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A new diagnostic test can accurately distinguish osteoarthritis (OA) from inflammatory arthritis using two synovial fluid biomarkers, according to research published in the Journal of Orthopaedic Research on December 18, 2024.

However, experts question whether such a test would be useful.

“The need would seem to be fairly limited, mostly those with single joint involvement and a lack of other systemic features to specify a diagnosis, which is not that common, at least in rheumatology, where there are usually features in the history and physical that can clarify the diagnosis,” said Amanda E. Nelson, MD, MSCR, professor of medicine in the Division of Rheumatology, Allergy, and Immunology at the University of North Carolina at Chapel Hill. She was not involved with the research.

The test uses an algorithm that incorporates concentrations of cartilage oligomeric matrix protein (COMP) and interleukin 8 (IL-8) in synovial fluid. The researchers hypothesized that a ratio of the two biomarkers could distinguish between primary OA and other inflammatory arthritic diagnoses.

“Primary OA is unlikely when either COMP concentration or COMP/IL‐8 ratio in the synovial fluid is low since these conditions indicate either lack of cartilage degradation or presence of high inflammation,” wrote Daniel Keter and coauthors at CD Diagnostics, Claymont, Delaware, and CD Laboratories, Towson, Maryland. “In contrast, a high COMP concentration result in combination with high COMP/IL‐8 ratio would be suggestive of low inflammation in the setting of cartilage deterioration, which is indicative of primary OA.”

In patients with OA, synovial fluid can be difficult to aspirate in sufficient amounts for testing, Nelson said.

“If synovial fluid is present and able to be aspirated, it is unclear if this test has any benefit over a simple, standard cell count and crystal assessment, which can also distinguish between osteoarthritis and more inflammatory arthritides,” she said.

 

Differentiating OA

To test this potential diagnostic algorithm, researchers obtained 171 knee synovial fluid samples from approved clinical remnant sample sources and a biovendor. All samples were annotated with an existing arthritic diagnosis, including 54 with primary OA, 57 with rheumatoid arthritis (RA), 30 with crystal arthritis (CA), and 30 with native septic arthritis (NSA).

Researchers assigned a CA diagnosis based on the presence of monosodium urate or calcium pyrophosphate dehydrate crystals in the synovial fluid, and NSA was determined via the Synovasure Alpha Defensin test. OA was confirmed via radiograph as Kellgren‐Lawrence grades 2‐4 with no other arthritic diagnoses. RA samples were purchased via a biovendor, and researchers were not provided with diagnosis‐confirming data.

All samples were randomized and blinded before testing, and researchers used enzyme-linked immunosorbent assay tests for both COMP and IL-8 biomarkers.

Of the 54 OA samples, 47 tested positive for OA using the COMP + COMP/IL-8 ratio algorithm. Of the 117 samples with inflammatory arthritis, 13 tested positive for OA. Overall, the diagnostic algorithm demonstrated a clinical sensitivity of 87.0% and specificity of 88.9%. The positive predictive value was 78.3%, while the negative predictive value was 93.7%.

 

Unclear Clinical Need

Nelson noted that while this test aims to differentiate between arthritic diagnoses, patients can also have multiple conditions.

“Many individuals with rheumatoid arthritis will develop osteoarthritis, but they can have both, so a yes/no test is of unclear utility,” she said. OA and calcium pyrophosphate deposition (CPPD) disease can often occur together, “but the driver is really the OA, and the CPPD is present but not actively inflammatory,” she continued. “Septic arthritis should be readily distinguishable by cell count alone [and again, can coexist with any of the other conditions], and a thorough history and physical should be able to differentiate in most cases.”

While these results from this study are “reasonably impressive,” more clinical information is needed to interpret these results, added C. Kent Kwoh, MD, director of the University of Arizona Arthritis Center and professor of medicine and medical imaging at the University of Arizona College of Medicine, Tucson, Arizona.

Because the study is retrospective in nature and researchers obtained specimens from different sources, it was not clear if these patients were being treated when these samples were taken and if their various conditions were controlled or flaring.

“I would say this is a reasonable first step,” Kwoh said. “We would need prospective studies, more clinical characterization, and potentially longitudinal studies to understand when this test may be useful.”

This research was internally funded by Zimmer Biomet. All authors were employees of CD Diagnostics or CD Laboratories, both of which are subsidiaries of Zimmer Biomet. Kwoh reported receiving grants or contracts with AbbVie, Artiva, Eli Lilly and Company, Bristol Myers Squibb, Cumberland, Pfizer, GSK, and Galapagos, and consulting fees from TrialSpark/Formation Bio, Express Scripts, GSK, TLC BioSciences, and AposHealth. He participates on Data Safety Monitoring or Advisory Boards of Moebius Medical, Sun Pharma, Novartis, Xalud, and Kolon TissueGene. Nelson reported no relevant disclosures.

 

A version of this article appeared on Medscape.com.

A new diagnostic test can accurately distinguish osteoarthritis (OA) from inflammatory arthritis using two synovial fluid biomarkers, according to research published in the Journal of Orthopaedic Research on December 18, 2024.

However, experts question whether such a test would be useful.

“The need would seem to be fairly limited, mostly those with single joint involvement and a lack of other systemic features to specify a diagnosis, which is not that common, at least in rheumatology, where there are usually features in the history and physical that can clarify the diagnosis,” said Amanda E. Nelson, MD, MSCR, professor of medicine in the Division of Rheumatology, Allergy, and Immunology at the University of North Carolina at Chapel Hill. She was not involved with the research.

The test uses an algorithm that incorporates concentrations of cartilage oligomeric matrix protein (COMP) and interleukin 8 (IL-8) in synovial fluid. The researchers hypothesized that a ratio of the two biomarkers could distinguish between primary OA and other inflammatory arthritic diagnoses.

“Primary OA is unlikely when either COMP concentration or COMP/IL‐8 ratio in the synovial fluid is low since these conditions indicate either lack of cartilage degradation or presence of high inflammation,” wrote Daniel Keter and coauthors at CD Diagnostics, Claymont, Delaware, and CD Laboratories, Towson, Maryland. “In contrast, a high COMP concentration result in combination with high COMP/IL‐8 ratio would be suggestive of low inflammation in the setting of cartilage deterioration, which is indicative of primary OA.”

In patients with OA, synovial fluid can be difficult to aspirate in sufficient amounts for testing, Nelson said.

“If synovial fluid is present and able to be aspirated, it is unclear if this test has any benefit over a simple, standard cell count and crystal assessment, which can also distinguish between osteoarthritis and more inflammatory arthritides,” she said.

 

Differentiating OA

To test this potential diagnostic algorithm, researchers obtained 171 knee synovial fluid samples from approved clinical remnant sample sources and a biovendor. All samples were annotated with an existing arthritic diagnosis, including 54 with primary OA, 57 with rheumatoid arthritis (RA), 30 with crystal arthritis (CA), and 30 with native septic arthritis (NSA).

Researchers assigned a CA diagnosis based on the presence of monosodium urate or calcium pyrophosphate dehydrate crystals in the synovial fluid, and NSA was determined via the Synovasure Alpha Defensin test. OA was confirmed via radiograph as Kellgren‐Lawrence grades 2‐4 with no other arthritic diagnoses. RA samples were purchased via a biovendor, and researchers were not provided with diagnosis‐confirming data.

All samples were randomized and blinded before testing, and researchers used enzyme-linked immunosorbent assay tests for both COMP and IL-8 biomarkers.

Of the 54 OA samples, 47 tested positive for OA using the COMP + COMP/IL-8 ratio algorithm. Of the 117 samples with inflammatory arthritis, 13 tested positive for OA. Overall, the diagnostic algorithm demonstrated a clinical sensitivity of 87.0% and specificity of 88.9%. The positive predictive value was 78.3%, while the negative predictive value was 93.7%.

 

Unclear Clinical Need

Nelson noted that while this test aims to differentiate between arthritic diagnoses, patients can also have multiple conditions.

“Many individuals with rheumatoid arthritis will develop osteoarthritis, but they can have both, so a yes/no test is of unclear utility,” she said. OA and calcium pyrophosphate deposition (CPPD) disease can often occur together, “but the driver is really the OA, and the CPPD is present but not actively inflammatory,” she continued. “Septic arthritis should be readily distinguishable by cell count alone [and again, can coexist with any of the other conditions], and a thorough history and physical should be able to differentiate in most cases.”

While these results from this study are “reasonably impressive,” more clinical information is needed to interpret these results, added C. Kent Kwoh, MD, director of the University of Arizona Arthritis Center and professor of medicine and medical imaging at the University of Arizona College of Medicine, Tucson, Arizona.

Because the study is retrospective in nature and researchers obtained specimens from different sources, it was not clear if these patients were being treated when these samples were taken and if their various conditions were controlled or flaring.

“I would say this is a reasonable first step,” Kwoh said. “We would need prospective studies, more clinical characterization, and potentially longitudinal studies to understand when this test may be useful.”

This research was internally funded by Zimmer Biomet. All authors were employees of CD Diagnostics or CD Laboratories, both of which are subsidiaries of Zimmer Biomet. Kwoh reported receiving grants or contracts with AbbVie, Artiva, Eli Lilly and Company, Bristol Myers Squibb, Cumberland, Pfizer, GSK, and Galapagos, and consulting fees from TrialSpark/Formation Bio, Express Scripts, GSK, TLC BioSciences, and AposHealth. He participates on Data Safety Monitoring or Advisory Boards of Moebius Medical, Sun Pharma, Novartis, Xalud, and Kolon TissueGene. Nelson reported no relevant disclosures.

 

A version of this article appeared on Medscape.com.

A new diagnostic test can accurately distinguish osteoarthritis (OA) from inflammatory arthritis using two synovial fluid biomarkers, according to research published in the Journal of Orthopaedic Research on December 18, 2024.

However, experts question whether such a test would be useful.

“The need would seem to be fairly limited, mostly those with single joint involvement and a lack of other systemic features to specify a diagnosis, which is not that common, at least in rheumatology, where there are usually features in the history and physical that can clarify the diagnosis,” said Amanda E. Nelson, MD, MSCR, professor of medicine in the Division of Rheumatology, Allergy, and Immunology at the University of North Carolina at Chapel Hill. She was not involved with the research.

The test uses an algorithm that incorporates concentrations of cartilage oligomeric matrix protein (COMP) and interleukin 8 (IL-8) in synovial fluid. The researchers hypothesized that a ratio of the two biomarkers could distinguish between primary OA and other inflammatory arthritic diagnoses.

“Primary OA is unlikely when either COMP concentration or COMP/IL‐8 ratio in the synovial fluid is low since these conditions indicate either lack of cartilage degradation or presence of high inflammation,” wrote Daniel Keter and coauthors at CD Diagnostics, Claymont, Delaware, and CD Laboratories, Towson, Maryland. “In contrast, a high COMP concentration result in combination with high COMP/IL‐8 ratio would be suggestive of low inflammation in the setting of cartilage deterioration, which is indicative of primary OA.”

In patients with OA, synovial fluid can be difficult to aspirate in sufficient amounts for testing, Nelson said.

“If synovial fluid is present and able to be aspirated, it is unclear if this test has any benefit over a simple, standard cell count and crystal assessment, which can also distinguish between osteoarthritis and more inflammatory arthritides,” she said.

 

Differentiating OA

To test this potential diagnostic algorithm, researchers obtained 171 knee synovial fluid samples from approved clinical remnant sample sources and a biovendor. All samples were annotated with an existing arthritic diagnosis, including 54 with primary OA, 57 with rheumatoid arthritis (RA), 30 with crystal arthritis (CA), and 30 with native septic arthritis (NSA).

Researchers assigned a CA diagnosis based on the presence of monosodium urate or calcium pyrophosphate dehydrate crystals in the synovial fluid, and NSA was determined via the Synovasure Alpha Defensin test. OA was confirmed via radiograph as Kellgren‐Lawrence grades 2‐4 with no other arthritic diagnoses. RA samples were purchased via a biovendor, and researchers were not provided with diagnosis‐confirming data.

All samples were randomized and blinded before testing, and researchers used enzyme-linked immunosorbent assay tests for both COMP and IL-8 biomarkers.

Of the 54 OA samples, 47 tested positive for OA using the COMP + COMP/IL-8 ratio algorithm. Of the 117 samples with inflammatory arthritis, 13 tested positive for OA. Overall, the diagnostic algorithm demonstrated a clinical sensitivity of 87.0% and specificity of 88.9%. The positive predictive value was 78.3%, while the negative predictive value was 93.7%.

 

Unclear Clinical Need

Nelson noted that while this test aims to differentiate between arthritic diagnoses, patients can also have multiple conditions.

“Many individuals with rheumatoid arthritis will develop osteoarthritis, but they can have both, so a yes/no test is of unclear utility,” she said. OA and calcium pyrophosphate deposition (CPPD) disease can often occur together, “but the driver is really the OA, and the CPPD is present but not actively inflammatory,” she continued. “Septic arthritis should be readily distinguishable by cell count alone [and again, can coexist with any of the other conditions], and a thorough history and physical should be able to differentiate in most cases.”

While these results from this study are “reasonably impressive,” more clinical information is needed to interpret these results, added C. Kent Kwoh, MD, director of the University of Arizona Arthritis Center and professor of medicine and medical imaging at the University of Arizona College of Medicine, Tucson, Arizona.

Because the study is retrospective in nature and researchers obtained specimens from different sources, it was not clear if these patients were being treated when these samples were taken and if their various conditions were controlled or flaring.

“I would say this is a reasonable first step,” Kwoh said. “We would need prospective studies, more clinical characterization, and potentially longitudinal studies to understand when this test may be useful.”

This research was internally funded by Zimmer Biomet. All authors were employees of CD Diagnostics or CD Laboratories, both of which are subsidiaries of Zimmer Biomet. Kwoh reported receiving grants or contracts with AbbVie, Artiva, Eli Lilly and Company, Bristol Myers Squibb, Cumberland, Pfizer, GSK, and Galapagos, and consulting fees from TrialSpark/Formation Bio, Express Scripts, GSK, TLC BioSciences, and AposHealth. He participates on Data Safety Monitoring or Advisory Boards of Moebius Medical, Sun Pharma, Novartis, Xalud, and Kolon TissueGene. Nelson reported no relevant disclosures.

 

A version of this article appeared on Medscape.com.

TOPLINE:

Mannkind expects to submit a request for a supplemental new drug application meeting to the Food and Drug Administration (FDA) for its inhaled human insulin (Afrezza Inhalation Powder). Currently indicated to improve glycemic control in adults with diabetes, the company announced 6-month results from its phase 3 INHALE-1 study of inhaled human insulin in children and adolescents aged 4-17.

METHODOLOGY:

• INHALE-1 is a 26-week, open-label clinical trial that randomized 230 subjects aged 4-17 years with type 1 or type 2 diabetes to either inhaled pre-meal insulin or multiple daily injections (MDI) of rapid-acting insulin analog, both in combination with basal insulin.
• The primary endpoint was a noninferior change in hemoglobin A1c levels, compared with MDI after 26 weeks.
• A 26-week extension phase in which all remaining MDI patients were switched to inhaled insulin is ongoing.

TAKEAWAY:

• In the full intent-to-treat (ITT) population analysis, the between-group difference in mean A1c change over 26 weeks exceeded the prespecified non-inferiority margin of 0.4% (0.435%), but this was largely driven by the variability of a single patient who didn’t adhere to the study protocol.
• A modified ITT analysis excluding that person did not exceed the predetermined threshold of 0.4% (0.370%), thereby establishing noninferiority of inhaled insulin with MDI.
• Over 26 weeks of treatment, there were no differences in lung function parameters between the treatment groups, with mean forced expiratory volume at 1 second (FEV1) at baseline vs 26 weeks of 2.901 liters (99.6% of predicted) vs 2.934 L (96.6%) in the inhaled insulin group and 2.948 L (102.3%) vs 2.957 (98%), respectively, in the MDI group.
• There were no differences between groups or concerns in other safety measures, including hypoglycemia.

IN PRACTICE:

“It was exciting to partner with MannKind and help lead this study to potentially expand the use of inhaled insulin, which is currently used successfully by many adults with diabetes, to a population that hasn’t had a treatment option other than injectable insulin in the history of their care,” said INHALE-1 investigator Roy W. Beck, MD, PhD, founder of the Jaeb Center for Health Research, Tampa, Florida.

“The 6-month results are clinically meaningful and show Afrezza as a potential future treatment option for a growing pediatric population living with type 1 and type 2 diabetes,” Beck added.

 

SOURCE:

The results of the study were announced at a Mannkind press release on December 16, 2024.

SAFETY INFORMATION:

Inhaled insulin is not recommended for the treatment of diabetic ketoacidosis or in patients who smoke or have recently stopped smoking.

Warning: Risk for acute bronchospasm in patients with chronic lung disease

• Acute bronchospasm has been observed in Afrezza-treated patients with asthma and chronic obstructive pulmonary disease (COPD)
• Afrezza is contraindicated in patients with chronic lung disease such as asthma or COPD
• Before initiating Afrezza, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients
• Most common adverse reactions are hypoglycemia, cough, and throat pain or irritation.
•  

DISCLOSURES:

This study was funded by MannKind.

A version of this article appeared on Medscape.com.

TOPLINE:

Mannkind expects to submit a request for a supplemental new drug application meeting to the Food and Drug Administration (FDA) for its inhaled human insulin (Afrezza Inhalation Powder). Currently indicated to improve glycemic control in adults with diabetes, the company announced 6-month results from its phase 3 INHALE-1 study of inhaled human insulin in children and adolescents aged 4-17.

METHODOLOGY:

• INHALE-1 is a 26-week, open-label clinical trial that randomized 230 subjects aged 4-17 years with type 1 or type 2 diabetes to either inhaled pre-meal insulin or multiple daily injections (MDI) of rapid-acting insulin analog, both in combination with basal insulin.
• The primary endpoint was a noninferior change in hemoglobin A1c levels, compared with MDI after 26 weeks.
• A 26-week extension phase in which all remaining MDI patients were switched to inhaled insulin is ongoing.

TAKEAWAY:

• In the full intent-to-treat (ITT) population analysis, the between-group difference in mean A1c change over 26 weeks exceeded the prespecified non-inferiority margin of 0.4% (0.435%), but this was largely driven by the variability of a single patient who didn’t adhere to the study protocol.
• A modified ITT analysis excluding that person did not exceed the predetermined threshold of 0.4% (0.370%), thereby establishing noninferiority of inhaled insulin with MDI.
• Over 26 weeks of treatment, there were no differences in lung function parameters between the treatment groups, with mean forced expiratory volume at 1 second (FEV1) at baseline vs 26 weeks of 2.901 liters (99.6% of predicted) vs 2.934 L (96.6%) in the inhaled insulin group and 2.948 L (102.3%) vs 2.957 (98%), respectively, in the MDI group.
• There were no differences between groups or concerns in other safety measures, including hypoglycemia.

IN PRACTICE:

“It was exciting to partner with MannKind and help lead this study to potentially expand the use of inhaled insulin, which is currently used successfully by many adults with diabetes, to a population that hasn’t had a treatment option other than injectable insulin in the history of their care,” said INHALE-1 investigator Roy W. Beck, MD, PhD, founder of the Jaeb Center for Health Research, Tampa, Florida.

“The 6-month results are clinically meaningful and show Afrezza as a potential future treatment option for a growing pediatric population living with type 1 and type 2 diabetes,” Beck added.

 

SOURCE:

The results of the study were announced at a Mannkind press release on December 16, 2024.

SAFETY INFORMATION:

Inhaled insulin is not recommended for the treatment of diabetic ketoacidosis or in patients who smoke or have recently stopped smoking.

Warning: Risk for acute bronchospasm in patients with chronic lung disease

• Acute bronchospasm has been observed in Afrezza-treated patients with asthma and chronic obstructive pulmonary disease (COPD)
• Afrezza is contraindicated in patients with chronic lung disease such as asthma or COPD
• Before initiating Afrezza, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients
• Most common adverse reactions are hypoglycemia, cough, and throat pain or irritation.
•  

DISCLOSURES:

This study was funded by MannKind.

A version of this article appeared on Medscape.com.

TOPLINE:

Mannkind expects to submit a request for a supplemental new drug application meeting to the Food and Drug Administration (FDA) for its inhaled human insulin (Afrezza Inhalation Powder). Currently indicated to improve glycemic control in adults with diabetes, the company announced 6-month results from its phase 3 INHALE-1 study of inhaled human insulin in children and adolescents aged 4-17.

METHODOLOGY:

• INHALE-1 is a 26-week, open-label clinical trial that randomized 230 subjects aged 4-17 years with type 1 or type 2 diabetes to either inhaled pre-meal insulin or multiple daily injections (MDI) of rapid-acting insulin analog, both in combination with basal insulin.
• The primary endpoint was a noninferior change in hemoglobin A1c levels, compared with MDI after 26 weeks.
• A 26-week extension phase in which all remaining MDI patients were switched to inhaled insulin is ongoing.

TAKEAWAY:

• In the full intent-to-treat (ITT) population analysis, the between-group difference in mean A1c change over 26 weeks exceeded the prespecified non-inferiority margin of 0.4% (0.435%), but this was largely driven by the variability of a single patient who didn’t adhere to the study protocol.
• A modified ITT analysis excluding that person did not exceed the predetermined threshold of 0.4% (0.370%), thereby establishing noninferiority of inhaled insulin with MDI.
• Over 26 weeks of treatment, there were no differences in lung function parameters between the treatment groups, with mean forced expiratory volume at 1 second (FEV1) at baseline vs 26 weeks of 2.901 liters (99.6% of predicted) vs 2.934 L (96.6%) in the inhaled insulin group and 2.948 L (102.3%) vs 2.957 (98%), respectively, in the MDI group.
• There were no differences between groups or concerns in other safety measures, including hypoglycemia.

IN PRACTICE:

“It was exciting to partner with MannKind and help lead this study to potentially expand the use of inhaled insulin, which is currently used successfully by many adults with diabetes, to a population that hasn’t had a treatment option other than injectable insulin in the history of their care,” said INHALE-1 investigator Roy W. Beck, MD, PhD, founder of the Jaeb Center for Health Research, Tampa, Florida.

“The 6-month results are clinically meaningful and show Afrezza as a potential future treatment option for a growing pediatric population living with type 1 and type 2 diabetes,” Beck added.

 

SOURCE:

The results of the study were announced at a Mannkind press release on December 16, 2024.

SAFETY INFORMATION:

Inhaled insulin is not recommended for the treatment of diabetic ketoacidosis or in patients who smoke or have recently stopped smoking.

Warning: Risk for acute bronchospasm in patients with chronic lung disease

• Acute bronchospasm has been observed in Afrezza-treated patients with asthma and chronic obstructive pulmonary disease (COPD)
• Afrezza is contraindicated in patients with chronic lung disease such as asthma or COPD
• Before initiating Afrezza, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients
• Most common adverse reactions are hypoglycemia, cough, and throat pain or irritation.
•  

DISCLOSURES:

This study was funded by MannKind.

A version of this article appeared on Medscape.com.

In the latest effort to address the mental health crisis among adolescents, legislation in California would require social media platforms to come with a “black box” mental health warning label.

Despite growing evidence linking young people’s use of social media to significant health risks including depression, anxiety, and suicidal thoughts, social media companies have failed to be transparent about the risks, said Assembly member Rebecca Bauer-Kahan (D-Orinda), who introduced Assembly Bill (AB) 56.

“AB 56 ensures that families are armed with clear, actionable information to understand these dangers and make decisions that prioritizes their children’s well-being,” she said in a press release.

Bauer-Kahan noted that 95% of teens report using at least one social media platform and that more than one third say they use social media almost constantly.

“There is a powerful profit motive to keep our young people hooked online and engaged and it is exploiting the human psychology with notifications, likes, endless scrolling, and algorithmic amplification that is harming our children every day,” she said at a press conference on December 9 announcing the bill.

The warning labels are an equitable and transparent way to communicate the risks that social media poses to young users, California’s Attorney General Rob Bonta, a sponsor of AB 56, said in a press release.

Speaking at the press conference, Bonta said social media has many “incredible benefits” from giving people an outlet of expression to providing access to critical information but “there is no disputing the fact, it can have an enormously detrimental and dangerous impact on our young people. You cannot debate that. Our children are suffering.”

If AB 56 is successful, he said social media platforms would be required to display a “black box warning” for all users that would appear upon the first use of a platform and weekly thereafter.

The proposed language for the warning label is: “The Surgeon General has advised that there are ample indicators that social media can have a profound risk of harm to the mental health and well-being of children and adolescents.”

“This warning label isn’t a panacea, we know that, but it is another tool in our toolbox. It’s one prong in what has to be a multi-pronged continued, coordinated effort to address this public health crisis,” Bonta said.

Reached for comment, Bonta’s office said sponsorship of the bill was informed by their ongoing work to create a safer online space for children and teens and by the US Surgeon General’s call to Congress to add warning labels to social media.

In June, US Surgeon General Vivek Murthy, MD, said a Surgeon General’s warning label is needed to address the mental health emergency among adolescents and noted that evidence from tobacco studies shows warning labels can increase awareness and change behavior. In September, the attorneys general of 42 states announced their support of the proposal.

Also in September, US Senators John Fetterman (D-PA) and Katie Britt (R-AL) introduced the Stop the Scroll Act to create a mental health warning label requirement for social media platforms.

In a controversial move in November, Australia passed the world’s first law banning social media for children younger than 16 years. The law gives platforms such as TikTok, Facebook, X, Snapchat, and Instagram 1 year to figure out how to implement the ban before facing fines of up 50 million Australian dollars ($33 million) for systemic failures to prevent children younger than 16 years from holding accounts.

 

‘A Broken Fire Alarm’

“Slapping a warning label on social media is like a broken fire alarm going off with no evidence of smoke. It ignores the reality that most teens view social media as an important outlet for social connection,” Todd O’Boyle, with the tech industry policy group Chamber of Progress, said in a statement on AB 56.

He highlighted a 2022 Pew Research Center survey reporting that most teens credit social media with deepening connections and providing a support network and a 2020 study reporting that social media is not a strong or consistent risk factor for depressive symptoms in US adolescents.

O’Boyle predicted that, without strong evidence, AB 56 will run into the same “First Amendment buzzsaw” that has doomed other California kids’ bills.

Pediatrician Jason Nagata, MD, University of California San Francisco, points out in Bonta’s press release that social media can displace time for other healthful activities including sleep, exercise, and in-person socialization.

“While social media can provide educational content, it can also provide misinformation about health and expose children to content that damages their mental well-being. These are risks that adolescents and their parents should be aware of,” Nagata said.

Indeed, a tearful Victoria Hinks of Larkspur, California, spoke at the press conference of her 16-year-old daughter, Alexandra, who committed suicide 4 months ago after being sucked into social media and served content on self-harm, eating disorders, suicidal ideation, and glamorization of suicide.

“She was led down dark rabbit holes she had no hope of escaping,” Hinks said. “There is not a bone in my body that doubts social media played a role leading her to that final irreversible decision.”

Jim Steyer, CEO and founder of Common Sense Media, applauded California for being the first state to introduce social media warning label legislation. The group plans to lobby for similar proposals in other states he said at the press conference, noting that there are “tens of thousands of Alexandras out there.”

“We have seat belt laws, we have warning labels on cigarettes and alcohol, and that’s what we’re doing here,” Steyer said. “It’s a straightforward simple proposition, which is put your kids and teenagers first, put their self-interest first and hold the largest, most powerful, and wealthy companies in all of our lifetimes accountable for the harms that have happened on their platforms.”

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

In the latest effort to address the mental health crisis among adolescents, legislation in California would require social media platforms to come with a “black box” mental health warning label.

Despite growing evidence linking young people’s use of social media to significant health risks including depression, anxiety, and suicidal thoughts, social media companies have failed to be transparent about the risks, said Assembly member Rebecca Bauer-Kahan (D-Orinda), who introduced Assembly Bill (AB) 56.

“AB 56 ensures that families are armed with clear, actionable information to understand these dangers and make decisions that prioritizes their children’s well-being,” she said in a press release.

Bauer-Kahan noted that 95% of teens report using at least one social media platform and that more than one third say they use social media almost constantly.

“There is a powerful profit motive to keep our young people hooked online and engaged and it is exploiting the human psychology with notifications, likes, endless scrolling, and algorithmic amplification that is harming our children every day,” she said at a press conference on December 9 announcing the bill.

The warning labels are an equitable and transparent way to communicate the risks that social media poses to young users, California’s Attorney General Rob Bonta, a sponsor of AB 56, said in a press release.

Speaking at the press conference, Bonta said social media has many “incredible benefits” from giving people an outlet of expression to providing access to critical information but “there is no disputing the fact, it can have an enormously detrimental and dangerous impact on our young people. You cannot debate that. Our children are suffering.”

If AB 56 is successful, he said social media platforms would be required to display a “black box warning” for all users that would appear upon the first use of a platform and weekly thereafter.

The proposed language for the warning label is: “The Surgeon General has advised that there are ample indicators that social media can have a profound risk of harm to the mental health and well-being of children and adolescents.”

“This warning label isn’t a panacea, we know that, but it is another tool in our toolbox. It’s one prong in what has to be a multi-pronged continued, coordinated effort to address this public health crisis,” Bonta said.

Reached for comment, Bonta’s office said sponsorship of the bill was informed by their ongoing work to create a safer online space for children and teens and by the US Surgeon General’s call to Congress to add warning labels to social media.

In June, US Surgeon General Vivek Murthy, MD, said a Surgeon General’s warning label is needed to address the mental health emergency among adolescents and noted that evidence from tobacco studies shows warning labels can increase awareness and change behavior. In September, the attorneys general of 42 states announced their support of the proposal.

Also in September, US Senators John Fetterman (D-PA) and Katie Britt (R-AL) introduced the Stop the Scroll Act to create a mental health warning label requirement for social media platforms.

In a controversial move in November, Australia passed the world’s first law banning social media for children younger than 16 years. The law gives platforms such as TikTok, Facebook, X, Snapchat, and Instagram 1 year to figure out how to implement the ban before facing fines of up 50 million Australian dollars ($33 million) for systemic failures to prevent children younger than 16 years from holding accounts.

 

‘A Broken Fire Alarm’

“Slapping a warning label on social media is like a broken fire alarm going off with no evidence of smoke. It ignores the reality that most teens view social media as an important outlet for social connection,” Todd O’Boyle, with the tech industry policy group Chamber of Progress, said in a statement on AB 56.

He highlighted a 2022 Pew Research Center survey reporting that most teens credit social media with deepening connections and providing a support network and a 2020 study reporting that social media is not a strong or consistent risk factor for depressive symptoms in US adolescents.

O’Boyle predicted that, without strong evidence, AB 56 will run into the same “First Amendment buzzsaw” that has doomed other California kids’ bills.

Pediatrician Jason Nagata, MD, University of California San Francisco, points out in Bonta’s press release that social media can displace time for other healthful activities including sleep, exercise, and in-person socialization.

“While social media can provide educational content, it can also provide misinformation about health and expose children to content that damages their mental well-being. These are risks that adolescents and their parents should be aware of,” Nagata said.

Indeed, a tearful Victoria Hinks of Larkspur, California, spoke at the press conference of her 16-year-old daughter, Alexandra, who committed suicide 4 months ago after being sucked into social media and served content on self-harm, eating disorders, suicidal ideation, and glamorization of suicide.

“She was led down dark rabbit holes she had no hope of escaping,” Hinks said. “There is not a bone in my body that doubts social media played a role leading her to that final irreversible decision.”

Jim Steyer, CEO and founder of Common Sense Media, applauded California for being the first state to introduce social media warning label legislation. The group plans to lobby for similar proposals in other states he said at the press conference, noting that there are “tens of thousands of Alexandras out there.”

“We have seat belt laws, we have warning labels on cigarettes and alcohol, and that’s what we’re doing here,” Steyer said. “It’s a straightforward simple proposition, which is put your kids and teenagers first, put their self-interest first and hold the largest, most powerful, and wealthy companies in all of our lifetimes accountable for the harms that have happened on their platforms.”

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

In the latest effort to address the mental health crisis among adolescents, legislation in California would require social media platforms to come with a “black box” mental health warning label.

Despite growing evidence linking young people’s use of social media to significant health risks including depression, anxiety, and suicidal thoughts, social media companies have failed to be transparent about the risks, said Assembly member Rebecca Bauer-Kahan (D-Orinda), who introduced Assembly Bill (AB) 56.

“AB 56 ensures that families are armed with clear, actionable information to understand these dangers and make decisions that prioritizes their children’s well-being,” she said in a press release.

Bauer-Kahan noted that 95% of teens report using at least one social media platform and that more than one third say they use social media almost constantly.

“There is a powerful profit motive to keep our young people hooked online and engaged and it is exploiting the human psychology with notifications, likes, endless scrolling, and algorithmic amplification that is harming our children every day,” she said at a press conference on December 9 announcing the bill.

The warning labels are an equitable and transparent way to communicate the risks that social media poses to young users, California’s Attorney General Rob Bonta, a sponsor of AB 56, said in a press release.

Speaking at the press conference, Bonta said social media has many “incredible benefits” from giving people an outlet of expression to providing access to critical information but “there is no disputing the fact, it can have an enormously detrimental and dangerous impact on our young people. You cannot debate that. Our children are suffering.”

If AB 56 is successful, he said social media platforms would be required to display a “black box warning” for all users that would appear upon the first use of a platform and weekly thereafter.

The proposed language for the warning label is: “The Surgeon General has advised that there are ample indicators that social media can have a profound risk of harm to the mental health and well-being of children and adolescents.”

“This warning label isn’t a panacea, we know that, but it is another tool in our toolbox. It’s one prong in what has to be a multi-pronged continued, coordinated effort to address this public health crisis,” Bonta said.

Reached for comment, Bonta’s office said sponsorship of the bill was informed by their ongoing work to create a safer online space for children and teens and by the US Surgeon General’s call to Congress to add warning labels to social media.

In June, US Surgeon General Vivek Murthy, MD, said a Surgeon General’s warning label is needed to address the mental health emergency among adolescents and noted that evidence from tobacco studies shows warning labels can increase awareness and change behavior. In September, the attorneys general of 42 states announced their support of the proposal.

Also in September, US Senators John Fetterman (D-PA) and Katie Britt (R-AL) introduced the Stop the Scroll Act to create a mental health warning label requirement for social media platforms.

In a controversial move in November, Australia passed the world’s first law banning social media for children younger than 16 years. The law gives platforms such as TikTok, Facebook, X, Snapchat, and Instagram 1 year to figure out how to implement the ban before facing fines of up 50 million Australian dollars ($33 million) for systemic failures to prevent children younger than 16 years from holding accounts.

 

‘A Broken Fire Alarm’

“Slapping a warning label on social media is like a broken fire alarm going off with no evidence of smoke. It ignores the reality that most teens view social media as an important outlet for social connection,” Todd O’Boyle, with the tech industry policy group Chamber of Progress, said in a statement on AB 56.

He highlighted a 2022 Pew Research Center survey reporting that most teens credit social media with deepening connections and providing a support network and a 2020 study reporting that social media is not a strong or consistent risk factor for depressive symptoms in US adolescents.

O’Boyle predicted that, without strong evidence, AB 56 will run into the same “First Amendment buzzsaw” that has doomed other California kids’ bills.

Pediatrician Jason Nagata, MD, University of California San Francisco, points out in Bonta’s press release that social media can displace time for other healthful activities including sleep, exercise, and in-person socialization.

“While social media can provide educational content, it can also provide misinformation about health and expose children to content that damages their mental well-being. These are risks that adolescents and their parents should be aware of,” Nagata said.

Indeed, a tearful Victoria Hinks of Larkspur, California, spoke at the press conference of her 16-year-old daughter, Alexandra, who committed suicide 4 months ago after being sucked into social media and served content on self-harm, eating disorders, suicidal ideation, and glamorization of suicide.

“She was led down dark rabbit holes she had no hope of escaping,” Hinks said. “There is not a bone in my body that doubts social media played a role leading her to that final irreversible decision.”

Jim Steyer, CEO and founder of Common Sense Media, applauded California for being the first state to introduce social media warning label legislation. The group plans to lobby for similar proposals in other states he said at the press conference, noting that there are “tens of thousands of Alexandras out there.”

“We have seat belt laws, we have warning labels on cigarettes and alcohol, and that’s what we’re doing here,” Steyer said. “It’s a straightforward simple proposition, which is put your kids and teenagers first, put their self-interest first and hold the largest, most powerful, and wealthy companies in all of our lifetimes accountable for the harms that have happened on their platforms.”

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

Adults with high cholesterol taking statins may have a significantly higher risk of developing glaucoma than those not taking the cholesterol-lowering drugs, an observational study of a large research database found.

The study, published in Ophthalmology Glaucoma, analyzed electronic health records of 79,742 adults with hyperlipidemia in the All of Us Research Program database from 2017 to 2022. The repository is maintained by the National Institutes of Health and provides data for research into precision medicine.

The 6365 statin users in the study population had a 47% greater unadjusted prevalence of glaucoma than nonusers of the drugs (P < .001) and a 13% greater prevalence in models that adjusted for potential confounding variables (P = .02). The researchers also found statin users had significantly higher levels of low-density lipoprotein cholesterol (LDL-C), but even patients with optimal levels of LDL-C had higher rates of glaucoma.

 

‘A Little Unusual’

Drawing any clinically relevant conclusions from this latest study would be premature, said Victoria Tseng, MD, PhD, an assistant professor at UCLA Stein Eye Institute and Doheny Eye Centers UCLA, and the senior author of the study. “I certainly would not be telling my patients on statins to stop their statins.”

Tseng acknowledged her group’s finding runs counter to previous studies that found statins may help prevent glaucoma or at least have no effect on the eye disease, although the association between cholesterol and glaucoma has been well established.

A 2019 analysis of nearly 137,000 participants in three population studies found no connection between statin use and the risk for primary open-angle glaucoma. A 2012 study of more than 500,000 people with high cholesterol found statin use was associated with a significant reduction in the risk for open-angle glaucoma.

“It’s a little unusual that we found the opposite,” Tseng said in an interview.

One explanation is the observational nature of the AoU analysis Tseng’s group conducted. “We don’t know what these people look like or how well the data were collected, so we’re going off of what’s there in the database,” she said.

Another explanation could be the nature of hyperlipidemia itself, she said. “There have definitely been studies that suggest increased cholesterol levels are associated with an increased risk of glaucoma. Presumably, you’re not going to be taking a statin unless your cholesterol is a little worse.”

While the study analysis attempted to control for cholesterol levels, Tseng noted, “there could be some residual confounding from that.”

Statin users in the study had an average LDL-C level of 144.9 mg/dL vs 136.3 mg/dL in the population not taking any cholesterol medication (P < .001). Statin users with optimal LDL-C, defined as less than 100 mg/dL, had a 39% greater adjusted prevalence of glaucoma (P = .02), while those with high LDL-C (160-189 mg/dL) had a 37% greater adjusted prevalence (P = .005).

Age was another factor in the risk for glaucoma, the study found. Statin users aged 60-69 years had an adjusted rate of glaucoma 28% greater than that for nonusers (P = .05).

Laboratory studies may help clarify the relationships between statins and glaucoma, Tseng said. That could include putting statins directly on the optic nerve of laboratory mice and further investigating how statins affect the mechanisms that influence eye pressure, a key driver of glaucoma. From a population study perspective, a randomized trial of glaucoma patients comparing the effect of statins and other cholesterol-lowering medications with nonuse may provide answers.

 

Database Strengths and Limitations

The study “adds to the somewhat mixed literature on the potential association between statins and glaucoma,” Sophia Wang, MD, MS, a glaucoma specialist at Stanford Byers Eye Institute in Palo Alto, California, said in an interview.

The AoU research cohort is a “notable strength” of the new paper, added Wang, who has used the AoU database to study the relationship between blood pressure, blood pressure medications, and glaucoma.

“The population is especially large and diverse, with a large proportion of participants from backgrounds that are traditionally underrepresented in research,” she said. And The inclusion of both medical records and survey data means the health information on the cohort is detailed and longitudinal.

“The authors make excellent use here of the data by including in their analyses results of laboratory investigations — LDL-C, notably — which wouldn’t be readily available in other types of datasets such as claims datasets,” she said.

However, the database has limitations as well, including its reliance on coding, which is prone to errors, to determine glaucoma diagnosis and missing information on eye examinations. In addition, the study used one LDL-C measurement rather than multiple measurements, Wang pointed out, “and we know that LDL-C can vary over time.”

The study was funded by Research to Prevent Blindness. Tseng and Wang reported no relevant financial relationships to disclose.

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

Adults with high cholesterol taking statins may have a significantly higher risk of developing glaucoma than those not taking the cholesterol-lowering drugs, an observational study of a large research database found.

The study, published in Ophthalmology Glaucoma, analyzed electronic health records of 79,742 adults with hyperlipidemia in the All of Us Research Program database from 2017 to 2022. The repository is maintained by the National Institutes of Health and provides data for research into precision medicine.

The 6365 statin users in the study population had a 47% greater unadjusted prevalence of glaucoma than nonusers of the drugs (P < .001) and a 13% greater prevalence in models that adjusted for potential confounding variables (P = .02). The researchers also found statin users had significantly higher levels of low-density lipoprotein cholesterol (LDL-C), but even patients with optimal levels of LDL-C had higher rates of glaucoma.

 

‘A Little Unusual’

Drawing any clinically relevant conclusions from this latest study would be premature, said Victoria Tseng, MD, PhD, an assistant professor at UCLA Stein Eye Institute and Doheny Eye Centers UCLA, and the senior author of the study. “I certainly would not be telling my patients on statins to stop their statins.”

Tseng acknowledged her group’s finding runs counter to previous studies that found statins may help prevent glaucoma or at least have no effect on the eye disease, although the association between cholesterol and glaucoma has been well established.

A 2019 analysis of nearly 137,000 participants in three population studies found no connection between statin use and the risk for primary open-angle glaucoma. A 2012 study of more than 500,000 people with high cholesterol found statin use was associated with a significant reduction in the risk for open-angle glaucoma.

“It’s a little unusual that we found the opposite,” Tseng said in an interview.

One explanation is the observational nature of the AoU analysis Tseng’s group conducted. “We don’t know what these people look like or how well the data were collected, so we’re going off of what’s there in the database,” she said.

Another explanation could be the nature of hyperlipidemia itself, she said. “There have definitely been studies that suggest increased cholesterol levels are associated with an increased risk of glaucoma. Presumably, you’re not going to be taking a statin unless your cholesterol is a little worse.”

While the study analysis attempted to control for cholesterol levels, Tseng noted, “there could be some residual confounding from that.”

Statin users in the study had an average LDL-C level of 144.9 mg/dL vs 136.3 mg/dL in the population not taking any cholesterol medication (P < .001). Statin users with optimal LDL-C, defined as less than 100 mg/dL, had a 39% greater adjusted prevalence of glaucoma (P = .02), while those with high LDL-C (160-189 mg/dL) had a 37% greater adjusted prevalence (P = .005).

Age was another factor in the risk for glaucoma, the study found. Statin users aged 60-69 years had an adjusted rate of glaucoma 28% greater than that for nonusers (P = .05).

Laboratory studies may help clarify the relationships between statins and glaucoma, Tseng said. That could include putting statins directly on the optic nerve of laboratory mice and further investigating how statins affect the mechanisms that influence eye pressure, a key driver of glaucoma. From a population study perspective, a randomized trial of glaucoma patients comparing the effect of statins and other cholesterol-lowering medications with nonuse may provide answers.

 

Database Strengths and Limitations

The study “adds to the somewhat mixed literature on the potential association between statins and glaucoma,” Sophia Wang, MD, MS, a glaucoma specialist at Stanford Byers Eye Institute in Palo Alto, California, said in an interview.

The AoU research cohort is a “notable strength” of the new paper, added Wang, who has used the AoU database to study the relationship between blood pressure, blood pressure medications, and glaucoma.

“The population is especially large and diverse, with a large proportion of participants from backgrounds that are traditionally underrepresented in research,” she said. And The inclusion of both medical records and survey data means the health information on the cohort is detailed and longitudinal.

“The authors make excellent use here of the data by including in their analyses results of laboratory investigations — LDL-C, notably — which wouldn’t be readily available in other types of datasets such as claims datasets,” she said.

However, the database has limitations as well, including its reliance on coding, which is prone to errors, to determine glaucoma diagnosis and missing information on eye examinations. In addition, the study used one LDL-C measurement rather than multiple measurements, Wang pointed out, “and we know that LDL-C can vary over time.”

The study was funded by Research to Prevent Blindness. Tseng and Wang reported no relevant financial relationships to disclose.

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

Adults with high cholesterol taking statins may have a significantly higher risk of developing glaucoma than those not taking the cholesterol-lowering drugs, an observational study of a large research database found.

The study, published in Ophthalmology Glaucoma, analyzed electronic health records of 79,742 adults with hyperlipidemia in the All of Us Research Program database from 2017 to 2022. The repository is maintained by the National Institutes of Health and provides data for research into precision medicine.

The 6365 statin users in the study population had a 47% greater unadjusted prevalence of glaucoma than nonusers of the drugs (P < .001) and a 13% greater prevalence in models that adjusted for potential confounding variables (P = .02). The researchers also found statin users had significantly higher levels of low-density lipoprotein cholesterol (LDL-C), but even patients with optimal levels of LDL-C had higher rates of glaucoma.

 

‘A Little Unusual’

Drawing any clinically relevant conclusions from this latest study would be premature, said Victoria Tseng, MD, PhD, an assistant professor at UCLA Stein Eye Institute and Doheny Eye Centers UCLA, and the senior author of the study. “I certainly would not be telling my patients on statins to stop their statins.”

Tseng acknowledged her group’s finding runs counter to previous studies that found statins may help prevent glaucoma or at least have no effect on the eye disease, although the association between cholesterol and glaucoma has been well established.

A 2019 analysis of nearly 137,000 participants in three population studies found no connection between statin use and the risk for primary open-angle glaucoma. A 2012 study of more than 500,000 people with high cholesterol found statin use was associated with a significant reduction in the risk for open-angle glaucoma.

“It’s a little unusual that we found the opposite,” Tseng said in an interview.

One explanation is the observational nature of the AoU analysis Tseng’s group conducted. “We don’t know what these people look like or how well the data were collected, so we’re going off of what’s there in the database,” she said.

Another explanation could be the nature of hyperlipidemia itself, she said. “There have definitely been studies that suggest increased cholesterol levels are associated with an increased risk of glaucoma. Presumably, you’re not going to be taking a statin unless your cholesterol is a little worse.”

While the study analysis attempted to control for cholesterol levels, Tseng noted, “there could be some residual confounding from that.”

Statin users in the study had an average LDL-C level of 144.9 mg/dL vs 136.3 mg/dL in the population not taking any cholesterol medication (P < .001). Statin users with optimal LDL-C, defined as less than 100 mg/dL, had a 39% greater adjusted prevalence of glaucoma (P = .02), while those with high LDL-C (160-189 mg/dL) had a 37% greater adjusted prevalence (P = .005).

Age was another factor in the risk for glaucoma, the study found. Statin users aged 60-69 years had an adjusted rate of glaucoma 28% greater than that for nonusers (P = .05).

Laboratory studies may help clarify the relationships between statins and glaucoma, Tseng said. That could include putting statins directly on the optic nerve of laboratory mice and further investigating how statins affect the mechanisms that influence eye pressure, a key driver of glaucoma. From a population study perspective, a randomized trial of glaucoma patients comparing the effect of statins and other cholesterol-lowering medications with nonuse may provide answers.

 

Database Strengths and Limitations

The study “adds to the somewhat mixed literature on the potential association between statins and glaucoma,” Sophia Wang, MD, MS, a glaucoma specialist at Stanford Byers Eye Institute in Palo Alto, California, said in an interview.

The AoU research cohort is a “notable strength” of the new paper, added Wang, who has used the AoU database to study the relationship between blood pressure, blood pressure medications, and glaucoma.

“The population is especially large and diverse, with a large proportion of participants from backgrounds that are traditionally underrepresented in research,” she said. And The inclusion of both medical records and survey data means the health information on the cohort is detailed and longitudinal.

“The authors make excellent use here of the data by including in their analyses results of laboratory investigations — LDL-C, notably — which wouldn’t be readily available in other types of datasets such as claims datasets,” she said.

However, the database has limitations as well, including its reliance on coding, which is prone to errors, to determine glaucoma diagnosis and missing information on eye examinations. In addition, the study used one LDL-C measurement rather than multiple measurements, Wang pointed out, “and we know that LDL-C can vary over time.”

The study was funded by Research to Prevent Blindness. Tseng and Wang reported no relevant financial relationships to disclose.

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

TOPLINE:

Muscle-building dietary supplement (MBS) use among young men substantially increases the odds of subsequent anabolic-androgenic steroid (AAS) initiation. Users of MBS showed elevated odds of incident AAS use within 1-5 years, supporting the gateway hypothesis for escalating risk-taking behaviors to increase muscularity.

METHODOLOGY:

• Analysis included data from two Growing Up Today Study prospective cohorts spanning 14 years (2007-2021).
• Participants included 4073 cisgender boys and young men aged 10-27 years at baseline (mean age, 20.3 years).
• Demographics showed 92.8% White participants and 7.2% other races or ethnicities.
• Researchers assessed past-year substance use for muscle building, including protein supplements, creatine, amino acids, hydroxymethylbutyrate, and dehydroepiandrosterone.

TAKEAWAY:

• Initial survey results showed 11.1% of respondents reported past-year muscle-building supplement use, and 0.4% reported AAS use.
• Over the study period, 37.7% of respondents reported any past-year muscle-building supplement use, while 0.5% reported any past-year AAS use.
• Analysis revealed muscle-building supplement users had (odds ratio [OR], 8.31; 95% CI, 2.59-26.73) higher odds of initiating AAS use by the next survey wave than nonusers.
• Age (adjusted OR [AOR], 0.98; 95% CI, 0.85-1.12) and cohort (AOR, 0.83; 95% CI, 0.30-2.32) were not statistically significant factors.

IN PRACTICE:

“The health risks of MBS use are well documented, as inadequate federal regulation has resulted in a US MBS marketplace rife with inaccurate labeling and adulteration with toxic ingredients. Clinicians, coaches, and parents should counsel against MBS use. Future studies with larger and more diverse samples are needed,” wrote the authors of the study.

SOURCE:

The study was led by Abigail Bulens, Division of Adolescent and Young Adult Medicine, Boston Children’s Hospital in Boston. It was published online in JAMA Network Open.

LIMITATIONS:

The study had a wide CI around the OR, potentially affecting the precision of the risk estimates. Additionally, the sample lacked diversity, with 92.8% of participants being White, which may limit the generalizability of findings to other racial and ethnic groups.

DISCLOSURES:

One coauthor received support from grant 1F32MDO17452-01 from the National Institute on Minority Health and Health Disparities. Another coauthor received support from training grant T76-MC-00001 from the Maternal and Child Health Bureau, Health Resources and Services Administration, Department of Health and Human Services. The cohorts were supported by National Institutes of Health grants HD045763, HD057368, DK46834, and HLO3533. The funders had no role in the study design, data collection, analysis, interpretation, manuscript preparation, or publication decision.

This article was created 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.

TOPLINE:

Muscle-building dietary supplement (MBS) use among young men substantially increases the odds of subsequent anabolic-androgenic steroid (AAS) initiation. Users of MBS showed elevated odds of incident AAS use within 1-5 years, supporting the gateway hypothesis for escalating risk-taking behaviors to increase muscularity.

METHODOLOGY:

• Analysis included data from two Growing Up Today Study prospective cohorts spanning 14 years (2007-2021).
• Participants included 4073 cisgender boys and young men aged 10-27 years at baseline (mean age, 20.3 years).
• Demographics showed 92.8% White participants and 7.2% other races or ethnicities.
• Researchers assessed past-year substance use for muscle building, including protein supplements, creatine, amino acids, hydroxymethylbutyrate, and dehydroepiandrosterone.

TAKEAWAY:

• Initial survey results showed 11.1% of respondents reported past-year muscle-building supplement use, and 0.4% reported AAS use.
• Over the study period, 37.7% of respondents reported any past-year muscle-building supplement use, while 0.5% reported any past-year AAS use.
• Analysis revealed muscle-building supplement users had (odds ratio [OR], 8.31; 95% CI, 2.59-26.73) higher odds of initiating AAS use by the next survey wave than nonusers.
• Age (adjusted OR [AOR], 0.98; 95% CI, 0.85-1.12) and cohort (AOR, 0.83; 95% CI, 0.30-2.32) were not statistically significant factors.

IN PRACTICE:

“The health risks of MBS use are well documented, as inadequate federal regulation has resulted in a US MBS marketplace rife with inaccurate labeling and adulteration with toxic ingredients. Clinicians, coaches, and parents should counsel against MBS use. Future studies with larger and more diverse samples are needed,” wrote the authors of the study.

SOURCE:

The study was led by Abigail Bulens, Division of Adolescent and Young Adult Medicine, Boston Children’s Hospital in Boston. It was published online in JAMA Network Open.

LIMITATIONS:

The study had a wide CI around the OR, potentially affecting the precision of the risk estimates. Additionally, the sample lacked diversity, with 92.8% of participants being White, which may limit the generalizability of findings to other racial and ethnic groups.

DISCLOSURES:

One coauthor received support from grant 1F32MDO17452-01 from the National Institute on Minority Health and Health Disparities. Another coauthor received support from training grant T76-MC-00001 from the Maternal and Child Health Bureau, Health Resources and Services Administration, Department of Health and Human Services. The cohorts were supported by National Institutes of Health grants HD045763, HD057368, DK46834, and HLO3533. The funders had no role in the study design, data collection, analysis, interpretation, manuscript preparation, or publication decision.

This article was created 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.

TOPLINE:

Muscle-building dietary supplement (MBS) use among young men substantially increases the odds of subsequent anabolic-androgenic steroid (AAS) initiation. Users of MBS showed elevated odds of incident AAS use within 1-5 years, supporting the gateway hypothesis for escalating risk-taking behaviors to increase muscularity.

METHODOLOGY:

• Analysis included data from two Growing Up Today Study prospective cohorts spanning 14 years (2007-2021).
• Participants included 4073 cisgender boys and young men aged 10-27 years at baseline (mean age, 20.3 years).
• Demographics showed 92.8% White participants and 7.2% other races or ethnicities.
• Researchers assessed past-year substance use for muscle building, including protein supplements, creatine, amino acids, hydroxymethylbutyrate, and dehydroepiandrosterone.

TAKEAWAY:

• Initial survey results showed 11.1% of respondents reported past-year muscle-building supplement use, and 0.4% reported AAS use.
• Over the study period, 37.7% of respondents reported any past-year muscle-building supplement use, while 0.5% reported any past-year AAS use.
• Analysis revealed muscle-building supplement users had (odds ratio [OR], 8.31; 95% CI, 2.59-26.73) higher odds of initiating AAS use by the next survey wave than nonusers.
• Age (adjusted OR [AOR], 0.98; 95% CI, 0.85-1.12) and cohort (AOR, 0.83; 95% CI, 0.30-2.32) were not statistically significant factors.

IN PRACTICE:

“The health risks of MBS use are well documented, as inadequate federal regulation has resulted in a US MBS marketplace rife with inaccurate labeling and adulteration with toxic ingredients. Clinicians, coaches, and parents should counsel against MBS use. Future studies with larger and more diverse samples are needed,” wrote the authors of the study.

SOURCE:

The study was led by Abigail Bulens, Division of Adolescent and Young Adult Medicine, Boston Children’s Hospital in Boston. It was published online in JAMA Network Open.

LIMITATIONS:

The study had a wide CI around the OR, potentially affecting the precision of the risk estimates. Additionally, the sample lacked diversity, with 92.8% of participants being White, which may limit the generalizability of findings to other racial and ethnic groups.

DISCLOSURES:

One coauthor received support from grant 1F32MDO17452-01 from the National Institute on Minority Health and Health Disparities. Another coauthor received support from training grant T76-MC-00001 from the Maternal and Child Health Bureau, Health Resources and Services Administration, Department of Health and Human Services. The cohorts were supported by National Institutes of Health grants HD045763, HD057368, DK46834, and HLO3533. The funders had no role in the study design, data collection, analysis, interpretation, manuscript preparation, or publication decision.

This article was created 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 preparation for a future international treaty aimed at reducing plastic pollution, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices presented the conclusions of a public hearing on the impact of plastics on various aspects of human health.

Increased Global Plastic Production

Philippe Bolo, a member of the French Democratic Party and the rapporteur for the public mission on the health impacts of plastics, spoke about the latest round of treaty negotiations, held from November 25 to December 1 in South Korea, attended by leading French and global experts about the impact of plastics on human health.

The hearing highlighted a sharp increase in plastic production. “It has doubled in the last 20 years and is expected to exceed 500 million tons in 2024,” Bolo said. This is about 60 kg per person. According to projections from the Organization for Economic Co-operation and Development, on its current trajectory, plastic production will reach 750 million tons by 2040 and surpass 1 billion tons before 2050, he said.

 

Minimal Plastic Waste Recycling

Around one third (32%) of plastics are used for packaging. “Therefore, most plastic production is still intended for single-use purposes,” he said. Plastic waste follows a similar growth trajectory, with volumes expected to rise from 360 million tons in 2020 to 617 million tons by 2040 unless action is taken. Very little of this waste is recycled, even in the most countries that are most advanced in terms of collection, sorting, and processing.

In France, for example, in 2018, only 0.6 million tons of the 3.6 million tons of plastic waste produced was truly recycled. This is less than one fifth (17%). Globally, less than 10% of plastic waste is recycled. In 2020, plastic waste that ended up in the environment represented 81 million tons, or 22% of the total. “Beyond waste, this leads to pollution by microplastics and nanoplastics, resulting from their fragmentation. All environments are affected: Seas, rivers, soils, air, and even living organisms,” Bolo said.

 

Methodological Challenges

However, measuring the impact of plastics on health faces methodological difficulties due to the wide variety of composition, size, and shape of plastics. Nevertheless, the French Standardization Association (Association Française de Normalisation) has conducted work to establish a characterization standard for microplastics in water, which serves as an international reference.

“It is also very difficult to know what we are ingesting,” Bolo said. “A study conducted in 2019 estimated that the average human absorbs 5 grams of plastics per week, the equivalent of a credit card.» Since then, other studies have revised this estimate downward, but no consensus has been reached.

A recent study across 109 countries, both industrialized and developing, found significant exposure, estimated at 500 mg/d, particularly in Southeast Asian countries, where it was due mainly to seafood consumption.

A study concluded that plastic water bottles contain 240,000 particles per liter, 90% of which are nanoplastics. These nanoparticles can pass through the intestinal barrier to enter the bloodstream and reach several organs including the heart, brain, and placenta, as well as the fetus.

 

Changes to the Microbiome

Microplastics also accumulate in organs. Thus, the amount of plastic in the lungs increases with age, suggesting that particles may persist in the body without being eliminated. The health consequences of this are still poorly understood, but exposure to plastics appears to cause changes in the composition of the intestinal microbiota. Pathobionts (commensal bacteria with harmful potential) have been found in both adults and children, which could contribute to dysbiosis of the gut microbiome. Furthermore, a decrease in butyrate, a short-chain fatty acid beneficial to health, has been observed in children’s intestines.

Inhaled nanoplastics may disrupt the mucociliary clearance mechanisms of the respiratory system. The toxicity of inhaled plastic particles was demonstrated as early as the 1970s among workers in the flocking industry. Some developed lung function impairments, shortness of breath, inflammation, fibrosis, and even lung cancer. Similar symptoms have been observed in workers in the textile and polyvinyl chloride industries.

A study published recently in The New England Journal of Medicine measured the amount of microplastics collected from carotid plaque of more than 300 patients who had undergone carotid endarterectomy for asymptomatic carotid artery disease. It found a 4.53 times higher risk for the primary endpoint, a composite of myocardial infarction, stroke, and all-cause mortality, among individuals with microplastics and nanoplastics in plaque compared with those without.

 

Health Affects High

The danger of plastics is also directly linked to the chemical substances they contain. A general scientific review looked at the health impacts of three chemicals used almost exclusively in plastics: Polybromodiphenyl ethers (PBDEs), used as flame retardants in textiles or electronics; bisphenol A (BPA), used in the lining of cans and bottles; and phthalates, particularly diethylhexyl phthalate (DEHP), used to make plastics more flexible.

The review highlighted strong epidemiological evidence linking fetal exposure to PBDEs during pregnancy to low birth weight and later exposure to delayed or impaired cognitive development in children and even a loss of IQ. Statistically significant evidence of disruption of thyroid function in adults was also found.

BPA is linked to genital malformations in female newborns exposed to BPA in utero, type 2 diabetes in adults, insulin resistance, and polycystic ovary syndrome in women. BPA exposure also increases the risk for obesity and hypertension in both children and adults, as well as the risk for cardiovascular disease in adults.

Finally, the review established links between exposure to DEHP and miscarriages, genital malformations in male newborns, delayed or impaired cognitive development in children, loss of IQ, delayed psychomotor development, early puberty in young girls, and endometriosis in young women. DEHP exposure also has multiple effects on cardiometabolic health, including insulin resistance, obesity, and elevated blood pressure.

The economic costs associated with the health impacts of these three substances have been estimated at $675 billion in the United States.

Bolo said that the solution to this plastic pollution is necessarily international. “We need an ambitious and legally binding treaty to reduce plastic production,” he said. “The damage is already done; we need to act to protect human health,” he concluded. The parliamentary office has made nine recommendations to the treaty negotiators.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In preparation for a future international treaty aimed at reducing plastic pollution, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices presented the conclusions of a public hearing on the impact of plastics on various aspects of human health.

Increased Global Plastic Production

Philippe Bolo, a member of the French Democratic Party and the rapporteur for the public mission on the health impacts of plastics, spoke about the latest round of treaty negotiations, held from November 25 to December 1 in South Korea, attended by leading French and global experts about the impact of plastics on human health.

The hearing highlighted a sharp increase in plastic production. “It has doubled in the last 20 years and is expected to exceed 500 million tons in 2024,” Bolo said. This is about 60 kg per person. According to projections from the Organization for Economic Co-operation and Development, on its current trajectory, plastic production will reach 750 million tons by 2040 and surpass 1 billion tons before 2050, he said.

 

Minimal Plastic Waste Recycling

Around one third (32%) of plastics are used for packaging. “Therefore, most plastic production is still intended for single-use purposes,” he said. Plastic waste follows a similar growth trajectory, with volumes expected to rise from 360 million tons in 2020 to 617 million tons by 2040 unless action is taken. Very little of this waste is recycled, even in the most countries that are most advanced in terms of collection, sorting, and processing.

In France, for example, in 2018, only 0.6 million tons of the 3.6 million tons of plastic waste produced was truly recycled. This is less than one fifth (17%). Globally, less than 10% of plastic waste is recycled. In 2020, plastic waste that ended up in the environment represented 81 million tons, or 22% of the total. “Beyond waste, this leads to pollution by microplastics and nanoplastics, resulting from their fragmentation. All environments are affected: Seas, rivers, soils, air, and even living organisms,” Bolo said.

 

Methodological Challenges

However, measuring the impact of plastics on health faces methodological difficulties due to the wide variety of composition, size, and shape of plastics. Nevertheless, the French Standardization Association (Association Française de Normalisation) has conducted work to establish a characterization standard for microplastics in water, which serves as an international reference.

“It is also very difficult to know what we are ingesting,” Bolo said. “A study conducted in 2019 estimated that the average human absorbs 5 grams of plastics per week, the equivalent of a credit card.» Since then, other studies have revised this estimate downward, but no consensus has been reached.

A recent study across 109 countries, both industrialized and developing, found significant exposure, estimated at 500 mg/d, particularly in Southeast Asian countries, where it was due mainly to seafood consumption.

A study concluded that plastic water bottles contain 240,000 particles per liter, 90% of which are nanoplastics. These nanoparticles can pass through the intestinal barrier to enter the bloodstream and reach several organs including the heart, brain, and placenta, as well as the fetus.

 

Changes to the Microbiome

Microplastics also accumulate in organs. Thus, the amount of plastic in the lungs increases with age, suggesting that particles may persist in the body without being eliminated. The health consequences of this are still poorly understood, but exposure to plastics appears to cause changes in the composition of the intestinal microbiota. Pathobionts (commensal bacteria with harmful potential) have been found in both adults and children, which could contribute to dysbiosis of the gut microbiome. Furthermore, a decrease in butyrate, a short-chain fatty acid beneficial to health, has been observed in children’s intestines.

Inhaled nanoplastics may disrupt the mucociliary clearance mechanisms of the respiratory system. The toxicity of inhaled plastic particles was demonstrated as early as the 1970s among workers in the flocking industry. Some developed lung function impairments, shortness of breath, inflammation, fibrosis, and even lung cancer. Similar symptoms have been observed in workers in the textile and polyvinyl chloride industries.

A study published recently in The New England Journal of Medicine measured the amount of microplastics collected from carotid plaque of more than 300 patients who had undergone carotid endarterectomy for asymptomatic carotid artery disease. It found a 4.53 times higher risk for the primary endpoint, a composite of myocardial infarction, stroke, and all-cause mortality, among individuals with microplastics and nanoplastics in plaque compared with those without.

 

Health Affects High

The danger of plastics is also directly linked to the chemical substances they contain. A general scientific review looked at the health impacts of three chemicals used almost exclusively in plastics: Polybromodiphenyl ethers (PBDEs), used as flame retardants in textiles or electronics; bisphenol A (BPA), used in the lining of cans and bottles; and phthalates, particularly diethylhexyl phthalate (DEHP), used to make plastics more flexible.

The review highlighted strong epidemiological evidence linking fetal exposure to PBDEs during pregnancy to low birth weight and later exposure to delayed or impaired cognitive development in children and even a loss of IQ. Statistically significant evidence of disruption of thyroid function in adults was also found.

BPA is linked to genital malformations in female newborns exposed to BPA in utero, type 2 diabetes in adults, insulin resistance, and polycystic ovary syndrome in women. BPA exposure also increases the risk for obesity and hypertension in both children and adults, as well as the risk for cardiovascular disease in adults.

Finally, the review established links between exposure to DEHP and miscarriages, genital malformations in male newborns, delayed or impaired cognitive development in children, loss of IQ, delayed psychomotor development, early puberty in young girls, and endometriosis in young women. DEHP exposure also has multiple effects on cardiometabolic health, including insulin resistance, obesity, and elevated blood pressure.

The economic costs associated with the health impacts of these three substances have been estimated at $675 billion in the United States.

Bolo said that the solution to this plastic pollution is necessarily international. “We need an ambitious and legally binding treaty to reduce plastic production,” he said. “The damage is already done; we need to act to protect human health,” he concluded. The parliamentary office has made nine recommendations to the treaty negotiators.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In preparation for a future international treaty aimed at reducing plastic pollution, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices presented the conclusions of a public hearing on the impact of plastics on various aspects of human health.

Increased Global Plastic Production

Philippe Bolo, a member of the French Democratic Party and the rapporteur for the public mission on the health impacts of plastics, spoke about the latest round of treaty negotiations, held from November 25 to December 1 in South Korea, attended by leading French and global experts about the impact of plastics on human health.

The hearing highlighted a sharp increase in plastic production. “It has doubled in the last 20 years and is expected to exceed 500 million tons in 2024,” Bolo said. This is about 60 kg per person. According to projections from the Organization for Economic Co-operation and Development, on its current trajectory, plastic production will reach 750 million tons by 2040 and surpass 1 billion tons before 2050, he said.

 

Minimal Plastic Waste Recycling

Around one third (32%) of plastics are used for packaging. “Therefore, most plastic production is still intended for single-use purposes,” he said. Plastic waste follows a similar growth trajectory, with volumes expected to rise from 360 million tons in 2020 to 617 million tons by 2040 unless action is taken. Very little of this waste is recycled, even in the most countries that are most advanced in terms of collection, sorting, and processing.

In France, for example, in 2018, only 0.6 million tons of the 3.6 million tons of plastic waste produced was truly recycled. This is less than one fifth (17%). Globally, less than 10% of plastic waste is recycled. In 2020, plastic waste that ended up in the environment represented 81 million tons, or 22% of the total. “Beyond waste, this leads to pollution by microplastics and nanoplastics, resulting from their fragmentation. All environments are affected: Seas, rivers, soils, air, and even living organisms,” Bolo said.

 

Methodological Challenges

However, measuring the impact of plastics on health faces methodological difficulties due to the wide variety of composition, size, and shape of plastics. Nevertheless, the French Standardization Association (Association Française de Normalisation) has conducted work to establish a characterization standard for microplastics in water, which serves as an international reference.

“It is also very difficult to know what we are ingesting,” Bolo said. “A study conducted in 2019 estimated that the average human absorbs 5 grams of plastics per week, the equivalent of a credit card.» Since then, other studies have revised this estimate downward, but no consensus has been reached.

A recent study across 109 countries, both industrialized and developing, found significant exposure, estimated at 500 mg/d, particularly in Southeast Asian countries, where it was due mainly to seafood consumption.

A study concluded that plastic water bottles contain 240,000 particles per liter, 90% of which are nanoplastics. These nanoparticles can pass through the intestinal barrier to enter the bloodstream and reach several organs including the heart, brain, and placenta, as well as the fetus.

 

Changes to the Microbiome

Microplastics also accumulate in organs. Thus, the amount of plastic in the lungs increases with age, suggesting that particles may persist in the body without being eliminated. The health consequences of this are still poorly understood, but exposure to plastics appears to cause changes in the composition of the intestinal microbiota. Pathobionts (commensal bacteria with harmful potential) have been found in both adults and children, which could contribute to dysbiosis of the gut microbiome. Furthermore, a decrease in butyrate, a short-chain fatty acid beneficial to health, has been observed in children’s intestines.

Inhaled nanoplastics may disrupt the mucociliary clearance mechanisms of the respiratory system. The toxicity of inhaled plastic particles was demonstrated as early as the 1970s among workers in the flocking industry. Some developed lung function impairments, shortness of breath, inflammation, fibrosis, and even lung cancer. Similar symptoms have been observed in workers in the textile and polyvinyl chloride industries.

A study published recently in The New England Journal of Medicine measured the amount of microplastics collected from carotid plaque of more than 300 patients who had undergone carotid endarterectomy for asymptomatic carotid artery disease. It found a 4.53 times higher risk for the primary endpoint, a composite of myocardial infarction, stroke, and all-cause mortality, among individuals with microplastics and nanoplastics in plaque compared with those without.

 

Health Affects High

The danger of plastics is also directly linked to the chemical substances they contain. A general scientific review looked at the health impacts of three chemicals used almost exclusively in plastics: Polybromodiphenyl ethers (PBDEs), used as flame retardants in textiles or electronics; bisphenol A (BPA), used in the lining of cans and bottles; and phthalates, particularly diethylhexyl phthalate (DEHP), used to make plastics more flexible.

The review highlighted strong epidemiological evidence linking fetal exposure to PBDEs during pregnancy to low birth weight and later exposure to delayed or impaired cognitive development in children and even a loss of IQ. Statistically significant evidence of disruption of thyroid function in adults was also found.

BPA is linked to genital malformations in female newborns exposed to BPA in utero, type 2 diabetes in adults, insulin resistance, and polycystic ovary syndrome in women. BPA exposure also increases the risk for obesity and hypertension in both children and adults, as well as the risk for cardiovascular disease in adults.

Finally, the review established links between exposure to DEHP and miscarriages, genital malformations in male newborns, delayed or impaired cognitive development in children, loss of IQ, delayed psychomotor development, early puberty in young girls, and endometriosis in young women. DEHP exposure also has multiple effects on cardiometabolic health, including insulin resistance, obesity, and elevated blood pressure.

The economic costs associated with the health impacts of these three substances have been estimated at $675 billion in the United States.

Bolo said that the solution to this plastic pollution is necessarily international. “We need an ambitious and legally binding treaty to reduce plastic production,” he said. “The damage is already done; we need to act to protect human health,” he concluded. The parliamentary office has made nine recommendations to the treaty negotiators.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

LOS ANGELES — Angiotensin receptor blockers are more effective than other antihypertensive medications in reducing the risk for post-stroke epilepsy (PSE), new research showed.

Investigators found angiotensin receptor blockers are better at cutting the PSE risk in individuals with high blood pressure than angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and beta-blockers.

The results suggested angiotensin receptor blockers could be a frontline strategy to proactively forestall development of epilepsy in patients with a history of stroke and hypertension, said the study’s co-lead investigator Giacomo Evangelista, MD, PhD, a resident in neurology at the Epilepsy Center at “G. d’Annunzio” University of Chieti-Pescara, Italy.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Stroke and Seizures Tightly Linked

Stroke is the most common cause of seizures in patients older than 60 years. About 6%-8% of new epilepsy diagnoses in older adult patients are associated with a brain ischemic event.

Hypertension is among the most common risk factors for both epilepsy and stroke. The European Society of Cardiology recommends ACE inhibitors and angiotensin receptor blockers be considered first-line hypertension treatments.

Angiotensin receptor blockers seem to provide a protective effect in terms of seizures in the general population, but their possible preventive role in PSE has not been clear.

The retrospective, observational study included 528 patients (mean age, 71.4 years; 57.19% men) with hypertension and ischemic stroke without a history of epilepsy.

Researchers divided patients into those who developed PSE during the 2-year follow-up and those who didn’t. The main outcome was incidence of PSE associated with angiotensin receptor blocker therapy compared with other antihypertensive drug classes (ACE inhibitors, calcium channel blockers, and beta blockers).

Of the total, 7.2% of patients developed PSE. The study found patients treated with an angiotensin receptor blockers had a lower risk for PSE (P = .009). PSE incidence was higher among patients receiving calcium channel blockers (P = .019) and beta blockers (P = .008), but ACE inhibitors did not appear to affect PSE risk.

Further analysis showed that patients taking a beta blocker were 120% more likely to develop PSE, and those taking a calcium channel blocker were 110% more likely to develop PSE than those taking an angiotensin receptor blocker. The corresponding comparison was 65% for those taking an ACE inhibitor.

 

Potential Mechanisms

Angiotensin receptor blockers block the angiotensin II type 1 receptor, which may lead to numerous neuroprotective benefits such as improved blood flow to the brain and less neuroinflammation. The blockage may also reduce epilepsy severity and seizure frequency.

ACE inhibitors work in the same system as angiotensin receptor blockers but don’t bind directly to the angiotensin receptor. Experts believe these drugs may lead to inflammation that raises the risk for PSE.

Calcium channel blockers and beta blockers may increase the likelihood of seizures by inducing excessive excitability in the brain, which can trigger seizures.

Other research presented at the meeting found that angiotensin receptor blockers reduce the risk for epilepsy in patients with hypertension even in the absence of stroke.

Using data from an US national administrative database, the retrospective cohort study included 2,261,964 eligible adult beneficiaries diagnosed with hypertension and dispensed at least one angiotensin receptor blocker, ACE inhibitor, beta blocker, or calcium channel blocker from 2010 to 2017.

The study found angiotensin receptor blockers were associated with lower epilepsy incidence than ACE inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.58-0.96), beta blockers (HR, 0.70; 95% CI, 0.54-0.90), and calcium channel blockers (HR, 0.80; 95% CI, 0.61-1.04).

The effect was most robust for the angiotensin receptor blocker losartan and among patients with no preexisting stroke or cardiovascular conditions.

Researchers ran the analysis excluding stroke and the association was still there, said lead study author Kimford Meador, MD, professor of neurology and neurological sciences, Stanford University, Palo Alto, California. “People with hypertension who use angiotensin receptor blockers — even if they don’t have a stroke — are less likely to develop epilepsy than if they use other major anti-hypertensives.”

 

Exciting and Suggestive

These new studies are “exciting” and “very suggestive,” said Meador. “We don’t have any true antiepileptic drugs; we have antiseizure medications. If we could reduce the incidence of epilepsy, that would be a very big thing.”

But the research to date hasn’t been “definitive” and is subject to bias, he said. “What we really need is a large randomized controlled trial to see if this is real because any observational study in humans has the potential for confounding from unmeasured variables.”

If such a study does show the effect is real, “that would change clinical practice,” said Meador.

As angiotensin receptor blockers have anti-inflammatory effects, researchers are now investigating whether this class of drugs might be useful in other diseases linked to inflammation such as multiple sclerosis, said Meador.

Commenting on the research, Alain Zingraff Looti, MD, assistant professor of neurology and public health sciences, Penn State College of Medicine, Hershey, Pennsylvania, said this new research is “important” although still at a “very preliminary stage.”

As the studies so far have all been observational, “they showed an association, but that doesn’t mean causality,” said Looti. These studies just looked at known potential confounders, “and there may be some unknown confounders that could explain the association,” he added.

But he acknowledged the results make sense from a biological standpoint. He noted that infusing angiotensin receptor blockers into rats causes a “cascade reaction” leading to reduced inflammation in the brain and then to less epilepsy. “Inflammation plays a major role in several models of epilepsy,” he added.

While these new results are important, Looti, too, would like to see a randomized controlled trial to confirm the findings.

Looti and Meador reported no relevant financial disclosures.

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

LOS ANGELES — Angiotensin receptor blockers are more effective than other antihypertensive medications in reducing the risk for post-stroke epilepsy (PSE), new research showed.

Investigators found angiotensin receptor blockers are better at cutting the PSE risk in individuals with high blood pressure than angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and beta-blockers.

The results suggested angiotensin receptor blockers could be a frontline strategy to proactively forestall development of epilepsy in patients with a history of stroke and hypertension, said the study’s co-lead investigator Giacomo Evangelista, MD, PhD, a resident in neurology at the Epilepsy Center at “G. d’Annunzio” University of Chieti-Pescara, Italy.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Stroke and Seizures Tightly Linked

Stroke is the most common cause of seizures in patients older than 60 years. About 6%-8% of new epilepsy diagnoses in older adult patients are associated with a brain ischemic event.

Hypertension is among the most common risk factors for both epilepsy and stroke. The European Society of Cardiology recommends ACE inhibitors and angiotensin receptor blockers be considered first-line hypertension treatments.

Angiotensin receptor blockers seem to provide a protective effect in terms of seizures in the general population, but their possible preventive role in PSE has not been clear.

The retrospective, observational study included 528 patients (mean age, 71.4 years; 57.19% men) with hypertension and ischemic stroke without a history of epilepsy.

Researchers divided patients into those who developed PSE during the 2-year follow-up and those who didn’t. The main outcome was incidence of PSE associated with angiotensin receptor blocker therapy compared with other antihypertensive drug classes (ACE inhibitors, calcium channel blockers, and beta blockers).

Of the total, 7.2% of patients developed PSE. The study found patients treated with an angiotensin receptor blockers had a lower risk for PSE (P = .009). PSE incidence was higher among patients receiving calcium channel blockers (P = .019) and beta blockers (P = .008), but ACE inhibitors did not appear to affect PSE risk.

Further analysis showed that patients taking a beta blocker were 120% more likely to develop PSE, and those taking a calcium channel blocker were 110% more likely to develop PSE than those taking an angiotensin receptor blocker. The corresponding comparison was 65% for those taking an ACE inhibitor.

 

Potential Mechanisms

Angiotensin receptor blockers block the angiotensin II type 1 receptor, which may lead to numerous neuroprotective benefits such as improved blood flow to the brain and less neuroinflammation. The blockage may also reduce epilepsy severity and seizure frequency.

ACE inhibitors work in the same system as angiotensin receptor blockers but don’t bind directly to the angiotensin receptor. Experts believe these drugs may lead to inflammation that raises the risk for PSE.

Calcium channel blockers and beta blockers may increase the likelihood of seizures by inducing excessive excitability in the brain, which can trigger seizures.

Other research presented at the meeting found that angiotensin receptor blockers reduce the risk for epilepsy in patients with hypertension even in the absence of stroke.

Using data from an US national administrative database, the retrospective cohort study included 2,261,964 eligible adult beneficiaries diagnosed with hypertension and dispensed at least one angiotensin receptor blocker, ACE inhibitor, beta blocker, or calcium channel blocker from 2010 to 2017.

The study found angiotensin receptor blockers were associated with lower epilepsy incidence than ACE inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.58-0.96), beta blockers (HR, 0.70; 95% CI, 0.54-0.90), and calcium channel blockers (HR, 0.80; 95% CI, 0.61-1.04).

The effect was most robust for the angiotensin receptor blocker losartan and among patients with no preexisting stroke or cardiovascular conditions.

Researchers ran the analysis excluding stroke and the association was still there, said lead study author Kimford Meador, MD, professor of neurology and neurological sciences, Stanford University, Palo Alto, California. “People with hypertension who use angiotensin receptor blockers — even if they don’t have a stroke — are less likely to develop epilepsy than if they use other major anti-hypertensives.”

 

Exciting and Suggestive

These new studies are “exciting” and “very suggestive,” said Meador. “We don’t have any true antiepileptic drugs; we have antiseizure medications. If we could reduce the incidence of epilepsy, that would be a very big thing.”

But the research to date hasn’t been “definitive” and is subject to bias, he said. “What we really need is a large randomized controlled trial to see if this is real because any observational study in humans has the potential for confounding from unmeasured variables.”

If such a study does show the effect is real, “that would change clinical practice,” said Meador.

As angiotensin receptor blockers have anti-inflammatory effects, researchers are now investigating whether this class of drugs might be useful in other diseases linked to inflammation such as multiple sclerosis, said Meador.

Commenting on the research, Alain Zingraff Looti, MD, assistant professor of neurology and public health sciences, Penn State College of Medicine, Hershey, Pennsylvania, said this new research is “important” although still at a “very preliminary stage.”

As the studies so far have all been observational, “they showed an association, but that doesn’t mean causality,” said Looti. These studies just looked at known potential confounders, “and there may be some unknown confounders that could explain the association,” he added.

But he acknowledged the results make sense from a biological standpoint. He noted that infusing angiotensin receptor blockers into rats causes a “cascade reaction” leading to reduced inflammation in the brain and then to less epilepsy. “Inflammation plays a major role in several models of epilepsy,” he added.

While these new results are important, Looti, too, would like to see a randomized controlled trial to confirm the findings.

Looti and Meador reported no relevant financial disclosures.

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

LOS ANGELES — Angiotensin receptor blockers are more effective than other antihypertensive medications in reducing the risk for post-stroke epilepsy (PSE), new research showed.

Investigators found angiotensin receptor blockers are better at cutting the PSE risk in individuals with high blood pressure than angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and beta-blockers.

The results suggested angiotensin receptor blockers could be a frontline strategy to proactively forestall development of epilepsy in patients with a history of stroke and hypertension, said the study’s co-lead investigator Giacomo Evangelista, MD, PhD, a resident in neurology at the Epilepsy Center at “G. d’Annunzio” University of Chieti-Pescara, Italy.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Stroke and Seizures Tightly Linked

Stroke is the most common cause of seizures in patients older than 60 years. About 6%-8% of new epilepsy diagnoses in older adult patients are associated with a brain ischemic event.

Hypertension is among the most common risk factors for both epilepsy and stroke. The European Society of Cardiology recommends ACE inhibitors and angiotensin receptor blockers be considered first-line hypertension treatments.

Angiotensin receptor blockers seem to provide a protective effect in terms of seizures in the general population, but their possible preventive role in PSE has not been clear.

The retrospective, observational study included 528 patients (mean age, 71.4 years; 57.19% men) with hypertension and ischemic stroke without a history of epilepsy.

Researchers divided patients into those who developed PSE during the 2-year follow-up and those who didn’t. The main outcome was incidence of PSE associated with angiotensin receptor blocker therapy compared with other antihypertensive drug classes (ACE inhibitors, calcium channel blockers, and beta blockers).

Of the total, 7.2% of patients developed PSE. The study found patients treated with an angiotensin receptor blockers had a lower risk for PSE (P = .009). PSE incidence was higher among patients receiving calcium channel blockers (P = .019) and beta blockers (P = .008), but ACE inhibitors did not appear to affect PSE risk.

Further analysis showed that patients taking a beta blocker were 120% more likely to develop PSE, and those taking a calcium channel blocker were 110% more likely to develop PSE than those taking an angiotensin receptor blocker. The corresponding comparison was 65% for those taking an ACE inhibitor.

 

Potential Mechanisms

Angiotensin receptor blockers block the angiotensin II type 1 receptor, which may lead to numerous neuroprotective benefits such as improved blood flow to the brain and less neuroinflammation. The blockage may also reduce epilepsy severity and seizure frequency.

ACE inhibitors work in the same system as angiotensin receptor blockers but don’t bind directly to the angiotensin receptor. Experts believe these drugs may lead to inflammation that raises the risk for PSE.

Calcium channel blockers and beta blockers may increase the likelihood of seizures by inducing excessive excitability in the brain, which can trigger seizures.

Other research presented at the meeting found that angiotensin receptor blockers reduce the risk for epilepsy in patients with hypertension even in the absence of stroke.

Using data from an US national administrative database, the retrospective cohort study included 2,261,964 eligible adult beneficiaries diagnosed with hypertension and dispensed at least one angiotensin receptor blocker, ACE inhibitor, beta blocker, or calcium channel blocker from 2010 to 2017.

The study found angiotensin receptor blockers were associated with lower epilepsy incidence than ACE inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.58-0.96), beta blockers (HR, 0.70; 95% CI, 0.54-0.90), and calcium channel blockers (HR, 0.80; 95% CI, 0.61-1.04).

The effect was most robust for the angiotensin receptor blocker losartan and among patients with no preexisting stroke or cardiovascular conditions.

Researchers ran the analysis excluding stroke and the association was still there, said lead study author Kimford Meador, MD, professor of neurology and neurological sciences, Stanford University, Palo Alto, California. “People with hypertension who use angiotensin receptor blockers — even if they don’t have a stroke — are less likely to develop epilepsy than if they use other major anti-hypertensives.”

 

Exciting and Suggestive

These new studies are “exciting” and “very suggestive,” said Meador. “We don’t have any true antiepileptic drugs; we have antiseizure medications. If we could reduce the incidence of epilepsy, that would be a very big thing.”

But the research to date hasn’t been “definitive” and is subject to bias, he said. “What we really need is a large randomized controlled trial to see if this is real because any observational study in humans has the potential for confounding from unmeasured variables.”

If such a study does show the effect is real, “that would change clinical practice,” said Meador.

As angiotensin receptor blockers have anti-inflammatory effects, researchers are now investigating whether this class of drugs might be useful in other diseases linked to inflammation such as multiple sclerosis, said Meador.

Commenting on the research, Alain Zingraff Looti, MD, assistant professor of neurology and public health sciences, Penn State College of Medicine, Hershey, Pennsylvania, said this new research is “important” although still at a “very preliminary stage.”

As the studies so far have all been observational, “they showed an association, but that doesn’t mean causality,” said Looti. These studies just looked at known potential confounders, “and there may be some unknown confounders that could explain the association,” he added.

But he acknowledged the results make sense from a biological standpoint. He noted that infusing angiotensin receptor blockers into rats causes a “cascade reaction” leading to reduced inflammation in the brain and then to less epilepsy. “Inflammation plays a major role in several models of epilepsy,” he added.

While these new results are important, Looti, too, would like to see a randomized controlled trial to confirm the findings.

Looti and Meador reported no relevant financial disclosures.

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

TOPLINE:

Oral doxycycline (200 mg twice daily for 28 days) appears to be as effective as intravenous (IV) penicillin for the treatment of ocular syphilis for some patients with the condition.

METHODOLOGY:

• Researchers conducted a retrospective cohort study of ocular syphilis cases diagnosed from 2017 to 2023 in Los Angeles, analyzing 32 patients with a median age of 46 years (78% men).
• Patients treated before January 2022 received IV doxycycline, while those treated after that date were given the option to receive an oral form of the drug.
• A total of 16 patients received oral doxycycline (seven patients received only oral doxycycline; nine received a short course of parenteral penicillin followed by a full course of oral doxycycline); another 16 patients received a full course of IV penicillin.
• The analysis measured visual acuity (VA), ocular inflammation, and rapid plasma reagin (RPR).

TAKEAWAY:

• The doxycycline group had better median VA at both the initial presentation and the final follow-up than the penicillin group (VA, 0.44, 0.18; P = .04; VA, 1.0, 0.40; P = .03, respectively).
• Resolution of ocular inflammation showed no significant differences between the doxycycline and IV penicillin groups (P = .62 for both).
• All patients who had follow-up at 9 months demonstrated a fourfold decrease in RPR titers (four people in the oral doxycycline group and seven people in the IV penicillin group).

IN PRACTICE:

“We found that oral doxycycline for the treatment of ocular syphilis may be safe and effective in a selected subset of patients who completed an extended oral antibiotic regimen,” the study authors wrote. “Other studies have also demonstrated similar efficacy of oral therapy when compared with IV therapy. A fourfold decrease in RPR titers was considered an adequate serologic treatment response and corresponds with resolution of syphilis disease activity. This was observed in all patients with more than 9 months of follow-up. Long-term monitoring is recommended for those treated with doxycycline to ensure clinical and serologic response.”

SOURCE:

The study was led by Brian C. Toy, MD, of the Roski Eye Institute at the Keck School of Medicine at the University of Southern California in Los Angeles. It was published online in JAMA Network Open.

LIMITATIONS:

The study was retrospective in nature, used heterogeneous treatment methods, and lacked longitudinal RPR titers.

DISCLOSURES:

Toy served on physician advisory boards for Alimera, EyePoint, Bausch and Lomb, and Regeneron. No other disclosures were reported.

This article was created 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.

TOPLINE:

Oral doxycycline (200 mg twice daily for 28 days) appears to be as effective as intravenous (IV) penicillin for the treatment of ocular syphilis for some patients with the condition.

METHODOLOGY:

• Researchers conducted a retrospective cohort study of ocular syphilis cases diagnosed from 2017 to 2023 in Los Angeles, analyzing 32 patients with a median age of 46 years (78% men).
• Patients treated before January 2022 received IV doxycycline, while those treated after that date were given the option to receive an oral form of the drug.
• A total of 16 patients received oral doxycycline (seven patients received only oral doxycycline; nine received a short course of parenteral penicillin followed by a full course of oral doxycycline); another 16 patients received a full course of IV penicillin.
• The analysis measured visual acuity (VA), ocular inflammation, and rapid plasma reagin (RPR).

TAKEAWAY:

• The doxycycline group had better median VA at both the initial presentation and the final follow-up than the penicillin group (VA, 0.44, 0.18; P = .04; VA, 1.0, 0.40; P = .03, respectively).
• Resolution of ocular inflammation showed no significant differences between the doxycycline and IV penicillin groups (P = .62 for both).
• All patients who had follow-up at 9 months demonstrated a fourfold decrease in RPR titers (four people in the oral doxycycline group and seven people in the IV penicillin group).

IN PRACTICE:

“We found that oral doxycycline for the treatment of ocular syphilis may be safe and effective in a selected subset of patients who completed an extended oral antibiotic regimen,” the study authors wrote. “Other studies have also demonstrated similar efficacy of oral therapy when compared with IV therapy. A fourfold decrease in RPR titers was considered an adequate serologic treatment response and corresponds with resolution of syphilis disease activity. This was observed in all patients with more than 9 months of follow-up. Long-term monitoring is recommended for those treated with doxycycline to ensure clinical and serologic response.”

SOURCE:

The study was led by Brian C. Toy, MD, of the Roski Eye Institute at the Keck School of Medicine at the University of Southern California in Los Angeles. It was published online in JAMA Network Open.

LIMITATIONS:

The study was retrospective in nature, used heterogeneous treatment methods, and lacked longitudinal RPR titers.

DISCLOSURES:

Toy served on physician advisory boards for Alimera, EyePoint, Bausch and Lomb, and Regeneron. No other disclosures were reported.

This article was created 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.

TOPLINE:

Oral doxycycline (200 mg twice daily for 28 days) appears to be as effective as intravenous (IV) penicillin for the treatment of ocular syphilis for some patients with the condition.

METHODOLOGY:

• Researchers conducted a retrospective cohort study of ocular syphilis cases diagnosed from 2017 to 2023 in Los Angeles, analyzing 32 patients with a median age of 46 years (78% men).
• Patients treated before January 2022 received IV doxycycline, while those treated after that date were given the option to receive an oral form of the drug.
• A total of 16 patients received oral doxycycline (seven patients received only oral doxycycline; nine received a short course of parenteral penicillin followed by a full course of oral doxycycline); another 16 patients received a full course of IV penicillin.
• The analysis measured visual acuity (VA), ocular inflammation, and rapid plasma reagin (RPR).

TAKEAWAY:

• The doxycycline group had better median VA at both the initial presentation and the final follow-up than the penicillin group (VA, 0.44, 0.18; P = .04; VA, 1.0, 0.40; P = .03, respectively).
• Resolution of ocular inflammation showed no significant differences between the doxycycline and IV penicillin groups (P = .62 for both).
• All patients who had follow-up at 9 months demonstrated a fourfold decrease in RPR titers (four people in the oral doxycycline group and seven people in the IV penicillin group).

IN PRACTICE:

“We found that oral doxycycline for the treatment of ocular syphilis may be safe and effective in a selected subset of patients who completed an extended oral antibiotic regimen,” the study authors wrote. “Other studies have also demonstrated similar efficacy of oral therapy when compared with IV therapy. A fourfold decrease in RPR titers was considered an adequate serologic treatment response and corresponds with resolution of syphilis disease activity. This was observed in all patients with more than 9 months of follow-up. Long-term monitoring is recommended for those treated with doxycycline to ensure clinical and serologic response.”

SOURCE:

The study was led by Brian C. Toy, MD, of the Roski Eye Institute at the Keck School of Medicine at the University of Southern California in Los Angeles. It was published online in JAMA Network Open.

LIMITATIONS:

The study was retrospective in nature, used heterogeneous treatment methods, and lacked longitudinal RPR titers.

DISCLOSURES:

Toy served on physician advisory boards for Alimera, EyePoint, Bausch and Lomb, and Regeneron. No other disclosures were reported.

This article was created 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.

LOS ANGELES — The median cost of brand-name anti-seizure medications (ASMs) in the United States almost doubled from 2013 to 2023, whereas generic ASM prices declined over the same period, results of a new study showed.

These findings highlight an “urgent need” to examine ASM pricing, said study investigator Pradeep Javarayee, MD, MBA, assistant professor, Department of Neurology, Medical College of Wisconsin, Milwaukee.

“The price disparity between generic and brand-name anti-seizure medications is growing,” said Javarayee. “Understanding these trends is essential for clinicians to make cost-conscious prescribing decisions and to advocate for policies that ensure equitable access to treatment for patients with epilepsy.” 

The findings were presented at American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Concerning Trends

Researchers analyzed prices of ASMs using National Average Drug Acquisition Cost (NADAC) data provided by the Centers for Medicare & Medicaid Services from November 2013 to July 2023.

A publicly available resource, NADAC is widely regarded as the most reliable benchmark for drug reimbursement in the United States, said Javarayee. It is based on the price/unit of Medicaid-covered outpatient drugs collected though monthly surveys of retail community pharmacies across the United States.

The database includes medication names, strengths, formulations, and National Drug Codes.

The study examined 23 US Food and Drug Administration–approved ASMs, encompassing 223 oral formulations, which included 112 brand-name and 111 generic products.

To account for inflation, researchers adjusted ASM prices using the Consumer Price Index for Medicinal Drugs–Seasonally Adjusted. They also explored the effects of the COVID-19 pandemic on drug pricing.

The study uncovered trends that Javarayee found concerning. For example, between 2013 and 2023, the average price of brand-name ASMs increased from $8.71 to $15.43, whereas the average price of generic ASMs decreased from $1.39 to $1.26.

Most generic ASMs remained in the low-cost range ($0-$0.25) during the study period, whereas the proportion of higher-priced brand-name ASMs ($10-$50) increased.

The number of brand-name ASMs with a mean price exceeding $15 rose from two (2013-2016) to six (2017-2019) and then to eight (2020-2023).

 

Unsustainable Price Increases

The study uncovered examples of what Javarayee called “extreme” price differences. For instance, matched brand-name and generic ASMs with price differences of 1000%-9999% increased from 32.88% in 2013-2016 to 41.43% in 2020-2023.

Among brand-name ASMs, cenobamate (Xcopri), which is approved in the United States for partial-onset seizures, had the highest mean price between 2020 and 2023 ($35.59). For generic ASMs, topiramate had the highest mean price in the same time period ($6.64).

Looking at formulation-based cost differences, the study found generic immediate-release formulations were significantly cheaper than extended-release or delayed-release counterparts, with cost differences reaching as high as 7751.20%.

The study also showed the COVID-19 pandemic led to a 24.4% increase in brand-name ASM prices and a 23.1% decrease in generic ASM prices.

The results underscore the need to raise awareness of drug pricing dynamics and call for targeted policy interventions to alleviate the rising cost burden on patients, said Javarayee.

He emphasized that such price increases are unsustainable. “Addressing these disparities is critical not only for improving patient adherence and outcomes but also for reducing the overall economic strain on the healthcare system.”

 

‘Tip of the Iceberg’

Reached for a comment, Tim Welty, a pharmacist in Des Moines, Iowa, who specializes in epilepsy drugs, agreed that the issue of medication costs needs to be addressed.

“I absolutely think physicians and others need to advocate for transparency in pricing,” he said. It’s not unusual for physician requests to have newer ASMs covered for their patients to be denied, he added.

Welty also noted Congress is currently considering bills that address the lack of transparency in the way medications are reimbursed.

This new study doesn’t reveal what patients are paying for their medications, he said. “These data tell me the national average of the cost to the pharmacy, but don’t tell me what the patient is actually paying, or what the insurance companies are actually paying for these medications.”

A “hot topic” in the industry is the role of pharmacy benefit managers, who are contracted by health insurance companies to manage medication portfolios, in influencing drug prices.

Drug pricing is a complicated topic. “There’s a lot more behind this; this is just like a tip of the iceberg,” said Welty.

Also commenting, Jacqueline French, MD, professor, NYU Comprehensive Epilepsy Center, New York City, said the much higher ASM prices are “very problematic,” particularly for drugs that don’t have a generic.

“I wonder how much the drugs for orphan indications, which are usually higher priced, influenced the numbers.”

The good news, though, is that many people “can safely take generics if they’re available,” said French.

The investigators and Welty reported no relevant disclosures.

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

LOS ANGELES — The median cost of brand-name anti-seizure medications (ASMs) in the United States almost doubled from 2013 to 2023, whereas generic ASM prices declined over the same period, results of a new study showed.

These findings highlight an “urgent need” to examine ASM pricing, said study investigator Pradeep Javarayee, MD, MBA, assistant professor, Department of Neurology, Medical College of Wisconsin, Milwaukee.

“The price disparity between generic and brand-name anti-seizure medications is growing,” said Javarayee. “Understanding these trends is essential for clinicians to make cost-conscious prescribing decisions and to advocate for policies that ensure equitable access to treatment for patients with epilepsy.” 

The findings were presented at American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Concerning Trends

Researchers analyzed prices of ASMs using National Average Drug Acquisition Cost (NADAC) data provided by the Centers for Medicare & Medicaid Services from November 2013 to July 2023.

A publicly available resource, NADAC is widely regarded as the most reliable benchmark for drug reimbursement in the United States, said Javarayee. It is based on the price/unit of Medicaid-covered outpatient drugs collected though monthly surveys of retail community pharmacies across the United States.

The database includes medication names, strengths, formulations, and National Drug Codes.

The study examined 23 US Food and Drug Administration–approved ASMs, encompassing 223 oral formulations, which included 112 brand-name and 111 generic products.

To account for inflation, researchers adjusted ASM prices using the Consumer Price Index for Medicinal Drugs–Seasonally Adjusted. They also explored the effects of the COVID-19 pandemic on drug pricing.

The study uncovered trends that Javarayee found concerning. For example, between 2013 and 2023, the average price of brand-name ASMs increased from $8.71 to $15.43, whereas the average price of generic ASMs decreased from $1.39 to $1.26.

Most generic ASMs remained in the low-cost range ($0-$0.25) during the study period, whereas the proportion of higher-priced brand-name ASMs ($10-$50) increased.

The number of brand-name ASMs with a mean price exceeding $15 rose from two (2013-2016) to six (2017-2019) and then to eight (2020-2023).

 

Unsustainable Price Increases

The study uncovered examples of what Javarayee called “extreme” price differences. For instance, matched brand-name and generic ASMs with price differences of 1000%-9999% increased from 32.88% in 2013-2016 to 41.43% in 2020-2023.

Among brand-name ASMs, cenobamate (Xcopri), which is approved in the United States for partial-onset seizures, had the highest mean price between 2020 and 2023 ($35.59). For generic ASMs, topiramate had the highest mean price in the same time period ($6.64).

Looking at formulation-based cost differences, the study found generic immediate-release formulations were significantly cheaper than extended-release or delayed-release counterparts, with cost differences reaching as high as 7751.20%.

The study also showed the COVID-19 pandemic led to a 24.4% increase in brand-name ASM prices and a 23.1% decrease in generic ASM prices.

The results underscore the need to raise awareness of drug pricing dynamics and call for targeted policy interventions to alleviate the rising cost burden on patients, said Javarayee.

He emphasized that such price increases are unsustainable. “Addressing these disparities is critical not only for improving patient adherence and outcomes but also for reducing the overall economic strain on the healthcare system.”

 

‘Tip of the Iceberg’

Reached for a comment, Tim Welty, a pharmacist in Des Moines, Iowa, who specializes in epilepsy drugs, agreed that the issue of medication costs needs to be addressed.

“I absolutely think physicians and others need to advocate for transparency in pricing,” he said. It’s not unusual for physician requests to have newer ASMs covered for their patients to be denied, he added.

Welty also noted Congress is currently considering bills that address the lack of transparency in the way medications are reimbursed.

This new study doesn’t reveal what patients are paying for their medications, he said. “These data tell me the national average of the cost to the pharmacy, but don’t tell me what the patient is actually paying, or what the insurance companies are actually paying for these medications.”

A “hot topic” in the industry is the role of pharmacy benefit managers, who are contracted by health insurance companies to manage medication portfolios, in influencing drug prices.

Drug pricing is a complicated topic. “There’s a lot more behind this; this is just like a tip of the iceberg,” said Welty.

Also commenting, Jacqueline French, MD, professor, NYU Comprehensive Epilepsy Center, New York City, said the much higher ASM prices are “very problematic,” particularly for drugs that don’t have a generic.

“I wonder how much the drugs for orphan indications, which are usually higher priced, influenced the numbers.”

The good news, though, is that many people “can safely take generics if they’re available,” said French.

The investigators and Welty reported no relevant disclosures.

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

LOS ANGELES — The median cost of brand-name anti-seizure medications (ASMs) in the United States almost doubled from 2013 to 2023, whereas generic ASM prices declined over the same period, results of a new study showed.

These findings highlight an “urgent need” to examine ASM pricing, said study investigator Pradeep Javarayee, MD, MBA, assistant professor, Department of Neurology, Medical College of Wisconsin, Milwaukee.

“The price disparity between generic and brand-name anti-seizure medications is growing,” said Javarayee. “Understanding these trends is essential for clinicians to make cost-conscious prescribing decisions and to advocate for policies that ensure equitable access to treatment for patients with epilepsy.” 

The findings were presented at American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Concerning Trends

Researchers analyzed prices of ASMs using National Average Drug Acquisition Cost (NADAC) data provided by the Centers for Medicare & Medicaid Services from November 2013 to July 2023.

A publicly available resource, NADAC is widely regarded as the most reliable benchmark for drug reimbursement in the United States, said Javarayee. It is based on the price/unit of Medicaid-covered outpatient drugs collected though monthly surveys of retail community pharmacies across the United States.

The database includes medication names, strengths, formulations, and National Drug Codes.

The study examined 23 US Food and Drug Administration–approved ASMs, encompassing 223 oral formulations, which included 112 brand-name and 111 generic products.

To account for inflation, researchers adjusted ASM prices using the Consumer Price Index for Medicinal Drugs–Seasonally Adjusted. They also explored the effects of the COVID-19 pandemic on drug pricing.

The study uncovered trends that Javarayee found concerning. For example, between 2013 and 2023, the average price of brand-name ASMs increased from $8.71 to $15.43, whereas the average price of generic ASMs decreased from $1.39 to $1.26.

Most generic ASMs remained in the low-cost range ($0-$0.25) during the study period, whereas the proportion of higher-priced brand-name ASMs ($10-$50) increased.

The number of brand-name ASMs with a mean price exceeding $15 rose from two (2013-2016) to six (2017-2019) and then to eight (2020-2023).

 

Unsustainable Price Increases

The study uncovered examples of what Javarayee called “extreme” price differences. For instance, matched brand-name and generic ASMs with price differences of 1000%-9999% increased from 32.88% in 2013-2016 to 41.43% in 2020-2023.

Among brand-name ASMs, cenobamate (Xcopri), which is approved in the United States for partial-onset seizures, had the highest mean price between 2020 and 2023 ($35.59). For generic ASMs, topiramate had the highest mean price in the same time period ($6.64).

Looking at formulation-based cost differences, the study found generic immediate-release formulations were significantly cheaper than extended-release or delayed-release counterparts, with cost differences reaching as high as 7751.20%.

The study also showed the COVID-19 pandemic led to a 24.4% increase in brand-name ASM prices and a 23.1% decrease in generic ASM prices.

The results underscore the need to raise awareness of drug pricing dynamics and call for targeted policy interventions to alleviate the rising cost burden on patients, said Javarayee.

He emphasized that such price increases are unsustainable. “Addressing these disparities is critical not only for improving patient adherence and outcomes but also for reducing the overall economic strain on the healthcare system.”

 

‘Tip of the Iceberg’

Reached for a comment, Tim Welty, a pharmacist in Des Moines, Iowa, who specializes in epilepsy drugs, agreed that the issue of medication costs needs to be addressed.

“I absolutely think physicians and others need to advocate for transparency in pricing,” he said. It’s not unusual for physician requests to have newer ASMs covered for their patients to be denied, he added.

Welty also noted Congress is currently considering bills that address the lack of transparency in the way medications are reimbursed.

This new study doesn’t reveal what patients are paying for their medications, he said. “These data tell me the national average of the cost to the pharmacy, but don’t tell me what the patient is actually paying, or what the insurance companies are actually paying for these medications.”

A “hot topic” in the industry is the role of pharmacy benefit managers, who are contracted by health insurance companies to manage medication portfolios, in influencing drug prices.

Drug pricing is a complicated topic. “There’s a lot more behind this; this is just like a tip of the iceberg,” said Welty.

Also commenting, Jacqueline French, MD, professor, NYU Comprehensive Epilepsy Center, New York City, said the much higher ASM prices are “very problematic,” particularly for drugs that don’t have a generic.

“I wonder how much the drugs for orphan indications, which are usually higher priced, influenced the numbers.”

The good news, though, is that many people “can safely take generics if they’re available,” said French.

The investigators and Welty reported no relevant disclosures.

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

There was a recent flurry of excitement when UK researchers from the Wellcome Sanger Institute, a nonprofit genomics and genetics research organization in Cambridge, England, announced their creation of the most detailed cell map of the human gastrointestinal (GI) tract up to this point. Using spatial and single-cell data from 1.6 million cells (from 271 donors), the scientists’ work, published in Nature, yields valuable information about the gut’s health and disease states.

“We now have a nice idea of what cell types we can find in the gut,” said co-author Rasa Elmentaite, PhD, co-founder and head of Genomics and Data Science at Ensocell.

No small question: How, exactly, does one go about mapping the human gut?

The story behind the construction of the Gut Cell Atlas, an arm of the larger Human Cell Atlas project — which recently published more than 40 studies in Nature in November 2024 — is one of global collaboration and scientific precision across continents.

Most of all, Elmentaite said, it has taken the scientists involved down paths they never anticipated.

 

How It Began

Over the past 5-7 years, there have been many individual publications across institutes where research labs have created snippets of what the cells in the gut look like, said Elmentaite, referring to the GI tract, which in this case encompasses the mouth, throat, esophagus, stomach, small intestine, large intestine, rectum, and anus.

Labs studying gut cells often focus on one specific region, for example, the small intestine or the large intestine, if they’re working on Crohn’s disease research. “It makes sense. The GI tract is really regionalized,” she said.

In 2019 and 2021, Elmentaite and her colleagues published papers that mapped some cells in the human gut, and their work garnered attention from other scientists around the world. That’s how they decided to take on the challenge of creating a more comprehensive map of the cells in both the healthy gut and in GI tracts where disease is present.

“We realized there are so many other labs interested in understanding the intestinal tract holistically,” she said. “We thought it would be really interesting to look at the cells in the context of the whole GI system.”

 

Not a Bad ‘Lockdown Project’

During the pandemic, while the rest of society was playing with sourdough starter, Elmentaite’s lab decided to pool their datasets with data from other labs to see what happened. They had more than 20 datasets at the time and wanted to generate more to fill gaps where there was less information available (eg, data on the cells in the stomach).

“It required getting samples from surgeons, going into the lab and processing those samples into single cells, and then processing that data bioinformatically,” said Elmentaite.

She explained that generating more datasets was not a job for one person and “required convincing a lot of scientists that it was worthwhile,” including a cancer biologist and a mucosal immunologist. They also brought in more technical bioinformatics expertise and recruited an IT team — several people who only worked on processing data and clearing it, “so it was aligned very specifically, and processed very uniformly, across the study,” Elmentaite said.

In the end, with researchers coming together on many Zoom calls from Australia, Germany, Norway, Spain, and numerous locations across the United Kingdom, they were able to integrate 25 single-cell RNA sequencing datasets that encompassed the entire healthy GI tract in development and in adults, leading to a healthy gut reference atlas that includes about 1.1 million cells and 136 cell subgroups.

 

How to Build a Two-Dimensional (2D) Map of the Gut

Here’s where the weeds get taller: Raw sequencing reads — bits of different RNA that the researchers sequenced from individual biological samples — needed to be mapped back to genes so that the researchers could understand what kinds of genes were expressed in the samples.

“There is a lot of curation there that needs to happen because the versions of transcriptome [a complete set of RNA molecules in a single cell or tissue], and what the genome looks like, is evolving constantly. So we have to map it back to the same transcriptomic reference,” Elmentaite said.

Once they knew all the different genes active in a cell, the researchers were able, using bioinformatics, to pull all of the datasets together and visualize them in a 2D space — essentially, a representation of a map.

“The cells that are transcriptionally more similar to each other, they will cluster together. And the ones that are more distinct transcriptionally will be farther away from each other,” Elmentaite said.

For decades, GI tract researchers had individually studied which types of genes are activated in an epithelial cell vs a T cell vs a B cell, she said, and “then suddenly you’re seeing it on your screen all at once. It’s amazing to see.”

 

In Brutal Detail

One of the biggest challenges in interpreting the data involved many people who made sure that there were no technical differences between the samples, Elmentaite said.

For example, samples processed in different labs may have sequencing differences between them. Or the kind of enzymes used to process the tissue might have been different from lab to lab. Sometimes they’d even record down to the detail what time of the day a sample was collected, if that information was available.

“Computationally, we considered all of these variables and tried to regress as much of that as possible. And then, if we saw clusters that resembled gene expression that we know is consistent with some of the cell types, then we knew that we’d regressed all the batch effects,” said Elmentaite.

 

Before ‘Eureka’ Comes a Few ‘Aha’ Moments

There were many “aha moments,” but also some puzzling ones, she said. One of the biggest surprises was seeing that the identity of a cell believed to be set from development can actually change if a person has a lot of irritation and inflammation, as occurs in inflammatory bowel disease. Epithelial cell metaplasia was one of the surprises.

“Metaplasia describes an activation or differentiation of one differentiated cell type into another differentiated cell type. And we knew that that exists in some of the upper GI diseases, but we didn’t realize that the same sort of mechanism exists in the small intestine,” Elmentaite said.

Epithelial cells are among the most abundant cells in the body. The researchers knew from established research that these cells act a bit like first responders and provide healing to the gut. “We could see that they were producing a lot of mucous that helps to potentially flush down the microbes that are triggering inflammation. But the ‘aha moment’ for us was that actually there’s a dual function in these cells,” she said.

They could see in the transcriptional profile a significant production of chemokines (a family of proteins that play a role in the body’s immune responses) and major histocompatibility complex class II molecules (cell surface proteins involved in the body’s immune response), and the epithelial cells seemed to attract neutrophils and monocytes and to interact with certain T cells — adding to the cycle of chronic inflammation.

“I think for a lot of us, this was a surprise because we think of epithelial cells as more like a barrier, just a passive player in, for example, inflammatory bowel disease,” said Elmentaite.

In addition to reporting their findings on epithelial cell metaplasia, the researchers processed 12 GI disease datasets, including celiac disease, Crohn’s disease, GI-related cancers, and ulcerative colitis.

 

A Gut Cell Atlas for the People (Well, Scientific People)

“The Gut Cell Atlas is usable for everyone, and everyone has a chance to contribute,” said Elmentaite. But 1.6 million cells is only a start and more data are needed, she said, and efforts are being spearheaded at the broader Human Cell Atlas project to collect it. There are also efforts to get all researchers using the same cell annotation, research-wide standards that will make the atlas truly usable for everyone.

Keith Summa, MD, PhD, assistant professor of medicine in the Division of Gastroenterology and Hepatology at Feinberg School of Medicine, Northwestern University, Chicago, focuses much of his work on inflammatory bowel disease as well as disorders of the gut-brain interaction. He conducts basic and translational research using experimental models of intestinal inflammation.

At Northwestern University, they have a tissue biorepository. It includes colon and intestine tissue samples from healthy individuals as well as individuals with different disease states. “One potential area where I could see this being a useful tool for us is that we could utilize the Gut Cell Atlas in the analysis of our tissue samples to see if we find commonalities between what’s described in the atlas and then what we’re observing,” said Summa, who was not involved in the UK-based project.

He said Northwestern University’s biorepository has details about what medications people were on and the extent and severity of their disease.

“We may be able to utilize the Gut Cell Atlas to help us look at specific factors in terms of how people are responding to different treatments, how different cell types are affected by different treatments, or how they are active or not active in different severities of disease. It may help us provide more precision to our understanding of these different conditions,” said Summa.

He also noted how GI specialists use “Crohn’s disease” as a single diagnosis, “but that encompasses a pretty wide spectrum of phenotypes and behaviors,” he said. “I think looking at such a cell-specific level may help to better identify some of the different pathways that are active and the different phenotypes or behaviors of this disease.” 

 

Next Step: Visualize It in a Three-Dimensional (3D) Space

The next stage for Elmentaite and her colleagues is to evolve the 2D map into a 3D map so they can visualize which cells are where and how they are organized in space.

“The next step, which I think is super exciting, is understanding how these cells depend on each other,” she said. “Really functionally understanding if some of them are essential and others are not. And doing AI modeling to understand what we can learn from this vast amount of data that we’re generating. And of course, that includes how we use this knowledge to create precision therapies.”

 

A version of this article appeared on Medscape.com.

There was a recent flurry of excitement when UK researchers from the Wellcome Sanger Institute, a nonprofit genomics and genetics research organization in Cambridge, England, announced their creation of the most detailed cell map of the human gastrointestinal (GI) tract up to this point. Using spatial and single-cell data from 1.6 million cells (from 271 donors), the scientists’ work, published in Nature, yields valuable information about the gut’s health and disease states.

“We now have a nice idea of what cell types we can find in the gut,” said co-author Rasa Elmentaite, PhD, co-founder and head of Genomics and Data Science at Ensocell.

No small question: How, exactly, does one go about mapping the human gut?

The story behind the construction of the Gut Cell Atlas, an arm of the larger Human Cell Atlas project — which recently published more than 40 studies in Nature in November 2024 — is one of global collaboration and scientific precision across continents.

Most of all, Elmentaite said, it has taken the scientists involved down paths they never anticipated.

 

How It Began

Over the past 5-7 years, there have been many individual publications across institutes where research labs have created snippets of what the cells in the gut look like, said Elmentaite, referring to the GI tract, which in this case encompasses the mouth, throat, esophagus, stomach, small intestine, large intestine, rectum, and anus.

Labs studying gut cells often focus on one specific region, for example, the small intestine or the large intestine, if they’re working on Crohn’s disease research. “It makes sense. The GI tract is really regionalized,” she said.

In 2019 and 2021, Elmentaite and her colleagues published papers that mapped some cells in the human gut, and their work garnered attention from other scientists around the world. That’s how they decided to take on the challenge of creating a more comprehensive map of the cells in both the healthy gut and in GI tracts where disease is present.

“We realized there are so many other labs interested in understanding the intestinal tract holistically,” she said. “We thought it would be really interesting to look at the cells in the context of the whole GI system.”

 

Not a Bad ‘Lockdown Project’

During the pandemic, while the rest of society was playing with sourdough starter, Elmentaite’s lab decided to pool their datasets with data from other labs to see what happened. They had more than 20 datasets at the time and wanted to generate more to fill gaps where there was less information available (eg, data on the cells in the stomach).

“It required getting samples from surgeons, going into the lab and processing those samples into single cells, and then processing that data bioinformatically,” said Elmentaite.

She explained that generating more datasets was not a job for one person and “required convincing a lot of scientists that it was worthwhile,” including a cancer biologist and a mucosal immunologist. They also brought in more technical bioinformatics expertise and recruited an IT team — several people who only worked on processing data and clearing it, “so it was aligned very specifically, and processed very uniformly, across the study,” Elmentaite said.

In the end, with researchers coming together on many Zoom calls from Australia, Germany, Norway, Spain, and numerous locations across the United Kingdom, they were able to integrate 25 single-cell RNA sequencing datasets that encompassed the entire healthy GI tract in development and in adults, leading to a healthy gut reference atlas that includes about 1.1 million cells and 136 cell subgroups.

 

How to Build a Two-Dimensional (2D) Map of the Gut

Here’s where the weeds get taller: Raw sequencing reads — bits of different RNA that the researchers sequenced from individual biological samples — needed to be mapped back to genes so that the researchers could understand what kinds of genes were expressed in the samples.

“There is a lot of curation there that needs to happen because the versions of transcriptome [a complete set of RNA molecules in a single cell or tissue], and what the genome looks like, is evolving constantly. So we have to map it back to the same transcriptomic reference,” Elmentaite said.

Once they knew all the different genes active in a cell, the researchers were able, using bioinformatics, to pull all of the datasets together and visualize them in a 2D space — essentially, a representation of a map.

“The cells that are transcriptionally more similar to each other, they will cluster together. And the ones that are more distinct transcriptionally will be farther away from each other,” Elmentaite said.

For decades, GI tract researchers had individually studied which types of genes are activated in an epithelial cell vs a T cell vs a B cell, she said, and “then suddenly you’re seeing it on your screen all at once. It’s amazing to see.”

 

In Brutal Detail

One of the biggest challenges in interpreting the data involved many people who made sure that there were no technical differences between the samples, Elmentaite said.

For example, samples processed in different labs may have sequencing differences between them. Or the kind of enzymes used to process the tissue might have been different from lab to lab. Sometimes they’d even record down to the detail what time of the day a sample was collected, if that information was available.

“Computationally, we considered all of these variables and tried to regress as much of that as possible. And then, if we saw clusters that resembled gene expression that we know is consistent with some of the cell types, then we knew that we’d regressed all the batch effects,” said Elmentaite.

 

Before ‘Eureka’ Comes a Few ‘Aha’ Moments

There were many “aha moments,” but also some puzzling ones, she said. One of the biggest surprises was seeing that the identity of a cell believed to be set from development can actually change if a person has a lot of irritation and inflammation, as occurs in inflammatory bowel disease. Epithelial cell metaplasia was one of the surprises.

“Metaplasia describes an activation or differentiation of one differentiated cell type into another differentiated cell type. And we knew that that exists in some of the upper GI diseases, but we didn’t realize that the same sort of mechanism exists in the small intestine,” Elmentaite said.

Epithelial cells are among the most abundant cells in the body. The researchers knew from established research that these cells act a bit like first responders and provide healing to the gut. “We could see that they were producing a lot of mucous that helps to potentially flush down the microbes that are triggering inflammation. But the ‘aha moment’ for us was that actually there’s a dual function in these cells,” she said.

They could see in the transcriptional profile a significant production of chemokines (a family of proteins that play a role in the body’s immune responses) and major histocompatibility complex class II molecules (cell surface proteins involved in the body’s immune response), and the epithelial cells seemed to attract neutrophils and monocytes and to interact with certain T cells — adding to the cycle of chronic inflammation.

“I think for a lot of us, this was a surprise because we think of epithelial cells as more like a barrier, just a passive player in, for example, inflammatory bowel disease,” said Elmentaite.

In addition to reporting their findings on epithelial cell metaplasia, the researchers processed 12 GI disease datasets, including celiac disease, Crohn’s disease, GI-related cancers, and ulcerative colitis.

 

A Gut Cell Atlas for the People (Well, Scientific People)

“The Gut Cell Atlas is usable for everyone, and everyone has a chance to contribute,” said Elmentaite. But 1.6 million cells is only a start and more data are needed, she said, and efforts are being spearheaded at the broader Human Cell Atlas project to collect it. There are also efforts to get all researchers using the same cell annotation, research-wide standards that will make the atlas truly usable for everyone.

Keith Summa, MD, PhD, assistant professor of medicine in the Division of Gastroenterology and Hepatology at Feinberg School of Medicine, Northwestern University, Chicago, focuses much of his work on inflammatory bowel disease as well as disorders of the gut-brain interaction. He conducts basic and translational research using experimental models of intestinal inflammation.

At Northwestern University, they have a tissue biorepository. It includes colon and intestine tissue samples from healthy individuals as well as individuals with different disease states. “One potential area where I could see this being a useful tool for us is that we could utilize the Gut Cell Atlas in the analysis of our tissue samples to see if we find commonalities between what’s described in the atlas and then what we’re observing,” said Summa, who was not involved in the UK-based project.

He said Northwestern University’s biorepository has details about what medications people were on and the extent and severity of their disease.

“We may be able to utilize the Gut Cell Atlas to help us look at specific factors in terms of how people are responding to different treatments, how different cell types are affected by different treatments, or how they are active or not active in different severities of disease. It may help us provide more precision to our understanding of these different conditions,” said Summa.

He also noted how GI specialists use “Crohn’s disease” as a single diagnosis, “but that encompasses a pretty wide spectrum of phenotypes and behaviors,” he said. “I think looking at such a cell-specific level may help to better identify some of the different pathways that are active and the different phenotypes or behaviors of this disease.” 

 

Next Step: Visualize It in a Three-Dimensional (3D) Space

The next stage for Elmentaite and her colleagues is to evolve the 2D map into a 3D map so they can visualize which cells are where and how they are organized in space.

“The next step, which I think is super exciting, is understanding how these cells depend on each other,” she said. “Really functionally understanding if some of them are essential and others are not. And doing AI modeling to understand what we can learn from this vast amount of data that we’re generating. And of course, that includes how we use this knowledge to create precision therapies.”

 

A version of this article appeared on Medscape.com.

There was a recent flurry of excitement when UK researchers from the Wellcome Sanger Institute, a nonprofit genomics and genetics research organization in Cambridge, England, announced their creation of the most detailed cell map of the human gastrointestinal (GI) tract up to this point. Using spatial and single-cell data from 1.6 million cells (from 271 donors), the scientists’ work, published in Nature, yields valuable information about the gut’s health and disease states.

“We now have a nice idea of what cell types we can find in the gut,” said co-author Rasa Elmentaite, PhD, co-founder and head of Genomics and Data Science at Ensocell.

No small question: How, exactly, does one go about mapping the human gut?

The story behind the construction of the Gut Cell Atlas, an arm of the larger Human Cell Atlas project — which recently published more than 40 studies in Nature in November 2024 — is one of global collaboration and scientific precision across continents.

Most of all, Elmentaite said, it has taken the scientists involved down paths they never anticipated.

 

How It Began

Over the past 5-7 years, there have been many individual publications across institutes where research labs have created snippets of what the cells in the gut look like, said Elmentaite, referring to the GI tract, which in this case encompasses the mouth, throat, esophagus, stomach, small intestine, large intestine, rectum, and anus.

Labs studying gut cells often focus on one specific region, for example, the small intestine or the large intestine, if they’re working on Crohn’s disease research. “It makes sense. The GI tract is really regionalized,” she said.

In 2019 and 2021, Elmentaite and her colleagues published papers that mapped some cells in the human gut, and their work garnered attention from other scientists around the world. That’s how they decided to take on the challenge of creating a more comprehensive map of the cells in both the healthy gut and in GI tracts where disease is present.

“We realized there are so many other labs interested in understanding the intestinal tract holistically,” she said. “We thought it would be really interesting to look at the cells in the context of the whole GI system.”

 

Not a Bad ‘Lockdown Project’

During the pandemic, while the rest of society was playing with sourdough starter, Elmentaite’s lab decided to pool their datasets with data from other labs to see what happened. They had more than 20 datasets at the time and wanted to generate more to fill gaps where there was less information available (eg, data on the cells in the stomach).

“It required getting samples from surgeons, going into the lab and processing those samples into single cells, and then processing that data bioinformatically,” said Elmentaite.

She explained that generating more datasets was not a job for one person and “required convincing a lot of scientists that it was worthwhile,” including a cancer biologist and a mucosal immunologist. They also brought in more technical bioinformatics expertise and recruited an IT team — several people who only worked on processing data and clearing it, “so it was aligned very specifically, and processed very uniformly, across the study,” Elmentaite said.

In the end, with researchers coming together on many Zoom calls from Australia, Germany, Norway, Spain, and numerous locations across the United Kingdom, they were able to integrate 25 single-cell RNA sequencing datasets that encompassed the entire healthy GI tract in development and in adults, leading to a healthy gut reference atlas that includes about 1.1 million cells and 136 cell subgroups.

 

How to Build a Two-Dimensional (2D) Map of the Gut

Here’s where the weeds get taller: Raw sequencing reads — bits of different RNA that the researchers sequenced from individual biological samples — needed to be mapped back to genes so that the researchers could understand what kinds of genes were expressed in the samples.

“There is a lot of curation there that needs to happen because the versions of transcriptome [a complete set of RNA molecules in a single cell or tissue], and what the genome looks like, is evolving constantly. So we have to map it back to the same transcriptomic reference,” Elmentaite said.

Once they knew all the different genes active in a cell, the researchers were able, using bioinformatics, to pull all of the datasets together and visualize them in a 2D space — essentially, a representation of a map.

“The cells that are transcriptionally more similar to each other, they will cluster together. And the ones that are more distinct transcriptionally will be farther away from each other,” Elmentaite said.

For decades, GI tract researchers had individually studied which types of genes are activated in an epithelial cell vs a T cell vs a B cell, she said, and “then suddenly you’re seeing it on your screen all at once. It’s amazing to see.”

 

In Brutal Detail

One of the biggest challenges in interpreting the data involved many people who made sure that there were no technical differences between the samples, Elmentaite said.

For example, samples processed in different labs may have sequencing differences between them. Or the kind of enzymes used to process the tissue might have been different from lab to lab. Sometimes they’d even record down to the detail what time of the day a sample was collected, if that information was available.

“Computationally, we considered all of these variables and tried to regress as much of that as possible. And then, if we saw clusters that resembled gene expression that we know is consistent with some of the cell types, then we knew that we’d regressed all the batch effects,” said Elmentaite.

 

Before ‘Eureka’ Comes a Few ‘Aha’ Moments

There were many “aha moments,” but also some puzzling ones, she said. One of the biggest surprises was seeing that the identity of a cell believed to be set from development can actually change if a person has a lot of irritation and inflammation, as occurs in inflammatory bowel disease. Epithelial cell metaplasia was one of the surprises.

“Metaplasia describes an activation or differentiation of one differentiated cell type into another differentiated cell type. And we knew that that exists in some of the upper GI diseases, but we didn’t realize that the same sort of mechanism exists in the small intestine,” Elmentaite said.

Epithelial cells are among the most abundant cells in the body. The researchers knew from established research that these cells act a bit like first responders and provide healing to the gut. “We could see that they were producing a lot of mucous that helps to potentially flush down the microbes that are triggering inflammation. But the ‘aha moment’ for us was that actually there’s a dual function in these cells,” she said.

They could see in the transcriptional profile a significant production of chemokines (a family of proteins that play a role in the body’s immune responses) and major histocompatibility complex class II molecules (cell surface proteins involved in the body’s immune response), and the epithelial cells seemed to attract neutrophils and monocytes and to interact with certain T cells — adding to the cycle of chronic inflammation.

“I think for a lot of us, this was a surprise because we think of epithelial cells as more like a barrier, just a passive player in, for example, inflammatory bowel disease,” said Elmentaite.

In addition to reporting their findings on epithelial cell metaplasia, the researchers processed 12 GI disease datasets, including celiac disease, Crohn’s disease, GI-related cancers, and ulcerative colitis.

 

A Gut Cell Atlas for the People (Well, Scientific People)

“The Gut Cell Atlas is usable for everyone, and everyone has a chance to contribute,” said Elmentaite. But 1.6 million cells is only a start and more data are needed, she said, and efforts are being spearheaded at the broader Human Cell Atlas project to collect it. There are also efforts to get all researchers using the same cell annotation, research-wide standards that will make the atlas truly usable for everyone.

Keith Summa, MD, PhD, assistant professor of medicine in the Division of Gastroenterology and Hepatology at Feinberg School of Medicine, Northwestern University, Chicago, focuses much of his work on inflammatory bowel disease as well as disorders of the gut-brain interaction. He conducts basic and translational research using experimental models of intestinal inflammation.

At Northwestern University, they have a tissue biorepository. It includes colon and intestine tissue samples from healthy individuals as well as individuals with different disease states. “One potential area where I could see this being a useful tool for us is that we could utilize the Gut Cell Atlas in the analysis of our tissue samples to see if we find commonalities between what’s described in the atlas and then what we’re observing,” said Summa, who was not involved in the UK-based project.

He said Northwestern University’s biorepository has details about what medications people were on and the extent and severity of their disease.

“We may be able to utilize the Gut Cell Atlas to help us look at specific factors in terms of how people are responding to different treatments, how different cell types are affected by different treatments, or how they are active or not active in different severities of disease. It may help us provide more precision to our understanding of these different conditions,” said Summa.

He also noted how GI specialists use “Crohn’s disease” as a single diagnosis, “but that encompasses a pretty wide spectrum of phenotypes and behaviors,” he said. “I think looking at such a cell-specific level may help to better identify some of the different pathways that are active and the different phenotypes or behaviors of this disease.” 

 

Next Step: Visualize It in a Three-Dimensional (3D) Space

The next stage for Elmentaite and her colleagues is to evolve the 2D map into a 3D map so they can visualize which cells are where and how they are organized in space.

“The next step, which I think is super exciting, is understanding how these cells depend on each other,” she said. “Really functionally understanding if some of them are essential and others are not. And doing AI modeling to understand what we can learn from this vast amount of data that we’re generating. And of course, that includes how we use this knowledge to create precision therapies.”

 

A version of this article appeared on Medscape.com.