From the Journals

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Peter Doshi, PhD, senior editor at The BMJ, obtained primary records for the trial and unpublished data through a Freedom of Information Act request, and has detailed inconsistencies and omissions in data reporting from the 2009 trial originally published in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.

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.

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.

TOPLINE:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

• Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
• To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
• Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
• Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

• Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
• Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
• Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
• Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

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:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

• Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
• To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
• Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
• Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

• Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
• Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
• Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
• Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

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:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

• Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
• To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
• Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
• Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

• Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
• Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
• Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
• Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

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.

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

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

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

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

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

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

TOPLINE:

The beneficial effect of clopidogrel monotherapy over aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) and remained event free for 6-18 months on dual antiplatelet therapy (DAPT) is consistent, regardless of bleeding risk or PCI complexity, according to a post hoc analysis of the HOST-EXAM trial.

METHODOLOGY:

• The HOST-EXAM Extended study conducted across 37 sites in South Korea included patients who underwent PCI with drug-eluting stents and remained free of clinical events for 6-18 months post-PCI, while receiving DAPT.
• This post hoc analysis of the HOST-EXAM Extended study compared the effectiveness of long-term daily clopidogrel (75 mg) with that of aspirin monotherapy (100 mg) after PCI, according to bleeding risk and procedural complexity in 3974 patients (mean age, 63 years; 75% men) who were followed for up to 5.9 years.
• High bleeding risk was reported in 866 patients, and 849 patients underwent complex PCI.
• Patients were classified into four distinct risk groups: No bleeding risk and noncomplex PCI, no bleeding risk and complex PCI, high bleeding risk and noncomplex PCI, and high bleeding risk and complex PCI.
• The co-primary endpoints were thrombotic composite events (cardiovascular death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and definite/probable stent thrombosis) and any bleeding event.

TAKEAWAY:

• Thrombotic composite events (hazard ratio [HR], 2.15; P < .001) and any bleeding event (HR, 3.64; P < .001) were more frequent in patients with a high bleeding risk than in those without.
• However, there was no difference in the risk for thrombotic composite events or any bleeding event by PCI complexity.
• The long-term benefits of clopidogrel monotherapy over aspirin monotherapy were seen in all patients, regardless of bleeding risks (P for interaction = .38 for thrombotic composite events and P for interaction = .20 for any bleeding event) or PCI complexity (P for interaction = .12 for thrombotic composite events and P for interaction = .62 for any bleeding event).
• The greatest risk reduction in thrombotic composite events with clopidogrel monotherapy occurred in patients with a high bleeding risk who underwent complex PCI (HR, 0.46; P = .03).

IN PRACTICE:

“[In this study], no significant interaction was found between treatment arms and risk groups, denoting that the beneficial impact of clopidogrel monotherapy was consistent regardless of HBR [high bleeding risk] or PCI complexity,” the authors wrote.

SOURCE:

This study was led by Jeehoon Kang, MD, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. It was published online on November 27, 2024, in JAMA Cardiology.

LIMITATIONS:

As this study is a post hoc analysis, the findings should be considered primarily hypothesis generating. This study was conducted exclusively in an East Asian population and may not be generalizable to other ethnic groups. The definitions of high bleeding risk and complex PCI used in this analysis were not prespecified in the study protocol of the HOST-EXAM trial. Certain criteria defining high bleeding risk were not analyzed as they fell under the exclusion criteria of the HOST-EXAM trial or were not recorded in the study case report form.

DISCLOSURES:

This study was supported by grants from the Patient-Centered Clinical Research Coordinating Center and Seoul National University Hospital. One author reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.

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:

The beneficial effect of clopidogrel monotherapy over aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) and remained event free for 6-18 months on dual antiplatelet therapy (DAPT) is consistent, regardless of bleeding risk or PCI complexity, according to a post hoc analysis of the HOST-EXAM trial.

METHODOLOGY:

• The HOST-EXAM Extended study conducted across 37 sites in South Korea included patients who underwent PCI with drug-eluting stents and remained free of clinical events for 6-18 months post-PCI, while receiving DAPT.
• This post hoc analysis of the HOST-EXAM Extended study compared the effectiveness of long-term daily clopidogrel (75 mg) with that of aspirin monotherapy (100 mg) after PCI, according to bleeding risk and procedural complexity in 3974 patients (mean age, 63 years; 75% men) who were followed for up to 5.9 years.
• High bleeding risk was reported in 866 patients, and 849 patients underwent complex PCI.
• Patients were classified into four distinct risk groups: No bleeding risk and noncomplex PCI, no bleeding risk and complex PCI, high bleeding risk and noncomplex PCI, and high bleeding risk and complex PCI.
• The co-primary endpoints were thrombotic composite events (cardiovascular death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and definite/probable stent thrombosis) and any bleeding event.

TAKEAWAY:

• Thrombotic composite events (hazard ratio [HR], 2.15; P < .001) and any bleeding event (HR, 3.64; P < .001) were more frequent in patients with a high bleeding risk than in those without.
• However, there was no difference in the risk for thrombotic composite events or any bleeding event by PCI complexity.
• The long-term benefits of clopidogrel monotherapy over aspirin monotherapy were seen in all patients, regardless of bleeding risks (P for interaction = .38 for thrombotic composite events and P for interaction = .20 for any bleeding event) or PCI complexity (P for interaction = .12 for thrombotic composite events and P for interaction = .62 for any bleeding event).
• The greatest risk reduction in thrombotic composite events with clopidogrel monotherapy occurred in patients with a high bleeding risk who underwent complex PCI (HR, 0.46; P = .03).

IN PRACTICE:

“[In this study], no significant interaction was found between treatment arms and risk groups, denoting that the beneficial impact of clopidogrel monotherapy was consistent regardless of HBR [high bleeding risk] or PCI complexity,” the authors wrote.

SOURCE:

This study was led by Jeehoon Kang, MD, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. It was published online on November 27, 2024, in JAMA Cardiology.

LIMITATIONS:

As this study is a post hoc analysis, the findings should be considered primarily hypothesis generating. This study was conducted exclusively in an East Asian population and may not be generalizable to other ethnic groups. The definitions of high bleeding risk and complex PCI used in this analysis were not prespecified in the study protocol of the HOST-EXAM trial. Certain criteria defining high bleeding risk were not analyzed as they fell under the exclusion criteria of the HOST-EXAM trial or were not recorded in the study case report form.

DISCLOSURES:

This study was supported by grants from the Patient-Centered Clinical Research Coordinating Center and Seoul National University Hospital. One author reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.

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:

The beneficial effect of clopidogrel monotherapy over aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) and remained event free for 6-18 months on dual antiplatelet therapy (DAPT) is consistent, regardless of bleeding risk or PCI complexity, according to a post hoc analysis of the HOST-EXAM trial.

METHODOLOGY:

• The HOST-EXAM Extended study conducted across 37 sites in South Korea included patients who underwent PCI with drug-eluting stents and remained free of clinical events for 6-18 months post-PCI, while receiving DAPT.
• This post hoc analysis of the HOST-EXAM Extended study compared the effectiveness of long-term daily clopidogrel (75 mg) with that of aspirin monotherapy (100 mg) after PCI, according to bleeding risk and procedural complexity in 3974 patients (mean age, 63 years; 75% men) who were followed for up to 5.9 years.
• High bleeding risk was reported in 866 patients, and 849 patients underwent complex PCI.
• Patients were classified into four distinct risk groups: No bleeding risk and noncomplex PCI, no bleeding risk and complex PCI, high bleeding risk and noncomplex PCI, and high bleeding risk and complex PCI.
• The co-primary endpoints were thrombotic composite events (cardiovascular death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and definite/probable stent thrombosis) and any bleeding event.

TAKEAWAY:

• Thrombotic composite events (hazard ratio [HR], 2.15; P < .001) and any bleeding event (HR, 3.64; P < .001) were more frequent in patients with a high bleeding risk than in those without.
• However, there was no difference in the risk for thrombotic composite events or any bleeding event by PCI complexity.
• The long-term benefits of clopidogrel monotherapy over aspirin monotherapy were seen in all patients, regardless of bleeding risks (P for interaction = .38 for thrombotic composite events and P for interaction = .20 for any bleeding event) or PCI complexity (P for interaction = .12 for thrombotic composite events and P for interaction = .62 for any bleeding event).
• The greatest risk reduction in thrombotic composite events with clopidogrel monotherapy occurred in patients with a high bleeding risk who underwent complex PCI (HR, 0.46; P = .03).

IN PRACTICE:

“[In this study], no significant interaction was found between treatment arms and risk groups, denoting that the beneficial impact of clopidogrel monotherapy was consistent regardless of HBR [high bleeding risk] or PCI complexity,” the authors wrote.

SOURCE:

This study was led by Jeehoon Kang, MD, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. It was published online on November 27, 2024, in JAMA Cardiology.

LIMITATIONS:

As this study is a post hoc analysis, the findings should be considered primarily hypothesis generating. This study was conducted exclusively in an East Asian population and may not be generalizable to other ethnic groups. The definitions of high bleeding risk and complex PCI used in this analysis were not prespecified in the study protocol of the HOST-EXAM trial. Certain criteria defining high bleeding risk were not analyzed as they fell under the exclusion criteria of the HOST-EXAM trial or were not recorded in the study case report form.

DISCLOSURES:

This study was supported by grants from the Patient-Centered Clinical Research Coordinating Center and Seoul National University Hospital. One author reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.

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:

Patients receiving > 200 mL/kg of fluid resuscitation for burn injuries show higher rates of worsening neurologic findings on imaging, with follow-up scans showing deterioration in high-volume recipients compared with low-volume recipients.

METHODOLOGY:

• Researchers conducted a single-center review of 5176 patients with burn injuries who were admitted to a verified American Burn Association center (2003-2017); 622 of them underwent head CT within 96 hours of admission, and 83 showed intracranial abnormalities.
• Of 42 patients (mean age, 49.7 years; 80.5% men) who were admitted within 24 hours of burn, 30 patients received < 200 mL/kg and 11 received > 200 mL/kg of total resuscitation fluids, with a median total body surface area (TBSA) of 20.0.
• The primary outcome assessed was the worsening of neurologic findings on imaging related to the volume of the resuscitation fluid administered; the secondary outcomes were the incidence of new or worsening intracranial abnormalities, including hemorrhage, edema, ischemia, or infarction.

TAKEAWAY:

• Neurologic findings worsened in 47.6% patients receiving < 200 mL/kg of fluid resuscitation and 85.7% of those receiving > 200 mL/kg (P =.064).
• Repeat imaging was performed in 21 (70.0%) patients receiving < 200 mL/kg and 7 (63.6%) patients receiving > 200 mL/kg of resuscitation who underwent follow-up imaging.
• The median TBSA was 16.5 in the < 200 mL/kg group and 53.2 in the > 200 mL/kg group (P <.001).
• Intracranial abnormalities were found in 31.3% patients with hemorrhage, 18.8% with worsening edema, and 43.8% with ischemia or infarction.

IN PRACTICE:

“Patients who received over 200 mL/kg of resuscitation had an increased progression of intracranial abnormalities when compared with patients receiving less volume resuscitation,” the authors wrote. “Neurologic changes prompting imaging in burn patients may be undetectable, and our study further highlights the need for routine evaluation with neurologic imaging when undergoing large-volume resuscitations.”

SOURCE:

The study was led by Connor L. Kenney, MD, Brooke Army Medical Center, San Antonio, and was published online on November 07, 2024, in the Journal of Surgical Research.

LIMITATIONS:

Study limitations included a small patient sample and unclear guidelines for obtaining head CT scans, making it difficult to distinguish between trauma-related brain changes and disease progression. Additionally, the study lacked data on hypotensive episodes and long-term neurologic outcomes.

DISCLOSURES:

This study did not receive any specific funding. The authors declared no conflicts of interest.

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:

Patients receiving > 200 mL/kg of fluid resuscitation for burn injuries show higher rates of worsening neurologic findings on imaging, with follow-up scans showing deterioration in high-volume recipients compared with low-volume recipients.

METHODOLOGY:

• Researchers conducted a single-center review of 5176 patients with burn injuries who were admitted to a verified American Burn Association center (2003-2017); 622 of them underwent head CT within 96 hours of admission, and 83 showed intracranial abnormalities.
• Of 42 patients (mean age, 49.7 years; 80.5% men) who were admitted within 24 hours of burn, 30 patients received < 200 mL/kg and 11 received > 200 mL/kg of total resuscitation fluids, with a median total body surface area (TBSA) of 20.0.
• The primary outcome assessed was the worsening of neurologic findings on imaging related to the volume of the resuscitation fluid administered; the secondary outcomes were the incidence of new or worsening intracranial abnormalities, including hemorrhage, edema, ischemia, or infarction.

TAKEAWAY:

• Neurologic findings worsened in 47.6% patients receiving < 200 mL/kg of fluid resuscitation and 85.7% of those receiving > 200 mL/kg (P =.064).
• Repeat imaging was performed in 21 (70.0%) patients receiving < 200 mL/kg and 7 (63.6%) patients receiving > 200 mL/kg of resuscitation who underwent follow-up imaging.
• The median TBSA was 16.5 in the < 200 mL/kg group and 53.2 in the > 200 mL/kg group (P <.001).
• Intracranial abnormalities were found in 31.3% patients with hemorrhage, 18.8% with worsening edema, and 43.8% with ischemia or infarction.

IN PRACTICE:

“Patients who received over 200 mL/kg of resuscitation had an increased progression of intracranial abnormalities when compared with patients receiving less volume resuscitation,” the authors wrote. “Neurologic changes prompting imaging in burn patients may be undetectable, and our study further highlights the need for routine evaluation with neurologic imaging when undergoing large-volume resuscitations.”

SOURCE:

The study was led by Connor L. Kenney, MD, Brooke Army Medical Center, San Antonio, and was published online on November 07, 2024, in the Journal of Surgical Research.

LIMITATIONS:

Study limitations included a small patient sample and unclear guidelines for obtaining head CT scans, making it difficult to distinguish between trauma-related brain changes and disease progression. Additionally, the study lacked data on hypotensive episodes and long-term neurologic outcomes.

DISCLOSURES:

This study did not receive any specific funding. The authors declared no conflicts of interest.

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:

Patients receiving > 200 mL/kg of fluid resuscitation for burn injuries show higher rates of worsening neurologic findings on imaging, with follow-up scans showing deterioration in high-volume recipients compared with low-volume recipients.

METHODOLOGY:

• Researchers conducted a single-center review of 5176 patients with burn injuries who were admitted to a verified American Burn Association center (2003-2017); 622 of them underwent head CT within 96 hours of admission, and 83 showed intracranial abnormalities.
• Of 42 patients (mean age, 49.7 years; 80.5% men) who were admitted within 24 hours of burn, 30 patients received < 200 mL/kg and 11 received > 200 mL/kg of total resuscitation fluids, with a median total body surface area (TBSA) of 20.0.
• The primary outcome assessed was the worsening of neurologic findings on imaging related to the volume of the resuscitation fluid administered; the secondary outcomes were the incidence of new or worsening intracranial abnormalities, including hemorrhage, edema, ischemia, or infarction.

TAKEAWAY:

• Neurologic findings worsened in 47.6% patients receiving < 200 mL/kg of fluid resuscitation and 85.7% of those receiving > 200 mL/kg (P =.064).
• Repeat imaging was performed in 21 (70.0%) patients receiving < 200 mL/kg and 7 (63.6%) patients receiving > 200 mL/kg of resuscitation who underwent follow-up imaging.
• The median TBSA was 16.5 in the < 200 mL/kg group and 53.2 in the > 200 mL/kg group (P <.001).
• Intracranial abnormalities were found in 31.3% patients with hemorrhage, 18.8% with worsening edema, and 43.8% with ischemia or infarction.

IN PRACTICE:

“Patients who received over 200 mL/kg of resuscitation had an increased progression of intracranial abnormalities when compared with patients receiving less volume resuscitation,” the authors wrote. “Neurologic changes prompting imaging in burn patients may be undetectable, and our study further highlights the need for routine evaluation with neurologic imaging when undergoing large-volume resuscitations.”

SOURCE:

The study was led by Connor L. Kenney, MD, Brooke Army Medical Center, San Antonio, and was published online on November 07, 2024, in the Journal of Surgical Research.

LIMITATIONS:

Study limitations included a small patient sample and unclear guidelines for obtaining head CT scans, making it difficult to distinguish between trauma-related brain changes and disease progression. Additionally, the study lacked data on hypotensive episodes and long-term neurologic outcomes.

DISCLOSURES:

This study did not receive any specific funding. The authors declared no conflicts of interest.

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.