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New questions about the landmark trial that launched the antiplatelet drug ticagrelor worldwide are being raised after an investigation uncovered more information about how the PLATO study was conducted.

Peter Doshi, PhD, senior editor at The BMJ, obtained primary records for the trial and unpublished data through a Freedom of Information Act request, and has detailed inconsistencies and omissions in data reporting from the 2009 trial originally published in The New England Journal of Medicine (NEJM). The new investigation into the Platelet Inhibition and Patient Outcomes (PLATO) trial is published in The BMJ.

The findings come as generic versions of ticagrelor (Brilinta) are expected to become available soon in the United States. Ticagrelor is the only P2Y12 inhibitor still under patent, and in 2022, the United States spent more than $750 million on it, according to the report.

PLATO, sponsored by ticagrelor manufacturer AstraZeneca, included more than 18,000 patients in 43 countries. Investigators reported that ticagrelor reduced deaths from vascular causes, heart attack, or stroke compared with clopidogrel (Plavix). However, in a subgroup analysis, among US patients, there were more deaths in the ticagrelor group, and AstraZeneca failed its first bid for approval from the US Food and Drug Administration (FDA).

 

Failed First Bid for FDA Approval

AstraZeneca resubmitted its application, which was met with objections by some FDA staff members, including medical officer Thomas Marciniak, who called the resubmission “the worst in my experience regarding completeness of the submissions and the sponsor responding completely and accurately to requests,” Doshi reports.

Despite the objections, the FDA in 2011 approved ticagrelor for acute coronary syndrome, kicking off intense controversy over the trial, as several other studies have failed to replicate PLATO’s positive results.

Doubts have grown about its apparent advantage over cheaper, off-patent P2Y12 inhibitors such as clopidogrel and prasugrel.

“Critics said it was noteworthy that ticagrelor failed in the US,” Doshi writes, “the only high enrolling country where sites were not monitored by the sponsor itself.” Doshi’s report points out that critics of the trial “highlight that AstraZeneca itself carried out the data monitoring for PLATO except for sites that were monitored by third party contract research organizations. In the four countries exclusively monitored by non-sponsor personnel—Georgia, Israel, Russia, and the US—ticagrelor fared worse.”

Victor Serebruany, MD, from Johns Hopkins University, said he was initially impressed by the trial results but became skeptical after noticing inconsistencies and anomalies in the data. He filed a complaint with the US District Court in the District of Columbia, suggesting that the cardiovascular events in the study “may have been manipulated.”

 

US Department of Justice Investigation

The US Department of Justice (DOJ) opened an investigation in 2013 and closed it in 2014 with no further action. Serebruany continues to publish critiques of the trial 15 years later but told The BMJ he has little hope that the questions will be resolved unless the DOJ re-engages with an investigation.

Doshi also points out discrepancies in the data reported. In the 2009 paper, published as an intent-to-treat analysis, investigators said there were 905 total deaths from any cause among all randomized patients. “An internal company report states, however, that 983 patients had died at this point. While 33 deaths occurred after the follow-up period, the NEJM tally still leaves out 45 deaths ‘discovered after withdrawal of consent,’” he reports.

The NEJM responded to Doshi that while it didn’t dispute the error in the number of deaths, it was uncertain about publishing a correction, citing new — not yet published — guidelines from the International Committee of Medical Journal Editors. NEJM Editor-in-Chief Eric Rubin told The BMJ that “for older manuscripts, correction is not necessarily appropriate unless there would be an effect on clinical practice.”

Doshi’s investigation includes an interview with Eric Bates, MD, professor of internal medicine at the University of Michigan in Ann Arbor, and a co-author of the US guidelines that recommend ticagrelor, who said he was “increasingly disturbed by how trial after trial came out as being not dramatically positive in any way.” Bates is now calling for a review of ticagrelor’s recommendation in guidelines, according to the report.

AstraZeneca declined to be interviewed for the BMJ investigation, according to Doshi, and a spokesperson from the company told the journal by email that they have “nothing to add,” directing editors to its 2014 public statement after the DOJ’s investigation into PLATO. The BMJ said PLATO trial co-chairs Robert A. Harrington, MD, and Lars Wallentin, MD, did not respond to The BMJ’s requests for comment.

 

Will the Guidelines Be Changed Now?

“I know and have worked with Drs Wallentin and Harrington,” Bates told Medscape Medical News, “and find them to be honest, intelligent clinical scientists with the highest ethical standards who manage conflicts of interest as well as can be done in the clinical research arena, where industry support is required to develop new knowledge,” he said.

“If there is a concern that AstraZeneca was manipulating the dataset and FDA submission, that is an important issue,” Bates said. “The US paradox and the failure of any other antiplatelet trial to find a comparative mortality advantage are two unexplained issues with PLATO that provide good fodder for conspiracy theories. I agree with the NEJM that this trial is 15 years old and may not be worth readjudicating in the current treatment era.”

Other calls for revisiting guidelines have come after disappointing postlicensure studies have repeatedly demonstrated that ticagrelor has “similar efficacy to clopidogrel but with increased bleeding and [dyspnea],” Doshi reports.

“My concern is the marketing spin by AstraZeneca and the promotion of ticagrelor by six to eight ‘thought leaders’ consistently funded by AstraZeneca over the past 10 years,” said Bates. “They have flooded the literature with supportive subset and post hoc analyses, review articles, and ‘meta-analyses’ flawed by selection and intellectual bias, and public interviews that consistently discount the findings of the many subsequent randomized controlled trials that have not supported the superiority of ticagrelor over clopidogrel or prasugrel.”

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

New questions about the landmark trial that launched the antiplatelet drug ticagrelor worldwide are being raised after an investigation uncovered more information about how the PLATO study was conducted.

Peter Doshi, PhD, senior editor at The BMJ, obtained primary records for the trial and unpublished data through a Freedom of Information Act request, and has detailed inconsistencies and omissions in data reporting from the 2009 trial originally published in The New England Journal of Medicine (NEJM). The new investigation into the Platelet Inhibition and Patient Outcomes (PLATO) trial is published in The BMJ.

The findings come as generic versions of ticagrelor (Brilinta) are expected to become available soon in the United States. Ticagrelor is the only P2Y12 inhibitor still under patent, and in 2022, the United States spent more than $750 million on it, according to the report.

PLATO, sponsored by ticagrelor manufacturer AstraZeneca, included more than 18,000 patients in 43 countries. Investigators reported that ticagrelor reduced deaths from vascular causes, heart attack, or stroke compared with clopidogrel (Plavix). However, in a subgroup analysis, among US patients, there were more deaths in the ticagrelor group, and AstraZeneca failed its first bid for approval from the US Food and Drug Administration (FDA).

 

Failed First Bid for FDA Approval

AstraZeneca resubmitted its application, which was met with objections by some FDA staff members, including medical officer Thomas Marciniak, who called the resubmission “the worst in my experience regarding completeness of the submissions and the sponsor responding completely and accurately to requests,” Doshi reports.

Despite the objections, the FDA in 2011 approved ticagrelor for acute coronary syndrome, kicking off intense controversy over the trial, as several other studies have failed to replicate PLATO’s positive results.

Doubts have grown about its apparent advantage over cheaper, off-patent P2Y12 inhibitors such as clopidogrel and prasugrel.

“Critics said it was noteworthy that ticagrelor failed in the US,” Doshi writes, “the only high enrolling country where sites were not monitored by the sponsor itself.” Doshi’s report points out that critics of the trial “highlight that AstraZeneca itself carried out the data monitoring for PLATO except for sites that were monitored by third party contract research organizations. In the four countries exclusively monitored by non-sponsor personnel—Georgia, Israel, Russia, and the US—ticagrelor fared worse.”

Victor Serebruany, MD, from Johns Hopkins University, said he was initially impressed by the trial results but became skeptical after noticing inconsistencies and anomalies in the data. He filed a complaint with the US District Court in the District of Columbia, suggesting that the cardiovascular events in the study “may have been manipulated.”

 

US Department of Justice Investigation

The US Department of Justice (DOJ) opened an investigation in 2013 and closed it in 2014 with no further action. Serebruany continues to publish critiques of the trial 15 years later but told The BMJ he has little hope that the questions will be resolved unless the DOJ re-engages with an investigation.

Doshi also points out discrepancies in the data reported. In the 2009 paper, published as an intent-to-treat analysis, investigators said there were 905 total deaths from any cause among all randomized patients. “An internal company report states, however, that 983 patients had died at this point. While 33 deaths occurred after the follow-up period, the NEJM tally still leaves out 45 deaths ‘discovered after withdrawal of consent,’” he reports.

The NEJM responded to Doshi that while it didn’t dispute the error in the number of deaths, it was uncertain about publishing a correction, citing new — not yet published — guidelines from the International Committee of Medical Journal Editors. NEJM Editor-in-Chief Eric Rubin told The BMJ that “for older manuscripts, correction is not necessarily appropriate unless there would be an effect on clinical practice.”

Doshi’s investigation includes an interview with Eric Bates, MD, professor of internal medicine at the University of Michigan in Ann Arbor, and a co-author of the US guidelines that recommend ticagrelor, who said he was “increasingly disturbed by how trial after trial came out as being not dramatically positive in any way.” Bates is now calling for a review of ticagrelor’s recommendation in guidelines, according to the report.

AstraZeneca declined to be interviewed for the BMJ investigation, according to Doshi, and a spokesperson from the company told the journal by email that they have “nothing to add,” directing editors to its 2014 public statement after the DOJ’s investigation into PLATO. The BMJ said PLATO trial co-chairs Robert A. Harrington, MD, and Lars Wallentin, MD, did not respond to The BMJ’s requests for comment.

 

Will the Guidelines Be Changed Now?

“I know and have worked with Drs Wallentin and Harrington,” Bates told Medscape Medical News, “and find them to be honest, intelligent clinical scientists with the highest ethical standards who manage conflicts of interest as well as can be done in the clinical research arena, where industry support is required to develop new knowledge,” he said.

“If there is a concern that AstraZeneca was manipulating the dataset and FDA submission, that is an important issue,” Bates said. “The US paradox and the failure of any other antiplatelet trial to find a comparative mortality advantage are two unexplained issues with PLATO that provide good fodder for conspiracy theories. I agree with the NEJM that this trial is 15 years old and may not be worth readjudicating in the current treatment era.”

Other calls for revisiting guidelines have come after disappointing postlicensure studies have repeatedly demonstrated that ticagrelor has “similar efficacy to clopidogrel but with increased bleeding and [dyspnea],” Doshi reports.

“My concern is the marketing spin by AstraZeneca and the promotion of ticagrelor by six to eight ‘thought leaders’ consistently funded by AstraZeneca over the past 10 years,” said Bates. “They have flooded the literature with supportive subset and post hoc analyses, review articles, and ‘meta-analyses’ flawed by selection and intellectual bias, and public interviews that consistently discount the findings of the many subsequent randomized controlled trials that have not supported the superiority of ticagrelor over clopidogrel or prasugrel.”

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

New questions about the landmark trial that launched the antiplatelet drug ticagrelor worldwide are being raised after an investigation uncovered more information about how the PLATO study was conducted.

Peter Doshi, PhD, senior editor at The BMJ, obtained primary records for the trial and unpublished data through a Freedom of Information Act request, and has detailed inconsistencies and omissions in data reporting from the 2009 trial originally published in The New England Journal of Medicine (NEJM). The new investigation into the Platelet Inhibition and Patient Outcomes (PLATO) trial is published in The BMJ.

The findings come as generic versions of ticagrelor (Brilinta) are expected to become available soon in the United States. Ticagrelor is the only P2Y12 inhibitor still under patent, and in 2022, the United States spent more than $750 million on it, according to the report.

PLATO, sponsored by ticagrelor manufacturer AstraZeneca, included more than 18,000 patients in 43 countries. Investigators reported that ticagrelor reduced deaths from vascular causes, heart attack, or stroke compared with clopidogrel (Plavix). However, in a subgroup analysis, among US patients, there were more deaths in the ticagrelor group, and AstraZeneca failed its first bid for approval from the US Food and Drug Administration (FDA).

 

Failed First Bid for FDA Approval

AstraZeneca resubmitted its application, which was met with objections by some FDA staff members, including medical officer Thomas Marciniak, who called the resubmission “the worst in my experience regarding completeness of the submissions and the sponsor responding completely and accurately to requests,” Doshi reports.

Despite the objections, the FDA in 2011 approved ticagrelor for acute coronary syndrome, kicking off intense controversy over the trial, as several other studies have failed to replicate PLATO’s positive results.

Doubts have grown about its apparent advantage over cheaper, off-patent P2Y12 inhibitors such as clopidogrel and prasugrel.

“Critics said it was noteworthy that ticagrelor failed in the US,” Doshi writes, “the only high enrolling country where sites were not monitored by the sponsor itself.” Doshi’s report points out that critics of the trial “highlight that AstraZeneca itself carried out the data monitoring for PLATO except for sites that were monitored by third party contract research organizations. In the four countries exclusively monitored by non-sponsor personnel—Georgia, Israel, Russia, and the US—ticagrelor fared worse.”

Victor Serebruany, MD, from Johns Hopkins University, said he was initially impressed by the trial results but became skeptical after noticing inconsistencies and anomalies in the data. He filed a complaint with the US District Court in the District of Columbia, suggesting that the cardiovascular events in the study “may have been manipulated.”

 

US Department of Justice Investigation

The US Department of Justice (DOJ) opened an investigation in 2013 and closed it in 2014 with no further action. Serebruany continues to publish critiques of the trial 15 years later but told The BMJ he has little hope that the questions will be resolved unless the DOJ re-engages with an investigation.

Doshi also points out discrepancies in the data reported. In the 2009 paper, published as an intent-to-treat analysis, investigators said there were 905 total deaths from any cause among all randomized patients. “An internal company report states, however, that 983 patients had died at this point. While 33 deaths occurred after the follow-up period, the NEJM tally still leaves out 45 deaths ‘discovered after withdrawal of consent,’” he reports.

The NEJM responded to Doshi that while it didn’t dispute the error in the number of deaths, it was uncertain about publishing a correction, citing new — not yet published — guidelines from the International Committee of Medical Journal Editors. NEJM Editor-in-Chief Eric Rubin told The BMJ that “for older manuscripts, correction is not necessarily appropriate unless there would be an effect on clinical practice.”

Doshi’s investigation includes an interview with Eric Bates, MD, professor of internal medicine at the University of Michigan in Ann Arbor, and a co-author of the US guidelines that recommend ticagrelor, who said he was “increasingly disturbed by how trial after trial came out as being not dramatically positive in any way.” Bates is now calling for a review of ticagrelor’s recommendation in guidelines, according to the report.

AstraZeneca declined to be interviewed for the BMJ investigation, according to Doshi, and a spokesperson from the company told the journal by email that they have “nothing to add,” directing editors to its 2014 public statement after the DOJ’s investigation into PLATO. The BMJ said PLATO trial co-chairs Robert A. Harrington, MD, and Lars Wallentin, MD, did not respond to The BMJ’s requests for comment.

 

Will the Guidelines Be Changed Now?

“I know and have worked with Drs Wallentin and Harrington,” Bates told Medscape Medical News, “and find them to be honest, intelligent clinical scientists with the highest ethical standards who manage conflicts of interest as well as can be done in the clinical research arena, where industry support is required to develop new knowledge,” he said.

“If there is a concern that AstraZeneca was manipulating the dataset and FDA submission, that is an important issue,” Bates said. “The US paradox and the failure of any other antiplatelet trial to find a comparative mortality advantage are two unexplained issues with PLATO that provide good fodder for conspiracy theories. I agree with the NEJM that this trial is 15 years old and may not be worth readjudicating in the current treatment era.”

Other calls for revisiting guidelines have come after disappointing postlicensure studies have repeatedly demonstrated that ticagrelor has “similar efficacy to clopidogrel but with increased bleeding and [dyspnea],” Doshi reports.

“My concern is the marketing spin by AstraZeneca and the promotion of ticagrelor by six to eight ‘thought leaders’ consistently funded by AstraZeneca over the past 10 years,” said Bates. “They have flooded the literature with supportive subset and post hoc analyses, review articles, and ‘meta-analyses’ flawed by selection and intellectual bias, and public interviews that consistently discount the findings of the many subsequent randomized controlled trials that have not supported the superiority of ticagrelor over clopidogrel or prasugrel.”

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

TOPLINE:

Elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), a key biomarker for diagnosing heart failure, show a nearly fourfold increased risk for atrial fibrillation (AF) in at-risk individuals. The utility of this biomarker was particularly evident in older adults and when serum-based measurements were used.

METHODOLOGY:

• Researchers conducted a meta-analysis of prospective cohort, case-cohort, or nested case-control studies to examine the association between NT-proBNP and the incidence of AF.
• They also explored the potential of NT-proBNP in improving risk prediction models for AF.
• Overall, 136,089 adults were included from 16 cohorts, and 8017 cases of incident AF were reported over a median follow-up of 4-20 years.
• Most of the included cohorts were from Europe (n = 12), followed by America (n = 3) and Asia (n = 1).
• The accuracy of the risk prediction models was evaluated using C-indexes, with values in the range of 0.50-0.70, low accuracy; 0.70-0.90, moderate accuracy; and > 0.90, high accuracy.

TAKEAWAY:

• Elevated NT-proBNP levels showed a strong association with the risk for AF, with individuals in the highest quintile of NT-proBNP facing a 3.84-fold higher risk for incident AF (pooled relative risk [RR], 3.84; 95% CI, 3.03-4.87) than those in the lowest quintile.
• The risk increased by 9% for each 10 pg/mL increase in NT-proBNP (RR, 1.09; 95% CI, 1.04-1.14), with a significant nonlinear dose-response association found between NT-proBNP and the risk for AF (P for nonlinearity < .001).
• The association was stronger in the subgroups of older adults and when the biomarker was measured in serum samples.
• The addition of NT-proBNP to traditional risk prediction models for AF may improve predictive accuracy, with the ΔC-indexes ranging from 0.010 to 0.060.

IN PRACTICE:

“The significance of NT-proBNP in enhancing AF risk stratification deserves greater attention, with potential expansion to routine health screening,” the authors wrote.

SOURCE:

The study was led by Wanyue Wang, Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and was published online on December 06, 2024, in Heart.

LIMITATIONS:

Significant heterogeneity was observed in this meta-analysis, with the subgroup articles only providing exploratory and indicative findings. Due to the observational nature of this study, residual confounding could not be excluded. None of the prospective studies included differentiated subtypes of AF, such as paroxysmal and asymptomatic forms, which might have influenced the observed outcomes.

DISCLOSURES:

This study was supported by grants from the National Key Research and Development Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and National High Level Hospital Clinical Research Funding. The authors declared no conflicts of interest.

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:

Elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), a key biomarker for diagnosing heart failure, show a nearly fourfold increased risk for atrial fibrillation (AF) in at-risk individuals. The utility of this biomarker was particularly evident in older adults and when serum-based measurements were used.

METHODOLOGY:

• Researchers conducted a meta-analysis of prospective cohort, case-cohort, or nested case-control studies to examine the association between NT-proBNP and the incidence of AF.
• They also explored the potential of NT-proBNP in improving risk prediction models for AF.
• Overall, 136,089 adults were included from 16 cohorts, and 8017 cases of incident AF were reported over a median follow-up of 4-20 years.
• Most of the included cohorts were from Europe (n = 12), followed by America (n = 3) and Asia (n = 1).
• The accuracy of the risk prediction models was evaluated using C-indexes, with values in the range of 0.50-0.70, low accuracy; 0.70-0.90, moderate accuracy; and > 0.90, high accuracy.

TAKEAWAY:

• Elevated NT-proBNP levels showed a strong association with the risk for AF, with individuals in the highest quintile of NT-proBNP facing a 3.84-fold higher risk for incident AF (pooled relative risk [RR], 3.84; 95% CI, 3.03-4.87) than those in the lowest quintile.
• The risk increased by 9% for each 10 pg/mL increase in NT-proBNP (RR, 1.09; 95% CI, 1.04-1.14), with a significant nonlinear dose-response association found between NT-proBNP and the risk for AF (P for nonlinearity < .001).
• The association was stronger in the subgroups of older adults and when the biomarker was measured in serum samples.
• The addition of NT-proBNP to traditional risk prediction models for AF may improve predictive accuracy, with the ΔC-indexes ranging from 0.010 to 0.060.

IN PRACTICE:

“The significance of NT-proBNP in enhancing AF risk stratification deserves greater attention, with potential expansion to routine health screening,” the authors wrote.

SOURCE:

The study was led by Wanyue Wang, Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and was published online on December 06, 2024, in Heart.

LIMITATIONS:

Significant heterogeneity was observed in this meta-analysis, with the subgroup articles only providing exploratory and indicative findings. Due to the observational nature of this study, residual confounding could not be excluded. None of the prospective studies included differentiated subtypes of AF, such as paroxysmal and asymptomatic forms, which might have influenced the observed outcomes.

DISCLOSURES:

This study was supported by grants from the National Key Research and Development Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and National High Level Hospital Clinical Research Funding. The authors declared no conflicts of interest.

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:

Elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), a key biomarker for diagnosing heart failure, show a nearly fourfold increased risk for atrial fibrillation (AF) in at-risk individuals. The utility of this biomarker was particularly evident in older adults and when serum-based measurements were used.

METHODOLOGY:

• Researchers conducted a meta-analysis of prospective cohort, case-cohort, or nested case-control studies to examine the association between NT-proBNP and the incidence of AF.
• They also explored the potential of NT-proBNP in improving risk prediction models for AF.
• Overall, 136,089 adults were included from 16 cohorts, and 8017 cases of incident AF were reported over a median follow-up of 4-20 years.
• Most of the included cohorts were from Europe (n = 12), followed by America (n = 3) and Asia (n = 1).
• The accuracy of the risk prediction models was evaluated using C-indexes, with values in the range of 0.50-0.70, low accuracy; 0.70-0.90, moderate accuracy; and > 0.90, high accuracy.

TAKEAWAY:

• Elevated NT-proBNP levels showed a strong association with the risk for AF, with individuals in the highest quintile of NT-proBNP facing a 3.84-fold higher risk for incident AF (pooled relative risk [RR], 3.84; 95% CI, 3.03-4.87) than those in the lowest quintile.
• The risk increased by 9% for each 10 pg/mL increase in NT-proBNP (RR, 1.09; 95% CI, 1.04-1.14), with a significant nonlinear dose-response association found between NT-proBNP and the risk for AF (P for nonlinearity < .001).
• The association was stronger in the subgroups of older adults and when the biomarker was measured in serum samples.
• The addition of NT-proBNP to traditional risk prediction models for AF may improve predictive accuracy, with the ΔC-indexes ranging from 0.010 to 0.060.

IN PRACTICE:

“The significance of NT-proBNP in enhancing AF risk stratification deserves greater attention, with potential expansion to routine health screening,” the authors wrote.

SOURCE:

The study was led by Wanyue Wang, Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and was published online on December 06, 2024, in Heart.

LIMITATIONS:

Significant heterogeneity was observed in this meta-analysis, with the subgroup articles only providing exploratory and indicative findings. Due to the observational nature of this study, residual confounding could not be excluded. None of the prospective studies included differentiated subtypes of AF, such as paroxysmal and asymptomatic forms, which might have influenced the observed outcomes.

DISCLOSURES:

This study was supported by grants from the National Key Research and Development Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and National High Level Hospital Clinical Research Funding. The authors declared no conflicts of interest.

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.

The story of antimicrobial peptides (AMPs), particularly in tackling antibiotic resistance, has been one of false dawns and unfulfilled promises. But perhaps a new generation of “smarter” compounds could see them find a wider role in clinical practice, said experts.

AMPs may be small molecules, consisting of short chains of amino acids, but these naturally occurring compounds have an important function: They are the “frontline defense” against invasive bacteria, said Henrik Franzyk, MSc Engineering, associate professor in the Department of Drug Design and Pharmacology at the University of Copenhagen in Denmark.

 

Multifunction Line of Defense

AMPs are cationic, meaning they are positively charged. “The reason why nature has maintained these molecules is that all the microbes out there have a negative surface charge,” explained Hans-Georg Sahl, PhD, emeritus professor of pharmaceutical microbiology at the University of Bonn in Germany.

While AMPs are also hydrophobic, they are often amphipathic, with both hydrophobic and hydrophilic regions that allow them to target cell membranes and cause them to rupture similarly to how detergent acts. 

“Thus, the content of a cell gets released, and it destroys the pathogen,” explained Paulina Szymczak, a PhD candidate in the Institute of AI for Health at Helmholtz Munich, Neuherberg, Germany.

“There are variations of that theme,” said Eefjan Breukink, PhD, professor of microbial membranes and antibiotics at Utrecht University in the Netherlands. “And then it depends on the sequence of the particular peptide,” as some can cross the cell membrane and damage the bacterium internally.

Szymczak explained that AMPs can, in this way, target the cell DNA, as both the membrane and the DNA are negatively charged. “That’s also what makes them so powerful because they don’t have just one mechanism of action, as opposed to conventional antibiotics.” 

 

Indiscriminate Killers

But they also have another crucial function. They activate the innate immune system via so-called resident immune cells that are “sitting in the tissues and waiting for bacteria to turn up,” explained Franzyk.

“The problem with antibodies is that they typically need to replicate,” he continued, which takes between 4 and 7 days — a timeline that is much better suited to tackling a viral infection. Bacteria, on the other hand, have a replication cycle of just 30 minutes.

Another big problem is that AMPs kill cells indiscriminately, including our own.

“But the human body is clever in that it only produces these antimicrobial peptides where the bacteria are, so they are not circulating in the blood,” said Franzyk. If a small part of tissue becomes infected, the innate immune cells start producing AMPs, which may kill the bacteria, or call on other immune cells to help.

As part of this process, “they will also kill part of our own tissue, but that’s the price we have to pay,” he said.

 

Local Applications

It is this aspect that has, so far, limited the use of AMPs in clinical practice, certainly as a replacement for conventional antibiotics limited by bacterial resistance. The trials conducted so far have been, by and large, negative, which has dampened enthusiasm and led to the perception that the risk they pose is too great for large-scale investment.

AMPs “are not made for what we need from antibiotics in the first place,” explained Sahl. “That is, a nice, easy distribution in the body, going into abscesses” and throughout the tissues.

He continued that AMPs are “more about controlling the flora in our bodies,” and they are “really not made for being used systemically.” 

Szymczak and colleagues are now working on designing active peptides with a strong antibacterial profile but limited toxicity for systematic use.

However, the “downside with these peptides is that they are not orally available, so you can’t take a pill,” Breukink said, but instead they need to be administered intravenously.

There are, nevertheless, some antibiotics in clinical use that have the same molecular features as AMPs. These include colistin, a last-resort treatment for multidrug-resistant gram-negative bacteria, and daptomycin, which is used in the treatment of systemic infections caused by gram-positive species.

Szymczak added that there have been successes in using AMPs in a more targeted way, such as using a topical cream. Another potentially promising avenue is lung infections, which are being studied in mouse models.

 

Less Prone to Resistance

Crucially, AMPs are markedly less prone to bacterial resistance than conventional antibiotics, partly because of their typical target: the cell membrane.

“Biologically and evolutionarily, it is a very costly operation to rebuild the membrane and change its charge,” Szymczak explained. “It’s quite hard for bacteria to learn this because it’s not a single protein that you have to mutate but the whole membrane.”

This is seen in the laboratory, where it takes around five generations, or passages, for bacteria to develop resistance when grown in the presence of antibiotics, but up to 40 passages when cultured with an AMP.

The limits of the ability of AMPs to withstand the development of bacterial resistance have been tested in the real world.

Colistin has been used widely in Asia as a growth promoter, especially in pig farming. Franzyk explained that farmers have used enormous quantities of this AMP-based antibiotic, which has indeed led to the development of resistance, including contamination of meat for human consumption, leading to resistance spreading to other parts of the world.

“The bad thing about this is it’s not something each individual bacteria needs to acquire,” he said. Because resistance is stored on small, cyclic DNA called plasmids, it “can be transferred from one bacterial species to another.”

 

Novel Avenues

Franzyk suggested that AMPs could nevertheless be used in combination with, or to modify, existing antibiotics to revitalize those for which there is already bacterial resistance, or to allow antibiotics that ordinarily target only gram-positive bacteria to also treat gram-negative infections, for example.

Szymczak and her colleagues are using artificial intelligence to design novel AMP candidates. Instead of manually going through compounds and checking their activity profiles in the lab, those steps are carried out computationally “so that, in the end, you synthesize as few candidates as possible” and can proceed to a mouse model “as fast as possible.”

She personally is looking at the issue of strain-specific activity to design a compound that would target, for example, only multidrug-resistant strains. “What we can do now is something that will target everything, so a kind of last resort peptide. But we are trying to make them smarter in their targets.”

Szymczak also pointed out that cancer cells are “negatively charged, similarly to bacterial cells, as opposed to mammalian cells, which are neutral.”

“So in theory, maybe we could design something that will target cancer cells but not our host cells, and that would be extremely exciting.” However, she underlined that, first, they are trying to tackle antimicrobial resistance before looking at other spaces.

Finally, Breukink is screening for small antibacterial compounds in fungi that are around half the size of a normal peptide and more hydrophobic, meaning there is a much greater chance of them being orally available.

But “you first have to test, of course,” he said, as “if you don’t have specific targets, then you will get problems with toxicity, or other issues that you do not foresee.” 

No funding was declared. No relevant financial relationships were declared.

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

The story of antimicrobial peptides (AMPs), particularly in tackling antibiotic resistance, has been one of false dawns and unfulfilled promises. But perhaps a new generation of “smarter” compounds could see them find a wider role in clinical practice, said experts.

AMPs may be small molecules, consisting of short chains of amino acids, but these naturally occurring compounds have an important function: They are the “frontline defense” against invasive bacteria, said Henrik Franzyk, MSc Engineering, associate professor in the Department of Drug Design and Pharmacology at the University of Copenhagen in Denmark.

 

Multifunction Line of Defense

AMPs are cationic, meaning they are positively charged. “The reason why nature has maintained these molecules is that all the microbes out there have a negative surface charge,” explained Hans-Georg Sahl, PhD, emeritus professor of pharmaceutical microbiology at the University of Bonn in Germany.

While AMPs are also hydrophobic, they are often amphipathic, with both hydrophobic and hydrophilic regions that allow them to target cell membranes and cause them to rupture similarly to how detergent acts. 

“Thus, the content of a cell gets released, and it destroys the pathogen,” explained Paulina Szymczak, a PhD candidate in the Institute of AI for Health at Helmholtz Munich, Neuherberg, Germany.

“There are variations of that theme,” said Eefjan Breukink, PhD, professor of microbial membranes and antibiotics at Utrecht University in the Netherlands. “And then it depends on the sequence of the particular peptide,” as some can cross the cell membrane and damage the bacterium internally.

Szymczak explained that AMPs can, in this way, target the cell DNA, as both the membrane and the DNA are negatively charged. “That’s also what makes them so powerful because they don’t have just one mechanism of action, as opposed to conventional antibiotics.” 

 

Indiscriminate Killers

But they also have another crucial function. They activate the innate immune system via so-called resident immune cells that are “sitting in the tissues and waiting for bacteria to turn up,” explained Franzyk.

“The problem with antibodies is that they typically need to replicate,” he continued, which takes between 4 and 7 days — a timeline that is much better suited to tackling a viral infection. Bacteria, on the other hand, have a replication cycle of just 30 minutes.

Another big problem is that AMPs kill cells indiscriminately, including our own.

“But the human body is clever in that it only produces these antimicrobial peptides where the bacteria are, so they are not circulating in the blood,” said Franzyk. If a small part of tissue becomes infected, the innate immune cells start producing AMPs, which may kill the bacteria, or call on other immune cells to help.

As part of this process, “they will also kill part of our own tissue, but that’s the price we have to pay,” he said.

 

Local Applications

It is this aspect that has, so far, limited the use of AMPs in clinical practice, certainly as a replacement for conventional antibiotics limited by bacterial resistance. The trials conducted so far have been, by and large, negative, which has dampened enthusiasm and led to the perception that the risk they pose is too great for large-scale investment.

AMPs “are not made for what we need from antibiotics in the first place,” explained Sahl. “That is, a nice, easy distribution in the body, going into abscesses” and throughout the tissues.

He continued that AMPs are “more about controlling the flora in our bodies,” and they are “really not made for being used systemically.” 

Szymczak and colleagues are now working on designing active peptides with a strong antibacterial profile but limited toxicity for systematic use.

However, the “downside with these peptides is that they are not orally available, so you can’t take a pill,” Breukink said, but instead they need to be administered intravenously.

There are, nevertheless, some antibiotics in clinical use that have the same molecular features as AMPs. These include colistin, a last-resort treatment for multidrug-resistant gram-negative bacteria, and daptomycin, which is used in the treatment of systemic infections caused by gram-positive species.

Szymczak added that there have been successes in using AMPs in a more targeted way, such as using a topical cream. Another potentially promising avenue is lung infections, which are being studied in mouse models.

 

Less Prone to Resistance

Crucially, AMPs are markedly less prone to bacterial resistance than conventional antibiotics, partly because of their typical target: the cell membrane.

“Biologically and evolutionarily, it is a very costly operation to rebuild the membrane and change its charge,” Szymczak explained. “It’s quite hard for bacteria to learn this because it’s not a single protein that you have to mutate but the whole membrane.”

This is seen in the laboratory, where it takes around five generations, or passages, for bacteria to develop resistance when grown in the presence of antibiotics, but up to 40 passages when cultured with an AMP.

The limits of the ability of AMPs to withstand the development of bacterial resistance have been tested in the real world.

Colistin has been used widely in Asia as a growth promoter, especially in pig farming. Franzyk explained that farmers have used enormous quantities of this AMP-based antibiotic, which has indeed led to the development of resistance, including contamination of meat for human consumption, leading to resistance spreading to other parts of the world.

“The bad thing about this is it’s not something each individual bacteria needs to acquire,” he said. Because resistance is stored on small, cyclic DNA called plasmids, it “can be transferred from one bacterial species to another.”

 

Novel Avenues

Franzyk suggested that AMPs could nevertheless be used in combination with, or to modify, existing antibiotics to revitalize those for which there is already bacterial resistance, or to allow antibiotics that ordinarily target only gram-positive bacteria to also treat gram-negative infections, for example.

Szymczak and her colleagues are using artificial intelligence to design novel AMP candidates. Instead of manually going through compounds and checking their activity profiles in the lab, those steps are carried out computationally “so that, in the end, you synthesize as few candidates as possible” and can proceed to a mouse model “as fast as possible.”

She personally is looking at the issue of strain-specific activity to design a compound that would target, for example, only multidrug-resistant strains. “What we can do now is something that will target everything, so a kind of last resort peptide. But we are trying to make them smarter in their targets.”

Szymczak also pointed out that cancer cells are “negatively charged, similarly to bacterial cells, as opposed to mammalian cells, which are neutral.”

“So in theory, maybe we could design something that will target cancer cells but not our host cells, and that would be extremely exciting.” However, she underlined that, first, they are trying to tackle antimicrobial resistance before looking at other spaces.

Finally, Breukink is screening for small antibacterial compounds in fungi that are around half the size of a normal peptide and more hydrophobic, meaning there is a much greater chance of them being orally available.

But “you first have to test, of course,” he said, as “if you don’t have specific targets, then you will get problems with toxicity, or other issues that you do not foresee.” 

No funding was declared. No relevant financial relationships were declared.

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

The story of antimicrobial peptides (AMPs), particularly in tackling antibiotic resistance, has been one of false dawns and unfulfilled promises. But perhaps a new generation of “smarter” compounds could see them find a wider role in clinical practice, said experts.

AMPs may be small molecules, consisting of short chains of amino acids, but these naturally occurring compounds have an important function: They are the “frontline defense” against invasive bacteria, said Henrik Franzyk, MSc Engineering, associate professor in the Department of Drug Design and Pharmacology at the University of Copenhagen in Denmark.

 

Multifunction Line of Defense

AMPs are cationic, meaning they are positively charged. “The reason why nature has maintained these molecules is that all the microbes out there have a negative surface charge,” explained Hans-Georg Sahl, PhD, emeritus professor of pharmaceutical microbiology at the University of Bonn in Germany.

While AMPs are also hydrophobic, they are often amphipathic, with both hydrophobic and hydrophilic regions that allow them to target cell membranes and cause them to rupture similarly to how detergent acts. 

“Thus, the content of a cell gets released, and it destroys the pathogen,” explained Paulina Szymczak, a PhD candidate in the Institute of AI for Health at Helmholtz Munich, Neuherberg, Germany.

“There are variations of that theme,” said Eefjan Breukink, PhD, professor of microbial membranes and antibiotics at Utrecht University in the Netherlands. “And then it depends on the sequence of the particular peptide,” as some can cross the cell membrane and damage the bacterium internally.

Szymczak explained that AMPs can, in this way, target the cell DNA, as both the membrane and the DNA are negatively charged. “That’s also what makes them so powerful because they don’t have just one mechanism of action, as opposed to conventional antibiotics.” 

 

Indiscriminate Killers

But they also have another crucial function. They activate the innate immune system via so-called resident immune cells that are “sitting in the tissues and waiting for bacteria to turn up,” explained Franzyk.

“The problem with antibodies is that they typically need to replicate,” he continued, which takes between 4 and 7 days — a timeline that is much better suited to tackling a viral infection. Bacteria, on the other hand, have a replication cycle of just 30 minutes.

Another big problem is that AMPs kill cells indiscriminately, including our own.

“But the human body is clever in that it only produces these antimicrobial peptides where the bacteria are, so they are not circulating in the blood,” said Franzyk. If a small part of tissue becomes infected, the innate immune cells start producing AMPs, which may kill the bacteria, or call on other immune cells to help.

As part of this process, “they will also kill part of our own tissue, but that’s the price we have to pay,” he said.

 

Local Applications

It is this aspect that has, so far, limited the use of AMPs in clinical practice, certainly as a replacement for conventional antibiotics limited by bacterial resistance. The trials conducted so far have been, by and large, negative, which has dampened enthusiasm and led to the perception that the risk they pose is too great for large-scale investment.

AMPs “are not made for what we need from antibiotics in the first place,” explained Sahl. “That is, a nice, easy distribution in the body, going into abscesses” and throughout the tissues.

He continued that AMPs are “more about controlling the flora in our bodies,” and they are “really not made for being used systemically.” 

Szymczak and colleagues are now working on designing active peptides with a strong antibacterial profile but limited toxicity for systematic use.

However, the “downside with these peptides is that they are not orally available, so you can’t take a pill,” Breukink said, but instead they need to be administered intravenously.

There are, nevertheless, some antibiotics in clinical use that have the same molecular features as AMPs. These include colistin, a last-resort treatment for multidrug-resistant gram-negative bacteria, and daptomycin, which is used in the treatment of systemic infections caused by gram-positive species.

Szymczak added that there have been successes in using AMPs in a more targeted way, such as using a topical cream. Another potentially promising avenue is lung infections, which are being studied in mouse models.

 

Less Prone to Resistance

Crucially, AMPs are markedly less prone to bacterial resistance than conventional antibiotics, partly because of their typical target: the cell membrane.

“Biologically and evolutionarily, it is a very costly operation to rebuild the membrane and change its charge,” Szymczak explained. “It’s quite hard for bacteria to learn this because it’s not a single protein that you have to mutate but the whole membrane.”

This is seen in the laboratory, where it takes around five generations, or passages, for bacteria to develop resistance when grown in the presence of antibiotics, but up to 40 passages when cultured with an AMP.

The limits of the ability of AMPs to withstand the development of bacterial resistance have been tested in the real world.

Colistin has been used widely in Asia as a growth promoter, especially in pig farming. Franzyk explained that farmers have used enormous quantities of this AMP-based antibiotic, which has indeed led to the development of resistance, including contamination of meat for human consumption, leading to resistance spreading to other parts of the world.

“The bad thing about this is it’s not something each individual bacteria needs to acquire,” he said. Because resistance is stored on small, cyclic DNA called plasmids, it “can be transferred from one bacterial species to another.”

 

Novel Avenues

Franzyk suggested that AMPs could nevertheless be used in combination with, or to modify, existing antibiotics to revitalize those for which there is already bacterial resistance, or to allow antibiotics that ordinarily target only gram-positive bacteria to also treat gram-negative infections, for example.

Szymczak and her colleagues are using artificial intelligence to design novel AMP candidates. Instead of manually going through compounds and checking their activity profiles in the lab, those steps are carried out computationally “so that, in the end, you synthesize as few candidates as possible” and can proceed to a mouse model “as fast as possible.”

She personally is looking at the issue of strain-specific activity to design a compound that would target, for example, only multidrug-resistant strains. “What we can do now is something that will target everything, so a kind of last resort peptide. But we are trying to make them smarter in their targets.”

Szymczak also pointed out that cancer cells are “negatively charged, similarly to bacterial cells, as opposed to mammalian cells, which are neutral.”

“So in theory, maybe we could design something that will target cancer cells but not our host cells, and that would be extremely exciting.” However, she underlined that, first, they are trying to tackle antimicrobial resistance before looking at other spaces.

Finally, Breukink is screening for small antibacterial compounds in fungi that are around half the size of a normal peptide and more hydrophobic, meaning there is a much greater chance of them being orally available.

But “you first have to test, of course,” he said, as “if you don’t have specific targets, then you will get problems with toxicity, or other issues that you do not foresee.” 

No funding was declared. No relevant financial relationships were declared.

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

TOPLINE:

Indoor tanning exposure was not associated with tumor mutational burden (TMB) in patients with cutaneous melanoma, in a retrospective cohort study. Higher TMB was linked to older age, head and neck tumors, and a history of nonmelanoma skin cancer (NMSC).

METHODOLOGY:

• Researchers conducted a retrospective cohort study at a tertiary care cancer center between 2013 and 2022.
• A total of 617 patients (median age at diagnosis, 61 years; 62.9% men) with melanoma who had next-generation sequencing data and indoor tanning bed exposure history available were included.
• Analysis involved multivariable modeling to evaluate the association between tanning bed use and TMB.
• Patients’ demographics, pathologic staging, TMB, and dermatologic history, including Fitzpatrick skin type, history of exposure to ultraviolet (UV) light, indoor tanning, NMSC, atypical nevi, and blistering sunburns, were considered for the analysis.

TAKEAWAY:

• About 22% of participants had an indoor tanning history. Indoor tanning exposure showed no association with TMB after adjustment for all possible predictors.
• A significant association was found between TMB and age at diagnosis, primary melanoma site, and history of NMSC (P < .001 for all).
• Patients with a history of atypical nevi demonstrated a significantly lower TMB than those without (log2 TMB, 3.89 vs 4.15; P = .01).
• Tumors of the head and neck exhibited a significantly higher TMB than those occurring in other primary sites, while skin-localized melanomas at diagnosis showed a significantly higher TMB than node-positive or metastatic stage III or IV tumors (log2 TMB, 3.88 vs 3.48; P = .005).

IN PRACTICE:

“Despite the known association between indoor tanning and melanoma risk,” the study did not find an association between indoor tanning and melanoma TMB, which “suggests that cumulative lifetime sun exposure may be a greater primary driver of TMB than intermittent radiation during indoor tanning,” the authors of the study wrote.

SOURCE:

The study was led by Grace B. Hanrahan, BA, of the Center for Melanoma Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, and was published online on December 11 in JAMA Dermatology.

LIMITATIONS:

The study was conducted at a tertiary referral center, potentially representing a higher-risk subset with more advanced disease than the broader population. Additionally, the retrospective collection of UV exposure history, including indoor tanning and blistering sunburns, may have introduced recall bias.

DISCLOSURES:

The authors did not disclose any funding information. No conflicts of interest were reported.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Indoor tanning exposure was not associated with tumor mutational burden (TMB) in patients with cutaneous melanoma, in a retrospective cohort study. Higher TMB was linked to older age, head and neck tumors, and a history of nonmelanoma skin cancer (NMSC).

METHODOLOGY:

• Researchers conducted a retrospective cohort study at a tertiary care cancer center between 2013 and 2022.
• A total of 617 patients (median age at diagnosis, 61 years; 62.9% men) with melanoma who had next-generation sequencing data and indoor tanning bed exposure history available were included.
• Analysis involved multivariable modeling to evaluate the association between tanning bed use and TMB.
• Patients’ demographics, pathologic staging, TMB, and dermatologic history, including Fitzpatrick skin type, history of exposure to ultraviolet (UV) light, indoor tanning, NMSC, atypical nevi, and blistering sunburns, were considered for the analysis.

TAKEAWAY:

• About 22% of participants had an indoor tanning history. Indoor tanning exposure showed no association with TMB after adjustment for all possible predictors.
• A significant association was found between TMB and age at diagnosis, primary melanoma site, and history of NMSC (P < .001 for all).
• Patients with a history of atypical nevi demonstrated a significantly lower TMB than those without (log2 TMB, 3.89 vs 4.15; P = .01).
• Tumors of the head and neck exhibited a significantly higher TMB than those occurring in other primary sites, while skin-localized melanomas at diagnosis showed a significantly higher TMB than node-positive or metastatic stage III or IV tumors (log2 TMB, 3.88 vs 3.48; P = .005).

IN PRACTICE:

“Despite the known association between indoor tanning and melanoma risk,” the study did not find an association between indoor tanning and melanoma TMB, which “suggests that cumulative lifetime sun exposure may be a greater primary driver of TMB than intermittent radiation during indoor tanning,” the authors of the study wrote.

SOURCE:

The study was led by Grace B. Hanrahan, BA, of the Center for Melanoma Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, and was published online on December 11 in JAMA Dermatology.

LIMITATIONS:

The study was conducted at a tertiary referral center, potentially representing a higher-risk subset with more advanced disease than the broader population. Additionally, the retrospective collection of UV exposure history, including indoor tanning and blistering sunburns, may have introduced recall bias.

DISCLOSURES:

The authors did not disclose any funding information. No conflicts of interest were reported.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Indoor tanning exposure was not associated with tumor mutational burden (TMB) in patients with cutaneous melanoma, in a retrospective cohort study. Higher TMB was linked to older age, head and neck tumors, and a history of nonmelanoma skin cancer (NMSC).

METHODOLOGY:

• Researchers conducted a retrospective cohort study at a tertiary care cancer center between 2013 and 2022.
• A total of 617 patients (median age at diagnosis, 61 years; 62.9% men) with melanoma who had next-generation sequencing data and indoor tanning bed exposure history available were included.
• Analysis involved multivariable modeling to evaluate the association between tanning bed use and TMB.
• Patients’ demographics, pathologic staging, TMB, and dermatologic history, including Fitzpatrick skin type, history of exposure to ultraviolet (UV) light, indoor tanning, NMSC, atypical nevi, and blistering sunburns, were considered for the analysis.

TAKEAWAY:

• About 22% of participants had an indoor tanning history. Indoor tanning exposure showed no association with TMB after adjustment for all possible predictors.
• A significant association was found between TMB and age at diagnosis, primary melanoma site, and history of NMSC (P < .001 for all).
• Patients with a history of atypical nevi demonstrated a significantly lower TMB than those without (log2 TMB, 3.89 vs 4.15; P = .01).
• Tumors of the head and neck exhibited a significantly higher TMB than those occurring in other primary sites, while skin-localized melanomas at diagnosis showed a significantly higher TMB than node-positive or metastatic stage III or IV tumors (log2 TMB, 3.88 vs 3.48; P = .005).

IN PRACTICE:

“Despite the known association between indoor tanning and melanoma risk,” the study did not find an association between indoor tanning and melanoma TMB, which “suggests that cumulative lifetime sun exposure may be a greater primary driver of TMB than intermittent radiation during indoor tanning,” the authors of the study wrote.

SOURCE:

The study was led by Grace B. Hanrahan, BA, of the Center for Melanoma Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, and was published online on December 11 in JAMA Dermatology.

LIMITATIONS:

The study was conducted at a tertiary referral center, potentially representing a higher-risk subset with more advanced disease than the broader population. Additionally, the retrospective collection of UV exposure history, including indoor tanning and blistering sunburns, may have introduced recall bias.

DISCLOSURES:

The authors did not disclose any funding information. No conflicts of interest were reported.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Early treatment with oseltamivir on the same day as hospital admission was associated with fewer severe clinical outcomes, such as worsening pulmonary disease, need for invasive ventilation, organ failure, and in-hospital death in adults hospitalized with influenza. 

METHODOLOGY:

• The 2018 guidelines from the Infectious Disease Society of America recommend prompt administration of oseltamivir to hospitalized patients with suspected or confirmed influenza, regardless of the time of symptom onset; however, variations in treatment practices and circulating virus strains may affect the effectiveness of this practice guideline.
• Researchers conducted a multicenter observational study across 24 hospitals in the United States during the 2022-2023 flu season to assess the benefits of initiating oseltamivir treatment on the same day as hospital admission for adults with acute influenza, compared with late or no treatment.
• They included 840 adults (age, ≥ 18 years) with laboratory-confirmed influenza, of which 415 patients initiated oseltamivir on the same day as hospital admission (early treatment).
• Among the 425 patients in the late/no treatment group, most (78%) received oseltamivir 1 day after admission, while 124 did not receive oseltamivir at all.
• The primary outcome was the peak pulmonary disease severity level that patients experienced during hospitalization, and secondary outcomes included hospital length of stay, ICU admission, initiation of extrapulmonary organ support using vasopressors or kidney replacement therapy, and in-hospital death.

TAKEAWAY:

• Patients in the early treatment group were less likely to experience progression and severe progression of pulmonary disease after the day of hospital admission, compared with those in the late or no treatment group (P < .001 and P = .027, respectively).
• Patients who received early oseltamivir treatment had 40% lower peak pulmonary disease severity than those who received late or no treatment (proportional adjusted odds ratio [paOR], 0.60; 95% CI, 0.49-0.72).
• They also showed lower odds of ICU admission (aOR, 0.25; 95% CI, 0.13-0.49) and use of acute kidney replacement therapy or vasopressors (aOR, 0.40; 95% CI, 0.22-0.67).
• Those in the early treatment group also had a shorter hospital length of stay (median, 4 days vs 4 days) and faced a 64% lower risk for in-hospital mortality (aOR, 0.36; 95% CI, 0.19-0.69) compared with those in the late or no treatment group.

IN PRACTICE:

“These findings support current recommendations, such as the IDSA [Infectious Disease Society of America] Influenza Clinical Practice Guidelines and CDC [Centers for Disease Control and Prevention] guidance, to initiate oseltamivir treatment as soon as possible for adult patients hospitalized with influenza,” the authors wrote.

SOURCE:

The study was led by Nathaniel M. Lewis, PhD, Influenza Division, CDC, Atlanta, Georgia, and was published online  in Clinical Infectious Diseases.

LIMITATIONS:

This study may not be generalizable to seasons when influenza A(H1N1)pdm09 or B viruses are predominant as it was conducted during an influenza A(H3N2) virus–predominant season. The study lacked sufficient power to examine various oseltamivir treatment initiation timepoints or identify a potential maximum time-to-treatment threshold for effectiveness. Moreover, variables such as outpatient antiviral treatment before hospital admission and other treatments using macrolides, statins, corticosteroids, or immunomodulators before or during hospitalization were not collected, which may have influenced the study findings.

DISCLOSURES:

The study received funding from the CDC and the National Center for Immunization and Respiratory Diseases. Some authors reported receiving research support, consulting fees, funding, grants, or fees for participation in an advisory board and having other ties with certain institutions and pharmaceutical companies.

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:

Early treatment with oseltamivir on the same day as hospital admission was associated with fewer severe clinical outcomes, such as worsening pulmonary disease, need for invasive ventilation, organ failure, and in-hospital death in adults hospitalized with influenza. 

METHODOLOGY:

• The 2018 guidelines from the Infectious Disease Society of America recommend prompt administration of oseltamivir to hospitalized patients with suspected or confirmed influenza, regardless of the time of symptom onset; however, variations in treatment practices and circulating virus strains may affect the effectiveness of this practice guideline.
• Researchers conducted a multicenter observational study across 24 hospitals in the United States during the 2022-2023 flu season to assess the benefits of initiating oseltamivir treatment on the same day as hospital admission for adults with acute influenza, compared with late or no treatment.
• They included 840 adults (age, ≥ 18 years) with laboratory-confirmed influenza, of which 415 patients initiated oseltamivir on the same day as hospital admission (early treatment).
• Among the 425 patients in the late/no treatment group, most (78%) received oseltamivir 1 day after admission, while 124 did not receive oseltamivir at all.
• The primary outcome was the peak pulmonary disease severity level that patients experienced during hospitalization, and secondary outcomes included hospital length of stay, ICU admission, initiation of extrapulmonary organ support using vasopressors or kidney replacement therapy, and in-hospital death.

TAKEAWAY:

• Patients in the early treatment group were less likely to experience progression and severe progression of pulmonary disease after the day of hospital admission, compared with those in the late or no treatment group (P < .001 and P = .027, respectively).
• Patients who received early oseltamivir treatment had 40% lower peak pulmonary disease severity than those who received late or no treatment (proportional adjusted odds ratio [paOR], 0.60; 95% CI, 0.49-0.72).
• They also showed lower odds of ICU admission (aOR, 0.25; 95% CI, 0.13-0.49) and use of acute kidney replacement therapy or vasopressors (aOR, 0.40; 95% CI, 0.22-0.67).
• Those in the early treatment group also had a shorter hospital length of stay (median, 4 days vs 4 days) and faced a 64% lower risk for in-hospital mortality (aOR, 0.36; 95% CI, 0.19-0.69) compared with those in the late or no treatment group.

IN PRACTICE:

“These findings support current recommendations, such as the IDSA [Infectious Disease Society of America] Influenza Clinical Practice Guidelines and CDC [Centers for Disease Control and Prevention] guidance, to initiate oseltamivir treatment as soon as possible for adult patients hospitalized with influenza,” the authors wrote.

SOURCE:

The study was led by Nathaniel M. Lewis, PhD, Influenza Division, CDC, Atlanta, Georgia, and was published online  in Clinical Infectious Diseases.

LIMITATIONS:

This study may not be generalizable to seasons when influenza A(H1N1)pdm09 or B viruses are predominant as it was conducted during an influenza A(H3N2) virus–predominant season. The study lacked sufficient power to examine various oseltamivir treatment initiation timepoints or identify a potential maximum time-to-treatment threshold for effectiveness. Moreover, variables such as outpatient antiviral treatment before hospital admission and other treatments using macrolides, statins, corticosteroids, or immunomodulators before or during hospitalization were not collected, which may have influenced the study findings.

DISCLOSURES:

The study received funding from the CDC and the National Center for Immunization and Respiratory Diseases. Some authors reported receiving research support, consulting fees, funding, grants, or fees for participation in an advisory board and having other ties with certain institutions and pharmaceutical companies.

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:

Early treatment with oseltamivir on the same day as hospital admission was associated with fewer severe clinical outcomes, such as worsening pulmonary disease, need for invasive ventilation, organ failure, and in-hospital death in adults hospitalized with influenza. 

METHODOLOGY:

• The 2018 guidelines from the Infectious Disease Society of America recommend prompt administration of oseltamivir to hospitalized patients with suspected or confirmed influenza, regardless of the time of symptom onset; however, variations in treatment practices and circulating virus strains may affect the effectiveness of this practice guideline.
• Researchers conducted a multicenter observational study across 24 hospitals in the United States during the 2022-2023 flu season to assess the benefits of initiating oseltamivir treatment on the same day as hospital admission for adults with acute influenza, compared with late or no treatment.
• They included 840 adults (age, ≥ 18 years) with laboratory-confirmed influenza, of which 415 patients initiated oseltamivir on the same day as hospital admission (early treatment).
• Among the 425 patients in the late/no treatment group, most (78%) received oseltamivir 1 day after admission, while 124 did not receive oseltamivir at all.
• The primary outcome was the peak pulmonary disease severity level that patients experienced during hospitalization, and secondary outcomes included hospital length of stay, ICU admission, initiation of extrapulmonary organ support using vasopressors or kidney replacement therapy, and in-hospital death.

TAKEAWAY:

• Patients in the early treatment group were less likely to experience progression and severe progression of pulmonary disease after the day of hospital admission, compared with those in the late or no treatment group (P < .001 and P = .027, respectively).
• Patients who received early oseltamivir treatment had 40% lower peak pulmonary disease severity than those who received late or no treatment (proportional adjusted odds ratio [paOR], 0.60; 95% CI, 0.49-0.72).
• They also showed lower odds of ICU admission (aOR, 0.25; 95% CI, 0.13-0.49) and use of acute kidney replacement therapy or vasopressors (aOR, 0.40; 95% CI, 0.22-0.67).
• Those in the early treatment group also had a shorter hospital length of stay (median, 4 days vs 4 days) and faced a 64% lower risk for in-hospital mortality (aOR, 0.36; 95% CI, 0.19-0.69) compared with those in the late or no treatment group.

IN PRACTICE:

“These findings support current recommendations, such as the IDSA [Infectious Disease Society of America] Influenza Clinical Practice Guidelines and CDC [Centers for Disease Control and Prevention] guidance, to initiate oseltamivir treatment as soon as possible for adult patients hospitalized with influenza,” the authors wrote.

SOURCE:

The study was led by Nathaniel M. Lewis, PhD, Influenza Division, CDC, Atlanta, Georgia, and was published online  in Clinical Infectious Diseases.

LIMITATIONS:

This study may not be generalizable to seasons when influenza A(H1N1)pdm09 or B viruses are predominant as it was conducted during an influenza A(H3N2) virus–predominant season. The study lacked sufficient power to examine various oseltamivir treatment initiation timepoints or identify a potential maximum time-to-treatment threshold for effectiveness. Moreover, variables such as outpatient antiviral treatment before hospital admission and other treatments using macrolides, statins, corticosteroids, or immunomodulators before or during hospitalization were not collected, which may have influenced the study findings.

DISCLOSURES:

The study received funding from the CDC and the National Center for Immunization and Respiratory Diseases. Some authors reported receiving research support, consulting fees, funding, grants, or fees for participation in an advisory board and having other ties with certain institutions and pharmaceutical companies.

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.

The updated COVID vaccines for 2024-2025 are officially here, designed to target the latest variants and offer robust protection — but getting Americans to roll up their sleeves could prove harder than ever. With COVID cases on the decline, many people feel the urgency has passed.

As of December 2, the CDC reports that COVID test positivity remains low, rising slightly to 4.5% for the week ending November 23, compared with 4.2% the previous week. That’s a far cry from the early days of 2022, when positivity rates soared above 30%. Emergency room visits for COVID now make up just 0.5%, and deaths are down to 0.8% of total weekly fatalities, compared to 1% the previous week.

This steady improvement in the numbers may explain why a recent Pew Research Center survey revealed that 6 in 10 US adults have no plans to get the updated vaccine this year.

As of December 2, according to the CDC, just 19.7% of the US adult population and 9.4% of children had gotten the updated vaccine. The age group most likely? Adults ages 65 and older, with 41.6% getting the updated shot.

Despite the good news about declining cases, our pandemic history suggests a pre-holiday increase is likely. On November 20, the CDC warned it expects levels of both COVID and RSV (respiratory syncytial virus) to rise in the coming weeks — the familiar post-Thanksgiving, pre-Christmas, and Hanukkah increase.

Here’s what to know about the 2024-2025 vaccines — what’s available, how the updated versions are tested, how well each protects you, side effects and other safety information, the best time to get them, and where.



 

What’s Available?

Three updated vaccines, which work two different ways, are authorized or licensed by the FDA for the 2024-2025 season:

Novavax. A protein subunit vaccine, Novavax is authorized for emergency use by the FDA in people ages 12 and older. The vaccine makes a protein that mimics the SARS-CoV-2 virus’ version of the spike protein and combines it with an adjuvant or “booster” to stimulate a protective immune response. This year’s version targets the JN.1 variant.

Pfizer/BioNTech. Its Comirnaty is a fully licensed vaccine for people ages 12 and older. Its mechanism of action is by messenger RNA (mRNA). It works by instructing cells to produce viral proteins, triggering an immune response. Pfizer’s COVID vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

Moderna. Its Spikevax is a fully licensed vaccine for people ages 12 and older. It is also an mRNA vaccine. Moderna’s COVID-19 vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

 

How Effective Are They?

Before being approved for this year’s use, each company had to show its updated vaccine is effective against the currently circulating variants. For the 2 weeks ending November 23, KP.3.1.1 and XEC, from the Omicron lineage, made up the majority of cases, according to CDC data.

How do the vaccine makers know their updated vaccines are targeting the circulating variants? The companies use “pre-clinical” data, which means the updated versions have not yet been tested in people but in other ways, such as animal studies. But they do have to prove to the FDA that their updated vaccine can neutralize the circulating variants.

Companies continue to monitor their updated vaccines as new variants appear. Later in the season, there will be more specific information about how well each vaccine protects in people after tracking real-world data.

 

What About Side Effects?

The CDC lists comparable side effects for both mRNA and protein COVID vaccines, including pain and soreness from the needle, fatigue, headache, muscle pain joint pain, chills, fever, nausea, and vomiting.

Severe allergic reactions are rare, the CDC says, but cautions to be alert for low blood pressure, swelling of the lips, tongue, or throat, or difficulty breathing.

 

Which One Is Best?

“I consider the three currently available COVID vaccines — Pfizer, Moderna, and Novavax — interchangeable,’’ said Scott Roberts, MD, an infectious diseases specialist and assistant professor of medicine at Yale School of Medicine in New Haven, Connecticut. “There have not been head-to-head studies, and the initial vaccine studies for each were performed at different phases of the pandemic, so we do not have great data to guide which one is better than another.”

He does point out the different mechanisms of action, which may make a difference in people’s choice of vaccines. “So if someone has a reaction to one of them, they can switch to a different brand.”

 

Best Time to Get It?

“We have consistently seen COVID rates rise quite significantly in the winter season, especially around the holidays. So if anyone is on the fence and hasn’t gotten the updated vaccine yet, now is a great time to get it to maximize immunity for the holidays,” he said.

What’s next? In late October, the CDC recommended a second dose of the 2024-2025 vaccine 6 months after the first one for those age 65 and above and those 6 months old and older who are moderately or severely immunocompromised.

Now, while it’s tempting to think rates are down and will continue to drop steadily, Roberts reminds people that pandemic history suggests otherwise.

 

Coverage

Most people can get COVID-19 vaccines at no cost through their private health insurance, Medicaid, or Medicare. For the uninsured, there’s also the Vaccines for Children (VFC) program or access through state and local health departments and some health centers. Find details on the CDC website.

A version of this article first appeared on WebMD.

The updated COVID vaccines for 2024-2025 are officially here, designed to target the latest variants and offer robust protection — but getting Americans to roll up their sleeves could prove harder than ever. With COVID cases on the decline, many people feel the urgency has passed.

As of December 2, the CDC reports that COVID test positivity remains low, rising slightly to 4.5% for the week ending November 23, compared with 4.2% the previous week. That’s a far cry from the early days of 2022, when positivity rates soared above 30%. Emergency room visits for COVID now make up just 0.5%, and deaths are down to 0.8% of total weekly fatalities, compared to 1% the previous week.

This steady improvement in the numbers may explain why a recent Pew Research Center survey revealed that 6 in 10 US adults have no plans to get the updated vaccine this year.

As of December 2, according to the CDC, just 19.7% of the US adult population and 9.4% of children had gotten the updated vaccine. The age group most likely? Adults ages 65 and older, with 41.6% getting the updated shot.

Despite the good news about declining cases, our pandemic history suggests a pre-holiday increase is likely. On November 20, the CDC warned it expects levels of both COVID and RSV (respiratory syncytial virus) to rise in the coming weeks — the familiar post-Thanksgiving, pre-Christmas, and Hanukkah increase.

Here’s what to know about the 2024-2025 vaccines — what’s available, how the updated versions are tested, how well each protects you, side effects and other safety information, the best time to get them, and where.



 

What’s Available?

Three updated vaccines, which work two different ways, are authorized or licensed by the FDA for the 2024-2025 season:

Novavax. A protein subunit vaccine, Novavax is authorized for emergency use by the FDA in people ages 12 and older. The vaccine makes a protein that mimics the SARS-CoV-2 virus’ version of the spike protein and combines it with an adjuvant or “booster” to stimulate a protective immune response. This year’s version targets the JN.1 variant.

Pfizer/BioNTech. Its Comirnaty is a fully licensed vaccine for people ages 12 and older. Its mechanism of action is by messenger RNA (mRNA). It works by instructing cells to produce viral proteins, triggering an immune response. Pfizer’s COVID vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

Moderna. Its Spikevax is a fully licensed vaccine for people ages 12 and older. It is also an mRNA vaccine. Moderna’s COVID-19 vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

 

How Effective Are They?

Before being approved for this year’s use, each company had to show its updated vaccine is effective against the currently circulating variants. For the 2 weeks ending November 23, KP.3.1.1 and XEC, from the Omicron lineage, made up the majority of cases, according to CDC data.

How do the vaccine makers know their updated vaccines are targeting the circulating variants? The companies use “pre-clinical” data, which means the updated versions have not yet been tested in people but in other ways, such as animal studies. But they do have to prove to the FDA that their updated vaccine can neutralize the circulating variants.

Companies continue to monitor their updated vaccines as new variants appear. Later in the season, there will be more specific information about how well each vaccine protects in people after tracking real-world data.

 

What About Side Effects?

The CDC lists comparable side effects for both mRNA and protein COVID vaccines, including pain and soreness from the needle, fatigue, headache, muscle pain joint pain, chills, fever, nausea, and vomiting.

Severe allergic reactions are rare, the CDC says, but cautions to be alert for low blood pressure, swelling of the lips, tongue, or throat, or difficulty breathing.

 

Which One Is Best?

“I consider the three currently available COVID vaccines — Pfizer, Moderna, and Novavax — interchangeable,’’ said Scott Roberts, MD, an infectious diseases specialist and assistant professor of medicine at Yale School of Medicine in New Haven, Connecticut. “There have not been head-to-head studies, and the initial vaccine studies for each were performed at different phases of the pandemic, so we do not have great data to guide which one is better than another.”

He does point out the different mechanisms of action, which may make a difference in people’s choice of vaccines. “So if someone has a reaction to one of them, they can switch to a different brand.”

 

Best Time to Get It?

“We have consistently seen COVID rates rise quite significantly in the winter season, especially around the holidays. So if anyone is on the fence and hasn’t gotten the updated vaccine yet, now is a great time to get it to maximize immunity for the holidays,” he said.

What’s next? In late October, the CDC recommended a second dose of the 2024-2025 vaccine 6 months after the first one for those age 65 and above and those 6 months old and older who are moderately or severely immunocompromised.

Now, while it’s tempting to think rates are down and will continue to drop steadily, Roberts reminds people that pandemic history suggests otherwise.

 

Coverage

Most people can get COVID-19 vaccines at no cost through their private health insurance, Medicaid, or Medicare. For the uninsured, there’s also the Vaccines for Children (VFC) program or access through state and local health departments and some health centers. Find details on the CDC website.

A version of this article first appeared on WebMD.

The updated COVID vaccines for 2024-2025 are officially here, designed to target the latest variants and offer robust protection — but getting Americans to roll up their sleeves could prove harder than ever. With COVID cases on the decline, many people feel the urgency has passed.

As of December 2, the CDC reports that COVID test positivity remains low, rising slightly to 4.5% for the week ending November 23, compared with 4.2% the previous week. That’s a far cry from the early days of 2022, when positivity rates soared above 30%. Emergency room visits for COVID now make up just 0.5%, and deaths are down to 0.8% of total weekly fatalities, compared to 1% the previous week.

This steady improvement in the numbers may explain why a recent Pew Research Center survey revealed that 6 in 10 US adults have no plans to get the updated vaccine this year.

As of December 2, according to the CDC, just 19.7% of the US adult population and 9.4% of children had gotten the updated vaccine. The age group most likely? Adults ages 65 and older, with 41.6% getting the updated shot.

Despite the good news about declining cases, our pandemic history suggests a pre-holiday increase is likely. On November 20, the CDC warned it expects levels of both COVID and RSV (respiratory syncytial virus) to rise in the coming weeks — the familiar post-Thanksgiving, pre-Christmas, and Hanukkah increase.

Here’s what to know about the 2024-2025 vaccines — what’s available, how the updated versions are tested, how well each protects you, side effects and other safety information, the best time to get them, and where.



 

What’s Available?

Three updated vaccines, which work two different ways, are authorized or licensed by the FDA for the 2024-2025 season:

Novavax. A protein subunit vaccine, Novavax is authorized for emergency use by the FDA in people ages 12 and older. The vaccine makes a protein that mimics the SARS-CoV-2 virus’ version of the spike protein and combines it with an adjuvant or “booster” to stimulate a protective immune response. This year’s version targets the JN.1 variant.

Pfizer/BioNTech. Its Comirnaty is a fully licensed vaccine for people ages 12 and older. Its mechanism of action is by messenger RNA (mRNA). It works by instructing cells to produce viral proteins, triggering an immune response. Pfizer’s COVID vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

Moderna. Its Spikevax is a fully licensed vaccine for people ages 12 and older. It is also an mRNA vaccine. Moderna’s COVID-19 vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

 

How Effective Are They?

Before being approved for this year’s use, each company had to show its updated vaccine is effective against the currently circulating variants. For the 2 weeks ending November 23, KP.3.1.1 and XEC, from the Omicron lineage, made up the majority of cases, according to CDC data.

How do the vaccine makers know their updated vaccines are targeting the circulating variants? The companies use “pre-clinical” data, which means the updated versions have not yet been tested in people but in other ways, such as animal studies. But they do have to prove to the FDA that their updated vaccine can neutralize the circulating variants.

Companies continue to monitor their updated vaccines as new variants appear. Later in the season, there will be more specific information about how well each vaccine protects in people after tracking real-world data.

 

What About Side Effects?

The CDC lists comparable side effects for both mRNA and protein COVID vaccines, including pain and soreness from the needle, fatigue, headache, muscle pain joint pain, chills, fever, nausea, and vomiting.

Severe allergic reactions are rare, the CDC says, but cautions to be alert for low blood pressure, swelling of the lips, tongue, or throat, or difficulty breathing.

 

Which One Is Best?

“I consider the three currently available COVID vaccines — Pfizer, Moderna, and Novavax — interchangeable,’’ said Scott Roberts, MD, an infectious diseases specialist and assistant professor of medicine at Yale School of Medicine in New Haven, Connecticut. “There have not been head-to-head studies, and the initial vaccine studies for each were performed at different phases of the pandemic, so we do not have great data to guide which one is better than another.”

He does point out the different mechanisms of action, which may make a difference in people’s choice of vaccines. “So if someone has a reaction to one of them, they can switch to a different brand.”

 

Best Time to Get It?

“We have consistently seen COVID rates rise quite significantly in the winter season, especially around the holidays. So if anyone is on the fence and hasn’t gotten the updated vaccine yet, now is a great time to get it to maximize immunity for the holidays,” he said.

What’s next? In late October, the CDC recommended a second dose of the 2024-2025 vaccine 6 months after the first one for those age 65 and above and those 6 months old and older who are moderately or severely immunocompromised.

Now, while it’s tempting to think rates are down and will continue to drop steadily, Roberts reminds people that pandemic history suggests otherwise.

 

Coverage

Most people can get COVID-19 vaccines at no cost through their private health insurance, Medicaid, or Medicare. For the uninsured, there’s also the Vaccines for Children (VFC) program or access through state and local health departments and some health centers. Find details on the CDC website.

A version of this article first appeared on WebMD.

Instead of sitting behind a laptop during patient visits, the pediatrician directly faces the patient and parent, relying on an ambient artificial intelligence (AI) scribe to capture the conversation for the electronic health record (EHR). A geriatrician doing rounds at the senior living facility plugs each patient’s medications into an AI tool, checking for drug interactions. And a busy hospital radiology department runs all its emergency head CTs through an AI algorithm, triaging potential stroke patients to ensure they receive the highest priority. None of these physicians have been sued for malpractice for AI usage, but they wonder if they’re at risk.

In a recent Medscape report, AI Adoption in Healthcare, 224 physicians responded to the statement: “I want to do more with AI but I worry about malpractice risk if I move too fast.” Seventeen percent said that they strongly agreed while 23% said they agreed — a full 40% were concerned about using the technology for legal reasons.  

Malpractice and AI are on many minds in healthcare, especially in large health systems, Deepika Srivastava, chief operating officer at The Doctors Company, told this news organization. “AI is at the forefront of the conversation, and they’re [large health systems] raising questions. Larger systems want to protect themselves.” 

The good news is there’s currently no sign of legal action over the clinical use of AI. “We’re not seeing even a few AI-related suits just yet,” but the risk is growing, Srivastava said, “and that’s why we’re talking about it. The legal system will need to adapt to address the role of AI in healthcare.”

 

How Doctors Are Using AI

Healthcare is incorporating AI in multiple ways based on the type of tool and function needed. Narrow AI is popular in fields like radiology, comparing two large data sets to find differences between them. Narrow AI can help differentiate between normal and abnormal tissue, such as breast or lung tumors. Almost 900 AI health tools have Food and Drug Administration approval as of July 2024, discerning abnormalities and recognizing patterns better than many humans, said Robert Pearl, MD, author of ChatGPT, MD: How AI-Empowered Patients & Doctors Can Take Back Control of American Medicine and former CEO of The Permanente Medical Group.

Narrow AI can improve diagnostic speed and accuracy for other specialties, too, including dermatology and ophthalmology, Pearl said. “It’s less clear to me if it will be very beneficial in primary care, neurology, and psychiatry, areas of medicine that involve a lot of words.” In those specialties, some may use generative AI as a repository of resources. In clinical practice, ambient AI is also used to create health records based on patient/clinician conversations.

In clinical administration, AI is used for scheduling, billing, and submitting insurance claims. On the insurer side, denying claims based on AI algorithms has been at the heart of legal actions, making recent headlines. 

 

Malpractice Risks When Using AI

Accuracy and privacy should be at the top of the list for malpractice concerns with AI. With accuracy, liability could partially be determined by use type. If a diagnostic application makes the wrong diagnosis, “the company has legal accountability because it created and had to test it specific to the application that it’s being recommended for,” Pearl said. 

However, keeping a human in the loop is a smart move when using AI diagnostic tools. The physician should still choose the AI-suggested diagnosis or a different one. If it’s the wrong diagnosis, “it’s really hard to currently say where is the source of the error? Was it the physician? Was it the tool?” Srivastava added.

With an incorrect diagnosis by generative AI, liability is more apparent. “You’re taking that accountability,” Pearl said. Generative AI operates in a black box, predicting the correct answer based on information stored in a database. “Generative AI tries to draw a correlation between what it has seen and predicting the next output,” said Alex Shahrestani, managing partner of Promise Legal PLLC, a law firm in Austin, Texas. He serves on the State Bar of Texas’s Taskforce on AI and the Law and has participated in advisory groups related to AI policies with the National Institute of Standards and Technology. “A doctor should know to validate information given back to them by AI,” applying their own medical training and judgment.

Generative AI can provide ideas. Pearl shared a story about a surgeon who was unable to remove a breathing tube that was stuck in a patients’ throat at the end of a procedure. The surgeon checked ChatGPT in the operating room, finding a similar case. Adrenaline in the anesthetic restricted the blood vessels, causing the vocal cords to stick together. Following the AI information, the surgeon allowed more time for the anesthesia to diffuse. As it wore off, the vocal cords separated, easing the removal of the breathing tube. “That is the kind of expertise it can provide,” Pearl said.

Privacy is a common AI concern, but it may be more problematic than it should be. “Many think if you talk to an AI system, you’re surrendering personal information the model can learn from,” said Shahrestani. Platforms offer opt-outs. Even without opting out, the model won’t automatically ingest your interactions. That’s not a privacy feature, but a concern by the developer that the information may not help the model. 

“If you do use these opt-out mechanisms, and you have the requisite amount of confidentiality, you can use ChatGPT without too much concern about the patient information being released into the wild,” Shahrestani said. Or use systems with stricter requirements that keep all data on site.

 

Malpractice Insurance Policies and AI

Currently, malpractice policies do not specify AI coverage. “We don’t ask right now to list all the technology you’re using,” said Srivastava. Many EHR systems already incorporate AI. If a human provider is in the loop, already vetted and insured, “we should be okay when it comes to the risk of malpractice when doctors are using AI because it’s still the risk that we’re ensuring.”

Insurers are paying attention, though. “Traditional medical malpractice law does require re-evaluation because the rapid pace of AI development has outpaced the efforts to integrate it into the legal system,” Srivastava said.

Some, including Pearl, believe AI will actually lower the malpractice risk. Having more data points to consider can make doctors’ jobs faster, easier, and more accurate. “I believe the technology will decrease lawsuits, not increase them,” said Pearl.

 

Meanwhile, How Can Doctors Protect Themselves From an AI Malpractice Suit?

Know your tool: Providers should understand the tool they’re deploying, what it provides, how it was built and trained (including potential biases), how it was tested, and the guidelines for how to use it or not use it, said Srivastava. Evaluate each tool, use case, and risk separately. “Don’t just say it’s all AI.” 

With generative AI, users will have better success requesting information that has been available longer and is more widely accessed. “It’s more likely to come back correctly,” said Shahrestani. If the information sought is fairly new or not widespread, the tool may try to draw problematic conclusions. 

Document: “Document, document, document. Just making sure you have good documentation can really help you if litigation comes up and it’s related to the AI tools,” Srivastava said.

Try it out: “I recommend you use [generative AI] a lot so you understand its strengths and shortcomings,” said Shahrestani. “If you wait until things settle, you’ll be further behind.” 

Pretend you’re the patient and give the tool the information you’d give a doctor and see the results, said Pearl. It will provide you with an idea of what it can do. “No one would sue you because you went to the library to look up information in the textbooks,” he said — using generative AI is similar. Try the free versions first; if you begin relying on it more, the paid versions have better features and are inexpensive. 

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

Instead of sitting behind a laptop during patient visits, the pediatrician directly faces the patient and parent, relying on an ambient artificial intelligence (AI) scribe to capture the conversation for the electronic health record (EHR). A geriatrician doing rounds at the senior living facility plugs each patient’s medications into an AI tool, checking for drug interactions. And a busy hospital radiology department runs all its emergency head CTs through an AI algorithm, triaging potential stroke patients to ensure they receive the highest priority. None of these physicians have been sued for malpractice for AI usage, but they wonder if they’re at risk.

In a recent Medscape report, AI Adoption in Healthcare, 224 physicians responded to the statement: “I want to do more with AI but I worry about malpractice risk if I move too fast.” Seventeen percent said that they strongly agreed while 23% said they agreed — a full 40% were concerned about using the technology for legal reasons.  

Malpractice and AI are on many minds in healthcare, especially in large health systems, Deepika Srivastava, chief operating officer at The Doctors Company, told this news organization. “AI is at the forefront of the conversation, and they’re [large health systems] raising questions. Larger systems want to protect themselves.” 

The good news is there’s currently no sign of legal action over the clinical use of AI. “We’re not seeing even a few AI-related suits just yet,” but the risk is growing, Srivastava said, “and that’s why we’re talking about it. The legal system will need to adapt to address the role of AI in healthcare.”

 

How Doctors Are Using AI

Healthcare is incorporating AI in multiple ways based on the type of tool and function needed. Narrow AI is popular in fields like radiology, comparing two large data sets to find differences between them. Narrow AI can help differentiate between normal and abnormal tissue, such as breast or lung tumors. Almost 900 AI health tools have Food and Drug Administration approval as of July 2024, discerning abnormalities and recognizing patterns better than many humans, said Robert Pearl, MD, author of ChatGPT, MD: How AI-Empowered Patients & Doctors Can Take Back Control of American Medicine and former CEO of The Permanente Medical Group.

Narrow AI can improve diagnostic speed and accuracy for other specialties, too, including dermatology and ophthalmology, Pearl said. “It’s less clear to me if it will be very beneficial in primary care, neurology, and psychiatry, areas of medicine that involve a lot of words.” In those specialties, some may use generative AI as a repository of resources. In clinical practice, ambient AI is also used to create health records based on patient/clinician conversations.

In clinical administration, AI is used for scheduling, billing, and submitting insurance claims. On the insurer side, denying claims based on AI algorithms has been at the heart of legal actions, making recent headlines. 

 

Malpractice Risks When Using AI

Accuracy and privacy should be at the top of the list for malpractice concerns with AI. With accuracy, liability could partially be determined by use type. If a diagnostic application makes the wrong diagnosis, “the company has legal accountability because it created and had to test it specific to the application that it’s being recommended for,” Pearl said. 

However, keeping a human in the loop is a smart move when using AI diagnostic tools. The physician should still choose the AI-suggested diagnosis or a different one. If it’s the wrong diagnosis, “it’s really hard to currently say where is the source of the error? Was it the physician? Was it the tool?” Srivastava added.

With an incorrect diagnosis by generative AI, liability is more apparent. “You’re taking that accountability,” Pearl said. Generative AI operates in a black box, predicting the correct answer based on information stored in a database. “Generative AI tries to draw a correlation between what it has seen and predicting the next output,” said Alex Shahrestani, managing partner of Promise Legal PLLC, a law firm in Austin, Texas. He serves on the State Bar of Texas’s Taskforce on AI and the Law and has participated in advisory groups related to AI policies with the National Institute of Standards and Technology. “A doctor should know to validate information given back to them by AI,” applying their own medical training and judgment.

Generative AI can provide ideas. Pearl shared a story about a surgeon who was unable to remove a breathing tube that was stuck in a patients’ throat at the end of a procedure. The surgeon checked ChatGPT in the operating room, finding a similar case. Adrenaline in the anesthetic restricted the blood vessels, causing the vocal cords to stick together. Following the AI information, the surgeon allowed more time for the anesthesia to diffuse. As it wore off, the vocal cords separated, easing the removal of the breathing tube. “That is the kind of expertise it can provide,” Pearl said.

Privacy is a common AI concern, but it may be more problematic than it should be. “Many think if you talk to an AI system, you’re surrendering personal information the model can learn from,” said Shahrestani. Platforms offer opt-outs. Even without opting out, the model won’t automatically ingest your interactions. That’s not a privacy feature, but a concern by the developer that the information may not help the model. 

“If you do use these opt-out mechanisms, and you have the requisite amount of confidentiality, you can use ChatGPT without too much concern about the patient information being released into the wild,” Shahrestani said. Or use systems with stricter requirements that keep all data on site.

 

Malpractice Insurance Policies and AI

Currently, malpractice policies do not specify AI coverage. “We don’t ask right now to list all the technology you’re using,” said Srivastava. Many EHR systems already incorporate AI. If a human provider is in the loop, already vetted and insured, “we should be okay when it comes to the risk of malpractice when doctors are using AI because it’s still the risk that we’re ensuring.”

Insurers are paying attention, though. “Traditional medical malpractice law does require re-evaluation because the rapid pace of AI development has outpaced the efforts to integrate it into the legal system,” Srivastava said.

Some, including Pearl, believe AI will actually lower the malpractice risk. Having more data points to consider can make doctors’ jobs faster, easier, and more accurate. “I believe the technology will decrease lawsuits, not increase them,” said Pearl.

 

Meanwhile, How Can Doctors Protect Themselves From an AI Malpractice Suit?

Know your tool: Providers should understand the tool they’re deploying, what it provides, how it was built and trained (including potential biases), how it was tested, and the guidelines for how to use it or not use it, said Srivastava. Evaluate each tool, use case, and risk separately. “Don’t just say it’s all AI.” 

With generative AI, users will have better success requesting information that has been available longer and is more widely accessed. “It’s more likely to come back correctly,” said Shahrestani. If the information sought is fairly new or not widespread, the tool may try to draw problematic conclusions. 

Document: “Document, document, document. Just making sure you have good documentation can really help you if litigation comes up and it’s related to the AI tools,” Srivastava said.

Try it out: “I recommend you use [generative AI] a lot so you understand its strengths and shortcomings,” said Shahrestani. “If you wait until things settle, you’ll be further behind.” 

Pretend you’re the patient and give the tool the information you’d give a doctor and see the results, said Pearl. It will provide you with an idea of what it can do. “No one would sue you because you went to the library to look up information in the textbooks,” he said — using generative AI is similar. Try the free versions first; if you begin relying on it more, the paid versions have better features and are inexpensive. 

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

Instead of sitting behind a laptop during patient visits, the pediatrician directly faces the patient and parent, relying on an ambient artificial intelligence (AI) scribe to capture the conversation for the electronic health record (EHR). A geriatrician doing rounds at the senior living facility plugs each patient’s medications into an AI tool, checking for drug interactions. And a busy hospital radiology department runs all its emergency head CTs through an AI algorithm, triaging potential stroke patients to ensure they receive the highest priority. None of these physicians have been sued for malpractice for AI usage, but they wonder if they’re at risk.

In a recent Medscape report, AI Adoption in Healthcare, 224 physicians responded to the statement: “I want to do more with AI but I worry about malpractice risk if I move too fast.” Seventeen percent said that they strongly agreed while 23% said they agreed — a full 40% were concerned about using the technology for legal reasons.  

Malpractice and AI are on many minds in healthcare, especially in large health systems, Deepika Srivastava, chief operating officer at The Doctors Company, told this news organization. “AI is at the forefront of the conversation, and they’re [large health systems] raising questions. Larger systems want to protect themselves.” 

The good news is there’s currently no sign of legal action over the clinical use of AI. “We’re not seeing even a few AI-related suits just yet,” but the risk is growing, Srivastava said, “and that’s why we’re talking about it. The legal system will need to adapt to address the role of AI in healthcare.”

 

How Doctors Are Using AI

Healthcare is incorporating AI in multiple ways based on the type of tool and function needed. Narrow AI is popular in fields like radiology, comparing two large data sets to find differences between them. Narrow AI can help differentiate between normal and abnormal tissue, such as breast or lung tumors. Almost 900 AI health tools have Food and Drug Administration approval as of July 2024, discerning abnormalities and recognizing patterns better than many humans, said Robert Pearl, MD, author of ChatGPT, MD: How AI-Empowered Patients & Doctors Can Take Back Control of American Medicine and former CEO of The Permanente Medical Group.

Narrow AI can improve diagnostic speed and accuracy for other specialties, too, including dermatology and ophthalmology, Pearl said. “It’s less clear to me if it will be very beneficial in primary care, neurology, and psychiatry, areas of medicine that involve a lot of words.” In those specialties, some may use generative AI as a repository of resources. In clinical practice, ambient AI is also used to create health records based on patient/clinician conversations.

In clinical administration, AI is used for scheduling, billing, and submitting insurance claims. On the insurer side, denying claims based on AI algorithms has been at the heart of legal actions, making recent headlines. 

 

Malpractice Risks When Using AI

Accuracy and privacy should be at the top of the list for malpractice concerns with AI. With accuracy, liability could partially be determined by use type. If a diagnostic application makes the wrong diagnosis, “the company has legal accountability because it created and had to test it specific to the application that it’s being recommended for,” Pearl said. 

However, keeping a human in the loop is a smart move when using AI diagnostic tools. The physician should still choose the AI-suggested diagnosis or a different one. If it’s the wrong diagnosis, “it’s really hard to currently say where is the source of the error? Was it the physician? Was it the tool?” Srivastava added.

With an incorrect diagnosis by generative AI, liability is more apparent. “You’re taking that accountability,” Pearl said. Generative AI operates in a black box, predicting the correct answer based on information stored in a database. “Generative AI tries to draw a correlation between what it has seen and predicting the next output,” said Alex Shahrestani, managing partner of Promise Legal PLLC, a law firm in Austin, Texas. He serves on the State Bar of Texas’s Taskforce on AI and the Law and has participated in advisory groups related to AI policies with the National Institute of Standards and Technology. “A doctor should know to validate information given back to them by AI,” applying their own medical training and judgment.

Generative AI can provide ideas. Pearl shared a story about a surgeon who was unable to remove a breathing tube that was stuck in a patients’ throat at the end of a procedure. The surgeon checked ChatGPT in the operating room, finding a similar case. Adrenaline in the anesthetic restricted the blood vessels, causing the vocal cords to stick together. Following the AI information, the surgeon allowed more time for the anesthesia to diffuse. As it wore off, the vocal cords separated, easing the removal of the breathing tube. “That is the kind of expertise it can provide,” Pearl said.

Privacy is a common AI concern, but it may be more problematic than it should be. “Many think if you talk to an AI system, you’re surrendering personal information the model can learn from,” said Shahrestani. Platforms offer opt-outs. Even without opting out, the model won’t automatically ingest your interactions. That’s not a privacy feature, but a concern by the developer that the information may not help the model. 

“If you do use these opt-out mechanisms, and you have the requisite amount of confidentiality, you can use ChatGPT without too much concern about the patient information being released into the wild,” Shahrestani said. Or use systems with stricter requirements that keep all data on site.

 

Malpractice Insurance Policies and AI

Currently, malpractice policies do not specify AI coverage. “We don’t ask right now to list all the technology you’re using,” said Srivastava. Many EHR systems already incorporate AI. If a human provider is in the loop, already vetted and insured, “we should be okay when it comes to the risk of malpractice when doctors are using AI because it’s still the risk that we’re ensuring.”

Insurers are paying attention, though. “Traditional medical malpractice law does require re-evaluation because the rapid pace of AI development has outpaced the efforts to integrate it into the legal system,” Srivastava said.

Some, including Pearl, believe AI will actually lower the malpractice risk. Having more data points to consider can make doctors’ jobs faster, easier, and more accurate. “I believe the technology will decrease lawsuits, not increase them,” said Pearl.

 

Meanwhile, How Can Doctors Protect Themselves From an AI Malpractice Suit?

Know your tool: Providers should understand the tool they’re deploying, what it provides, how it was built and trained (including potential biases), how it was tested, and the guidelines for how to use it or not use it, said Srivastava. Evaluate each tool, use case, and risk separately. “Don’t just say it’s all AI.” 

With generative AI, users will have better success requesting information that has been available longer and is more widely accessed. “It’s more likely to come back correctly,” said Shahrestani. If the information sought is fairly new or not widespread, the tool may try to draw problematic conclusions. 

Document: “Document, document, document. Just making sure you have good documentation can really help you if litigation comes up and it’s related to the AI tools,” Srivastava said.

Try it out: “I recommend you use [generative AI] a lot so you understand its strengths and shortcomings,” said Shahrestani. “If you wait until things settle, you’ll be further behind.” 

Pretend you’re the patient and give the tool the information you’d give a doctor and see the results, said Pearl. It will provide you with an idea of what it can do. “No one would sue you because you went to the library to look up information in the textbooks,” he said — using generative AI is similar. Try the free versions first; if you begin relying on it more, the paid versions have better features and are inexpensive. 

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

Childhood exposure to leaded gasoline via car exhaust over the past 75 years is linked to 151 million excess cases of psychiatric disorders in the United States, new research suggested.

The data revealed that the group most heavily exposed to lead — individuals born between 1966 and 1986, commonly known as Generation X — experienced the biggest increases in mental health issues.

Within this cohort, those born between 1966 and 1970 were affected the most. This timeline, the investigators noted, aligns with the peak use of leaded gasoline during the mid-1960s and 1970s. Specifically for this group, overall mental health issues increase by 0.35 times the average, anxiety and depression by 1.75 times, and attention-deficit/hyperactivity disorder (ADHD) symptoms by 1.17 times.

“Lead exposure across the country has probably played a significant role in worsening mental health in ways that had previously been unappreciated and invisible,” study investigator Aaron Reuben, PhD, assistant professor of clinical neuropsychology at the University of Virginia, Charlottesville, said in an interview.

However, the investigators emphasized that the study only establishes an association and not a causal relationship between leaded gas exposure and subsequent psychopathology.

The findings were published online on December 4 in The Journal of Child Psychology and Psychiatry.

 

Lead Astray?

Leaded gasoline was first used in the 1920s to stop engine knocking and improve performance. Despite early evidence of neurotoxicity its use continued until 1996 when it was banned.

The investigators noted that over half of the current US population was exposed to adverse lead levels from gasoline in childhood. However, they added the total contribution of childhood lead exposure to the population’s mental health and personality has not previously been evaluated.

For the study, the researchers combined serial, cross-sectional data on blood lead levels (BLLs) from the National Health and Nutrition Examination Survey and integrated it with historical data on gasoline usage, allowing them to estimate childhood BLLs in the United States from 1940 to 2015.

They calculated the impact of lead exposure on mental health using general psychopathology factor points, also referred to as mental illness points, which function similarly to IQ points.

These measures used were based on a prior study led by Reuben in 2019 from a New Zealand cohort and a study by a different group that followed a longitudinal birth cohort in Chicago .

Using these data, the researchers calculated population-level elevations in mental health symptoms on the basis of lead exposure and five key psychiatric outcomes in the US population.

These included general psychopathology, which reflects an individual’s overall liability to mental disorders and was scaled to match IQ scores with a mean of 100 and an SD of 15.

They also evaluated symptoms of internalizing disorders including anxiety and depression and ADHD and standardized them to a mean of 0 and an SD of 1.

The researchers also looked at differences in the personality traits of neuroticism, which relate to emotional instability and conscientiousness and reflect organization and responsibility. Both of these were assessed using similar standardized scales.

 

151 Million Excess Cases of Mental Illness

Using this approach, the researchers were able to assess the historical and long-term implications of lead exposure on mental health and personality traits in the US population over time.

Results showed that during the peak era of leaded gasoline in the United States, children were routinely exposed to lead levels three to six times higher than the current reference point for clinical concern (3.5 μg/dL of blood), the authors noted.

While the United States banned leaded gasoline in 1996, lead can still be present in water pipes, old paint, and soil. The Centers for Disease Control and Prevention cautions that no BLLs are safe.

The investigators found that between 1940 and 2015, the US population gained 602 million general psychopathology points, which the investigators said equates to 151 million excess instances of mental disorders that are primarily, but not completely, attributable to early life exposure to leaded gasoline.

“Assuming that published lead-psychopathology associations are causal and not purely correlational, we estimate that by 2015, the US population had gained 602 million General Psychopathology factor points because of exposure arising from leaded gasoline, reflecting a 0.13 standard deviation increase in overall liability to mental illness in the population and an estimated 151 million excess mental disorders attributable to lead exposure,” the researchers wrote.

Specific effects included a 0.64 SD increase in anxiety and depression symptoms, a 0.42 SD increase in ADHD symptoms, a 0.14 SD increase in ADHD symptoms, a 0.14 SD increase in emotional instability (neuroticism), and a 0.20 SD decrease in traits like organization and responsibility (conscientiousness).

These mental health and personality changes were not distributed evenly among the generations, most significant in those born between 1966 and 1986, the investigators reported.

For example, children between 1966 and 1970, the period when leaded gasoline use was at its peak, had BLLs > 5 μg/dL and experienced a 1.75 SD increase in internalizing symptoms and a 1.17 SD increase in ADHD symptoms.

 

Assess Lead Risk

The study had several limitations. Causality could not be established, and the accuracy of the estimates relied on findings from the researchers’ two previous key studies.

However, the investigators noted that these findings have been replicated across multiple cohorts and settings. Additionally, the results may not be fully generalizable to the entire US population, as one study was based in New Zealand and the other in urban Chicago.

Reuben cautioned that even though gasoline and new paint no longer contain lead, exposure is still possible.

“We saw this most acutely in Flint, Michigan,” when aging water pipes exposed more than 100,000 residents to high lead levels in 2014. “This situation made us aware that thousands of communities are exposed to lead service lines.”

He recommended that physicians consider screening patients for lead exposure — both new and old. Experts estimate that 90% of lead in the body is stored in the skeleton and can be released back into the bloodstream over time, particularly in cases of calcium deficiency, pregnancy, or osteoporosis.

While reversing childhood lead exposure is not possible, Reuben noted that healthy lifestyle choices and multimodal interventions such as medication and therapy can effectively address and alleviate mental illness.

 

‘Legacy of Lead’

In a comment, Terrie Moffitt, PhD, who was not involved in the research, said the study “is important because it gives us a crystal ball to see into the future of children living with lead today.”

“It’s called the ‘legacy of lead,’ and what a legacy,” said Moffitt, professor in the Department of Psychology and Neuroscience, Nannerl O. Keohane University at Duke University in Durham, North Carolina.

Moffitt emphasized that children exposed to lead today often live in areas of poverty and disadvantage, making it difficult to disentangle the potential effects of lead exposure from those of childhood adversity that predispose individuals to mental illness.

“This study tells us about lead’s damage in an era when it was everywhere, not just in poor communities,” she said.

The study was funded by a fellowship from the National Institute of Environmental Health Sciences. Reuben and Moffitt reported no relevant financial relationships.

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

Childhood exposure to leaded gasoline via car exhaust over the past 75 years is linked to 151 million excess cases of psychiatric disorders in the United States, new research suggested.

The data revealed that the group most heavily exposed to lead — individuals born between 1966 and 1986, commonly known as Generation X — experienced the biggest increases in mental health issues.

Within this cohort, those born between 1966 and 1970 were affected the most. This timeline, the investigators noted, aligns with the peak use of leaded gasoline during the mid-1960s and 1970s. Specifically for this group, overall mental health issues increase by 0.35 times the average, anxiety and depression by 1.75 times, and attention-deficit/hyperactivity disorder (ADHD) symptoms by 1.17 times.

“Lead exposure across the country has probably played a significant role in worsening mental health in ways that had previously been unappreciated and invisible,” study investigator Aaron Reuben, PhD, assistant professor of clinical neuropsychology at the University of Virginia, Charlottesville, said in an interview.

However, the investigators emphasized that the study only establishes an association and not a causal relationship between leaded gas exposure and subsequent psychopathology.

The findings were published online on December 4 in The Journal of Child Psychology and Psychiatry.

 

Lead Astray?

Leaded gasoline was first used in the 1920s to stop engine knocking and improve performance. Despite early evidence of neurotoxicity its use continued until 1996 when it was banned.

The investigators noted that over half of the current US population was exposed to adverse lead levels from gasoline in childhood. However, they added the total contribution of childhood lead exposure to the population’s mental health and personality has not previously been evaluated.

For the study, the researchers combined serial, cross-sectional data on blood lead levels (BLLs) from the National Health and Nutrition Examination Survey and integrated it with historical data on gasoline usage, allowing them to estimate childhood BLLs in the United States from 1940 to 2015.

They calculated the impact of lead exposure on mental health using general psychopathology factor points, also referred to as mental illness points, which function similarly to IQ points.

These measures used were based on a prior study led by Reuben in 2019 from a New Zealand cohort and a study by a different group that followed a longitudinal birth cohort in Chicago .

Using these data, the researchers calculated population-level elevations in mental health symptoms on the basis of lead exposure and five key psychiatric outcomes in the US population.

These included general psychopathology, which reflects an individual’s overall liability to mental disorders and was scaled to match IQ scores with a mean of 100 and an SD of 15.

They also evaluated symptoms of internalizing disorders including anxiety and depression and ADHD and standardized them to a mean of 0 and an SD of 1.

The researchers also looked at differences in the personality traits of neuroticism, which relate to emotional instability and conscientiousness and reflect organization and responsibility. Both of these were assessed using similar standardized scales.

 

151 Million Excess Cases of Mental Illness

Using this approach, the researchers were able to assess the historical and long-term implications of lead exposure on mental health and personality traits in the US population over time.

Results showed that during the peak era of leaded gasoline in the United States, children were routinely exposed to lead levels three to six times higher than the current reference point for clinical concern (3.5 μg/dL of blood), the authors noted.

While the United States banned leaded gasoline in 1996, lead can still be present in water pipes, old paint, and soil. The Centers for Disease Control and Prevention cautions that no BLLs are safe.

The investigators found that between 1940 and 2015, the US population gained 602 million general psychopathology points, which the investigators said equates to 151 million excess instances of mental disorders that are primarily, but not completely, attributable to early life exposure to leaded gasoline.

“Assuming that published lead-psychopathology associations are causal and not purely correlational, we estimate that by 2015, the US population had gained 602 million General Psychopathology factor points because of exposure arising from leaded gasoline, reflecting a 0.13 standard deviation increase in overall liability to mental illness in the population and an estimated 151 million excess mental disorders attributable to lead exposure,” the researchers wrote.

Specific effects included a 0.64 SD increase in anxiety and depression symptoms, a 0.42 SD increase in ADHD symptoms, a 0.14 SD increase in ADHD symptoms, a 0.14 SD increase in emotional instability (neuroticism), and a 0.20 SD decrease in traits like organization and responsibility (conscientiousness).

These mental health and personality changes were not distributed evenly among the generations, most significant in those born between 1966 and 1986, the investigators reported.

For example, children between 1966 and 1970, the period when leaded gasoline use was at its peak, had BLLs > 5 μg/dL and experienced a 1.75 SD increase in internalizing symptoms and a 1.17 SD increase in ADHD symptoms.

 

Assess Lead Risk

The study had several limitations. Causality could not be established, and the accuracy of the estimates relied on findings from the researchers’ two previous key studies.

However, the investigators noted that these findings have been replicated across multiple cohorts and settings. Additionally, the results may not be fully generalizable to the entire US population, as one study was based in New Zealand and the other in urban Chicago.

Reuben cautioned that even though gasoline and new paint no longer contain lead, exposure is still possible.

“We saw this most acutely in Flint, Michigan,” when aging water pipes exposed more than 100,000 residents to high lead levels in 2014. “This situation made us aware that thousands of communities are exposed to lead service lines.”

He recommended that physicians consider screening patients for lead exposure — both new and old. Experts estimate that 90% of lead in the body is stored in the skeleton and can be released back into the bloodstream over time, particularly in cases of calcium deficiency, pregnancy, or osteoporosis.

While reversing childhood lead exposure is not possible, Reuben noted that healthy lifestyle choices and multimodal interventions such as medication and therapy can effectively address and alleviate mental illness.

 

‘Legacy of Lead’

In a comment, Terrie Moffitt, PhD, who was not involved in the research, said the study “is important because it gives us a crystal ball to see into the future of children living with lead today.”

“It’s called the ‘legacy of lead,’ and what a legacy,” said Moffitt, professor in the Department of Psychology and Neuroscience, Nannerl O. Keohane University at Duke University in Durham, North Carolina.

Moffitt emphasized that children exposed to lead today often live in areas of poverty and disadvantage, making it difficult to disentangle the potential effects of lead exposure from those of childhood adversity that predispose individuals to mental illness.

“This study tells us about lead’s damage in an era when it was everywhere, not just in poor communities,” she said.

The study was funded by a fellowship from the National Institute of Environmental Health Sciences. Reuben and Moffitt reported no relevant financial relationships.

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

Childhood exposure to leaded gasoline via car exhaust over the past 75 years is linked to 151 million excess cases of psychiatric disorders in the United States, new research suggested.

The data revealed that the group most heavily exposed to lead — individuals born between 1966 and 1986, commonly known as Generation X — experienced the biggest increases in mental health issues.

Within this cohort, those born between 1966 and 1970 were affected the most. This timeline, the investigators noted, aligns with the peak use of leaded gasoline during the mid-1960s and 1970s. Specifically for this group, overall mental health issues increase by 0.35 times the average, anxiety and depression by 1.75 times, and attention-deficit/hyperactivity disorder (ADHD) symptoms by 1.17 times.

“Lead exposure across the country has probably played a significant role in worsening mental health in ways that had previously been unappreciated and invisible,” study investigator Aaron Reuben, PhD, assistant professor of clinical neuropsychology at the University of Virginia, Charlottesville, said in an interview.

However, the investigators emphasized that the study only establishes an association and not a causal relationship between leaded gas exposure and subsequent psychopathology.

The findings were published online on December 4 in The Journal of Child Psychology and Psychiatry.

 

Lead Astray?

Leaded gasoline was first used in the 1920s to stop engine knocking and improve performance. Despite early evidence of neurotoxicity its use continued until 1996 when it was banned.

The investigators noted that over half of the current US population was exposed to adverse lead levels from gasoline in childhood. However, they added the total contribution of childhood lead exposure to the population’s mental health and personality has not previously been evaluated.

For the study, the researchers combined serial, cross-sectional data on blood lead levels (BLLs) from the National Health and Nutrition Examination Survey and integrated it with historical data on gasoline usage, allowing them to estimate childhood BLLs in the United States from 1940 to 2015.

They calculated the impact of lead exposure on mental health using general psychopathology factor points, also referred to as mental illness points, which function similarly to IQ points.

These measures used were based on a prior study led by Reuben in 2019 from a New Zealand cohort and a study by a different group that followed a longitudinal birth cohort in Chicago .

Using these data, the researchers calculated population-level elevations in mental health symptoms on the basis of lead exposure and five key psychiatric outcomes in the US population.

These included general psychopathology, which reflects an individual’s overall liability to mental disorders and was scaled to match IQ scores with a mean of 100 and an SD of 15.

They also evaluated symptoms of internalizing disorders including anxiety and depression and ADHD and standardized them to a mean of 0 and an SD of 1.

The researchers also looked at differences in the personality traits of neuroticism, which relate to emotional instability and conscientiousness and reflect organization and responsibility. Both of these were assessed using similar standardized scales.

 

151 Million Excess Cases of Mental Illness

Using this approach, the researchers were able to assess the historical and long-term implications of lead exposure on mental health and personality traits in the US population over time.

Results showed that during the peak era of leaded gasoline in the United States, children were routinely exposed to lead levels three to six times higher than the current reference point for clinical concern (3.5 μg/dL of blood), the authors noted.

While the United States banned leaded gasoline in 1996, lead can still be present in water pipes, old paint, and soil. The Centers for Disease Control and Prevention cautions that no BLLs are safe.

The investigators found that between 1940 and 2015, the US population gained 602 million general psychopathology points, which the investigators said equates to 151 million excess instances of mental disorders that are primarily, but not completely, attributable to early life exposure to leaded gasoline.

“Assuming that published lead-psychopathology associations are causal and not purely correlational, we estimate that by 2015, the US population had gained 602 million General Psychopathology factor points because of exposure arising from leaded gasoline, reflecting a 0.13 standard deviation increase in overall liability to mental illness in the population and an estimated 151 million excess mental disorders attributable to lead exposure,” the researchers wrote.

Specific effects included a 0.64 SD increase in anxiety and depression symptoms, a 0.42 SD increase in ADHD symptoms, a 0.14 SD increase in ADHD symptoms, a 0.14 SD increase in emotional instability (neuroticism), and a 0.20 SD decrease in traits like organization and responsibility (conscientiousness).

These mental health and personality changes were not distributed evenly among the generations, most significant in those born between 1966 and 1986, the investigators reported.

For example, children between 1966 and 1970, the period when leaded gasoline use was at its peak, had BLLs > 5 μg/dL and experienced a 1.75 SD increase in internalizing symptoms and a 1.17 SD increase in ADHD symptoms.

 

Assess Lead Risk

The study had several limitations. Causality could not be established, and the accuracy of the estimates relied on findings from the researchers’ two previous key studies.

However, the investigators noted that these findings have been replicated across multiple cohorts and settings. Additionally, the results may not be fully generalizable to the entire US population, as one study was based in New Zealand and the other in urban Chicago.

Reuben cautioned that even though gasoline and new paint no longer contain lead, exposure is still possible.

“We saw this most acutely in Flint, Michigan,” when aging water pipes exposed more than 100,000 residents to high lead levels in 2014. “This situation made us aware that thousands of communities are exposed to lead service lines.”

He recommended that physicians consider screening patients for lead exposure — both new and old. Experts estimate that 90% of lead in the body is stored in the skeleton and can be released back into the bloodstream over time, particularly in cases of calcium deficiency, pregnancy, or osteoporosis.

While reversing childhood lead exposure is not possible, Reuben noted that healthy lifestyle choices and multimodal interventions such as medication and therapy can effectively address and alleviate mental illness.

 

‘Legacy of Lead’

In a comment, Terrie Moffitt, PhD, who was not involved in the research, said the study “is important because it gives us a crystal ball to see into the future of children living with lead today.”

“It’s called the ‘legacy of lead,’ and what a legacy,” said Moffitt, professor in the Department of Psychology and Neuroscience, Nannerl O. Keohane University at Duke University in Durham, North Carolina.

Moffitt emphasized that children exposed to lead today often live in areas of poverty and disadvantage, making it difficult to disentangle the potential effects of lead exposure from those of childhood adversity that predispose individuals to mental illness.

“This study tells us about lead’s damage in an era when it was everywhere, not just in poor communities,” she said.

The study was funded by a fellowship from the National Institute of Environmental Health Sciences. Reuben and Moffitt reported no relevant financial relationships.

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

For the first time since 2001, the American Psychiatric Association (APA) has updated its clinical practice guideline on borderline personality disorder (BPD).

The new guideline is “quite substantial and really serves as a rich textbook of the literature, about borderline personality disorder that any clinician would find very valuable,” John Oldham, MD, MS, member of the guideline writing group, said in an interview.

“The overall goal is to improve the quality of care and treatment outcomes for patients with BPD,” said Oldham, distinguished emeritus professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine in Houston, Texas. 

The updated guideline was published online in The American Journal of Psychiatry. 

It includes eight evidence-based recommendation statements covering assessment and determination of treatment plan, psychosocial interventions, and pharmacology. 

Recommendations denoted by the numeral 1 after the guideline statement indicates confidence that the benefits of the intervention clearly outweigh the harms. A suggestion (denoted by the numeral 2 after the guideline statement) indicates greater uncertainty. 

Each guideline statement also has an associated rating for the strength of supporting research evidence — high, moderate, and low, denoted by the letters A, B, and C, respectively.

The APA recommends (1C) that the initial assessment of a patient with possible BPD include the reason the individual is presenting for evaluation; the patient’s goals and preferences for treatment; a review of psychiatric symptoms, including core features of personality disorders and common co-occurring disorders; a psychiatric treatment history; assessment of physical health and psychosocial and cultural factors; a mental status examination; and an assessment of risk of suicide, self-injury, and aggressive behaviors, as outlined in APA Practice Guidelines for the Psychiatric Evaluation of Adults, Third Edition. 

The APA suggests (2C) that the initial psychiatric evaluation of a patient with BPD include a quantitative measure to identify and determine the severity of symptoms and impairments of functioning that may be a focus of treatment. 

The guideline lists several options, including (but not limited to) the 23-item version of the Borderline Symptom List; the Borderline Evaluation of Severity Over Time; 11-item Borderline Personality Features Scale for Children; and Difficulty in Emotional Regulation Scale.

The APA recommends (1C) that a patient with BPD have a documented, comprehensive, and person-centered treatment plan and be engaged in a collaborative discussion about their diagnosis and treatment, which includes psychoeducation related to the disorder. “This is a new recommendation,” Oldham said.

Another new recommendation (1B) advises a structured approach to psychotherapy that has support in the literature and targets the core features of the disorder. These include dialectical behavior therapy and mentalization-based therapy along with other therapies that have demonstrated efficacy in recent studies.

The APA recommends (1C) that a patient with BPD have a review of co-occurring disorders, prior psychotherapies, other nonpharmacological treatments, past medication trials, and current medications before initiating any new medication.

The APA suggests (2C) that that any psychotropic medication treatment of BPD be “time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.”

“Medication is not a primary treatment but may help diminish symptoms such as affective instability, impulsivity, or psychotic-like symptoms in individual patients, helping them to remain engaged in treatment or reducing short-term risks of self-harm,” said Oldham.

The APA recommends (1C) a review and reconciliation of medications at least every 6 months to assess the effectiveness of treatment and identify medications that warrant tapering or discontinuation.

 

An Alternative Model of Care

Oldham said it’s important to note that the Alternative DSM-5 Model for Personality Disorders (AMPD) is increasingly being integrated into clinical practice with adolescents and adults. 

Unlike the traditional categorical system, which diagnoses personality disorders as distinct and separate conditions, the AMPD views personality disorders along a continuum of severity and impairment. 

The AMPD recognizes the variability and overlap in personality disorder symptoms and provides a nuanced, individualized framework for assessment and treatment planning. 

Oldham co-chaired the work group that developed the proposal for the alternative model. 

“Despite the growing recognition of the importance of the alternative model, our systematic reviews did not identify treatment studies using the alternative model that met our inclusion criteria. Therefore, it is not included in the new guideline,” he said. 

Development of the guideline had no commercial funding. Oldham reported no conflicts of interest with his work on the guideline.

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

For the first time since 2001, the American Psychiatric Association (APA) has updated its clinical practice guideline on borderline personality disorder (BPD).

The new guideline is “quite substantial and really serves as a rich textbook of the literature, about borderline personality disorder that any clinician would find very valuable,” John Oldham, MD, MS, member of the guideline writing group, said in an interview.

“The overall goal is to improve the quality of care and treatment outcomes for patients with BPD,” said Oldham, distinguished emeritus professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine in Houston, Texas. 

The updated guideline was published online in The American Journal of Psychiatry. 

It includes eight evidence-based recommendation statements covering assessment and determination of treatment plan, psychosocial interventions, and pharmacology. 

Recommendations denoted by the numeral 1 after the guideline statement indicates confidence that the benefits of the intervention clearly outweigh the harms. A suggestion (denoted by the numeral 2 after the guideline statement) indicates greater uncertainty. 

Each guideline statement also has an associated rating for the strength of supporting research evidence — high, moderate, and low, denoted by the letters A, B, and C, respectively.

The APA recommends (1C) that the initial assessment of a patient with possible BPD include the reason the individual is presenting for evaluation; the patient’s goals and preferences for treatment; a review of psychiatric symptoms, including core features of personality disorders and common co-occurring disorders; a psychiatric treatment history; assessment of physical health and psychosocial and cultural factors; a mental status examination; and an assessment of risk of suicide, self-injury, and aggressive behaviors, as outlined in APA Practice Guidelines for the Psychiatric Evaluation of Adults, Third Edition. 

The APA suggests (2C) that the initial psychiatric evaluation of a patient with BPD include a quantitative measure to identify and determine the severity of symptoms and impairments of functioning that may be a focus of treatment. 

The guideline lists several options, including (but not limited to) the 23-item version of the Borderline Symptom List; the Borderline Evaluation of Severity Over Time; 11-item Borderline Personality Features Scale for Children; and Difficulty in Emotional Regulation Scale.

The APA recommends (1C) that a patient with BPD have a documented, comprehensive, and person-centered treatment plan and be engaged in a collaborative discussion about their diagnosis and treatment, which includes psychoeducation related to the disorder. “This is a new recommendation,” Oldham said.

Another new recommendation (1B) advises a structured approach to psychotherapy that has support in the literature and targets the core features of the disorder. These include dialectical behavior therapy and mentalization-based therapy along with other therapies that have demonstrated efficacy in recent studies.

The APA recommends (1C) that a patient with BPD have a review of co-occurring disorders, prior psychotherapies, other nonpharmacological treatments, past medication trials, and current medications before initiating any new medication.

The APA suggests (2C) that that any psychotropic medication treatment of BPD be “time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.”

“Medication is not a primary treatment but may help diminish symptoms such as affective instability, impulsivity, or psychotic-like symptoms in individual patients, helping them to remain engaged in treatment or reducing short-term risks of self-harm,” said Oldham.

The APA recommends (1C) a review and reconciliation of medications at least every 6 months to assess the effectiveness of treatment and identify medications that warrant tapering or discontinuation.

 

An Alternative Model of Care

Oldham said it’s important to note that the Alternative DSM-5 Model for Personality Disorders (AMPD) is increasingly being integrated into clinical practice with adolescents and adults. 

Unlike the traditional categorical system, which diagnoses personality disorders as distinct and separate conditions, the AMPD views personality disorders along a continuum of severity and impairment. 

The AMPD recognizes the variability and overlap in personality disorder symptoms and provides a nuanced, individualized framework for assessment and treatment planning. 

Oldham co-chaired the work group that developed the proposal for the alternative model. 

“Despite the growing recognition of the importance of the alternative model, our systematic reviews did not identify treatment studies using the alternative model that met our inclusion criteria. Therefore, it is not included in the new guideline,” he said. 

Development of the guideline had no commercial funding. Oldham reported no conflicts of interest with his work on the guideline.

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

For the first time since 2001, the American Psychiatric Association (APA) has updated its clinical practice guideline on borderline personality disorder (BPD).

The new guideline is “quite substantial and really serves as a rich textbook of the literature, about borderline personality disorder that any clinician would find very valuable,” John Oldham, MD, MS, member of the guideline writing group, said in an interview.

“The overall goal is to improve the quality of care and treatment outcomes for patients with BPD,” said Oldham, distinguished emeritus professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine in Houston, Texas. 

The updated guideline was published online in The American Journal of Psychiatry. 

It includes eight evidence-based recommendation statements covering assessment and determination of treatment plan, psychosocial interventions, and pharmacology. 

Recommendations denoted by the numeral 1 after the guideline statement indicates confidence that the benefits of the intervention clearly outweigh the harms. A suggestion (denoted by the numeral 2 after the guideline statement) indicates greater uncertainty. 

Each guideline statement also has an associated rating for the strength of supporting research evidence — high, moderate, and low, denoted by the letters A, B, and C, respectively.

The APA recommends (1C) that the initial assessment of a patient with possible BPD include the reason the individual is presenting for evaluation; the patient’s goals and preferences for treatment; a review of psychiatric symptoms, including core features of personality disorders and common co-occurring disorders; a psychiatric treatment history; assessment of physical health and psychosocial and cultural factors; a mental status examination; and an assessment of risk of suicide, self-injury, and aggressive behaviors, as outlined in APA Practice Guidelines for the Psychiatric Evaluation of Adults, Third Edition. 

The APA suggests (2C) that the initial psychiatric evaluation of a patient with BPD include a quantitative measure to identify and determine the severity of symptoms and impairments of functioning that may be a focus of treatment. 

The guideline lists several options, including (but not limited to) the 23-item version of the Borderline Symptom List; the Borderline Evaluation of Severity Over Time; 11-item Borderline Personality Features Scale for Children; and Difficulty in Emotional Regulation Scale.

The APA recommends (1C) that a patient with BPD have a documented, comprehensive, and person-centered treatment plan and be engaged in a collaborative discussion about their diagnosis and treatment, which includes psychoeducation related to the disorder. “This is a new recommendation,” Oldham said.

Another new recommendation (1B) advises a structured approach to psychotherapy that has support in the literature and targets the core features of the disorder. These include dialectical behavior therapy and mentalization-based therapy along with other therapies that have demonstrated efficacy in recent studies.

The APA recommends (1C) that a patient with BPD have a review of co-occurring disorders, prior psychotherapies, other nonpharmacological treatments, past medication trials, and current medications before initiating any new medication.

The APA suggests (2C) that that any psychotropic medication treatment of BPD be “time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.”

“Medication is not a primary treatment but may help diminish symptoms such as affective instability, impulsivity, or psychotic-like symptoms in individual patients, helping them to remain engaged in treatment or reducing short-term risks of self-harm,” said Oldham.

The APA recommends (1C) a review and reconciliation of medications at least every 6 months to assess the effectiveness of treatment and identify medications that warrant tapering or discontinuation.

 

An Alternative Model of Care

Oldham said it’s important to note that the Alternative DSM-5 Model for Personality Disorders (AMPD) is increasingly being integrated into clinical practice with adolescents and adults. 

Unlike the traditional categorical system, which diagnoses personality disorders as distinct and separate conditions, the AMPD views personality disorders along a continuum of severity and impairment. 

The AMPD recognizes the variability and overlap in personality disorder symptoms and provides a nuanced, individualized framework for assessment and treatment planning. 

Oldham co-chaired the work group that developed the proposal for the alternative model. 

“Despite the growing recognition of the importance of the alternative model, our systematic reviews did not identify treatment studies using the alternative model that met our inclusion criteria. Therefore, it is not included in the new guideline,” he said. 

Development of the guideline had no commercial funding. Oldham reported no conflicts of interest with his work on the guideline.

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

LOS ANGELES — The majority of women with epilepsy are inadequately educated about the potential risks associated with anti-seizure medications (ASMs), which include teratogenicity and a reduction in the efficacy of hormonal birth control, early results of a new survey suggested.

In addition, only about a third of survey respondents indicated that they were taking folic acid if pregnant or planning to be or using an effective contraceptive if they wanted to avoid pregnancy.

“Physicians should see it as inside their scope to ask about the family planning aspect of things because it’s relevant to their patients’ neurologic care,” first study author Tori Valachovic, a fourth-year medical student at the University of Rochester School of Medicine, New York, told this news organization.

She noted patients may be taking ASMs not just for seizures but potentially to manage migraines or a mood disorder.

The findings were presented on December 8 at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Unique Survey

Research shows that about half of pregnancies in the United States are unplanned, and the number is even higher among people with epilepsy, said senior author Sarah Betstadt, MD, associate professor of obstetrics and gynecology, University of Rochester. That may be because women aren’t appropriately counseled about ASMs, possibly reducing the effectiveness of their hormonal birth control, she said.

The American Academy of Neurology recommends women with seizure disorders who could become pregnant receive yearly counseling about reproductive health, including ASM teratogenicity and interactions with hormonal contraceptive medications.

The study included 107 women aged 18-49 years at two general neurology outpatient clinics who were taking an ASM and completed a survey between July 2023 and May 2024. Of these, six were pregnant or planning to become pregnant, and 69 were using a barrier, hormonal, or implant form of contraception.

Researchers collected medical histories for each respondent, including how long they had had a seizure disorder, how often they experienced seizures, what anti-seizure drugs they were taking, the type of birth control they used, their pregnancy intentions, and whether they were taking folic acid.

The survey was unique in that questions were personalized. Previous surveys have asked general questions, but for the current survey, patients were required to input their specific ASM and specific birth control, so it was also a test of their knowledge of their specific medications, said Valachovic.

When responding to questions about the safety of their ASMs for pregnancy or whether there were interactions between ASMs and birth control, about two thirds (67.3%) of the participants answered at least one question incorrectly.

The study found 36.2% of those using a barrier, hormonal, or implant contraceptive answered at least one question incorrectly regarding whether their ASM decreased birth control effectiveness.

ASMs such as carbamazepine, phenytoin, phenobarbital, higher doses of topiramate (over 200 mg daily), and oxcarbazepine can make hormonal contraceptives such as pills, patches, and rings less effective, noted Valachovic.

There’s also a bidirectional relationship at play, she added. Hormonal contraceptives can make ASMs such as lamotrigine, valproate, zonisamide, and rufinamide less effective because they decrease the levels of the ASMs.

For questions specifically about the teratogenicity of their medications, about 56.1% of participants did not answer correctly.

ASMs that increase the risk for birth defects include valproic acid (a drug that would be at the top of the list), topiramate, carbamazepine, phenobarbital, and phenytoin, said Valachovic.

However, she added, “It’s a little bit more nuanced” than simply saying, “Don’t take this medication during pregnancy” because the first aim is to control seizures. “Uncontrolled seizures are more dangerous for the fetus and the expectant mother than any ASM,” she explained.

Neurologists and reproductive healthcare providers should work together to better disseminate relevant information to their female patients who could become pregnant, said Betstadt. “We need to have better ways to collaborate. And I think we have to start with educating neurologists,” who care for these women throughout their journey with epilepsy and who during that time may become pregnant.

They “should be talking to their patients annually about whether they plan to be pregnant,” so they can educate them and make them aware of dangers to the fetus with certain medications and the effect of ASMs on birth control, added Betstadt, whose practice focuses on complex family planning.

“Our hope is that patients will have better care that’s in line with their reproductive goals,” she said.

 

No Trickle-Down Effect

Commenting for this news organization, Alison M. Pack, MD, professor of neurology and Epilepsy Division Chief, Columbia University, New York City, said the study underlines an important quandary: Despite guidelines on risks of combining ASMs and hormonal birth control, this information doesn’t seem to be “trickling down” to women with epilepsy.

“I think part of it is just the state of healthcare delivery these days,” where clinicians are expected to accomplish more and more within a 20-30–minute follow-up visit. It’s tough, too, to keep up with all the potential drug interactions involved with newer ASMs, she said.

“I also think it speaks to the complexity” of healthcare for young women with epilepsy, which involves not just neurologists but obstetricians, gynecologists, and primary care doctors, she added.

Pack doesn’t think epilepsy specialists “integrate” enough with these other specialties. “You need to communicate with the gynecologist; you need to open that line of communication.”

She believes advanced practice providers could play a role in reducing the complexity of treating young women with epilepsy by regularly reviewing how patients are adhering to recommended protocols.

But she pointed out that “in the overall picture, most women with epilepsy do have normal, healthy pregnancies.”

The investigators and Pack reported no relevant conflicts of interest.

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

LOS ANGELES — The majority of women with epilepsy are inadequately educated about the potential risks associated with anti-seizure medications (ASMs), which include teratogenicity and a reduction in the efficacy of hormonal birth control, early results of a new survey suggested.

In addition, only about a third of survey respondents indicated that they were taking folic acid if pregnant or planning to be or using an effective contraceptive if they wanted to avoid pregnancy.

“Physicians should see it as inside their scope to ask about the family planning aspect of things because it’s relevant to their patients’ neurologic care,” first study author Tori Valachovic, a fourth-year medical student at the University of Rochester School of Medicine, New York, told this news organization.

She noted patients may be taking ASMs not just for seizures but potentially to manage migraines or a mood disorder.

The findings were presented on December 8 at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Unique Survey

Research shows that about half of pregnancies in the United States are unplanned, and the number is even higher among people with epilepsy, said senior author Sarah Betstadt, MD, associate professor of obstetrics and gynecology, University of Rochester. That may be because women aren’t appropriately counseled about ASMs, possibly reducing the effectiveness of their hormonal birth control, she said.

The American Academy of Neurology recommends women with seizure disorders who could become pregnant receive yearly counseling about reproductive health, including ASM teratogenicity and interactions with hormonal contraceptive medications.

The study included 107 women aged 18-49 years at two general neurology outpatient clinics who were taking an ASM and completed a survey between July 2023 and May 2024. Of these, six were pregnant or planning to become pregnant, and 69 were using a barrier, hormonal, or implant form of contraception.

Researchers collected medical histories for each respondent, including how long they had had a seizure disorder, how often they experienced seizures, what anti-seizure drugs they were taking, the type of birth control they used, their pregnancy intentions, and whether they were taking folic acid.

The survey was unique in that questions were personalized. Previous surveys have asked general questions, but for the current survey, patients were required to input their specific ASM and specific birth control, so it was also a test of their knowledge of their specific medications, said Valachovic.

When responding to questions about the safety of their ASMs for pregnancy or whether there were interactions between ASMs and birth control, about two thirds (67.3%) of the participants answered at least one question incorrectly.

The study found 36.2% of those using a barrier, hormonal, or implant contraceptive answered at least one question incorrectly regarding whether their ASM decreased birth control effectiveness.

ASMs such as carbamazepine, phenytoin, phenobarbital, higher doses of topiramate (over 200 mg daily), and oxcarbazepine can make hormonal contraceptives such as pills, patches, and rings less effective, noted Valachovic.

There’s also a bidirectional relationship at play, she added. Hormonal contraceptives can make ASMs such as lamotrigine, valproate, zonisamide, and rufinamide less effective because they decrease the levels of the ASMs.

For questions specifically about the teratogenicity of their medications, about 56.1% of participants did not answer correctly.

ASMs that increase the risk for birth defects include valproic acid (a drug that would be at the top of the list), topiramate, carbamazepine, phenobarbital, and phenytoin, said Valachovic.

However, she added, “It’s a little bit more nuanced” than simply saying, “Don’t take this medication during pregnancy” because the first aim is to control seizures. “Uncontrolled seizures are more dangerous for the fetus and the expectant mother than any ASM,” she explained.

Neurologists and reproductive healthcare providers should work together to better disseminate relevant information to their female patients who could become pregnant, said Betstadt. “We need to have better ways to collaborate. And I think we have to start with educating neurologists,” who care for these women throughout their journey with epilepsy and who during that time may become pregnant.

They “should be talking to their patients annually about whether they plan to be pregnant,” so they can educate them and make them aware of dangers to the fetus with certain medications and the effect of ASMs on birth control, added Betstadt, whose practice focuses on complex family planning.

“Our hope is that patients will have better care that’s in line with their reproductive goals,” she said.

 

No Trickle-Down Effect

Commenting for this news organization, Alison M. Pack, MD, professor of neurology and Epilepsy Division Chief, Columbia University, New York City, said the study underlines an important quandary: Despite guidelines on risks of combining ASMs and hormonal birth control, this information doesn’t seem to be “trickling down” to women with epilepsy.

“I think part of it is just the state of healthcare delivery these days,” where clinicians are expected to accomplish more and more within a 20-30–minute follow-up visit. It’s tough, too, to keep up with all the potential drug interactions involved with newer ASMs, she said.

“I also think it speaks to the complexity” of healthcare for young women with epilepsy, which involves not just neurologists but obstetricians, gynecologists, and primary care doctors, she added.

Pack doesn’t think epilepsy specialists “integrate” enough with these other specialties. “You need to communicate with the gynecologist; you need to open that line of communication.”

She believes advanced practice providers could play a role in reducing the complexity of treating young women with epilepsy by regularly reviewing how patients are adhering to recommended protocols.

But she pointed out that “in the overall picture, most women with epilepsy do have normal, healthy pregnancies.”

The investigators and Pack reported no relevant conflicts of interest.

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

LOS ANGELES — The majority of women with epilepsy are inadequately educated about the potential risks associated with anti-seizure medications (ASMs), which include teratogenicity and a reduction in the efficacy of hormonal birth control, early results of a new survey suggested.

In addition, only about a third of survey respondents indicated that they were taking folic acid if pregnant or planning to be or using an effective contraceptive if they wanted to avoid pregnancy.

“Physicians should see it as inside their scope to ask about the family planning aspect of things because it’s relevant to their patients’ neurologic care,” first study author Tori Valachovic, a fourth-year medical student at the University of Rochester School of Medicine, New York, told this news organization.

She noted patients may be taking ASMs not just for seizures but potentially to manage migraines or a mood disorder.

The findings were presented on December 8 at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Unique Survey

Research shows that about half of pregnancies in the United States are unplanned, and the number is even higher among people with epilepsy, said senior author Sarah Betstadt, MD, associate professor of obstetrics and gynecology, University of Rochester. That may be because women aren’t appropriately counseled about ASMs, possibly reducing the effectiveness of their hormonal birth control, she said.

The American Academy of Neurology recommends women with seizure disorders who could become pregnant receive yearly counseling about reproductive health, including ASM teratogenicity and interactions with hormonal contraceptive medications.

The study included 107 women aged 18-49 years at two general neurology outpatient clinics who were taking an ASM and completed a survey between July 2023 and May 2024. Of these, six were pregnant or planning to become pregnant, and 69 were using a barrier, hormonal, or implant form of contraception.

Researchers collected medical histories for each respondent, including how long they had had a seizure disorder, how often they experienced seizures, what anti-seizure drugs they were taking, the type of birth control they used, their pregnancy intentions, and whether they were taking folic acid.

The survey was unique in that questions were personalized. Previous surveys have asked general questions, but for the current survey, patients were required to input their specific ASM and specific birth control, so it was also a test of their knowledge of their specific medications, said Valachovic.

When responding to questions about the safety of their ASMs for pregnancy or whether there were interactions between ASMs and birth control, about two thirds (67.3%) of the participants answered at least one question incorrectly.

The study found 36.2% of those using a barrier, hormonal, or implant contraceptive answered at least one question incorrectly regarding whether their ASM decreased birth control effectiveness.

ASMs such as carbamazepine, phenytoin, phenobarbital, higher doses of topiramate (over 200 mg daily), and oxcarbazepine can make hormonal contraceptives such as pills, patches, and rings less effective, noted Valachovic.

There’s also a bidirectional relationship at play, she added. Hormonal contraceptives can make ASMs such as lamotrigine, valproate, zonisamide, and rufinamide less effective because they decrease the levels of the ASMs.

For questions specifically about the teratogenicity of their medications, about 56.1% of participants did not answer correctly.

ASMs that increase the risk for birth defects include valproic acid (a drug that would be at the top of the list), topiramate, carbamazepine, phenobarbital, and phenytoin, said Valachovic.

However, she added, “It’s a little bit more nuanced” than simply saying, “Don’t take this medication during pregnancy” because the first aim is to control seizures. “Uncontrolled seizures are more dangerous for the fetus and the expectant mother than any ASM,” she explained.

Neurologists and reproductive healthcare providers should work together to better disseminate relevant information to their female patients who could become pregnant, said Betstadt. “We need to have better ways to collaborate. And I think we have to start with educating neurologists,” who care for these women throughout their journey with epilepsy and who during that time may become pregnant.

They “should be talking to their patients annually about whether they plan to be pregnant,” so they can educate them and make them aware of dangers to the fetus with certain medications and the effect of ASMs on birth control, added Betstadt, whose practice focuses on complex family planning.

“Our hope is that patients will have better care that’s in line with their reproductive goals,” she said.

 

No Trickle-Down Effect

Commenting for this news organization, Alison M. Pack, MD, professor of neurology and Epilepsy Division Chief, Columbia University, New York City, said the study underlines an important quandary: Despite guidelines on risks of combining ASMs and hormonal birth control, this information doesn’t seem to be “trickling down” to women with epilepsy.

“I think part of it is just the state of healthcare delivery these days,” where clinicians are expected to accomplish more and more within a 20-30–minute follow-up visit. It’s tough, too, to keep up with all the potential drug interactions involved with newer ASMs, she said.

“I also think it speaks to the complexity” of healthcare for young women with epilepsy, which involves not just neurologists but obstetricians, gynecologists, and primary care doctors, she added.

Pack doesn’t think epilepsy specialists “integrate” enough with these other specialties. “You need to communicate with the gynecologist; you need to open that line of communication.”

She believes advanced practice providers could play a role in reducing the complexity of treating young women with epilepsy by regularly reviewing how patients are adhering to recommended protocols.

But she pointed out that “in the overall picture, most women with epilepsy do have normal, healthy pregnancies.”

The investigators and Pack reported no relevant conflicts of interest.

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