.

French writer Victor Hugo is credited with stating, “There is nothing as powerful as an idea whose time has come.” A majority of Americans, physicians, and other healthcare professionals believe in basic fairness. The time for DEI in all aspects of medicine is now.

Dr. Lundberg, editor in chief of Cancer Commons, disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.

In most Western countries, professional standards dictate that physicians should practice medicine with compassion. Patients also expect compassionate care from physicians because it represents a model capable of providing greater patient satisfaction, fostering better doctor-patient relationships, and enabling better psychological states among patients.

The etymology of the term “compassion” derives from the Latin roots “com,” meaning “together with,” and “pati,” meaning “to endure or suffer.” When discussing compassion, it is necessary to distinguish it from empathy, a term generally used to refer to cognitive or emotional processes in which the perspective of the other (in this case, the patient) is taken. Compassion implies or requires empathy and includes the desire to help or alleviate the suffering of others. Compassion in the medical context is likely a specific instance of a more complex adaptive system that has evolved, not only among humans, to motivate recognition and assistance when others suffer.
 

Compassion Fatigue

Physicians’ compassion is expected by patients and the profession. It is fundamental for effective clinical practice. Although compassion is central to medical practice, most research related to the topic has focused on “compassion fatigue,” which is understood as a specific type of professional burnout, as if physicians had a limited reserve of compassion that dwindles or becomes exhausted with use or overuse. This is one aspect of a much more complex problem, in which compassion represents the endpoint of a dynamic process that encompasses the influences of the physician, the patient, the clinic, and the institution.

Compassion Capacity: Conditioning Factors

Chronic exposure of physicians to conflicting work demands may be associated with the depletion of their psychological resources and, consequently, emotional and cognitive fatigue that can contribute to poorer work outcomes, including the ability to express compassion.

Rates of professional burnout in medicine are increasing. The driving factors of this phenomenon are largely rooted in organizations and healthcare systems and include excessive workloads, inefficient work processes, administrative burdens, and lack of input or control by physicians regarding issues concerning their work life. The outcome often is early retirement of physicians, a current, increasingly widespread phenomenon and a critical issue not only for the Italian National Health Service but also for other healthcare systems worldwide.
 

Organizational and Personal Values

There is no clear empirical evidence supporting the hypothesis that working in healthcare environments experienced as discrepant with one’s own values has negative effects on key professional outcomes. However, a study published in the Journal of Internal Medicine highlighted the overall negative effect of misalignment between system values and physicians’ personal values, including impaired ability to provide compassionate care, as well as reduced job satisfaction, burnout, absenteeism, and considering the possibility of early retirement. Results from 1000 surveyed professionals indicate that physicians’ subjective competence in providing compassionate care may remain high, but their ability to express it is compromised. From data analysis, the authors hypothesize that when working in environments with discrepant values, occupational contingencies may repeatedly require physicians to set aside their personal values, which can lead them to refrain from using available skills to keep their performance in line with organizational requirements.

These results and hypotheses are not consistent with the notion of compassion fatigue as a reflection of the cost of care resulting from exposure to repeated suffering. Previous evidence shows that expressing compassion in healthcare facilitates greater understanding, suggesting that providing compassion does not impoverish physicians but rather supports them in the effectiveness of interventions and in their satisfaction.

In summary, this study suggests that what prevents compassion is the inability to provide it when hindered by factors related to the situation in which the physician operates. Improving compassion does not simply depend on motivating individual professionals to be more compassionate or on promoting fundamental skills, but probably on the creation of organizational and clinical conditions in which physician compassion can thrive.

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

In most Western countries, professional standards dictate that physicians should practice medicine with compassion. Patients also expect compassionate care from physicians because it represents a model capable of providing greater patient satisfaction, fostering better doctor-patient relationships, and enabling better psychological states among patients.

The etymology of the term “compassion” derives from the Latin roots “com,” meaning “together with,” and “pati,” meaning “to endure or suffer.” When discussing compassion, it is necessary to distinguish it from empathy, a term generally used to refer to cognitive or emotional processes in which the perspective of the other (in this case, the patient) is taken. Compassion implies or requires empathy and includes the desire to help or alleviate the suffering of others. Compassion in the medical context is likely a specific instance of a more complex adaptive system that has evolved, not only among humans, to motivate recognition and assistance when others suffer.
 

Compassion Fatigue

Physicians’ compassion is expected by patients and the profession. It is fundamental for effective clinical practice. Although compassion is central to medical practice, most research related to the topic has focused on “compassion fatigue,” which is understood as a specific type of professional burnout, as if physicians had a limited reserve of compassion that dwindles or becomes exhausted with use or overuse. This is one aspect of a much more complex problem, in which compassion represents the endpoint of a dynamic process that encompasses the influences of the physician, the patient, the clinic, and the institution.

Compassion Capacity: Conditioning Factors

Chronic exposure of physicians to conflicting work demands may be associated with the depletion of their psychological resources and, consequently, emotional and cognitive fatigue that can contribute to poorer work outcomes, including the ability to express compassion.

Rates of professional burnout in medicine are increasing. The driving factors of this phenomenon are largely rooted in organizations and healthcare systems and include excessive workloads, inefficient work processes, administrative burdens, and lack of input or control by physicians regarding issues concerning their work life. The outcome often is early retirement of physicians, a current, increasingly widespread phenomenon and a critical issue not only for the Italian National Health Service but also for other healthcare systems worldwide.
 

Organizational and Personal Values

There is no clear empirical evidence supporting the hypothesis that working in healthcare environments experienced as discrepant with one’s own values has negative effects on key professional outcomes. However, a study published in the Journal of Internal Medicine highlighted the overall negative effect of misalignment between system values and physicians’ personal values, including impaired ability to provide compassionate care, as well as reduced job satisfaction, burnout, absenteeism, and considering the possibility of early retirement. Results from 1000 surveyed professionals indicate that physicians’ subjective competence in providing compassionate care may remain high, but their ability to express it is compromised. From data analysis, the authors hypothesize that when working in environments with discrepant values, occupational contingencies may repeatedly require physicians to set aside their personal values, which can lead them to refrain from using available skills to keep their performance in line with organizational requirements.

These results and hypotheses are not consistent with the notion of compassion fatigue as a reflection of the cost of care resulting from exposure to repeated suffering. Previous evidence shows that expressing compassion in healthcare facilitates greater understanding, suggesting that providing compassion does not impoverish physicians but rather supports them in the effectiveness of interventions and in their satisfaction.

In summary, this study suggests that what prevents compassion is the inability to provide it when hindered by factors related to the situation in which the physician operates. Improving compassion does not simply depend on motivating individual professionals to be more compassionate or on promoting fundamental skills, but probably on the creation of organizational and clinical conditions in which physician compassion can thrive.

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

In most Western countries, professional standards dictate that physicians should practice medicine with compassion. Patients also expect compassionate care from physicians because it represents a model capable of providing greater patient satisfaction, fostering better doctor-patient relationships, and enabling better psychological states among patients.

The etymology of the term “compassion” derives from the Latin roots “com,” meaning “together with,” and “pati,” meaning “to endure or suffer.” When discussing compassion, it is necessary to distinguish it from empathy, a term generally used to refer to cognitive or emotional processes in which the perspective of the other (in this case, the patient) is taken. Compassion implies or requires empathy and includes the desire to help or alleviate the suffering of others. Compassion in the medical context is likely a specific instance of a more complex adaptive system that has evolved, not only among humans, to motivate recognition and assistance when others suffer.
 

Compassion Fatigue

Physicians’ compassion is expected by patients and the profession. It is fundamental for effective clinical practice. Although compassion is central to medical practice, most research related to the topic has focused on “compassion fatigue,” which is understood as a specific type of professional burnout, as if physicians had a limited reserve of compassion that dwindles or becomes exhausted with use or overuse. This is one aspect of a much more complex problem, in which compassion represents the endpoint of a dynamic process that encompasses the influences of the physician, the patient, the clinic, and the institution.

Compassion Capacity: Conditioning Factors

Chronic exposure of physicians to conflicting work demands may be associated with the depletion of their psychological resources and, consequently, emotional and cognitive fatigue that can contribute to poorer work outcomes, including the ability to express compassion.

Rates of professional burnout in medicine are increasing. The driving factors of this phenomenon are largely rooted in organizations and healthcare systems and include excessive workloads, inefficient work processes, administrative burdens, and lack of input or control by physicians regarding issues concerning their work life. The outcome often is early retirement of physicians, a current, increasingly widespread phenomenon and a critical issue not only for the Italian National Health Service but also for other healthcare systems worldwide.
 

Organizational and Personal Values

There is no clear empirical evidence supporting the hypothesis that working in healthcare environments experienced as discrepant with one’s own values has negative effects on key professional outcomes. However, a study published in the Journal of Internal Medicine highlighted the overall negative effect of misalignment between system values and physicians’ personal values, including impaired ability to provide compassionate care, as well as reduced job satisfaction, burnout, absenteeism, and considering the possibility of early retirement. Results from 1000 surveyed professionals indicate that physicians’ subjective competence in providing compassionate care may remain high, but their ability to express it is compromised. From data analysis, the authors hypothesize that when working in environments with discrepant values, occupational contingencies may repeatedly require physicians to set aside their personal values, which can lead them to refrain from using available skills to keep their performance in line with organizational requirements.

These results and hypotheses are not consistent with the notion of compassion fatigue as a reflection of the cost of care resulting from exposure to repeated suffering. Previous evidence shows that expressing compassion in healthcare facilitates greater understanding, suggesting that providing compassion does not impoverish physicians but rather supports them in the effectiveness of interventions and in their satisfaction.

In summary, this study suggests that what prevents compassion is the inability to provide it when hindered by factors related to the situation in which the physician operates. Improving compassion does not simply depend on motivating individual professionals to be more compassionate or on promoting fundamental skills, but probably on the creation of organizational and clinical conditions in which physician compassion can thrive.

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

Whether you have totally bought into the “obesity is a disease” paradigm or are still in denial, you must admit that the development of a suite of effective weight loss medications has created a tsunami of interest and economic activity in this country on a scale not seen since the Beanie Baby craze of the mid-1990s. But, obesity management is serious business. While most of those soft cuddly toys are gathering dust in shoeboxes across this country, weight loss medications are likely to be the vanguard of rapidly evolving revolution in healthcare management that will be with us for the foreseeable future.

Most thoughtful folks who purchased Beanie Babies in 1994 had no illusions and knew that in a few short years this bubble of soft cuddly toys was going to burst. However, do those of us on the front line of medical care know what the future holds for the patients who are being prescribed or are scavenging those too-good-to-be-true medications?

My guess is that in the long run we will need a combination of some serious tinkering by the pharmaceutical industry and a trek up some steep learning curves before we eventually arrive at a safe and effective chemical management for obese patients. I recently read an article by an obesity management specialist at Harvard Medical School who voiced her concerns that we are missing an opportunity to make this explosion of popularity in GLP-1 drugs into an important learning experience.

In an opinion piece in JAMA Internal Medicine, Dr. Fatima Cody Stanford and her coauthors argue that we, actually the US Food and Drug Administration (FDA), is over-focused on weight loss in determining the efficacy of anti-obesity medications. Dr. Stanford and colleagues point out that when a patient loses weight it isn’t just fat — it is complex process that may include muscle and bone mineralization as well. She has consulted for at least one obesity-drug manufacturer and says that these companies have the resources to produce data on body composition that could help clinicians create management plans that would address the patients’ overall health. However, the FDA has not demanded this broader and deeper assessment of general health when reviewing the drug trials.

I don’t think we can blame the patients for not asking whether they will healthier while taking these medications. They have already spent a lifetime, even if it is just a decade, of suffering as the “fat one.” A new outfit and a look in the mirror can’t help but make them feel better ... in the short term anyway. We as physicians must shoulder some of the blame for focusing on weight. Our spoken or unspoken message has been “Lose weight and you will be healthier.” We may make our message sound more professional by tossing around terms like “BMI,” but as Dr. Stanford points out, “we have known BMI is a flawed metric for a long time.”

There is the notion that obese people have had to build more muscle to help them carry around the extra weight, so that we should expect them to lose that extra muscle along with the fat. However, in older adults there is an entity called sarcopenic obesity, in which the patient doesn’t have that extra muscle to lose.

In a brief Internet research venture, I could find little on the subject of muscle loss and GLP-1s, other than “it can happen.” And, nothing on the effect in adolescents. And that is one of Dr. Stanford’s points. We just don’t know. She said that looking at body composition can be costly and not something that the clinician can do. However, as far as muscle mass is concerned, we need to be alert to the potential for loss. Simple assessments of strength can help us tailor our management to the specific patient’s need.

The bottom line is this ... now that we have effective medications for “weight loss,” we need to redefine the relationship between weight and health. “We” means us as clinicians. It means the folks at FDA. And, if we can improve our messaging, it will osmose to the rest of the population. Just because you’ve dropped two dress sizes doesn’t mean you’re healthy.

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

Whether you have totally bought into the “obesity is a disease” paradigm or are still in denial, you must admit that the development of a suite of effective weight loss medications has created a tsunami of interest and economic activity in this country on a scale not seen since the Beanie Baby craze of the mid-1990s. But, obesity management is serious business. While most of those soft cuddly toys are gathering dust in shoeboxes across this country, weight loss medications are likely to be the vanguard of rapidly evolving revolution in healthcare management that will be with us for the foreseeable future.

Most thoughtful folks who purchased Beanie Babies in 1994 had no illusions and knew that in a few short years this bubble of soft cuddly toys was going to burst. However, do those of us on the front line of medical care know what the future holds for the patients who are being prescribed or are scavenging those too-good-to-be-true medications?

My guess is that in the long run we will need a combination of some serious tinkering by the pharmaceutical industry and a trek up some steep learning curves before we eventually arrive at a safe and effective chemical management for obese patients. I recently read an article by an obesity management specialist at Harvard Medical School who voiced her concerns that we are missing an opportunity to make this explosion of popularity in GLP-1 drugs into an important learning experience.

In an opinion piece in JAMA Internal Medicine, Dr. Fatima Cody Stanford and her coauthors argue that we, actually the US Food and Drug Administration (FDA), is over-focused on weight loss in determining the efficacy of anti-obesity medications. Dr. Stanford and colleagues point out that when a patient loses weight it isn’t just fat — it is complex process that may include muscle and bone mineralization as well. She has consulted for at least one obesity-drug manufacturer and says that these companies have the resources to produce data on body composition that could help clinicians create management plans that would address the patients’ overall health. However, the FDA has not demanded this broader and deeper assessment of general health when reviewing the drug trials.

I don’t think we can blame the patients for not asking whether they will healthier while taking these medications. They have already spent a lifetime, even if it is just a decade, of suffering as the “fat one.” A new outfit and a look in the mirror can’t help but make them feel better ... in the short term anyway. We as physicians must shoulder some of the blame for focusing on weight. Our spoken or unspoken message has been “Lose weight and you will be healthier.” We may make our message sound more professional by tossing around terms like “BMI,” but as Dr. Stanford points out, “we have known BMI is a flawed metric for a long time.”

There is the notion that obese people have had to build more muscle to help them carry around the extra weight, so that we should expect them to lose that extra muscle along with the fat. However, in older adults there is an entity called sarcopenic obesity, in which the patient doesn’t have that extra muscle to lose.

In a brief Internet research venture, I could find little on the subject of muscle loss and GLP-1s, other than “it can happen.” And, nothing on the effect in adolescents. And that is one of Dr. Stanford’s points. We just don’t know. She said that looking at body composition can be costly and not something that the clinician can do. However, as far as muscle mass is concerned, we need to be alert to the potential for loss. Simple assessments of strength can help us tailor our management to the specific patient’s need.

The bottom line is this ... now that we have effective medications for “weight loss,” we need to redefine the relationship between weight and health. “We” means us as clinicians. It means the folks at FDA. And, if we can improve our messaging, it will osmose to the rest of the population. Just because you’ve dropped two dress sizes doesn’t mean you’re healthy.

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

Whether you have totally bought into the “obesity is a disease” paradigm or are still in denial, you must admit that the development of a suite of effective weight loss medications has created a tsunami of interest and economic activity in this country on a scale not seen since the Beanie Baby craze of the mid-1990s. But, obesity management is serious business. While most of those soft cuddly toys are gathering dust in shoeboxes across this country, weight loss medications are likely to be the vanguard of rapidly evolving revolution in healthcare management that will be with us for the foreseeable future.

Most thoughtful folks who purchased Beanie Babies in 1994 had no illusions and knew that in a few short years this bubble of soft cuddly toys was going to burst. However, do those of us on the front line of medical care know what the future holds for the patients who are being prescribed or are scavenging those too-good-to-be-true medications?

My guess is that in the long run we will need a combination of some serious tinkering by the pharmaceutical industry and a trek up some steep learning curves before we eventually arrive at a safe and effective chemical management for obese patients. I recently read an article by an obesity management specialist at Harvard Medical School who voiced her concerns that we are missing an opportunity to make this explosion of popularity in GLP-1 drugs into an important learning experience.

In an opinion piece in JAMA Internal Medicine, Dr. Fatima Cody Stanford and her coauthors argue that we, actually the US Food and Drug Administration (FDA), is over-focused on weight loss in determining the efficacy of anti-obesity medications. Dr. Stanford and colleagues point out that when a patient loses weight it isn’t just fat — it is complex process that may include muscle and bone mineralization as well. She has consulted for at least one obesity-drug manufacturer and says that these companies have the resources to produce data on body composition that could help clinicians create management plans that would address the patients’ overall health. However, the FDA has not demanded this broader and deeper assessment of general health when reviewing the drug trials.

I don’t think we can blame the patients for not asking whether they will healthier while taking these medications. They have already spent a lifetime, even if it is just a decade, of suffering as the “fat one.” A new outfit and a look in the mirror can’t help but make them feel better ... in the short term anyway. We as physicians must shoulder some of the blame for focusing on weight. Our spoken or unspoken message has been “Lose weight and you will be healthier.” We may make our message sound more professional by tossing around terms like “BMI,” but as Dr. Stanford points out, “we have known BMI is a flawed metric for a long time.”

There is the notion that obese people have had to build more muscle to help them carry around the extra weight, so that we should expect them to lose that extra muscle along with the fat. However, in older adults there is an entity called sarcopenic obesity, in which the patient doesn’t have that extra muscle to lose.

In a brief Internet research venture, I could find little on the subject of muscle loss and GLP-1s, other than “it can happen.” And, nothing on the effect in adolescents. And that is one of Dr. Stanford’s points. We just don’t know. She said that looking at body composition can be costly and not something that the clinician can do. However, as far as muscle mass is concerned, we need to be alert to the potential for loss. Simple assessments of strength can help us tailor our management to the specific patient’s need.

The bottom line is this ... now that we have effective medications for “weight loss,” we need to redefine the relationship between weight and health. “We” means us as clinicians. It means the folks at FDA. And, if we can improve our messaging, it will osmose to the rest of the population. Just because you’ve dropped two dress sizes doesn’t mean you’re healthy.

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