VENICE, ITALY — Obesity as defined by adiposity measures corresponds to a lower body mass index (BMI) cutoff (≥ 27) in men and women of middle age or older than does the widely used conventional obesity threshold of ≥ 30, shows a study performed in Italy.

Presenting at this year’s European Congress on Obesity (ECO), researchers from the University of Rome Tor Vergata and University of Modena and Reggio Emilia, Italy, and Beirut Arab University, Lebanon, conducted the study to compare the validity of the traditional World Health Organization (WHO) BMI threshold for obesity classification (≥ 30) vs adiposity levels as an alternative measure in middle-aged and older Italians. 

Marwan El Ghoch, PhD, a professor in the Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, presented the findings as a poster (GC4.152). “If you classify obesity with only BMI and without consideration of body composition, then this will not be enough. I believe BMI can be considered as a screening starting point, but we need to understand the body composition of fat and muscle too,” he said.

“We recommend this new cutoff point be applied in clinical settings when screening individuals for obesity in Italy,” El Ghoch asserted.

BMI Limitations Misses Body Composition 

If obesity is a chronic disease defined as excessive accumulation of body fat and leading to increased risk for disease, disability, and mortality, then “the identification of obesity based on body fat measurements is the most reliable method,” but he acknowledged that measuring this is not readily available in most clinical settings, and as such, “simple BMI has a place,” Dr. El Ghoch said.

“Use of BMI has its limitations, for example, it does not distinguish between body composition compartments — so between muscle and fat mass, nor does it detect changes across the lifespan of an individual [for example, the shift to more fat and less muscle with age] and it varies by ethnicity,” he pointed out. 

This led El Ghoch to ask whether using BMI as a threshold for obesity was suitable for all age groups. 

The researchers included 4800 participants of mixed gender aged 40-80 years of age. Based on the WHO’s BMI classification, 1087 people had normal body weight, 1826 had overweight, and 1887 had obesity. The participants were then categorized by adiposity status on the basis of the total body fat percentage as measured by dual-energy x-ray absorptiometry (DXA), and obesity was predicted by statistical analysis.

The analysis found that around 38% of men and 41% of women had a BMI ≥ 30 based on conventional BMI criteria, indicating obesity. However, when assessed according to body fat percentage, around 71% of the men and 64% of the women were determined to have obesity. 

Dr. El Ghoch and his colleagues calculated that a lower BMI cutoff of around 27 for obesity in people older than 40 years may be more appropriate than the existing BMI threshold of 30. 

The researchers noted some limitations of their work, including that it was a single-center, cross-sectional observational study conducted in one area of Italy. In addition, they did not account for possible confounders, such as dietary habits, and physical activity patterns, and sleep health, all of which can increase the likelihood of obesity and may interact with age-related differences. 

Missing a Significant Proportion of the Population at Risk for Obesity-Related Diseases

In an interview, Luca Busetto, MD, obesity specialist and research assistant at the Center for the Study and the Integrated Treatment of the Obesity, University of Padova, Italy, and local ECO president, commented on the study and the issue of BMI as a measure and threshold. “I think the problem we face with a classic cutoff using BMI is that we miss a significant group of people who have BMI less than 30 but have a high fat mass,” he said, adding, “but these people have the same risk of developing chronic diseases as those people with higher BMI. If they have a bad fat distribution, then their risk of complications is even higher. 

“Dr El Ghoch’s study underlines the lack of treatment for this significant part of the population,” he remarked. “We also need to use waist circumference and waist-to-height [ratio] as additional measures in this population.” 

Dr. Busetto also presented a population-based study at ECO that included over 400,000 people with a follow-up of 8 years. “We found the risk of developing obesity complications, including type 2 diabetes, hypertension, osteoarthritis, and cardiovascular disease, is not only dependent on BMI but [also] dependent on your waist-to-height ratio,” he said, highlighting that “some of these complications are only predicted by the waist-to-height ratio and not by your BMI — in particular cardiovascular diseases.

“I honestly think any screening process today needs to include both BMI and waist-to-height ratio. Having a DXA scan is great in a specialist setting, but routinely we need a measure that is valid in every office in every country and small town.”

Francesco Rubino, MD, chair of metabolic and bariatric surgery at King›s College London, United Kingdom, also remarked that understanding the changes in fat and lean mass proportions and distribution in middle years will affect health in later life, and importantly from a clinical perspective, it is a time where there is still some opportunity to intervene. 

Reflecting further on how it underscores the limitations of BMI in misclassifying people as having obesity or not, Rubino asked, “Importantly, does this make a difference to health and longevity? Really, we need an active measure of adiposity first, and then even if we do say someone has obesity — so excess adiposity — then does this translate into illness, because [excess adiposity] does not translate into disease for every individual?

“Any measure we use as a diagnostic criterion needs to reflect the ongoing disease in an individual, not only the risk of future disease — because not every person experiences this. As a doctor, we deal with the individual and how the diagnosis of disease relates to the individual in a clinic now, as well as the risk of tomorrow,” he concluded. 

Dr. El Ghoch declares no conflicts of interest. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, MetaDeq, GHP Scientific, and ViBo Health for no remuneration. Dr. Busetto discloses relationships with Burno Farmaceutici, Novo Nordisk, PronoKal, Rhythm, and Therascience. 

A version of this article appeared on Medscape.com.

VENICE, ITALY — Obesity as defined by adiposity measures corresponds to a lower body mass index (BMI) cutoff (≥ 27) in men and women of middle age or older than does the widely used conventional obesity threshold of ≥ 30, shows a study performed in Italy.

Presenting at this year’s European Congress on Obesity (ECO), researchers from the University of Rome Tor Vergata and University of Modena and Reggio Emilia, Italy, and Beirut Arab University, Lebanon, conducted the study to compare the validity of the traditional World Health Organization (WHO) BMI threshold for obesity classification (≥ 30) vs adiposity levels as an alternative measure in middle-aged and older Italians. 

Marwan El Ghoch, PhD, a professor in the Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, presented the findings as a poster (GC4.152). “If you classify obesity with only BMI and without consideration of body composition, then this will not be enough. I believe BMI can be considered as a screening starting point, but we need to understand the body composition of fat and muscle too,” he said.

“We recommend this new cutoff point be applied in clinical settings when screening individuals for obesity in Italy,” El Ghoch asserted.

BMI Limitations Misses Body Composition 

If obesity is a chronic disease defined as excessive accumulation of body fat and leading to increased risk for disease, disability, and mortality, then “the identification of obesity based on body fat measurements is the most reliable method,” but he acknowledged that measuring this is not readily available in most clinical settings, and as such, “simple BMI has a place,” Dr. El Ghoch said.

“Use of BMI has its limitations, for example, it does not distinguish between body composition compartments — so between muscle and fat mass, nor does it detect changes across the lifespan of an individual [for example, the shift to more fat and less muscle with age] and it varies by ethnicity,” he pointed out. 

This led El Ghoch to ask whether using BMI as a threshold for obesity was suitable for all age groups. 

The researchers included 4800 participants of mixed gender aged 40-80 years of age. Based on the WHO’s BMI classification, 1087 people had normal body weight, 1826 had overweight, and 1887 had obesity. The participants were then categorized by adiposity status on the basis of the total body fat percentage as measured by dual-energy x-ray absorptiometry (DXA), and obesity was predicted by statistical analysis.

The analysis found that around 38% of men and 41% of women had a BMI ≥ 30 based on conventional BMI criteria, indicating obesity. However, when assessed according to body fat percentage, around 71% of the men and 64% of the women were determined to have obesity. 

Dr. El Ghoch and his colleagues calculated that a lower BMI cutoff of around 27 for obesity in people older than 40 years may be more appropriate than the existing BMI threshold of 30. 

The researchers noted some limitations of their work, including that it was a single-center, cross-sectional observational study conducted in one area of Italy. In addition, they did not account for possible confounders, such as dietary habits, and physical activity patterns, and sleep health, all of which can increase the likelihood of obesity and may interact with age-related differences. 

Missing a Significant Proportion of the Population at Risk for Obesity-Related Diseases

In an interview, Luca Busetto, MD, obesity specialist and research assistant at the Center for the Study and the Integrated Treatment of the Obesity, University of Padova, Italy, and local ECO president, commented on the study and the issue of BMI as a measure and threshold. “I think the problem we face with a classic cutoff using BMI is that we miss a significant group of people who have BMI less than 30 but have a high fat mass,” he said, adding, “but these people have the same risk of developing chronic diseases as those people with higher BMI. If they have a bad fat distribution, then their risk of complications is even higher. 

“Dr El Ghoch’s study underlines the lack of treatment for this significant part of the population,” he remarked. “We also need to use waist circumference and waist-to-height [ratio] as additional measures in this population.” 

Dr. Busetto also presented a population-based study at ECO that included over 400,000 people with a follow-up of 8 years. “We found the risk of developing obesity complications, including type 2 diabetes, hypertension, osteoarthritis, and cardiovascular disease, is not only dependent on BMI but [also] dependent on your waist-to-height ratio,” he said, highlighting that “some of these complications are only predicted by the waist-to-height ratio and not by your BMI — in particular cardiovascular diseases.

“I honestly think any screening process today needs to include both BMI and waist-to-height ratio. Having a DXA scan is great in a specialist setting, but routinely we need a measure that is valid in every office in every country and small town.”

Francesco Rubino, MD, chair of metabolic and bariatric surgery at King›s College London, United Kingdom, also remarked that understanding the changes in fat and lean mass proportions and distribution in middle years will affect health in later life, and importantly from a clinical perspective, it is a time where there is still some opportunity to intervene. 

Reflecting further on how it underscores the limitations of BMI in misclassifying people as having obesity or not, Rubino asked, “Importantly, does this make a difference to health and longevity? Really, we need an active measure of adiposity first, and then even if we do say someone has obesity — so excess adiposity — then does this translate into illness, because [excess adiposity] does not translate into disease for every individual?

“Any measure we use as a diagnostic criterion needs to reflect the ongoing disease in an individual, not only the risk of future disease — because not every person experiences this. As a doctor, we deal with the individual and how the diagnosis of disease relates to the individual in a clinic now, as well as the risk of tomorrow,” he concluded. 

Dr. El Ghoch declares no conflicts of interest. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, MetaDeq, GHP Scientific, and ViBo Health for no remuneration. Dr. Busetto discloses relationships with Burno Farmaceutici, Novo Nordisk, PronoKal, Rhythm, and Therascience. 

A version of this article appeared on Medscape.com.

VENICE, ITALY — Obesity as defined by adiposity measures corresponds to a lower body mass index (BMI) cutoff (≥ 27) in men and women of middle age or older than does the widely used conventional obesity threshold of ≥ 30, shows a study performed in Italy.

Presenting at this year’s European Congress on Obesity (ECO), researchers from the University of Rome Tor Vergata and University of Modena and Reggio Emilia, Italy, and Beirut Arab University, Lebanon, conducted the study to compare the validity of the traditional World Health Organization (WHO) BMI threshold for obesity classification (≥ 30) vs adiposity levels as an alternative measure in middle-aged and older Italians. 

Marwan El Ghoch, PhD, a professor in the Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, presented the findings as a poster (GC4.152). “If you classify obesity with only BMI and without consideration of body composition, then this will not be enough. I believe BMI can be considered as a screening starting point, but we need to understand the body composition of fat and muscle too,” he said.

“We recommend this new cutoff point be applied in clinical settings when screening individuals for obesity in Italy,” El Ghoch asserted.

BMI Limitations Misses Body Composition 

If obesity is a chronic disease defined as excessive accumulation of body fat and leading to increased risk for disease, disability, and mortality, then “the identification of obesity based on body fat measurements is the most reliable method,” but he acknowledged that measuring this is not readily available in most clinical settings, and as such, “simple BMI has a place,” Dr. El Ghoch said.

“Use of BMI has its limitations, for example, it does not distinguish between body composition compartments — so between muscle and fat mass, nor does it detect changes across the lifespan of an individual [for example, the shift to more fat and less muscle with age] and it varies by ethnicity,” he pointed out. 

This led El Ghoch to ask whether using BMI as a threshold for obesity was suitable for all age groups. 

The researchers included 4800 participants of mixed gender aged 40-80 years of age. Based on the WHO’s BMI classification, 1087 people had normal body weight, 1826 had overweight, and 1887 had obesity. The participants were then categorized by adiposity status on the basis of the total body fat percentage as measured by dual-energy x-ray absorptiometry (DXA), and obesity was predicted by statistical analysis.

The analysis found that around 38% of men and 41% of women had a BMI ≥ 30 based on conventional BMI criteria, indicating obesity. However, when assessed according to body fat percentage, around 71% of the men and 64% of the women were determined to have obesity. 

Dr. El Ghoch and his colleagues calculated that a lower BMI cutoff of around 27 for obesity in people older than 40 years may be more appropriate than the existing BMI threshold of 30. 

The researchers noted some limitations of their work, including that it was a single-center, cross-sectional observational study conducted in one area of Italy. In addition, they did not account for possible confounders, such as dietary habits, and physical activity patterns, and sleep health, all of which can increase the likelihood of obesity and may interact with age-related differences. 

Missing a Significant Proportion of the Population at Risk for Obesity-Related Diseases

In an interview, Luca Busetto, MD, obesity specialist and research assistant at the Center for the Study and the Integrated Treatment of the Obesity, University of Padova, Italy, and local ECO president, commented on the study and the issue of BMI as a measure and threshold. “I think the problem we face with a classic cutoff using BMI is that we miss a significant group of people who have BMI less than 30 but have a high fat mass,” he said, adding, “but these people have the same risk of developing chronic diseases as those people with higher BMI. If they have a bad fat distribution, then their risk of complications is even higher. 

“Dr El Ghoch’s study underlines the lack of treatment for this significant part of the population,” he remarked. “We also need to use waist circumference and waist-to-height [ratio] as additional measures in this population.” 

Dr. Busetto also presented a population-based study at ECO that included over 400,000 people with a follow-up of 8 years. “We found the risk of developing obesity complications, including type 2 diabetes, hypertension, osteoarthritis, and cardiovascular disease, is not only dependent on BMI but [also] dependent on your waist-to-height ratio,” he said, highlighting that “some of these complications are only predicted by the waist-to-height ratio and not by your BMI — in particular cardiovascular diseases.

“I honestly think any screening process today needs to include both BMI and waist-to-height ratio. Having a DXA scan is great in a specialist setting, but routinely we need a measure that is valid in every office in every country and small town.”

Francesco Rubino, MD, chair of metabolic and bariatric surgery at King›s College London, United Kingdom, also remarked that understanding the changes in fat and lean mass proportions and distribution in middle years will affect health in later life, and importantly from a clinical perspective, it is a time where there is still some opportunity to intervene. 

Reflecting further on how it underscores the limitations of BMI in misclassifying people as having obesity or not, Rubino asked, “Importantly, does this make a difference to health and longevity? Really, we need an active measure of adiposity first, and then even if we do say someone has obesity — so excess adiposity — then does this translate into illness, because [excess adiposity] does not translate into disease for every individual?

“Any measure we use as a diagnostic criterion needs to reflect the ongoing disease in an individual, not only the risk of future disease — because not every person experiences this. As a doctor, we deal with the individual and how the diagnosis of disease relates to the individual in a clinic now, as well as the risk of tomorrow,” he concluded. 

Dr. El Ghoch declares no conflicts of interest. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, MetaDeq, GHP Scientific, and ViBo Health for no remuneration. Dr. Busetto discloses relationships with Burno Farmaceutici, Novo Nordisk, PronoKal, Rhythm, and Therascience. 

A version of this article appeared on Medscape.com.

Over the past few decades, the US Food and Drug Administration (FDA) has increasingly relied on surrogate measures such as blood tests instead of clinical outcomes for medication approvals. But critics say the agency lacks consistent standards to ensure the surrogate aligns with clinical outcomes that matter to patients — things like improvements in symptoms and gains in function.

Sometimes those decisions backfire. Consider: In July 2021, the FDA approved aducanumab for the treatment of Alzheimer’s disease, bucking the advice of an advisory panel for the agency that questioned the effectiveness of the medication. Regulators relied on data from the drugmaker, Biogen, showing the monoclonal antibody could reduce levels of amyloid beta plaques in blood — a surrogate marker officials hoped would translate to clinical benefit.

The FDA’s decision triggered significant controversy, and Biogen in January announced it is pulling it from the market this year, citing disappointing sales.

Although the case of aducanumab might seem extreme, given the stakes — Alzheimer’s remains a disease without an effective treatment — it’s far from unusual.

“When we prescribe a drug, there is an underlying assumption that the FDA has done its due diligence to confirm the drug is safe and of benefit,” said Reshma Ramachandran, MD, MPP, MHS, a researcher at Yale School of Medicine, New Haven, Connecticut, and a coauthor of a recent review of surrogate outcomes. “In fact, we found either no evidence or low-quality evidence.” Such markers are associated with clinical outcomes. “We just don’t know if they work meaningfully to treat the patient’s condition. The results were pretty shocking for us,” she said.

The FDA in 2018 released an Adult Surrogate Endpoint Table listing markers that can be used as substitutes for clinical outcomes to more quickly test, review, and approve new therapies. The analysis found the majority of these endpoints lacked subsequent confirmations, defined as published meta-analyses of clinical studies to validate the association between the marker and a clinical outcome important to patients.

In a paper published in JAMA, Dr. Ramachandran and her colleagues looked at 37 surrogate endpoints for nearly 3 dozen nononcologic diseases in the table.

Approval with surrogate markers implies responsibility for postapproval or validation studies — not just lab measures or imaging findings but mortality, morbidity, or improved quality of life, said Joshua D. Wallach, PhD, MS, assistant professor in the department of epidemiology at the Emory Rollins School of Public Health in Atlanta and lead author of the JAMA review.

Dr. Wallach said surrogate markers are easier to measure and do not require large and long trials. But the FDA has not provided clear rules for what makes a surrogate marker valid in clinical trials.

“They’ve said that at a minimum, it requires meta-analytical evidence from studies that have looked at the correlation or the association between the surrogate and the clinical outcome,” Dr. Wallach said. “Our understanding was that if that’s a minimum expectation, we should be able to find those studies in the literature. And the reality is that we were unable to find evidence from those types of studies supporting the association between the surrogate and the clinical outcome.”

Physicians generally do not receive training about the FDA approval process and the difference between biomarkers, surrogate markers, and clinical endpoints, Dr. Ramachandran said. “Our study shows that things are much more uncertain than we thought when it comes to the prescribing of new drugs,” she said.
 

Surrogate Markers on the Rise

Dr. Wallach’s group looked for published meta-analyses compiling randomized controlled trials reporting surrogate endpoints for more than 3 dozen chronic nononcologic conditions, including type 2 diabetes, Alzheimer’s, kidney disease, HIV, gout, and lupus. They found no meta-analyses at all for 59% of the surrogate markers, while for those that were studied, few reported high-strength evidence of an association with clinical outcomes.

The findings echo previous research. In a 2020 study in JAMA Network Open, researchers tallied primary endpoints for all FDA approvals of new drugs and therapies during three 3-year periods: 1995-1997, 2005-2007, and 2015-2017. The proportion of products whose approvals were based on the use of clinical endpoints decreased from 43.8% in 1995-1997 to 28.4% in 2005-2007 to 23.3% in 2015-2017. The share based on surrogate endpoints rose from 43.3% to roughly 60% over the same interval.

A 2017 study in the Journal of Health Economics found the use of “imperfect” surrogate endpoints helped support the approval of an average of 16 new drugs per year between 2010 and 2014 compared with six per year from 1998 to 2008.

Similar concerns about weak associations between surrogate markers and drugs used to treat cancer have been documented before, including in a 2020 study published in eClinicalMedicine. The researchers found the surrogate endpoints in the FDA table either were not tested or were tested but proven to be weak surrogates.

“And yet the FDA considered these as good enough not only for accelerated approval but also for regular approval,” said Bishal Gyawali, MD, PhD, associate professor in the department of oncology at Queen’s University, Kingston, Ontario, Canada, who led the group.

The use of surrogate endpoints is also increasing in Europe, said Huseyin Naci, MHS, PhD, associate professor of health policy at the London School of Economics and Political Science in England. He cited a cohort study of 298 randomized clinical trials (RCTs) in JAMA Oncology suggesting “contemporary oncology RCTs now largely measure putative surrogate endpoints.” Dr. Wallach called the FDA’s surrogate table “a great first step toward transparency. But a key column is missing from that table, telling us what is the basis for which the FDA allows drug companies to use the recognized surrogate markers. What is the evidence they are considering?”

If the agency allows companies the flexibility to validate surrogate endpoints, postmarketing studies designed to confirm the clinical utility of those endpoints should follow.

“We obviously want physicians to be guided by evidence when they’re selecting treatments, and they need to be able to interpret the clinical benefits of the drug that they’re prescribing,” he said. “This is really about having the research consumer, patients, and physicians, as well as industry, understand why certain markers are considered and not considered.”

Dr. Wallach reported receiving grants from the FDA (through the Yale University — Mayo Clinic Center of Excellence in Regulatory Science and Innovation), National Institute on Alcohol Abuse and Alcoholism (1K01AA028258), and Johnson & Johnson (through the Yale University Open Data Access Project); and consulting fees from Hagens Berman Sobol Shapiro LLP and Dugan Law Firm APLC outside the submitted work. Dr. Ramachandran reported receiving grants from the Stavros Niarchos Foundation and FDA; receiving consulting fees from ReAct Action on Antibiotic Resistance strategy policy program outside the submitted work; and serving in an unpaid capacity as chair of the FDA task force for the nonprofit organization Doctors for America and in an unpaid capacity as board president for Universities Allied for Essential Medicines North America.
 

A version of this article appeared on Medscape.com.

Over the past few decades, the US Food and Drug Administration (FDA) has increasingly relied on surrogate measures such as blood tests instead of clinical outcomes for medication approvals. But critics say the agency lacks consistent standards to ensure the surrogate aligns with clinical outcomes that matter to patients — things like improvements in symptoms and gains in function.

Sometimes those decisions backfire. Consider: In July 2021, the FDA approved aducanumab for the treatment of Alzheimer’s disease, bucking the advice of an advisory panel for the agency that questioned the effectiveness of the medication. Regulators relied on data from the drugmaker, Biogen, showing the monoclonal antibody could reduce levels of amyloid beta plaques in blood — a surrogate marker officials hoped would translate to clinical benefit.

The FDA’s decision triggered significant controversy, and Biogen in January announced it is pulling it from the market this year, citing disappointing sales.

Although the case of aducanumab might seem extreme, given the stakes — Alzheimer’s remains a disease without an effective treatment — it’s far from unusual.

“When we prescribe a drug, there is an underlying assumption that the FDA has done its due diligence to confirm the drug is safe and of benefit,” said Reshma Ramachandran, MD, MPP, MHS, a researcher at Yale School of Medicine, New Haven, Connecticut, and a coauthor of a recent review of surrogate outcomes. “In fact, we found either no evidence or low-quality evidence.” Such markers are associated with clinical outcomes. “We just don’t know if they work meaningfully to treat the patient’s condition. The results were pretty shocking for us,” she said.

The FDA in 2018 released an Adult Surrogate Endpoint Table listing markers that can be used as substitutes for clinical outcomes to more quickly test, review, and approve new therapies. The analysis found the majority of these endpoints lacked subsequent confirmations, defined as published meta-analyses of clinical studies to validate the association between the marker and a clinical outcome important to patients.

In a paper published in JAMA, Dr. Ramachandran and her colleagues looked at 37 surrogate endpoints for nearly 3 dozen nononcologic diseases in the table.

Approval with surrogate markers implies responsibility for postapproval or validation studies — not just lab measures or imaging findings but mortality, morbidity, or improved quality of life, said Joshua D. Wallach, PhD, MS, assistant professor in the department of epidemiology at the Emory Rollins School of Public Health in Atlanta and lead author of the JAMA review.

Dr. Wallach said surrogate markers are easier to measure and do not require large and long trials. But the FDA has not provided clear rules for what makes a surrogate marker valid in clinical trials.

“They’ve said that at a minimum, it requires meta-analytical evidence from studies that have looked at the correlation or the association between the surrogate and the clinical outcome,” Dr. Wallach said. “Our understanding was that if that’s a minimum expectation, we should be able to find those studies in the literature. And the reality is that we were unable to find evidence from those types of studies supporting the association between the surrogate and the clinical outcome.”

Physicians generally do not receive training about the FDA approval process and the difference between biomarkers, surrogate markers, and clinical endpoints, Dr. Ramachandran said. “Our study shows that things are much more uncertain than we thought when it comes to the prescribing of new drugs,” she said.
 

Surrogate Markers on the Rise

Dr. Wallach’s group looked for published meta-analyses compiling randomized controlled trials reporting surrogate endpoints for more than 3 dozen chronic nononcologic conditions, including type 2 diabetes, Alzheimer’s, kidney disease, HIV, gout, and lupus. They found no meta-analyses at all for 59% of the surrogate markers, while for those that were studied, few reported high-strength evidence of an association with clinical outcomes.

The findings echo previous research. In a 2020 study in JAMA Network Open, researchers tallied primary endpoints for all FDA approvals of new drugs and therapies during three 3-year periods: 1995-1997, 2005-2007, and 2015-2017. The proportion of products whose approvals were based on the use of clinical endpoints decreased from 43.8% in 1995-1997 to 28.4% in 2005-2007 to 23.3% in 2015-2017. The share based on surrogate endpoints rose from 43.3% to roughly 60% over the same interval.

A 2017 study in the Journal of Health Economics found the use of “imperfect” surrogate endpoints helped support the approval of an average of 16 new drugs per year between 2010 and 2014 compared with six per year from 1998 to 2008.

Similar concerns about weak associations between surrogate markers and drugs used to treat cancer have been documented before, including in a 2020 study published in eClinicalMedicine. The researchers found the surrogate endpoints in the FDA table either were not tested or were tested but proven to be weak surrogates.

“And yet the FDA considered these as good enough not only for accelerated approval but also for regular approval,” said Bishal Gyawali, MD, PhD, associate professor in the department of oncology at Queen’s University, Kingston, Ontario, Canada, who led the group.

The use of surrogate endpoints is also increasing in Europe, said Huseyin Naci, MHS, PhD, associate professor of health policy at the London School of Economics and Political Science in England. He cited a cohort study of 298 randomized clinical trials (RCTs) in JAMA Oncology suggesting “contemporary oncology RCTs now largely measure putative surrogate endpoints.” Dr. Wallach called the FDA’s surrogate table “a great first step toward transparency. But a key column is missing from that table, telling us what is the basis for which the FDA allows drug companies to use the recognized surrogate markers. What is the evidence they are considering?”

If the agency allows companies the flexibility to validate surrogate endpoints, postmarketing studies designed to confirm the clinical utility of those endpoints should follow.

“We obviously want physicians to be guided by evidence when they’re selecting treatments, and they need to be able to interpret the clinical benefits of the drug that they’re prescribing,” he said. “This is really about having the research consumer, patients, and physicians, as well as industry, understand why certain markers are considered and not considered.”

Dr. Wallach reported receiving grants from the FDA (through the Yale University — Mayo Clinic Center of Excellence in Regulatory Science and Innovation), National Institute on Alcohol Abuse and Alcoholism (1K01AA028258), and Johnson & Johnson (through the Yale University Open Data Access Project); and consulting fees from Hagens Berman Sobol Shapiro LLP and Dugan Law Firm APLC outside the submitted work. Dr. Ramachandran reported receiving grants from the Stavros Niarchos Foundation and FDA; receiving consulting fees from ReAct Action on Antibiotic Resistance strategy policy program outside the submitted work; and serving in an unpaid capacity as chair of the FDA task force for the nonprofit organization Doctors for America and in an unpaid capacity as board president for Universities Allied for Essential Medicines North America.
 

A version of this article appeared on Medscape.com.

Over the past few decades, the US Food and Drug Administration (FDA) has increasingly relied on surrogate measures such as blood tests instead of clinical outcomes for medication approvals. But critics say the agency lacks consistent standards to ensure the surrogate aligns with clinical outcomes that matter to patients — things like improvements in symptoms and gains in function.

Sometimes those decisions backfire. Consider: In July 2021, the FDA approved aducanumab for the treatment of Alzheimer’s disease, bucking the advice of an advisory panel for the agency that questioned the effectiveness of the medication. Regulators relied on data from the drugmaker, Biogen, showing the monoclonal antibody could reduce levels of amyloid beta plaques in blood — a surrogate marker officials hoped would translate to clinical benefit.

The FDA’s decision triggered significant controversy, and Biogen in January announced it is pulling it from the market this year, citing disappointing sales.

Although the case of aducanumab might seem extreme, given the stakes — Alzheimer’s remains a disease without an effective treatment — it’s far from unusual.

“When we prescribe a drug, there is an underlying assumption that the FDA has done its due diligence to confirm the drug is safe and of benefit,” said Reshma Ramachandran, MD, MPP, MHS, a researcher at Yale School of Medicine, New Haven, Connecticut, and a coauthor of a recent review of surrogate outcomes. “In fact, we found either no evidence or low-quality evidence.” Such markers are associated with clinical outcomes. “We just don’t know if they work meaningfully to treat the patient’s condition. The results were pretty shocking for us,” she said.

The FDA in 2018 released an Adult Surrogate Endpoint Table listing markers that can be used as substitutes for clinical outcomes to more quickly test, review, and approve new therapies. The analysis found the majority of these endpoints lacked subsequent confirmations, defined as published meta-analyses of clinical studies to validate the association between the marker and a clinical outcome important to patients.

In a paper published in JAMA, Dr. Ramachandran and her colleagues looked at 37 surrogate endpoints for nearly 3 dozen nononcologic diseases in the table.

Approval with surrogate markers implies responsibility for postapproval or validation studies — not just lab measures or imaging findings but mortality, morbidity, or improved quality of life, said Joshua D. Wallach, PhD, MS, assistant professor in the department of epidemiology at the Emory Rollins School of Public Health in Atlanta and lead author of the JAMA review.

Dr. Wallach said surrogate markers are easier to measure and do not require large and long trials. But the FDA has not provided clear rules for what makes a surrogate marker valid in clinical trials.

“They’ve said that at a minimum, it requires meta-analytical evidence from studies that have looked at the correlation or the association between the surrogate and the clinical outcome,” Dr. Wallach said. “Our understanding was that if that’s a minimum expectation, we should be able to find those studies in the literature. And the reality is that we were unable to find evidence from those types of studies supporting the association between the surrogate and the clinical outcome.”

Physicians generally do not receive training about the FDA approval process and the difference between biomarkers, surrogate markers, and clinical endpoints, Dr. Ramachandran said. “Our study shows that things are much more uncertain than we thought when it comes to the prescribing of new drugs,” she said.
 

Surrogate Markers on the Rise

Dr. Wallach’s group looked for published meta-analyses compiling randomized controlled trials reporting surrogate endpoints for more than 3 dozen chronic nononcologic conditions, including type 2 diabetes, Alzheimer’s, kidney disease, HIV, gout, and lupus. They found no meta-analyses at all for 59% of the surrogate markers, while for those that were studied, few reported high-strength evidence of an association with clinical outcomes.

The findings echo previous research. In a 2020 study in JAMA Network Open, researchers tallied primary endpoints for all FDA approvals of new drugs and therapies during three 3-year periods: 1995-1997, 2005-2007, and 2015-2017. The proportion of products whose approvals were based on the use of clinical endpoints decreased from 43.8% in 1995-1997 to 28.4% in 2005-2007 to 23.3% in 2015-2017. The share based on surrogate endpoints rose from 43.3% to roughly 60% over the same interval.

A 2017 study in the Journal of Health Economics found the use of “imperfect” surrogate endpoints helped support the approval of an average of 16 new drugs per year between 2010 and 2014 compared with six per year from 1998 to 2008.

Similar concerns about weak associations between surrogate markers and drugs used to treat cancer have been documented before, including in a 2020 study published in eClinicalMedicine. The researchers found the surrogate endpoints in the FDA table either were not tested or were tested but proven to be weak surrogates.

“And yet the FDA considered these as good enough not only for accelerated approval but also for regular approval,” said Bishal Gyawali, MD, PhD, associate professor in the department of oncology at Queen’s University, Kingston, Ontario, Canada, who led the group.

The use of surrogate endpoints is also increasing in Europe, said Huseyin Naci, MHS, PhD, associate professor of health policy at the London School of Economics and Political Science in England. He cited a cohort study of 298 randomized clinical trials (RCTs) in JAMA Oncology suggesting “contemporary oncology RCTs now largely measure putative surrogate endpoints.” Dr. Wallach called the FDA’s surrogate table “a great first step toward transparency. But a key column is missing from that table, telling us what is the basis for which the FDA allows drug companies to use the recognized surrogate markers. What is the evidence they are considering?”

If the agency allows companies the flexibility to validate surrogate endpoints, postmarketing studies designed to confirm the clinical utility of those endpoints should follow.

“We obviously want physicians to be guided by evidence when they’re selecting treatments, and they need to be able to interpret the clinical benefits of the drug that they’re prescribing,” he said. “This is really about having the research consumer, patients, and physicians, as well as industry, understand why certain markers are considered and not considered.”

Dr. Wallach reported receiving grants from the FDA (through the Yale University — Mayo Clinic Center of Excellence in Regulatory Science and Innovation), National Institute on Alcohol Abuse and Alcoholism (1K01AA028258), and Johnson & Johnson (through the Yale University Open Data Access Project); and consulting fees from Hagens Berman Sobol Shapiro LLP and Dugan Law Firm APLC outside the submitted work. Dr. Ramachandran reported receiving grants from the Stavros Niarchos Foundation and FDA; receiving consulting fees from ReAct Action on Antibiotic Resistance strategy policy program outside the submitted work; and serving in an unpaid capacity as chair of the FDA task force for the nonprofit organization Doctors for America and in an unpaid capacity as board president for Universities Allied for Essential Medicines North America.
 

A version of this article appeared on Medscape.com.

The number of Americans seeking permanent forms of contraception has surged in the nearly 2 years since the Dobbs v. Jackson Women’s Health Organization Supreme Court decision that overturned a federal right to abortion, according to a study presented on May 5 at the annual meeting of the American Urological Association (AUA) (abstract PD40-03). Several other studies at the conference reported similar findings.

Rates of vasectomy and tubal ligation have increased in states where abortion became illegal after the court’s June 2022 ruling, researchers found. Rates of tubal sterilization had already been higher in states where abortion was illegal compared with those where access to the procedure remained available and was expected to remain so, but the difference widened after the decision. 

“Our study showed trends of increasing utilization of permanent contraception post-Dobbs, with a significant increase in patients less than 30 years old pursuing any type of permanent contraception post-Dobbs,” Jessica N. Schardein, MD, MS, of University of Utah Health in Salt Lake City, told attendees. “Reproductive autonomy is important for people of all genders and may be influenced by legal climate. Understanding the relationship between state-level abortion laws and trends in permanent contraception is crucial for us to determine how to best allocate resources for education and services to ensure reproductive rights for all patients.”

Dr. Schardein told this news organization the increase in vasectomies post-Dobbs was consistent across most states regardless of legal climate, showing that “reproductive health matters to all people,” both women and men.

“We should continue to offer permanent contraception to patients who are not interested in future fertility, regardless of their age or marital status, to ensure reproductive autonomy for those patients,” Dr. Schardein said. “Patients may need increased access to these procedures if the increased rates continue over time.”

Dr. Schardein’s study investigated national trends in the use of permanent contraception before and after the Dobbs ruling. She and her colleagues analyzed data from the Epic Cosmos database of more than 217 million patients from an estimated 27,000 clinics and 1260 hospitals nationwide. The researchers identified all adults who underwent a vasectomy or tubal ligation from July to December 2021 and then from July to December 2022, in the 5 months following the decision.

Among adults aged 18-30 years, rates of vasectomy were 1.59 times higher and rates of tubal ligation were 1.29 times higher after the Dobbs ruling than before it (P < .001). Although overall rates of tubal ligation among single women did not change after Dobbs, rates of vasectomy in single men were 1.13 times higher (P < .001).

States were categorized as not hostile to abortion access (abortion access remained available), hostile (access was restricted or might become illegal), or illegal on the basis of information from the Center for Reproductive Rights. Vasectomies increased in most states, with the biggest gain in Tennessee, where abortions are illegal. 

The increase in vasectomy rates was similar across nonhostile (incidence rate ratio [IRR], 1.43), hostile (IRR, 1.46), and illegal (IRR, 1.41) states (P < .001). Although the rate of increase was similar regardless of legal climate, the rate of vasectomies was higher in hostile and illegal states than in nonhostile states both before and after the Dobbs ruling, according to the researchers.

Rates of tubal ligation did not change as substantially across the United States after Dobbs, remaining unchanged in states hostile to abortion access and rising slightly in nonhostile states (IRR, 1.06) and in states where abortion is now illegal (IRR, 1.12; P < .001 for both).

However, when the researchers looked at tubal ligation in nonhostile states and hostile or illegal states, they found that rates of the procedure were nearly double in the hostile or illegal states both before and after Dobbs, with a bigger increase after Dobbs in illegal states. Tubal ligation rates were 1.85 times higher in illegal states than in nonhostile states after Dobbs, compared with being 1.76 times higher than in nonhostile states before Dobbs.
 

Other Studies Support the Findings 

Another study assessed the change in the volume of vasectomy consultations at six US academic medical centers in the 17 months before and 5 months after Dobbs (abstract PD40-02). The researchers reported that the rate was roughly 7% higher after the ruling than before (143 vs 134 cases per month, respectively). Again, the men seeking vasectomies after Dobbs were younger than those who sought the procedure before Dobbs (median age, 38 vs 39 years; P < .001). Post-Dobbs patients were also significantly more likely to be non-Hispanic White, English-speaking, and privately insured. 

“Younger, childless people are choosing vasectomies as permanent method of birth control,” lead author Kara L. Watts, MD, associate professor of urology at Montefiore Medical Center in Bronx, New York, told attendees. “The impact of this decision is likely to be long-lasting, requiring urologists and medical centers to adjust practice patterns to account for the increased demand.”

Twice as many childless married men underwent vasectomies after Dobbs than before the ruling (11% vs 5%, respectively; P = .001), but substantially more childless single men had the procedure after Dobbs than before it (36% vs 21%; P = .003). Those seeking vasectomies after Dobbs had to wait a median of 8 days longer between consult and procedure (59 vs 51 days pre-Dobbs; P < .001). Several of the same researchers had identified an increase in online searches about vasectomies in the months just after the Dobbs decision.

“We’ve been trying to get men to take more responsibility” for their role in unplanned pregnancies, Ajay K. Nangia, MD, MBBS, professor and vice chair of urology at University of Kansas Medical Center in Overland Park, told this news organization. Dr. Nangia, who helped conduct the study of vasectomy consultations and has spent years on research related to pharmaceutical contraception options for men, said the sudden increase in interest in vasectomies can be ethically fraught. Only 25% of vasectomies can be reversed, and some patients who seek the surgery may not have permanently ruled out having children.

“They’re going into this with their eyes wide open, knowing that it’s not 100% going to be reversible with a vasectomy,” he said. But fear of not having abortion access for their partners is part of their motivation, which creates tension for providers in balancing ethical counseling with the potential paternalism of advising against a vasectomy if they’re not certain that they don’t want children. 

“What happens in that situation, when it’s a political decision making you change your medical decision?” Dr. Nangia said. “I worry about that ethically.”

Dr. Nangia noted that the findings of his study cannot show that the Dobbs decision was the cause of the increase in vasectomies. However, in another abstract from the same session (PD40-01), researchers at The Ohio State University College of Medicine in Columbus presented findings from a survey of 57 men who underwent vasectomies in the preceding 2 years. Those results revealed that abortion access had been a factor among some of the 47% of patients whose procedures were performed after Dobbs. Post-Dobbs patients were significantly more likely to say they sought a vasectomy because of concerns about not being able to get abortion (P = .026) and because they didn’t want “to bring children into the current political climate” (P = .002). 

A study presented on May 6 (abstract MP76-06) involved a retrospective review of all 631 patients who underwent a vasectomy consult at UC San Diego Medical Center from June 2021 to June 2023. More vasectomy consults occurred after the Dobbs decision than before it (56% vs 44%). The gap for vasectomy consults was slightly wider for partnerless patients after vs before Dobbs (58% vs 42%) and substantially larger for childless patients post-Dobbs compared with pre-Dobbs (63% vs 37%). The childless men undergoing vasectomies after Dobbs also were significantly younger than those who had had this procedure before the ruling (mean, 36.4 vs 39.8 years; P <.001). 

“Patients should be counseled on the permanent nature of this procedure, underscoring need for effective and reversible male contraception,” the authors concluded.

Dr. Schardein and Dr. Watts reported no relevant financial conflicts of interest. Dr. Nangia is conducting an idiopathic infertility study with funding from Ferring Pharmaceuticals. None of the studies reported external funding.

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

The number of Americans seeking permanent forms of contraception has surged in the nearly 2 years since the Dobbs v. Jackson Women’s Health Organization Supreme Court decision that overturned a federal right to abortion, according to a study presented on May 5 at the annual meeting of the American Urological Association (AUA) (abstract PD40-03). Several other studies at the conference reported similar findings.

Rates of vasectomy and tubal ligation have increased in states where abortion became illegal after the court’s June 2022 ruling, researchers found. Rates of tubal sterilization had already been higher in states where abortion was illegal compared with those where access to the procedure remained available and was expected to remain so, but the difference widened after the decision. 

“Our study showed trends of increasing utilization of permanent contraception post-Dobbs, with a significant increase in patients less than 30 years old pursuing any type of permanent contraception post-Dobbs,” Jessica N. Schardein, MD, MS, of University of Utah Health in Salt Lake City, told attendees. “Reproductive autonomy is important for people of all genders and may be influenced by legal climate. Understanding the relationship between state-level abortion laws and trends in permanent contraception is crucial for us to determine how to best allocate resources for education and services to ensure reproductive rights for all patients.”

Dr. Schardein told this news organization the increase in vasectomies post-Dobbs was consistent across most states regardless of legal climate, showing that “reproductive health matters to all people,” both women and men.

“We should continue to offer permanent contraception to patients who are not interested in future fertility, regardless of their age or marital status, to ensure reproductive autonomy for those patients,” Dr. Schardein said. “Patients may need increased access to these procedures if the increased rates continue over time.”

Dr. Schardein’s study investigated national trends in the use of permanent contraception before and after the Dobbs ruling. She and her colleagues analyzed data from the Epic Cosmos database of more than 217 million patients from an estimated 27,000 clinics and 1260 hospitals nationwide. The researchers identified all adults who underwent a vasectomy or tubal ligation from July to December 2021 and then from July to December 2022, in the 5 months following the decision.

Among adults aged 18-30 years, rates of vasectomy were 1.59 times higher and rates of tubal ligation were 1.29 times higher after the Dobbs ruling than before it (P < .001). Although overall rates of tubal ligation among single women did not change after Dobbs, rates of vasectomy in single men were 1.13 times higher (P < .001).

States were categorized as not hostile to abortion access (abortion access remained available), hostile (access was restricted or might become illegal), or illegal on the basis of information from the Center for Reproductive Rights. Vasectomies increased in most states, with the biggest gain in Tennessee, where abortions are illegal. 

The increase in vasectomy rates was similar across nonhostile (incidence rate ratio [IRR], 1.43), hostile (IRR, 1.46), and illegal (IRR, 1.41) states (P < .001). Although the rate of increase was similar regardless of legal climate, the rate of vasectomies was higher in hostile and illegal states than in nonhostile states both before and after the Dobbs ruling, according to the researchers.

Rates of tubal ligation did not change as substantially across the United States after Dobbs, remaining unchanged in states hostile to abortion access and rising slightly in nonhostile states (IRR, 1.06) and in states where abortion is now illegal (IRR, 1.12; P < .001 for both).

However, when the researchers looked at tubal ligation in nonhostile states and hostile or illegal states, they found that rates of the procedure were nearly double in the hostile or illegal states both before and after Dobbs, with a bigger increase after Dobbs in illegal states. Tubal ligation rates were 1.85 times higher in illegal states than in nonhostile states after Dobbs, compared with being 1.76 times higher than in nonhostile states before Dobbs.
 

Other Studies Support the Findings 

Another study assessed the change in the volume of vasectomy consultations at six US academic medical centers in the 17 months before and 5 months after Dobbs (abstract PD40-02). The researchers reported that the rate was roughly 7% higher after the ruling than before (143 vs 134 cases per month, respectively). Again, the men seeking vasectomies after Dobbs were younger than those who sought the procedure before Dobbs (median age, 38 vs 39 years; P < .001). Post-Dobbs patients were also significantly more likely to be non-Hispanic White, English-speaking, and privately insured. 

“Younger, childless people are choosing vasectomies as permanent method of birth control,” lead author Kara L. Watts, MD, associate professor of urology at Montefiore Medical Center in Bronx, New York, told attendees. “The impact of this decision is likely to be long-lasting, requiring urologists and medical centers to adjust practice patterns to account for the increased demand.”

Twice as many childless married men underwent vasectomies after Dobbs than before the ruling (11% vs 5%, respectively; P = .001), but substantially more childless single men had the procedure after Dobbs than before it (36% vs 21%; P = .003). Those seeking vasectomies after Dobbs had to wait a median of 8 days longer between consult and procedure (59 vs 51 days pre-Dobbs; P < .001). Several of the same researchers had identified an increase in online searches about vasectomies in the months just after the Dobbs decision.

“We’ve been trying to get men to take more responsibility” for their role in unplanned pregnancies, Ajay K. Nangia, MD, MBBS, professor and vice chair of urology at University of Kansas Medical Center in Overland Park, told this news organization. Dr. Nangia, who helped conduct the study of vasectomy consultations and has spent years on research related to pharmaceutical contraception options for men, said the sudden increase in interest in vasectomies can be ethically fraught. Only 25% of vasectomies can be reversed, and some patients who seek the surgery may not have permanently ruled out having children.

“They’re going into this with their eyes wide open, knowing that it’s not 100% going to be reversible with a vasectomy,” he said. But fear of not having abortion access for their partners is part of their motivation, which creates tension for providers in balancing ethical counseling with the potential paternalism of advising against a vasectomy if they’re not certain that they don’t want children. 

“What happens in that situation, when it’s a political decision making you change your medical decision?” Dr. Nangia said. “I worry about that ethically.”

Dr. Nangia noted that the findings of his study cannot show that the Dobbs decision was the cause of the increase in vasectomies. However, in another abstract from the same session (PD40-01), researchers at The Ohio State University College of Medicine in Columbus presented findings from a survey of 57 men who underwent vasectomies in the preceding 2 years. Those results revealed that abortion access had been a factor among some of the 47% of patients whose procedures were performed after Dobbs. Post-Dobbs patients were significantly more likely to say they sought a vasectomy because of concerns about not being able to get abortion (P = .026) and because they didn’t want “to bring children into the current political climate” (P = .002). 

A study presented on May 6 (abstract MP76-06) involved a retrospective review of all 631 patients who underwent a vasectomy consult at UC San Diego Medical Center from June 2021 to June 2023. More vasectomy consults occurred after the Dobbs decision than before it (56% vs 44%). The gap for vasectomy consults was slightly wider for partnerless patients after vs before Dobbs (58% vs 42%) and substantially larger for childless patients post-Dobbs compared with pre-Dobbs (63% vs 37%). The childless men undergoing vasectomies after Dobbs also were significantly younger than those who had had this procedure before the ruling (mean, 36.4 vs 39.8 years; P <.001). 

“Patients should be counseled on the permanent nature of this procedure, underscoring need for effective and reversible male contraception,” the authors concluded.

Dr. Schardein and Dr. Watts reported no relevant financial conflicts of interest. Dr. Nangia is conducting an idiopathic infertility study with funding from Ferring Pharmaceuticals. None of the studies reported external funding.

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

The number of Americans seeking permanent forms of contraception has surged in the nearly 2 years since the Dobbs v. Jackson Women’s Health Organization Supreme Court decision that overturned a federal right to abortion, according to a study presented on May 5 at the annual meeting of the American Urological Association (AUA) (abstract PD40-03). Several other studies at the conference reported similar findings.

Rates of vasectomy and tubal ligation have increased in states where abortion became illegal after the court’s June 2022 ruling, researchers found. Rates of tubal sterilization had already been higher in states where abortion was illegal compared with those where access to the procedure remained available and was expected to remain so, but the difference widened after the decision. 

“Our study showed trends of increasing utilization of permanent contraception post-Dobbs, with a significant increase in patients less than 30 years old pursuing any type of permanent contraception post-Dobbs,” Jessica N. Schardein, MD, MS, of University of Utah Health in Salt Lake City, told attendees. “Reproductive autonomy is important for people of all genders and may be influenced by legal climate. Understanding the relationship between state-level abortion laws and trends in permanent contraception is crucial for us to determine how to best allocate resources for education and services to ensure reproductive rights for all patients.”

Dr. Schardein told this news organization the increase in vasectomies post-Dobbs was consistent across most states regardless of legal climate, showing that “reproductive health matters to all people,” both women and men.

“We should continue to offer permanent contraception to patients who are not interested in future fertility, regardless of their age or marital status, to ensure reproductive autonomy for those patients,” Dr. Schardein said. “Patients may need increased access to these procedures if the increased rates continue over time.”

Dr. Schardein’s study investigated national trends in the use of permanent contraception before and after the Dobbs ruling. She and her colleagues analyzed data from the Epic Cosmos database of more than 217 million patients from an estimated 27,000 clinics and 1260 hospitals nationwide. The researchers identified all adults who underwent a vasectomy or tubal ligation from July to December 2021 and then from July to December 2022, in the 5 months following the decision.

Among adults aged 18-30 years, rates of vasectomy were 1.59 times higher and rates of tubal ligation were 1.29 times higher after the Dobbs ruling than before it (P < .001). Although overall rates of tubal ligation among single women did not change after Dobbs, rates of vasectomy in single men were 1.13 times higher (P < .001).

States were categorized as not hostile to abortion access (abortion access remained available), hostile (access was restricted or might become illegal), or illegal on the basis of information from the Center for Reproductive Rights. Vasectomies increased in most states, with the biggest gain in Tennessee, where abortions are illegal. 

The increase in vasectomy rates was similar across nonhostile (incidence rate ratio [IRR], 1.43), hostile (IRR, 1.46), and illegal (IRR, 1.41) states (P < .001). Although the rate of increase was similar regardless of legal climate, the rate of vasectomies was higher in hostile and illegal states than in nonhostile states both before and after the Dobbs ruling, according to the researchers.

Rates of tubal ligation did not change as substantially across the United States after Dobbs, remaining unchanged in states hostile to abortion access and rising slightly in nonhostile states (IRR, 1.06) and in states where abortion is now illegal (IRR, 1.12; P < .001 for both).

However, when the researchers looked at tubal ligation in nonhostile states and hostile or illegal states, they found that rates of the procedure were nearly double in the hostile or illegal states both before and after Dobbs, with a bigger increase after Dobbs in illegal states. Tubal ligation rates were 1.85 times higher in illegal states than in nonhostile states after Dobbs, compared with being 1.76 times higher than in nonhostile states before Dobbs.
 

Other Studies Support the Findings 

Another study assessed the change in the volume of vasectomy consultations at six US academic medical centers in the 17 months before and 5 months after Dobbs (abstract PD40-02). The researchers reported that the rate was roughly 7% higher after the ruling than before (143 vs 134 cases per month, respectively). Again, the men seeking vasectomies after Dobbs were younger than those who sought the procedure before Dobbs (median age, 38 vs 39 years; P < .001). Post-Dobbs patients were also significantly more likely to be non-Hispanic White, English-speaking, and privately insured. 

“Younger, childless people are choosing vasectomies as permanent method of birth control,” lead author Kara L. Watts, MD, associate professor of urology at Montefiore Medical Center in Bronx, New York, told attendees. “The impact of this decision is likely to be long-lasting, requiring urologists and medical centers to adjust practice patterns to account for the increased demand.”

Twice as many childless married men underwent vasectomies after Dobbs than before the ruling (11% vs 5%, respectively; P = .001), but substantially more childless single men had the procedure after Dobbs than before it (36% vs 21%; P = .003). Those seeking vasectomies after Dobbs had to wait a median of 8 days longer between consult and procedure (59 vs 51 days pre-Dobbs; P < .001). Several of the same researchers had identified an increase in online searches about vasectomies in the months just after the Dobbs decision.

“We’ve been trying to get men to take more responsibility” for their role in unplanned pregnancies, Ajay K. Nangia, MD, MBBS, professor and vice chair of urology at University of Kansas Medical Center in Overland Park, told this news organization. Dr. Nangia, who helped conduct the study of vasectomy consultations and has spent years on research related to pharmaceutical contraception options for men, said the sudden increase in interest in vasectomies can be ethically fraught. Only 25% of vasectomies can be reversed, and some patients who seek the surgery may not have permanently ruled out having children.

“They’re going into this with their eyes wide open, knowing that it’s not 100% going to be reversible with a vasectomy,” he said. But fear of not having abortion access for their partners is part of their motivation, which creates tension for providers in balancing ethical counseling with the potential paternalism of advising against a vasectomy if they’re not certain that they don’t want children. 

“What happens in that situation, when it’s a political decision making you change your medical decision?” Dr. Nangia said. “I worry about that ethically.”

Dr. Nangia noted that the findings of his study cannot show that the Dobbs decision was the cause of the increase in vasectomies. However, in another abstract from the same session (PD40-01), researchers at The Ohio State University College of Medicine in Columbus presented findings from a survey of 57 men who underwent vasectomies in the preceding 2 years. Those results revealed that abortion access had been a factor among some of the 47% of patients whose procedures were performed after Dobbs. Post-Dobbs patients were significantly more likely to say they sought a vasectomy because of concerns about not being able to get abortion (P = .026) and because they didn’t want “to bring children into the current political climate” (P = .002). 

A study presented on May 6 (abstract MP76-06) involved a retrospective review of all 631 patients who underwent a vasectomy consult at UC San Diego Medical Center from June 2021 to June 2023. More vasectomy consults occurred after the Dobbs decision than before it (56% vs 44%). The gap for vasectomy consults was slightly wider for partnerless patients after vs before Dobbs (58% vs 42%) and substantially larger for childless patients post-Dobbs compared with pre-Dobbs (63% vs 37%). The childless men undergoing vasectomies after Dobbs also were significantly younger than those who had had this procedure before the ruling (mean, 36.4 vs 39.8 years; P <.001). 

“Patients should be counseled on the permanent nature of this procedure, underscoring need for effective and reversible male contraception,” the authors concluded.

Dr. Schardein and Dr. Watts reported no relevant financial conflicts of interest. Dr. Nangia is conducting an idiopathic infertility study with funding from Ferring Pharmaceuticals. None of the studies reported external funding.

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

The most reliable predictors of remission in newly diagnosed epilepsy include patient history, seizure characteristics, and onset age, according to authors of a recent review. Clinical prediction models can help neurologists identify which patients could benefit from more aggressive early treatment, authors added, although concerns over bias and model applicability leave room for improvement.

Triggering Aggressive Treatments

“These models are helpful because if you can predict that someone is going to do well with one or two medications, that’s great,” said Aatif M. Husain, MD. “But if you know early on that someone likely will not do well, will need many medications, and still not have their seizures under control, you’re much more likely to be more aggressive with their management, such as closely refer them to a specialist epilepsy center and evaluate them for surgical treatment options. This could minimize the amount of time their seizures are inadequately controlled.” Dr. Husain is an epileptologist, neurologist, and sleep medicine specialist at Duke University Health System in Durham, North Carolina. Dr. Husain was not involved with the study, which was published in Epilepsia.

“But the other important finding is that these models so far have not been that great,” he added.

Prognosis Predictors

Investigators Corey Ratcliffe of the University of Liverpool in England and colleagues systematically searched MEDLINE and Embase for relevant publications, ultimately analyzing 48 models across 32 studies. The strongest predictors of seizure remission were history and seizure types or characteristics, the authors wrote, followed by onset age.

Regarding seizure history, a March 2018 JAMA Neurology study and a December 2013 BMC Neurology study linked factors such as history of seizures in the year pre-diagnosis, family history of epilepsy, and history of febrile seizures and of migraines with lower chances of seizure remission. Seizure types with increased chances of poor outcomes in the review included status epilepticus and seizures with complex or mixed etiologies. Additional seizure types associated with poor control include tonic-clonic seizures, frequent focal seizures, and seizures stemming from certain genetic predispositions, said Dr. Husain.

Although the roles of many of the foregoing factors are easily explained, he added, other variables’ impact is less clear. Younger onset often signals more refractory seizures, for example, while data regarding older onset are mixed. “Sometimes older individuals will have mild epilepsy due to a stroke, tumor, or something that can be relatively easily treated,” said Dr. Husain. Conversely, epilepsy can become more complicated if such patients take several medications and/or have coexisting medical problems that seizures or antiseizure medications exacerbate. “So sometimes it’s not so obvious.”
 

Incorporating Imaging, AI

Dr. Husain found it surprising that very few of the selected models incorporated EEG and MRI findings. “Subsequent research should look at those, since they are important diagnostic tests.” Moreover, he recommended including more sophisticated quantitative and connectivity analyses of EEG and MRI data. These analyses might provide additional prognostic information beyond a simple visual analysis of these tests, Dr. Husain explained, although their potential here remains unproven.

As for factors not represented in the review, he said, future studies will help clarify AI’s role in predicting newly diagnosed epilepsy outcomes. A study published in Epilepsia showed that among 248 potential pediatric surgical candidates, those whose providers received alerts based on machine learning analysis of prior visit notes were more likely to be referred for presurgical evaluation (9.8% versus 3.1%). Future clinical models will use AI to examine not only established elements of neurologic history, said Dr. Husain, but also other types of history such as socioeconomic characteristics, geographic location, and other such data.

Additionally, study authors recommended a standardized approach to prediction modeling, using Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines. Using consistent definitions, outcomes, and reporting requirements will facilitate communication among researchers, reduce bias, and support systematic between-study comparisons, Mr. Ratcliffe and colleagues wrote.
 

Reaching General Neurologists

Epilepsy specialists are generally aware of reliable outcome predictors, Dr. Husain said, though they do not use models per se. “But the vast majority of patients with epilepsy are seen by general neurologists.” And the lack of awareness among these physicians and primary care practitioners drives a need for education to facilitate appropriate referrals to subspecialty centers, he said.

The stakes for timely referrals can be high. Although using appropriate outcome models improves patients’ quality of life sooner, said Dr. Husain, allowing seizures to go untreated or undertreated results in neuroplastic changes that hinder long-term seizure control.

The fact that all 32 included studies reflected a high risk of bias, and 9 studies raised high applicability concerns, raises questions regarding the models’ validity, he added. Mr. Ratcliffe and colleagues attributed both types of concerns to the fact that 20% of included studies used baseline treatment response data as outcome predictors.

Nevertheless, Dr. Husain cautioned against dismissing prediction models in newly diagnosed epilepsy. “Practicing neurologists need to realize that the perfect model has yet to be developed. But the current tools can be used to help manage patients with epilepsy and predict who will do well and not as well,” he said.

Dr. Husain is a member of the American Epilepsy Society. He has been a consultant and researcher for Marinus Pharmaceuticals, PranaQ, and UCB, and a consultant for Eisai, Jazz Pharmaceuticals, Merck, and uniQure. Study authors reported no funding sources or relevant conflicts of interest.

The most reliable predictors of remission in newly diagnosed epilepsy include patient history, seizure characteristics, and onset age, according to authors of a recent review. Clinical prediction models can help neurologists identify which patients could benefit from more aggressive early treatment, authors added, although concerns over bias and model applicability leave room for improvement.

Triggering Aggressive Treatments

“These models are helpful because if you can predict that someone is going to do well with one or two medications, that’s great,” said Aatif M. Husain, MD. “But if you know early on that someone likely will not do well, will need many medications, and still not have their seizures under control, you’re much more likely to be more aggressive with their management, such as closely refer them to a specialist epilepsy center and evaluate them for surgical treatment options. This could minimize the amount of time their seizures are inadequately controlled.” Dr. Husain is an epileptologist, neurologist, and sleep medicine specialist at Duke University Health System in Durham, North Carolina. Dr. Husain was not involved with the study, which was published in Epilepsia.

“But the other important finding is that these models so far have not been that great,” he added.

Prognosis Predictors

Investigators Corey Ratcliffe of the University of Liverpool in England and colleagues systematically searched MEDLINE and Embase for relevant publications, ultimately analyzing 48 models across 32 studies. The strongest predictors of seizure remission were history and seizure types or characteristics, the authors wrote, followed by onset age.

Regarding seizure history, a March 2018 JAMA Neurology study and a December 2013 BMC Neurology study linked factors such as history of seizures in the year pre-diagnosis, family history of epilepsy, and history of febrile seizures and of migraines with lower chances of seizure remission. Seizure types with increased chances of poor outcomes in the review included status epilepticus and seizures with complex or mixed etiologies. Additional seizure types associated with poor control include tonic-clonic seizures, frequent focal seizures, and seizures stemming from certain genetic predispositions, said Dr. Husain.

Although the roles of many of the foregoing factors are easily explained, he added, other variables’ impact is less clear. Younger onset often signals more refractory seizures, for example, while data regarding older onset are mixed. “Sometimes older individuals will have mild epilepsy due to a stroke, tumor, or something that can be relatively easily treated,” said Dr. Husain. Conversely, epilepsy can become more complicated if such patients take several medications and/or have coexisting medical problems that seizures or antiseizure medications exacerbate. “So sometimes it’s not so obvious.”
 

Incorporating Imaging, AI

Dr. Husain found it surprising that very few of the selected models incorporated EEG and MRI findings. “Subsequent research should look at those, since they are important diagnostic tests.” Moreover, he recommended including more sophisticated quantitative and connectivity analyses of EEG and MRI data. These analyses might provide additional prognostic information beyond a simple visual analysis of these tests, Dr. Husain explained, although their potential here remains unproven.

As for factors not represented in the review, he said, future studies will help clarify AI’s role in predicting newly diagnosed epilepsy outcomes. A study published in Epilepsia showed that among 248 potential pediatric surgical candidates, those whose providers received alerts based on machine learning analysis of prior visit notes were more likely to be referred for presurgical evaluation (9.8% versus 3.1%). Future clinical models will use AI to examine not only established elements of neurologic history, said Dr. Husain, but also other types of history such as socioeconomic characteristics, geographic location, and other such data.

Additionally, study authors recommended a standardized approach to prediction modeling, using Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines. Using consistent definitions, outcomes, and reporting requirements will facilitate communication among researchers, reduce bias, and support systematic between-study comparisons, Mr. Ratcliffe and colleagues wrote.
 

Reaching General Neurologists

Epilepsy specialists are generally aware of reliable outcome predictors, Dr. Husain said, though they do not use models per se. “But the vast majority of patients with epilepsy are seen by general neurologists.” And the lack of awareness among these physicians and primary care practitioners drives a need for education to facilitate appropriate referrals to subspecialty centers, he said.

The stakes for timely referrals can be high. Although using appropriate outcome models improves patients’ quality of life sooner, said Dr. Husain, allowing seizures to go untreated or undertreated results in neuroplastic changes that hinder long-term seizure control.

The fact that all 32 included studies reflected a high risk of bias, and 9 studies raised high applicability concerns, raises questions regarding the models’ validity, he added. Mr. Ratcliffe and colleagues attributed both types of concerns to the fact that 20% of included studies used baseline treatment response data as outcome predictors.

Nevertheless, Dr. Husain cautioned against dismissing prediction models in newly diagnosed epilepsy. “Practicing neurologists need to realize that the perfect model has yet to be developed. But the current tools can be used to help manage patients with epilepsy and predict who will do well and not as well,” he said.

Dr. Husain is a member of the American Epilepsy Society. He has been a consultant and researcher for Marinus Pharmaceuticals, PranaQ, and UCB, and a consultant for Eisai, Jazz Pharmaceuticals, Merck, and uniQure. Study authors reported no funding sources or relevant conflicts of interest.

The most reliable predictors of remission in newly diagnosed epilepsy include patient history, seizure characteristics, and onset age, according to authors of a recent review. Clinical prediction models can help neurologists identify which patients could benefit from more aggressive early treatment, authors added, although concerns over bias and model applicability leave room for improvement.

Triggering Aggressive Treatments

“These models are helpful because if you can predict that someone is going to do well with one or two medications, that’s great,” said Aatif M. Husain, MD. “But if you know early on that someone likely will not do well, will need many medications, and still not have their seizures under control, you’re much more likely to be more aggressive with their management, such as closely refer them to a specialist epilepsy center and evaluate them for surgical treatment options. This could minimize the amount of time their seizures are inadequately controlled.” Dr. Husain is an epileptologist, neurologist, and sleep medicine specialist at Duke University Health System in Durham, North Carolina. Dr. Husain was not involved with the study, which was published in Epilepsia.

“But the other important finding is that these models so far have not been that great,” he added.

Prognosis Predictors

Investigators Corey Ratcliffe of the University of Liverpool in England and colleagues systematically searched MEDLINE and Embase for relevant publications, ultimately analyzing 48 models across 32 studies. The strongest predictors of seizure remission were history and seizure types or characteristics, the authors wrote, followed by onset age.

Regarding seizure history, a March 2018 JAMA Neurology study and a December 2013 BMC Neurology study linked factors such as history of seizures in the year pre-diagnosis, family history of epilepsy, and history of febrile seizures and of migraines with lower chances of seizure remission. Seizure types with increased chances of poor outcomes in the review included status epilepticus and seizures with complex or mixed etiologies. Additional seizure types associated with poor control include tonic-clonic seizures, frequent focal seizures, and seizures stemming from certain genetic predispositions, said Dr. Husain.

Although the roles of many of the foregoing factors are easily explained, he added, other variables’ impact is less clear. Younger onset often signals more refractory seizures, for example, while data regarding older onset are mixed. “Sometimes older individuals will have mild epilepsy due to a stroke, tumor, or something that can be relatively easily treated,” said Dr. Husain. Conversely, epilepsy can become more complicated if such patients take several medications and/or have coexisting medical problems that seizures or antiseizure medications exacerbate. “So sometimes it’s not so obvious.”
 

Incorporating Imaging, AI

Dr. Husain found it surprising that very few of the selected models incorporated EEG and MRI findings. “Subsequent research should look at those, since they are important diagnostic tests.” Moreover, he recommended including more sophisticated quantitative and connectivity analyses of EEG and MRI data. These analyses might provide additional prognostic information beyond a simple visual analysis of these tests, Dr. Husain explained, although their potential here remains unproven.

As for factors not represented in the review, he said, future studies will help clarify AI’s role in predicting newly diagnosed epilepsy outcomes. A study published in Epilepsia showed that among 248 potential pediatric surgical candidates, those whose providers received alerts based on machine learning analysis of prior visit notes were more likely to be referred for presurgical evaluation (9.8% versus 3.1%). Future clinical models will use AI to examine not only established elements of neurologic history, said Dr. Husain, but also other types of history such as socioeconomic characteristics, geographic location, and other such data.

Additionally, study authors recommended a standardized approach to prediction modeling, using Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines. Using consistent definitions, outcomes, and reporting requirements will facilitate communication among researchers, reduce bias, and support systematic between-study comparisons, Mr. Ratcliffe and colleagues wrote.
 

Reaching General Neurologists

Epilepsy specialists are generally aware of reliable outcome predictors, Dr. Husain said, though they do not use models per se. “But the vast majority of patients with epilepsy are seen by general neurologists.” And the lack of awareness among these physicians and primary care practitioners drives a need for education to facilitate appropriate referrals to subspecialty centers, he said.

The stakes for timely referrals can be high. Although using appropriate outcome models improves patients’ quality of life sooner, said Dr. Husain, allowing seizures to go untreated or undertreated results in neuroplastic changes that hinder long-term seizure control.

The fact that all 32 included studies reflected a high risk of bias, and 9 studies raised high applicability concerns, raises questions regarding the models’ validity, he added. Mr. Ratcliffe and colleagues attributed both types of concerns to the fact that 20% of included studies used baseline treatment response data as outcome predictors.

Nevertheless, Dr. Husain cautioned against dismissing prediction models in newly diagnosed epilepsy. “Practicing neurologists need to realize that the perfect model has yet to be developed. But the current tools can be used to help manage patients with epilepsy and predict who will do well and not as well,” he said.

Dr. Husain is a member of the American Epilepsy Society. He has been a consultant and researcher for Marinus Pharmaceuticals, PranaQ, and UCB, and a consultant for Eisai, Jazz Pharmaceuticals, Merck, and uniQure. Study authors reported no funding sources or relevant conflicts of interest.

WASHINGTON — As part of a quality improvement initiative, gastroenterologists at the University of Texas Health Science Center reduced endoscopic waste by using a single tool rather than multiple tools during colonoscopies, according to a study presented at Digestive Disease Week^® (DDW).

After discussing environmentally conscious practices during regular meetings, the odds of gastroenterologists using a single tool — either biopsy forceps or a snare — compared with multiple disposable tools was three times higher.

“The burden of waste is massive, with GI being the third-largest waste generator in healthcare. The number of procedures is increasing, which just means more waste, and we have to look at ways to reduce it,” said lead author Prateek Harne, MD, a gastroenterology fellow at the University of Texas Health Science Center.

Overall, the healthcare industry generates 8.5% of U.S. greenhouse emissions, with more than 70% coming from used instruments and supplies, he said. GI endoscopy generates 85,000 metric tons of carbon dioxide waste annually. That waste stems from high case volumes, patient travel, the decontamination process, and single-use devices.

After seeing the waste at his institution, Dr. Harne wondered how to reduce single-use device and nonrenewable waste, particularly the tools used during polypectomies. He and colleagues decided to focus on single-tool use and collected data about the tools used during screening colonoscopies for 8 weeks before an intervention.

As part of the intervention, Dr. Harne and colleagues discussed green endoscopy initiatives supported by North American gastrointestinal societies during a journal club meeting with gastroenterology faculty. They also discussed potential strategies to reduce waste in day-to-day practice during a monthly business meeting, particularly focused on being mindful of using tools during polypectomies. The meetings occurred 3 days apart.

Then Dr. Harne and colleagues collected data regarding tool use during screening colonoscopies, looking at the number and type of instruments used. Before the meetings, 210 patients underwent colonoscopies, including 34% that required no intervention, 32% that required one tool, and 33% that required multiple tools.

After the meetings, 112 patients underwent colonoscopies, including 34% that required no tools, 49% that used one tool, and 17% that used multiple tools. This represented a 17% increase in the use of one tool (P < .01) and a 16% decrease in the use of multiple tools (P < .01). The odds of using a single tool compared with multiple tools was 2.98, and there was a statistically significant increase in uptake of snare for polypectomy.

The study was limited by being at a single center, having a small sample size, and using a short-term assessment. At the same time, the findings show potential for a low-cost solution through open discussion with gastroenterologists.

“Sir Isaac Newton had two holes for two different sized cats in his home, but all of his cats ended up using the bigger hole,” Dr. Harne said in his conclusion. “Maybe we can do the same for polypectomies and use only the tools that we need.”

In an interview, Dr. Harne noted he spoke with the janitorial staff at his institution to learn more about endoscopy unit waste, including how much is recycled, how much is incinerated, and who handles the waste. He recognized the work being done in Europe to understand and reduce endoscopic waste and hopes U.S. groups begin to implement more measures.

“Gastroenterologists and their teams need to be more cognizant of the impact we have on the environment,” Dr. Harne said. “As our study shows, if providers are aware that they can and should use fewer tools to get the same results, it can lead to a statistically significant impact, just with a friendly reminder to reduce use.”

After the presentation, Dr. Harne discussed other shifts with conference attendees, such as not opening or unwrapping tools until needed during a procedure.

“Small changes could have big impacts. Everything that we do in QI [quality improvement] is meant to help patients and the environment,” said Amanda Krouse, MD, a research fellow at the University of California, San Diego, who was a moderator of the DDW session on GI fellow–directed QI projects.

In an interview, Alana Persaud, MD, an endoscopy fellow at Geisinger Medical Center in Danville, Pennsylvania, also a moderator of the session, said: “Ultimately, the medical services we’re providing are for the longevity of our patients, but at the same time, we don’t want it to be to the detriment of the environment, so paying attention to green endoscopy when we can preserve and use more discretion with our devices is worth it so we can all thrive together.”

Dr. Harne did not have any disclosures.

WASHINGTON — As part of a quality improvement initiative, gastroenterologists at the University of Texas Health Science Center reduced endoscopic waste by using a single tool rather than multiple tools during colonoscopies, according to a study presented at Digestive Disease Week^® (DDW).

After discussing environmentally conscious practices during regular meetings, the odds of gastroenterologists using a single tool — either biopsy forceps or a snare — compared with multiple disposable tools was three times higher.

“The burden of waste is massive, with GI being the third-largest waste generator in healthcare. The number of procedures is increasing, which just means more waste, and we have to look at ways to reduce it,” said lead author Prateek Harne, MD, a gastroenterology fellow at the University of Texas Health Science Center.

Overall, the healthcare industry generates 8.5% of U.S. greenhouse emissions, with more than 70% coming from used instruments and supplies, he said. GI endoscopy generates 85,000 metric tons of carbon dioxide waste annually. That waste stems from high case volumes, patient travel, the decontamination process, and single-use devices.

After seeing the waste at his institution, Dr. Harne wondered how to reduce single-use device and nonrenewable waste, particularly the tools used during polypectomies. He and colleagues decided to focus on single-tool use and collected data about the tools used during screening colonoscopies for 8 weeks before an intervention.

As part of the intervention, Dr. Harne and colleagues discussed green endoscopy initiatives supported by North American gastrointestinal societies during a journal club meeting with gastroenterology faculty. They also discussed potential strategies to reduce waste in day-to-day practice during a monthly business meeting, particularly focused on being mindful of using tools during polypectomies. The meetings occurred 3 days apart.

Then Dr. Harne and colleagues collected data regarding tool use during screening colonoscopies, looking at the number and type of instruments used. Before the meetings, 210 patients underwent colonoscopies, including 34% that required no intervention, 32% that required one tool, and 33% that required multiple tools.

After the meetings, 112 patients underwent colonoscopies, including 34% that required no tools, 49% that used one tool, and 17% that used multiple tools. This represented a 17% increase in the use of one tool (P < .01) and a 16% decrease in the use of multiple tools (P < .01). The odds of using a single tool compared with multiple tools was 2.98, and there was a statistically significant increase in uptake of snare for polypectomy.

The study was limited by being at a single center, having a small sample size, and using a short-term assessment. At the same time, the findings show potential for a low-cost solution through open discussion with gastroenterologists.

“Sir Isaac Newton had two holes for two different sized cats in his home, but all of his cats ended up using the bigger hole,” Dr. Harne said in his conclusion. “Maybe we can do the same for polypectomies and use only the tools that we need.”

In an interview, Dr. Harne noted he spoke with the janitorial staff at his institution to learn more about endoscopy unit waste, including how much is recycled, how much is incinerated, and who handles the waste. He recognized the work being done in Europe to understand and reduce endoscopic waste and hopes U.S. groups begin to implement more measures.

“Gastroenterologists and their teams need to be more cognizant of the impact we have on the environment,” Dr. Harne said. “As our study shows, if providers are aware that they can and should use fewer tools to get the same results, it can lead to a statistically significant impact, just with a friendly reminder to reduce use.”

After the presentation, Dr. Harne discussed other shifts with conference attendees, such as not opening or unwrapping tools until needed during a procedure.

“Small changes could have big impacts. Everything that we do in QI [quality improvement] is meant to help patients and the environment,” said Amanda Krouse, MD, a research fellow at the University of California, San Diego, who was a moderator of the DDW session on GI fellow–directed QI projects.

In an interview, Alana Persaud, MD, an endoscopy fellow at Geisinger Medical Center in Danville, Pennsylvania, also a moderator of the session, said: “Ultimately, the medical services we’re providing are for the longevity of our patients, but at the same time, we don’t want it to be to the detriment of the environment, so paying attention to green endoscopy when we can preserve and use more discretion with our devices is worth it so we can all thrive together.”

Dr. Harne did not have any disclosures.

WASHINGTON — As part of a quality improvement initiative, gastroenterologists at the University of Texas Health Science Center reduced endoscopic waste by using a single tool rather than multiple tools during colonoscopies, according to a study presented at Digestive Disease Week^® (DDW).

After discussing environmentally conscious practices during regular meetings, the odds of gastroenterologists using a single tool — either biopsy forceps or a snare — compared with multiple disposable tools was three times higher.

“The burden of waste is massive, with GI being the third-largest waste generator in healthcare. The number of procedures is increasing, which just means more waste, and we have to look at ways to reduce it,” said lead author Prateek Harne, MD, a gastroenterology fellow at the University of Texas Health Science Center.

Overall, the healthcare industry generates 8.5% of U.S. greenhouse emissions, with more than 70% coming from used instruments and supplies, he said. GI endoscopy generates 85,000 metric tons of carbon dioxide waste annually. That waste stems from high case volumes, patient travel, the decontamination process, and single-use devices.

After seeing the waste at his institution, Dr. Harne wondered how to reduce single-use device and nonrenewable waste, particularly the tools used during polypectomies. He and colleagues decided to focus on single-tool use and collected data about the tools used during screening colonoscopies for 8 weeks before an intervention.

As part of the intervention, Dr. Harne and colleagues discussed green endoscopy initiatives supported by North American gastrointestinal societies during a journal club meeting with gastroenterology faculty. They also discussed potential strategies to reduce waste in day-to-day practice during a monthly business meeting, particularly focused on being mindful of using tools during polypectomies. The meetings occurred 3 days apart.

Then Dr. Harne and colleagues collected data regarding tool use during screening colonoscopies, looking at the number and type of instruments used. Before the meetings, 210 patients underwent colonoscopies, including 34% that required no intervention, 32% that required one tool, and 33% that required multiple tools.

After the meetings, 112 patients underwent colonoscopies, including 34% that required no tools, 49% that used one tool, and 17% that used multiple tools. This represented a 17% increase in the use of one tool (P < .01) and a 16% decrease in the use of multiple tools (P < .01). The odds of using a single tool compared with multiple tools was 2.98, and there was a statistically significant increase in uptake of snare for polypectomy.

The study was limited by being at a single center, having a small sample size, and using a short-term assessment. At the same time, the findings show potential for a low-cost solution through open discussion with gastroenterologists.

“Sir Isaac Newton had two holes for two different sized cats in his home, but all of his cats ended up using the bigger hole,” Dr. Harne said in his conclusion. “Maybe we can do the same for polypectomies and use only the tools that we need.”

In an interview, Dr. Harne noted he spoke with the janitorial staff at his institution to learn more about endoscopy unit waste, including how much is recycled, how much is incinerated, and who handles the waste. He recognized the work being done in Europe to understand and reduce endoscopic waste and hopes U.S. groups begin to implement more measures.

“Gastroenterologists and their teams need to be more cognizant of the impact we have on the environment,” Dr. Harne said. “As our study shows, if providers are aware that they can and should use fewer tools to get the same results, it can lead to a statistically significant impact, just with a friendly reminder to reduce use.”

After the presentation, Dr. Harne discussed other shifts with conference attendees, such as not opening or unwrapping tools until needed during a procedure.

“Small changes could have big impacts. Everything that we do in QI [quality improvement] is meant to help patients and the environment,” said Amanda Krouse, MD, a research fellow at the University of California, San Diego, who was a moderator of the DDW session on GI fellow–directed QI projects.

In an interview, Alana Persaud, MD, an endoscopy fellow at Geisinger Medical Center in Danville, Pennsylvania, also a moderator of the session, said: “Ultimately, the medical services we’re providing are for the longevity of our patients, but at the same time, we don’t want it to be to the detriment of the environment, so paying attention to green endoscopy when we can preserve and use more discretion with our devices is worth it so we can all thrive together.”

Dr. Harne did not have any disclosures.

The annual production of plastic worldwide has increased exponentially from about 2 million tons in 1950 to 460 million tons in 2019, and current levels are expected to triple by 2060.

Plastic contains more than 10,000 chemicals, including carcinogenic substances and endocrine disruptors. Plastic and associated chemicals are responsible for widespread pollution, contaminating aquatic (marine and freshwater), terrestrial, and atmospheric environments globally.

Atmospheric concentrations of plastic particles are on the rise, to the extent that in a remote station in the Eastern Alps in Austria, the contribution of micro- and nanoplastics (MNPs) to organic matter was comparable to data collected at an urban site.

The ocean is the ultimate destination for much of the plastic. All oceans, on the surface and in the depths, contain plastic, which is even found in polar sea ice. Many plastics seem to resist decomposition in the ocean and could persist in the environment for decades. Macro- and microplastic (MP) particles have been identified in hundreds of marine species, including species consumed by humans.

The quantity and fate of MP particles (> 10 µm) and smaller nanoplastics (< 10 µm) in aquatic environments are poorly understood, but what is most concerning is their ability to cross biologic barriers and the potential harm associated with their mobility in biologic systems.
 

MNP Exposure

MNPs can originate from a wide variety of sources, including food, beverages, and food product packaging. Water bottles represent a significant source of ingestible MNPs for people in their daily lives. Recent estimates, using stimulated Raman scattering imaging, documented a concentration of MNP of approximately 2.4 ± 1.3 × 10⁵ particles per liter of bottled water. Around 90% are nanoplastics, which is two to three orders of magnitude higher than previously reported results for larger MPs.

MNPs enter the body primarily through ingestion or inhalation. For example, MNPs can be ingested by drinking liquids or eating food that has been stored or heated in plastic containers from which they have leaked or by using toothpaste that contains them. Infants are exposed to MPs from artificial milk preparation in polypropylene baby bottles, with higher levels than previously detected and ranging from 14,600 to 4,550,000 particles per capita per day.
 

MNP and Biologic Systems

The possible formation of hetero-aggregates between nanoplastics and natural organic matter has long been recognized as a potential challenge in the analysis of nanoplastics and can influence toxicologic results in biologic exposure. The direct visualization of such hetero-aggregates in real-world samples supports these concerns, but the analysis of MNPs with traditional techniques remains challenging. Unlike engineered nanoparticles (prepared in the laboratory as model systems), the nanoplastics in the environment are label-free and exhibit significant heterogeneity in chemical composition and morphology.

A systematic analysis of evidence on the toxic effects of MNPs on murine models, however, showed that 52.78% of biologic endpoints (related to glucose metabolism, reproduction, oxidative stress, and lipid metabolism) were significantly affected by MNP exposure.
 

Between Risk and Toxicity

MNP can enter the body in vivo through the digestive tract, respiratory tract, and skin contact. On average, humans could ingest from 0.1 to 5 g of MNP per week through various exposure routes.

MNPs are a potential risk factor for cardiovascular diseases, as suggested by a recent study on 257 patients with carotid atheromatous plaques. In 58.4% of cases, polyvinyl chloride was detected in the carotid artery plaque, with an average level of 5.2 ± 2.4 μg/mg of plaque. Patients with MNPs inside the atheroma had a higher risk (relative risk, 4.53) for a composite cardiovascular event of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than participants where MNPs were not detectable inside the atheromatous plaque.

The potential link between inflammatory bowel disease (IBD) and MPs has been hypothesized by a study that reported a higher fecal MP concentration in patients with IBD than in healthy individuals. Fecal MP level was correlated with disease severity.

However, these studies have not demonstrated a causal relationship between MNPs and disease, and the way MNPs may influence cellular functions and induce stress responses is not yet well understood.
 

Future Scenarios

Current evidence confirms the fragmentation of plastic beyond the micrometer level and has unequivocally detected nanoplastics in real samples. As with many other particle distributions of the same size in the natural world, there are substantially more nanoplastics, despite their invisibility with conventional imaging techniques, than particles larger than the micron size.

The initial results of studies on MNPs in humans will stimulate future research on the amounts of MNPs that accumulate in tissue over a person’s lifetime. Researchers also will examine how the particles’ characteristics, including their chemical composition, size, and shape, can influence organs and tissues.

The way MNPs can cause harm, including through effects on the immune system and microbiome, will need to be clarified by investigating possible direct cytotoxic effects, consistent with the introductory statement of the Organization for Economic Cooperation and Development global policy forum on plastics, which states, “Plastic pollution is one of the great environmental challenges of the 21st century, causing wide-ranging damage to ecosystems and human health.”

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

The annual production of plastic worldwide has increased exponentially from about 2 million tons in 1950 to 460 million tons in 2019, and current levels are expected to triple by 2060.

Plastic contains more than 10,000 chemicals, including carcinogenic substances and endocrine disruptors. Plastic and associated chemicals are responsible for widespread pollution, contaminating aquatic (marine and freshwater), terrestrial, and atmospheric environments globally.

Atmospheric concentrations of plastic particles are on the rise, to the extent that in a remote station in the Eastern Alps in Austria, the contribution of micro- and nanoplastics (MNPs) to organic matter was comparable to data collected at an urban site.

The ocean is the ultimate destination for much of the plastic. All oceans, on the surface and in the depths, contain plastic, which is even found in polar sea ice. Many plastics seem to resist decomposition in the ocean and could persist in the environment for decades. Macro- and microplastic (MP) particles have been identified in hundreds of marine species, including species consumed by humans.

The quantity and fate of MP particles (> 10 µm) and smaller nanoplastics (< 10 µm) in aquatic environments are poorly understood, but what is most concerning is their ability to cross biologic barriers and the potential harm associated with their mobility in biologic systems.
 

MNP Exposure

MNPs can originate from a wide variety of sources, including food, beverages, and food product packaging. Water bottles represent a significant source of ingestible MNPs for people in their daily lives. Recent estimates, using stimulated Raman scattering imaging, documented a concentration of MNP of approximately 2.4 ± 1.3 × 10⁵ particles per liter of bottled water. Around 90% are nanoplastics, which is two to three orders of magnitude higher than previously reported results for larger MPs.

MNPs enter the body primarily through ingestion or inhalation. For example, MNPs can be ingested by drinking liquids or eating food that has been stored or heated in plastic containers from which they have leaked or by using toothpaste that contains them. Infants are exposed to MPs from artificial milk preparation in polypropylene baby bottles, with higher levels than previously detected and ranging from 14,600 to 4,550,000 particles per capita per day.
 

MNP and Biologic Systems

The possible formation of hetero-aggregates between nanoplastics and natural organic matter has long been recognized as a potential challenge in the analysis of nanoplastics and can influence toxicologic results in biologic exposure. The direct visualization of such hetero-aggregates in real-world samples supports these concerns, but the analysis of MNPs with traditional techniques remains challenging. Unlike engineered nanoparticles (prepared in the laboratory as model systems), the nanoplastics in the environment are label-free and exhibit significant heterogeneity in chemical composition and morphology.

A systematic analysis of evidence on the toxic effects of MNPs on murine models, however, showed that 52.78% of biologic endpoints (related to glucose metabolism, reproduction, oxidative stress, and lipid metabolism) were significantly affected by MNP exposure.
 

Between Risk and Toxicity

MNP can enter the body in vivo through the digestive tract, respiratory tract, and skin contact. On average, humans could ingest from 0.1 to 5 g of MNP per week through various exposure routes.

MNPs are a potential risk factor for cardiovascular diseases, as suggested by a recent study on 257 patients with carotid atheromatous plaques. In 58.4% of cases, polyvinyl chloride was detected in the carotid artery plaque, with an average level of 5.2 ± 2.4 μg/mg of plaque. Patients with MNPs inside the atheroma had a higher risk (relative risk, 4.53) for a composite cardiovascular event of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than participants where MNPs were not detectable inside the atheromatous plaque.

The potential link between inflammatory bowel disease (IBD) and MPs has been hypothesized by a study that reported a higher fecal MP concentration in patients with IBD than in healthy individuals. Fecal MP level was correlated with disease severity.

However, these studies have not demonstrated a causal relationship between MNPs and disease, and the way MNPs may influence cellular functions and induce stress responses is not yet well understood.
 

Future Scenarios

Current evidence confirms the fragmentation of plastic beyond the micrometer level and has unequivocally detected nanoplastics in real samples. As with many other particle distributions of the same size in the natural world, there are substantially more nanoplastics, despite their invisibility with conventional imaging techniques, than particles larger than the micron size.

The initial results of studies on MNPs in humans will stimulate future research on the amounts of MNPs that accumulate in tissue over a person’s lifetime. Researchers also will examine how the particles’ characteristics, including their chemical composition, size, and shape, can influence organs and tissues.

The way MNPs can cause harm, including through effects on the immune system and microbiome, will need to be clarified by investigating possible direct cytotoxic effects, consistent with the introductory statement of the Organization for Economic Cooperation and Development global policy forum on plastics, which states, “Plastic pollution is one of the great environmental challenges of the 21st century, causing wide-ranging damage to ecosystems and human health.”

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

The annual production of plastic worldwide has increased exponentially from about 2 million tons in 1950 to 460 million tons in 2019, and current levels are expected to triple by 2060.

Plastic contains more than 10,000 chemicals, including carcinogenic substances and endocrine disruptors. Plastic and associated chemicals are responsible for widespread pollution, contaminating aquatic (marine and freshwater), terrestrial, and atmospheric environments globally.

Atmospheric concentrations of plastic particles are on the rise, to the extent that in a remote station in the Eastern Alps in Austria, the contribution of micro- and nanoplastics (MNPs) to organic matter was comparable to data collected at an urban site.

The ocean is the ultimate destination for much of the plastic. All oceans, on the surface and in the depths, contain plastic, which is even found in polar sea ice. Many plastics seem to resist decomposition in the ocean and could persist in the environment for decades. Macro- and microplastic (MP) particles have been identified in hundreds of marine species, including species consumed by humans.

The quantity and fate of MP particles (> 10 µm) and smaller nanoplastics (< 10 µm) in aquatic environments are poorly understood, but what is most concerning is their ability to cross biologic barriers and the potential harm associated with their mobility in biologic systems.
 

MNP Exposure

MNPs can originate from a wide variety of sources, including food, beverages, and food product packaging. Water bottles represent a significant source of ingestible MNPs for people in their daily lives. Recent estimates, using stimulated Raman scattering imaging, documented a concentration of MNP of approximately 2.4 ± 1.3 × 10⁵ particles per liter of bottled water. Around 90% are nanoplastics, which is two to three orders of magnitude higher than previously reported results for larger MPs.

MNPs enter the body primarily through ingestion or inhalation. For example, MNPs can be ingested by drinking liquids or eating food that has been stored or heated in plastic containers from which they have leaked or by using toothpaste that contains them. Infants are exposed to MPs from artificial milk preparation in polypropylene baby bottles, with higher levels than previously detected and ranging from 14,600 to 4,550,000 particles per capita per day.
 

MNP and Biologic Systems

The possible formation of hetero-aggregates between nanoplastics and natural organic matter has long been recognized as a potential challenge in the analysis of nanoplastics and can influence toxicologic results in biologic exposure. The direct visualization of such hetero-aggregates in real-world samples supports these concerns, but the analysis of MNPs with traditional techniques remains challenging. Unlike engineered nanoparticles (prepared in the laboratory as model systems), the nanoplastics in the environment are label-free and exhibit significant heterogeneity in chemical composition and morphology.

A systematic analysis of evidence on the toxic effects of MNPs on murine models, however, showed that 52.78% of biologic endpoints (related to glucose metabolism, reproduction, oxidative stress, and lipid metabolism) were significantly affected by MNP exposure.
 

Between Risk and Toxicity

MNP can enter the body in vivo through the digestive tract, respiratory tract, and skin contact. On average, humans could ingest from 0.1 to 5 g of MNP per week through various exposure routes.

MNPs are a potential risk factor for cardiovascular diseases, as suggested by a recent study on 257 patients with carotid atheromatous plaques. In 58.4% of cases, polyvinyl chloride was detected in the carotid artery plaque, with an average level of 5.2 ± 2.4 μg/mg of plaque. Patients with MNPs inside the atheroma had a higher risk (relative risk, 4.53) for a composite cardiovascular event of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than participants where MNPs were not detectable inside the atheromatous plaque.

The potential link between inflammatory bowel disease (IBD) and MPs has been hypothesized by a study that reported a higher fecal MP concentration in patients with IBD than in healthy individuals. Fecal MP level was correlated with disease severity.

However, these studies have not demonstrated a causal relationship between MNPs and disease, and the way MNPs may influence cellular functions and induce stress responses is not yet well understood.
 

Future Scenarios

Current evidence confirms the fragmentation of plastic beyond the micrometer level and has unequivocally detected nanoplastics in real samples. As with many other particle distributions of the same size in the natural world, there are substantially more nanoplastics, despite their invisibility with conventional imaging techniques, than particles larger than the micron size.

The initial results of studies on MNPs in humans will stimulate future research on the amounts of MNPs that accumulate in tissue over a person’s lifetime. Researchers also will examine how the particles’ characteristics, including their chemical composition, size, and shape, can influence organs and tissues.

The way MNPs can cause harm, including through effects on the immune system and microbiome, will need to be clarified by investigating possible direct cytotoxic effects, consistent with the introductory statement of the Organization for Economic Cooperation and Development global policy forum on plastics, which states, “Plastic pollution is one of the great environmental challenges of the 21st century, causing wide-ranging damage to ecosystems and human health.”

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

People with HIV who wish to breastfeed their infants should have sustained viral suppression, with a viral load below 50 copies per mL, to have the least risk of transmitting HIV to their baby aside from avoiding breastfeeding altogether, according to a new clinical report from the American Academy of Pediatrics (AAP).

“The risk of HIV transmission via breastfeeding from a parent with HIV who is receiving antiretroviral treatment (ART) and is virally suppressed is estimated to be less than 1%,” Lisa Abuogi, MD, an associate professor of pediatric infectious disease at the University of Colorado Anschutz Medical Campus, and her colleagues wrote in Pediatrics. For people living with HIV in the United States, however, the AAP recommends that “avoidance of breastfeeding is the only infant feeding option with 0% risk of HIV transmission.”

The authors go on to suggest that pediatricians “be prepared to offer a family-centered, nonjudgmental, harm reduction approach” to support people with HIV who do want to breastfeed and have sustained viral suppression. Parents with HIV who are not on ART or who do not have adequate viral suppression should be advised against breastfeeding, the report states. Members of the AAP Committee on Pediatric and Adolescent HIV and of the AAP Section on Breastfeeding coauthored the clinical report.

“The new guidelines emphasize the importance of patient-centered counseling as the foundation for shared decision-making, allowing patients and pediatric providers to make feeding decisions together and for the first time really giving support to people with HIV in the U.S. who want to breastfeed,” Danna Biala, MD, MS, an attending pediatrician at Children’s Hospital at Montefiore and an assistant professor at Albert Einstein College of Medicine, told MDedge News.

Dr. Biala was not involved in the development of the report, but she said the AAP’s guidance reflects the recent shift in the stance of the Centers for Disease Control and Prevention (CDC) regarding breastfeeding among people who are HIV+. Recommendations from the CDC and the U.S. Department of Health and Human Services (HHS) were updated in 2023.

“I’m glad that the AAP is putting out guidelines on infant feeding for people with HIV,” Dr. Biala said. “For so long in the U.S., pediatricians have been advising all mothers with HIV to avoid breastfeeding, believing that the risk of transmission outweighed the benefits of breastfeeding.”

The updated guidance from HHS in 2023 “was revolutionary in supporting people with HIV in low-risk situations who want to breastfeed,” Dr. Biala said, but “clear protocols for monitoring and follow-up were not in place,” which these AAP guidelines help address.
 

Prior Discordance Between Global, U.S. Guidance

An estimated 5,000 people with HIV give birth each year in the United States, and up to one third of pregnant people with HIV may be unaware of their HIV status, the AAP report notes. Pediatric healthcare professionals in the United States therefore need to be aware of recommendations related to HIV testing of pregnant people and of counseling the feeding of infants exposed to HIV. The report recommends opt-out HIV testing at the first prenatal visit and then possibly retesting in the third trimester in areas with high HIV incidence or for people at high risk for HIV or with signs or symptoms of acute HIV infection.

The report also highlights the health benefits of breastfeeding to both the infant and the breastfeeding parent, but notes the CDC’s historical recommendation against breastfeeding for people who are HIV+. The WHO, meanwhile, began recommending in 2016 that infants be breastfed through 12 to 24 months old if the parent was on ART and/or the infant was receiving antiretroviral (ARV) prophylaxis, since research showed those treatments were effective in reducing transmission risk.

Still, an estimated 30% of perinatal HIV transmission occurs via breastfeeding worldwide, primarily from people with HIV who are not on ART or are not adequately virally suppressed. Without parental ART or infant ARV prophylaxis, HIV transmission risk to infants via breastfeeding is highest, about 5%-6%, in the first 4-6 weeks of life. Risk then declines to about 0.9% a month thereafter. The AAP report goes on to describe factors that increase or decrease the likelihood of transmission during breastfeeding, but it notes that neither ART in the breastfeeding person nor ARV prophylaxis in the infant completely eliminates the risk of HIV transmission during breastfeeding. There have been rare cases where transmission occurred despite viral suppression in the person with HIV.

Among the reasons people with HIV have expressed a desire to breastfeed are wanting to bond with their infant, wanting to provide optimal nutrition and health benefits to their baby, and meeting cultural expectations, including the desire not to disclose their HIV infection status to family or friends by virtue of not breastfeeding.

“Among immigrant and refugee populations, the discordance between infant feeding guidelines in the United States and their country of birth may result in confusion, especially among parents who breastfed previous infants,” the AAP report also notes. Further, not breastfeeding could compound health disparities already more likely to be present among those living with HIV.

Discussions about infant feeding with parents with HIV should therefore “begin as early as possible and involve a multidisciplinary team that might include the pediatric primary care provider (once identified), a pediatric HIV expert, the breastfeeding parent’s HIV care and obstetric providers, and lactation consultants,” the report states. ”The parent’s motivations for breastfeeding should be explored and counseling provided on the risks and benefits of each feeding option, including breastfeeding, formula feeding, or certified, banked donor human milk.” The statement emphasizes the need for providing counseling in a “non-judgmental, respectful way, recognizing potential drivers for their decisions such as avoidance of stigma, prior experience with breastfeeding, and cultural contributors.”
 

Clear Recommendations Can Help Providers

The AAP’s statement that “replacement feeding (with formula or certified, banked donor human milk) is the only option that is 100% certain to prevent postnatal transmission of HIV” feels like it takes a “more conservative or discouraging approach” to breastfeeding than the CDC or WHO guidelines, Alissa Parker-Smith, APRN, DNP, CPNP-PC, IBCLC, a nurse practitioner and lactation consultant at PrimaryPlus, a Federally Qualified Health Clinic in Ashland, Kentucky, told MDedge. But she said they do clearly align with the CDC guidelines, and their differences from the WHO guidelines make sense in light of the different populations served by the WHO versus the U.S. agencies.

“Unclean water for formula preparation and a reduced or lack of access to formula in general can lead to many other risks of death for the infant other than the very small risk of HIV infection from breastfeeding from an HIV+ parent,” Ms. Parker-Smith said. “In the U.S. we generally have consistent access to clean water and safe formula as well as social structures to help families have access to formula, so the very small risk of HIV being passed to the infant is far greater than an infant in the U.S. dying as a result of unclean water or formula contamination.”

Ms. Parker-Smith also said the AAP recommendations seem thorough in helping pediatric practitioners counsel and support parents with HIV. “If I had a parent who is HIV+ walk in the door today wanting to breastfeed their infant, the AAP guidelines give me specific steps to make me feel confident in helping that parent breastfeed as safely as possible as well as providing education to assist that parent through the decision process,” she said.

Dr. Biala agreed, noting that the clinical report “very clearly delineates recommendations for different groups of people: those in labor or postpartum with undocumented HIV infection status, pregnant and postpartum people with HIV, those without HIV but at high risk of acquiring it, and those with suspected acute HIV infection while breastfeeding.” Dr. Biala said the report “provides concrete, detailed, and easy-to-follow guidance on comprehensive counseling, strategies to minimize risk of transmission, and infant screening timelines.”

How easily the guidelines can be implemented will depend on the existing resources at different institutions in the United States, Dr. Biala added.

“In hospitals and clinics that have, or could easily have, systems in place to ensure follow-up and regular assessment during breastfeeding, the guidelines could be implemented fairly quickly,” she said. “It might be more challenging in areas with inadequate or limited access to multidisciplinary team members, including HIV care providers and lactation consultants.”

The report did not use external funding, and the authors reported no disclosures. Dr. Abuogi and Ms. Parker-Smith have no disclosures.

People with HIV who wish to breastfeed their infants should have sustained viral suppression, with a viral load below 50 copies per mL, to have the least risk of transmitting HIV to their baby aside from avoiding breastfeeding altogether, according to a new clinical report from the American Academy of Pediatrics (AAP).

“The risk of HIV transmission via breastfeeding from a parent with HIV who is receiving antiretroviral treatment (ART) and is virally suppressed is estimated to be less than 1%,” Lisa Abuogi, MD, an associate professor of pediatric infectious disease at the University of Colorado Anschutz Medical Campus, and her colleagues wrote in Pediatrics. For people living with HIV in the United States, however, the AAP recommends that “avoidance of breastfeeding is the only infant feeding option with 0% risk of HIV transmission.”

The authors go on to suggest that pediatricians “be prepared to offer a family-centered, nonjudgmental, harm reduction approach” to support people with HIV who do want to breastfeed and have sustained viral suppression. Parents with HIV who are not on ART or who do not have adequate viral suppression should be advised against breastfeeding, the report states. Members of the AAP Committee on Pediatric and Adolescent HIV and of the AAP Section on Breastfeeding coauthored the clinical report.

“The new guidelines emphasize the importance of patient-centered counseling as the foundation for shared decision-making, allowing patients and pediatric providers to make feeding decisions together and for the first time really giving support to people with HIV in the U.S. who want to breastfeed,” Danna Biala, MD, MS, an attending pediatrician at Children’s Hospital at Montefiore and an assistant professor at Albert Einstein College of Medicine, told MDedge News.

Dr. Biala was not involved in the development of the report, but she said the AAP’s guidance reflects the recent shift in the stance of the Centers for Disease Control and Prevention (CDC) regarding breastfeeding among people who are HIV+. Recommendations from the CDC and the U.S. Department of Health and Human Services (HHS) were updated in 2023.

“I’m glad that the AAP is putting out guidelines on infant feeding for people with HIV,” Dr. Biala said. “For so long in the U.S., pediatricians have been advising all mothers with HIV to avoid breastfeeding, believing that the risk of transmission outweighed the benefits of breastfeeding.”

The updated guidance from HHS in 2023 “was revolutionary in supporting people with HIV in low-risk situations who want to breastfeed,” Dr. Biala said, but “clear protocols for monitoring and follow-up were not in place,” which these AAP guidelines help address.
 

Prior Discordance Between Global, U.S. Guidance

An estimated 5,000 people with HIV give birth each year in the United States, and up to one third of pregnant people with HIV may be unaware of their HIV status, the AAP report notes. Pediatric healthcare professionals in the United States therefore need to be aware of recommendations related to HIV testing of pregnant people and of counseling the feeding of infants exposed to HIV. The report recommends opt-out HIV testing at the first prenatal visit and then possibly retesting in the third trimester in areas with high HIV incidence or for people at high risk for HIV or with signs or symptoms of acute HIV infection.

The report also highlights the health benefits of breastfeeding to both the infant and the breastfeeding parent, but notes the CDC’s historical recommendation against breastfeeding for people who are HIV+. The WHO, meanwhile, began recommending in 2016 that infants be breastfed through 12 to 24 months old if the parent was on ART and/or the infant was receiving antiretroviral (ARV) prophylaxis, since research showed those treatments were effective in reducing transmission risk.

Still, an estimated 30% of perinatal HIV transmission occurs via breastfeeding worldwide, primarily from people with HIV who are not on ART or are not adequately virally suppressed. Without parental ART or infant ARV prophylaxis, HIV transmission risk to infants via breastfeeding is highest, about 5%-6%, in the first 4-6 weeks of life. Risk then declines to about 0.9% a month thereafter. The AAP report goes on to describe factors that increase or decrease the likelihood of transmission during breastfeeding, but it notes that neither ART in the breastfeeding person nor ARV prophylaxis in the infant completely eliminates the risk of HIV transmission during breastfeeding. There have been rare cases where transmission occurred despite viral suppression in the person with HIV.

Among the reasons people with HIV have expressed a desire to breastfeed are wanting to bond with their infant, wanting to provide optimal nutrition and health benefits to their baby, and meeting cultural expectations, including the desire not to disclose their HIV infection status to family or friends by virtue of not breastfeeding.

“Among immigrant and refugee populations, the discordance between infant feeding guidelines in the United States and their country of birth may result in confusion, especially among parents who breastfed previous infants,” the AAP report also notes. Further, not breastfeeding could compound health disparities already more likely to be present among those living with HIV.

Discussions about infant feeding with parents with HIV should therefore “begin as early as possible and involve a multidisciplinary team that might include the pediatric primary care provider (once identified), a pediatric HIV expert, the breastfeeding parent’s HIV care and obstetric providers, and lactation consultants,” the report states. ”The parent’s motivations for breastfeeding should be explored and counseling provided on the risks and benefits of each feeding option, including breastfeeding, formula feeding, or certified, banked donor human milk.” The statement emphasizes the need for providing counseling in a “non-judgmental, respectful way, recognizing potential drivers for their decisions such as avoidance of stigma, prior experience with breastfeeding, and cultural contributors.”
 

Clear Recommendations Can Help Providers

The AAP’s statement that “replacement feeding (with formula or certified, banked donor human milk) is the only option that is 100% certain to prevent postnatal transmission of HIV” feels like it takes a “more conservative or discouraging approach” to breastfeeding than the CDC or WHO guidelines, Alissa Parker-Smith, APRN, DNP, CPNP-PC, IBCLC, a nurse practitioner and lactation consultant at PrimaryPlus, a Federally Qualified Health Clinic in Ashland, Kentucky, told MDedge. But she said they do clearly align with the CDC guidelines, and their differences from the WHO guidelines make sense in light of the different populations served by the WHO versus the U.S. agencies.

“Unclean water for formula preparation and a reduced or lack of access to formula in general can lead to many other risks of death for the infant other than the very small risk of HIV infection from breastfeeding from an HIV+ parent,” Ms. Parker-Smith said. “In the U.S. we generally have consistent access to clean water and safe formula as well as social structures to help families have access to formula, so the very small risk of HIV being passed to the infant is far greater than an infant in the U.S. dying as a result of unclean water or formula contamination.”

Ms. Parker-Smith also said the AAP recommendations seem thorough in helping pediatric practitioners counsel and support parents with HIV. “If I had a parent who is HIV+ walk in the door today wanting to breastfeed their infant, the AAP guidelines give me specific steps to make me feel confident in helping that parent breastfeed as safely as possible as well as providing education to assist that parent through the decision process,” she said.

Dr. Biala agreed, noting that the clinical report “very clearly delineates recommendations for different groups of people: those in labor or postpartum with undocumented HIV infection status, pregnant and postpartum people with HIV, those without HIV but at high risk of acquiring it, and those with suspected acute HIV infection while breastfeeding.” Dr. Biala said the report “provides concrete, detailed, and easy-to-follow guidance on comprehensive counseling, strategies to minimize risk of transmission, and infant screening timelines.”

How easily the guidelines can be implemented will depend on the existing resources at different institutions in the United States, Dr. Biala added.

“In hospitals and clinics that have, or could easily have, systems in place to ensure follow-up and regular assessment during breastfeeding, the guidelines could be implemented fairly quickly,” she said. “It might be more challenging in areas with inadequate or limited access to multidisciplinary team members, including HIV care providers and lactation consultants.”

The report did not use external funding, and the authors reported no disclosures. Dr. Abuogi and Ms. Parker-Smith have no disclosures.

People with HIV who wish to breastfeed their infants should have sustained viral suppression, with a viral load below 50 copies per mL, to have the least risk of transmitting HIV to their baby aside from avoiding breastfeeding altogether, according to a new clinical report from the American Academy of Pediatrics (AAP).

“The risk of HIV transmission via breastfeeding from a parent with HIV who is receiving antiretroviral treatment (ART) and is virally suppressed is estimated to be less than 1%,” Lisa Abuogi, MD, an associate professor of pediatric infectious disease at the University of Colorado Anschutz Medical Campus, and her colleagues wrote in Pediatrics. For people living with HIV in the United States, however, the AAP recommends that “avoidance of breastfeeding is the only infant feeding option with 0% risk of HIV transmission.”

The authors go on to suggest that pediatricians “be prepared to offer a family-centered, nonjudgmental, harm reduction approach” to support people with HIV who do want to breastfeed and have sustained viral suppression. Parents with HIV who are not on ART or who do not have adequate viral suppression should be advised against breastfeeding, the report states. Members of the AAP Committee on Pediatric and Adolescent HIV and of the AAP Section on Breastfeeding coauthored the clinical report.

“The new guidelines emphasize the importance of patient-centered counseling as the foundation for shared decision-making, allowing patients and pediatric providers to make feeding decisions together and for the first time really giving support to people with HIV in the U.S. who want to breastfeed,” Danna Biala, MD, MS, an attending pediatrician at Children’s Hospital at Montefiore and an assistant professor at Albert Einstein College of Medicine, told MDedge News.

Dr. Biala was not involved in the development of the report, but she said the AAP’s guidance reflects the recent shift in the stance of the Centers for Disease Control and Prevention (CDC) regarding breastfeeding among people who are HIV+. Recommendations from the CDC and the U.S. Department of Health and Human Services (HHS) were updated in 2023.

“I’m glad that the AAP is putting out guidelines on infant feeding for people with HIV,” Dr. Biala said. “For so long in the U.S., pediatricians have been advising all mothers with HIV to avoid breastfeeding, believing that the risk of transmission outweighed the benefits of breastfeeding.”

The updated guidance from HHS in 2023 “was revolutionary in supporting people with HIV in low-risk situations who want to breastfeed,” Dr. Biala said, but “clear protocols for monitoring and follow-up were not in place,” which these AAP guidelines help address.
 

Prior Discordance Between Global, U.S. Guidance

An estimated 5,000 people with HIV give birth each year in the United States, and up to one third of pregnant people with HIV may be unaware of their HIV status, the AAP report notes. Pediatric healthcare professionals in the United States therefore need to be aware of recommendations related to HIV testing of pregnant people and of counseling the feeding of infants exposed to HIV. The report recommends opt-out HIV testing at the first prenatal visit and then possibly retesting in the third trimester in areas with high HIV incidence or for people at high risk for HIV or with signs or symptoms of acute HIV infection.

The report also highlights the health benefits of breastfeeding to both the infant and the breastfeeding parent, but notes the CDC’s historical recommendation against breastfeeding for people who are HIV+. The WHO, meanwhile, began recommending in 2016 that infants be breastfed through 12 to 24 months old if the parent was on ART and/or the infant was receiving antiretroviral (ARV) prophylaxis, since research showed those treatments were effective in reducing transmission risk.

Still, an estimated 30% of perinatal HIV transmission occurs via breastfeeding worldwide, primarily from people with HIV who are not on ART or are not adequately virally suppressed. Without parental ART or infant ARV prophylaxis, HIV transmission risk to infants via breastfeeding is highest, about 5%-6%, in the first 4-6 weeks of life. Risk then declines to about 0.9% a month thereafter. The AAP report goes on to describe factors that increase or decrease the likelihood of transmission during breastfeeding, but it notes that neither ART in the breastfeeding person nor ARV prophylaxis in the infant completely eliminates the risk of HIV transmission during breastfeeding. There have been rare cases where transmission occurred despite viral suppression in the person with HIV.

Among the reasons people with HIV have expressed a desire to breastfeed are wanting to bond with their infant, wanting to provide optimal nutrition and health benefits to their baby, and meeting cultural expectations, including the desire not to disclose their HIV infection status to family or friends by virtue of not breastfeeding.

“Among immigrant and refugee populations, the discordance between infant feeding guidelines in the United States and their country of birth may result in confusion, especially among parents who breastfed previous infants,” the AAP report also notes. Further, not breastfeeding could compound health disparities already more likely to be present among those living with HIV.

Discussions about infant feeding with parents with HIV should therefore “begin as early as possible and involve a multidisciplinary team that might include the pediatric primary care provider (once identified), a pediatric HIV expert, the breastfeeding parent’s HIV care and obstetric providers, and lactation consultants,” the report states. ”The parent’s motivations for breastfeeding should be explored and counseling provided on the risks and benefits of each feeding option, including breastfeeding, formula feeding, or certified, banked donor human milk.” The statement emphasizes the need for providing counseling in a “non-judgmental, respectful way, recognizing potential drivers for their decisions such as avoidance of stigma, prior experience with breastfeeding, and cultural contributors.”
 

Clear Recommendations Can Help Providers

The AAP’s statement that “replacement feeding (with formula or certified, banked donor human milk) is the only option that is 100% certain to prevent postnatal transmission of HIV” feels like it takes a “more conservative or discouraging approach” to breastfeeding than the CDC or WHO guidelines, Alissa Parker-Smith, APRN, DNP, CPNP-PC, IBCLC, a nurse practitioner and lactation consultant at PrimaryPlus, a Federally Qualified Health Clinic in Ashland, Kentucky, told MDedge. But she said they do clearly align with the CDC guidelines, and their differences from the WHO guidelines make sense in light of the different populations served by the WHO versus the U.S. agencies.

“Unclean water for formula preparation and a reduced or lack of access to formula in general can lead to many other risks of death for the infant other than the very small risk of HIV infection from breastfeeding from an HIV+ parent,” Ms. Parker-Smith said. “In the U.S. we generally have consistent access to clean water and safe formula as well as social structures to help families have access to formula, so the very small risk of HIV being passed to the infant is far greater than an infant in the U.S. dying as a result of unclean water or formula contamination.”

Ms. Parker-Smith also said the AAP recommendations seem thorough in helping pediatric practitioners counsel and support parents with HIV. “If I had a parent who is HIV+ walk in the door today wanting to breastfeed their infant, the AAP guidelines give me specific steps to make me feel confident in helping that parent breastfeed as safely as possible as well as providing education to assist that parent through the decision process,” she said.

Dr. Biala agreed, noting that the clinical report “very clearly delineates recommendations for different groups of people: those in labor or postpartum with undocumented HIV infection status, pregnant and postpartum people with HIV, those without HIV but at high risk of acquiring it, and those with suspected acute HIV infection while breastfeeding.” Dr. Biala said the report “provides concrete, detailed, and easy-to-follow guidance on comprehensive counseling, strategies to minimize risk of transmission, and infant screening timelines.”

How easily the guidelines can be implemented will depend on the existing resources at different institutions in the United States, Dr. Biala added.

“In hospitals and clinics that have, or could easily have, systems in place to ensure follow-up and regular assessment during breastfeeding, the guidelines could be implemented fairly quickly,” she said. “It might be more challenging in areas with inadequate or limited access to multidisciplinary team members, including HIV care providers and lactation consultants.”

The report did not use external funding, and the authors reported no disclosures. Dr. Abuogi and Ms. Parker-Smith have no disclosures.

The combination of atezolizumab plus sacituzumab govitecan as first-line treatment showed encouraging anti-tumor activity in previously untreated patients with triple-negative breast cancer (TNBC), in an ongoing phase 1b/2 trial.

MORPHEUS-pan BC (NCT03424005) is evaluating multiple treatment combinations in patients with locally advanced or metastatic TNBC.

The trial’s interim clinical data was presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Rationale for Combining Antibody-Drug Conjugates with Immunotherapy

Peter Schmid, MD, PhD, professor at the Centre for Experimental Cancer Medicine in London, England, presented interim findings from one study arm of MORPHEUS-pan BC at the meeting. The arm consisted of patients with TNBC who were treated with a combination of atezolizumab, a PD-L1 inhibitor, and sacituzumab govitecan, an antibody-drug conjugate targeting the Trop-2 protein commonly expressed in TNBC.

TNBC is one of the most challenging subtypes of breast cancer to treat because of its aggressive characteristics and innate resistance to hormonal therapy and HER2-targeted treatments. However, the recent approval of immunotherapy for TNBC has provided renewed hope for patients, according to Dr. Schmid.

Atezolizumab, in combination with nab-paclitaxel, has already been approved as a first-line treatment for PD-L1–positive, unresectable locally advanced or metastatic TNBC; however, not all patients respond to this combination treatment. Sacituzumab govitecan is approved for second-line and subsequent-line treatment of metastatic TNBC.

“Cancer immunotherapy in combination with chemotherapy has transformed the TNBC treatment landscape, but new combinations are needed to further improve survival outcomes,” Dr. Schmid said during his presentation. “We hoped that combining immunotherapy with an antibody-drug conjugate would not only improve safety but also increase efficacy through enhanced immune activation.”
 

Study Design

The MORPHEUS-pan BC trial enrolled patients with previously untreated, PD-L1–positive, inoperable, locally advanced or metastatic TNBC. Patients were randomized to receive experimental treatment consisting of atezolizumab plus the antibody-drug conjugate sacituzumab govitecan. Patients in the second arm received a control regimen of atezolizumab plus nab-paclitaxel chemotherapy.

“The control regimen is part of the current standard of care for patients with PD-L1–positive TNBC,” Dr. Schmid explained in his presentation. As of the data cut-off, 11 patients were enrolled in the control arm and 31 in the atezolizumab plus sacituzumab govitecan arm.

During the discussion session after his talk, Dr. Schmid commented on the use of PD-L1 expression to select patients for enrollment, acknowledging that PD-L1 is not the best biomarker.

“Its expression is very dynamic and can change rapidly,” he said. He added, however, that it is currently the most suitable biomarker for patient selection for treatment with anti–PD-1/PD-L1 agents.

Sara M. Tolaney, MD, MPH, added that, because patients were selected based on PD-L1 expression, it is unclear whether this combination therapy would show anti-tumor activity in patients with PD-L1–negative tumors. Dr. Tolaney, a medical oncologist at the Dana-Farber Cancer Institute who was not involved in the study, served as a discussant, providing her expert opinion on the findings presented by Dr. Schmid.
 

Promising Anti-tumor Activity

The combination of atezolizumab and sacituzumab govitecan demonstrated promising anti-tumor activity as initial treatment for this patient population. The interim analysis at 18 weeks showed an objective response rate of 76.7% (95% CI, 57.7-90.1; n = 23, including five complete responses) in the atezolizumab plus sacituzumab govitecan arm, versus 66.7% (95% CI, 29.9-92.5; n = 6, all of which were partial responses) in the control arm.

“The 66% response rate in the control arm aligns with what we see in historical data from patients treated with immunotherapy plus chemotherapy,” noted Dr. Schmid during his talk.

The clinical benefit rate, which includes complete and partial responses as well as stable disease, was also encouraging at 83.3% (95% CI, 65.3-94.4) with the dual immunotherapy regimen versus 66.7% (95% CI, 29.9-92.5) with standard therapy.

Commenting on the potential mechanisms of the synergistic effect of this combination therapy, Dr. Tolaney said, “In addition to delivering chemotherapy payloads to cancer cells, antibody-drug conjugates can lead to dendritic cell activation, T-cell activation, and immune cell infiltration.”

She added that antibody-drug conjugates can cause Fc activation in NK cells, thereby enhancing antibody-dependent cytotoxicity.
 

Encouraging survival trends

Interim survival data showed trends favoring atezolizumab plus sacituzumab govitecan over the control arm of atezolizumab plus nab-paclitaxel chemotherapy. The median progression-free survival (PFS) was 12.2 months (95% CI, 7.4-not estimable) in the immunotherapy combination group versus 5.9 months (95% CI, 4.1-8.7) in the control group, yielding a hazard ratio of 0.29 (95% CI, 0.11-0.70). The overall survival data are still immature.

During the discussion session, Dr. Schmid cautioned that, although the benefit of this combination therapy in terms of PFS seems promising, the validity of the hazard ratio is limited because of the small cohort size. He added, “The survival data is still immature, and longer follow-up is needed.”

These encouraging response and PFS rates need to be confirmed in larger studies of this immunotherapy combination as a potential new first-line standard for PD-L1–positive TNBC, according to Dr. Schmid.
 

Relationship between biomarker expression and response

The MORPHEUS-pan BC trial enrolled only patients with PD-L1–positive tumors at baseline, defined as PD-L1 expression in at least 1% of immune cells infiltrating the tumor. Tumors at baseline were also tested for Trop-2 expression, CD8 immune phenotype, and stromal tumor-infiltrating lymphocytes (TILs).

“We wanted to get an idea of whether these biomarkers are associated with treatment response,” Dr. Schmid explained during his talk.

Although the benefit of sacituzumab govitecan treatment was observed across all Trop-2 expression levels, preliminary analyses suggest that high Trop-2 expression, CD8 immune phenotype, and stromal TILs may be associated with response to atezolizumab plus sacituzumab govitecan. However, Dr. Schmid noted that validation of these associations in larger cohorts is required.
 

Safety of combination treatment

The side effect profile of atezolizumab plus sacituzumab govitecan appeared consistent with that expected from the two individual drugs, with no new toxicity signals.

All patients in both treatment arms experienced at least one adverse event; however, there were no fatal adverse events. Grade 3-4 adverse events were more common in the experimental arm (70.0%) than in the control arm (44.4%), while serious adverse events were more common in the control group (44.4% versus 23.3%). Immune-related adverse events were considerably more common in the atezolizumab plus sacituzumab govitecan group than in the control group (80.0% versus 55.6%).

The most common adverse events in patients treated with atezolizumab plus sacituzumab govitecan were nausea, alopecia, diarrhea, and neutropenia. Dr. Schmid emphasized in his presentation that this toxicity profile was dominated by adverse events that are common in patients treated with chemotherapy.

“These safety data are significant as they suggest that the combination therapy does not introduce additional risks beyond those already associated with each drug,” he added.
 

Looking Ahead

Dr. Tolaney highlighted that the cohort size of this study was small and the follow-up time was insufficient to draw conclusions about survival outcomes. Larger studies with long-term follow-up are needed to confirm the efficacy of first-line atezolizumab plus sacituzumab govitecan, she said.

“While this was a small study, the response data is very intriguing, with 17% of patients experiencing complete responses. The PFS data are also impressive, and there seems to be an interesting trend towards better response in patients with high Trop-2 expression and those with high levels of stromal TILs,” she added.

Dr. Tolaney also noted that the response rates and PFS data presented are similar to those of one of the treatment arms in the BEGONIA trial (NCT03742102), which investigated different combinations of immunotherapy in patients with metastatic TNBC. Like MORPHEUS-pan BC (NCT03424005), this study evaluated the efficacy of a different antibody-drug conjugate with chemotherapy. Patients in the study arm of the BEGONIA trial she was referring to received durvalumab (an anti-PD-L1 agent) and datopotamab deruxtecan (an antibody-drug conjugate).

Dr. Schmid said that biomarker analyses are ongoing to assess whether there is a correlation between Trop-2 expression levels and the benefits of sacituzumab govitecan. Studies are also needed to determine whether this combination can improve pathologic complete response rates in early-stage TNBC.

Dr. Tolaney echoed the importance of evaluating the efficacy of antibody-drug conjugates plus immune checkpoint inhibitors in different settings, including patients with PD-L1–negative or immunologically cold tumors and those with early-stage disease. “Ultimately, we want this combination treatment to move forward to early-stage TNBC to see if we could cure more patients,” she said, during the discussion.

Dr. Schmid reported financial relationships with Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (consulting or advisory roles); Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (honoraria); and AstraZeneca, Genentech, Roche, Oncogenex, Novartis, Astellas, and Medivation (research funding). Dr. Tolaney reported financial relationships with Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., Beyond Spring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, and Jazz Pharmaceuticals (consulting or advisory roles); Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Nanostring, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, Cyclacel, Sanofi, and Seattle Genetics (research funding).

The combination of atezolizumab plus sacituzumab govitecan as first-line treatment showed encouraging anti-tumor activity in previously untreated patients with triple-negative breast cancer (TNBC), in an ongoing phase 1b/2 trial.

MORPHEUS-pan BC (NCT03424005) is evaluating multiple treatment combinations in patients with locally advanced or metastatic TNBC.

The trial’s interim clinical data was presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Rationale for Combining Antibody-Drug Conjugates with Immunotherapy

Peter Schmid, MD, PhD, professor at the Centre for Experimental Cancer Medicine in London, England, presented interim findings from one study arm of MORPHEUS-pan BC at the meeting. The arm consisted of patients with TNBC who were treated with a combination of atezolizumab, a PD-L1 inhibitor, and sacituzumab govitecan, an antibody-drug conjugate targeting the Trop-2 protein commonly expressed in TNBC.

TNBC is one of the most challenging subtypes of breast cancer to treat because of its aggressive characteristics and innate resistance to hormonal therapy and HER2-targeted treatments. However, the recent approval of immunotherapy for TNBC has provided renewed hope for patients, according to Dr. Schmid.

Atezolizumab, in combination with nab-paclitaxel, has already been approved as a first-line treatment for PD-L1–positive, unresectable locally advanced or metastatic TNBC; however, not all patients respond to this combination treatment. Sacituzumab govitecan is approved for second-line and subsequent-line treatment of metastatic TNBC.

“Cancer immunotherapy in combination with chemotherapy has transformed the TNBC treatment landscape, but new combinations are needed to further improve survival outcomes,” Dr. Schmid said during his presentation. “We hoped that combining immunotherapy with an antibody-drug conjugate would not only improve safety but also increase efficacy through enhanced immune activation.”
 

Study Design

The MORPHEUS-pan BC trial enrolled patients with previously untreated, PD-L1–positive, inoperable, locally advanced or metastatic TNBC. Patients were randomized to receive experimental treatment consisting of atezolizumab plus the antibody-drug conjugate sacituzumab govitecan. Patients in the second arm received a control regimen of atezolizumab plus nab-paclitaxel chemotherapy.

“The control regimen is part of the current standard of care for patients with PD-L1–positive TNBC,” Dr. Schmid explained in his presentation. As of the data cut-off, 11 patients were enrolled in the control arm and 31 in the atezolizumab plus sacituzumab govitecan arm.

During the discussion session after his talk, Dr. Schmid commented on the use of PD-L1 expression to select patients for enrollment, acknowledging that PD-L1 is not the best biomarker.

“Its expression is very dynamic and can change rapidly,” he said. He added, however, that it is currently the most suitable biomarker for patient selection for treatment with anti–PD-1/PD-L1 agents.

Sara M. Tolaney, MD, MPH, added that, because patients were selected based on PD-L1 expression, it is unclear whether this combination therapy would show anti-tumor activity in patients with PD-L1–negative tumors. Dr. Tolaney, a medical oncologist at the Dana-Farber Cancer Institute who was not involved in the study, served as a discussant, providing her expert opinion on the findings presented by Dr. Schmid.
 

Promising Anti-tumor Activity

The combination of atezolizumab and sacituzumab govitecan demonstrated promising anti-tumor activity as initial treatment for this patient population. The interim analysis at 18 weeks showed an objective response rate of 76.7% (95% CI, 57.7-90.1; n = 23, including five complete responses) in the atezolizumab plus sacituzumab govitecan arm, versus 66.7% (95% CI, 29.9-92.5; n = 6, all of which were partial responses) in the control arm.

“The 66% response rate in the control arm aligns with what we see in historical data from patients treated with immunotherapy plus chemotherapy,” noted Dr. Schmid during his talk.

The clinical benefit rate, which includes complete and partial responses as well as stable disease, was also encouraging at 83.3% (95% CI, 65.3-94.4) with the dual immunotherapy regimen versus 66.7% (95% CI, 29.9-92.5) with standard therapy.

Commenting on the potential mechanisms of the synergistic effect of this combination therapy, Dr. Tolaney said, “In addition to delivering chemotherapy payloads to cancer cells, antibody-drug conjugates can lead to dendritic cell activation, T-cell activation, and immune cell infiltration.”

She added that antibody-drug conjugates can cause Fc activation in NK cells, thereby enhancing antibody-dependent cytotoxicity.
 

Encouraging survival trends

Interim survival data showed trends favoring atezolizumab plus sacituzumab govitecan over the control arm of atezolizumab plus nab-paclitaxel chemotherapy. The median progression-free survival (PFS) was 12.2 months (95% CI, 7.4-not estimable) in the immunotherapy combination group versus 5.9 months (95% CI, 4.1-8.7) in the control group, yielding a hazard ratio of 0.29 (95% CI, 0.11-0.70). The overall survival data are still immature.

During the discussion session, Dr. Schmid cautioned that, although the benefit of this combination therapy in terms of PFS seems promising, the validity of the hazard ratio is limited because of the small cohort size. He added, “The survival data is still immature, and longer follow-up is needed.”

These encouraging response and PFS rates need to be confirmed in larger studies of this immunotherapy combination as a potential new first-line standard for PD-L1–positive TNBC, according to Dr. Schmid.
 

Relationship between biomarker expression and response

The MORPHEUS-pan BC trial enrolled only patients with PD-L1–positive tumors at baseline, defined as PD-L1 expression in at least 1% of immune cells infiltrating the tumor. Tumors at baseline were also tested for Trop-2 expression, CD8 immune phenotype, and stromal tumor-infiltrating lymphocytes (TILs).

“We wanted to get an idea of whether these biomarkers are associated with treatment response,” Dr. Schmid explained during his talk.

Although the benefit of sacituzumab govitecan treatment was observed across all Trop-2 expression levels, preliminary analyses suggest that high Trop-2 expression, CD8 immune phenotype, and stromal TILs may be associated with response to atezolizumab plus sacituzumab govitecan. However, Dr. Schmid noted that validation of these associations in larger cohorts is required.
 

Safety of combination treatment

The side effect profile of atezolizumab plus sacituzumab govitecan appeared consistent with that expected from the two individual drugs, with no new toxicity signals.

All patients in both treatment arms experienced at least one adverse event; however, there were no fatal adverse events. Grade 3-4 adverse events were more common in the experimental arm (70.0%) than in the control arm (44.4%), while serious adverse events were more common in the control group (44.4% versus 23.3%). Immune-related adverse events were considerably more common in the atezolizumab plus sacituzumab govitecan group than in the control group (80.0% versus 55.6%).

The most common adverse events in patients treated with atezolizumab plus sacituzumab govitecan were nausea, alopecia, diarrhea, and neutropenia. Dr. Schmid emphasized in his presentation that this toxicity profile was dominated by adverse events that are common in patients treated with chemotherapy.

“These safety data are significant as they suggest that the combination therapy does not introduce additional risks beyond those already associated with each drug,” he added.
 

Looking Ahead

Dr. Tolaney highlighted that the cohort size of this study was small and the follow-up time was insufficient to draw conclusions about survival outcomes. Larger studies with long-term follow-up are needed to confirm the efficacy of first-line atezolizumab plus sacituzumab govitecan, she said.

“While this was a small study, the response data is very intriguing, with 17% of patients experiencing complete responses. The PFS data are also impressive, and there seems to be an interesting trend towards better response in patients with high Trop-2 expression and those with high levels of stromal TILs,” she added.

Dr. Tolaney also noted that the response rates and PFS data presented are similar to those of one of the treatment arms in the BEGONIA trial (NCT03742102), which investigated different combinations of immunotherapy in patients with metastatic TNBC. Like MORPHEUS-pan BC (NCT03424005), this study evaluated the efficacy of a different antibody-drug conjugate with chemotherapy. Patients in the study arm of the BEGONIA trial she was referring to received durvalumab (an anti-PD-L1 agent) and datopotamab deruxtecan (an antibody-drug conjugate).

Dr. Schmid said that biomarker analyses are ongoing to assess whether there is a correlation between Trop-2 expression levels and the benefits of sacituzumab govitecan. Studies are also needed to determine whether this combination can improve pathologic complete response rates in early-stage TNBC.

Dr. Tolaney echoed the importance of evaluating the efficacy of antibody-drug conjugates plus immune checkpoint inhibitors in different settings, including patients with PD-L1–negative or immunologically cold tumors and those with early-stage disease. “Ultimately, we want this combination treatment to move forward to early-stage TNBC to see if we could cure more patients,” she said, during the discussion.

Dr. Schmid reported financial relationships with Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (consulting or advisory roles); Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (honoraria); and AstraZeneca, Genentech, Roche, Oncogenex, Novartis, Astellas, and Medivation (research funding). Dr. Tolaney reported financial relationships with Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., Beyond Spring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, and Jazz Pharmaceuticals (consulting or advisory roles); Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Nanostring, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, Cyclacel, Sanofi, and Seattle Genetics (research funding).

The combination of atezolizumab plus sacituzumab govitecan as first-line treatment showed encouraging anti-tumor activity in previously untreated patients with triple-negative breast cancer (TNBC), in an ongoing phase 1b/2 trial.

MORPHEUS-pan BC (NCT03424005) is evaluating multiple treatment combinations in patients with locally advanced or metastatic TNBC.

The trial’s interim clinical data was presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Rationale for Combining Antibody-Drug Conjugates with Immunotherapy

Peter Schmid, MD, PhD, professor at the Centre for Experimental Cancer Medicine in London, England, presented interim findings from one study arm of MORPHEUS-pan BC at the meeting. The arm consisted of patients with TNBC who were treated with a combination of atezolizumab, a PD-L1 inhibitor, and sacituzumab govitecan, an antibody-drug conjugate targeting the Trop-2 protein commonly expressed in TNBC.

TNBC is one of the most challenging subtypes of breast cancer to treat because of its aggressive characteristics and innate resistance to hormonal therapy and HER2-targeted treatments. However, the recent approval of immunotherapy for TNBC has provided renewed hope for patients, according to Dr. Schmid.

Atezolizumab, in combination with nab-paclitaxel, has already been approved as a first-line treatment for PD-L1–positive, unresectable locally advanced or metastatic TNBC; however, not all patients respond to this combination treatment. Sacituzumab govitecan is approved for second-line and subsequent-line treatment of metastatic TNBC.

“Cancer immunotherapy in combination with chemotherapy has transformed the TNBC treatment landscape, but new combinations are needed to further improve survival outcomes,” Dr. Schmid said during his presentation. “We hoped that combining immunotherapy with an antibody-drug conjugate would not only improve safety but also increase efficacy through enhanced immune activation.”
 

Study Design

The MORPHEUS-pan BC trial enrolled patients with previously untreated, PD-L1–positive, inoperable, locally advanced or metastatic TNBC. Patients were randomized to receive experimental treatment consisting of atezolizumab plus the antibody-drug conjugate sacituzumab govitecan. Patients in the second arm received a control regimen of atezolizumab plus nab-paclitaxel chemotherapy.

“The control regimen is part of the current standard of care for patients with PD-L1–positive TNBC,” Dr. Schmid explained in his presentation. As of the data cut-off, 11 patients were enrolled in the control arm and 31 in the atezolizumab plus sacituzumab govitecan arm.

During the discussion session after his talk, Dr. Schmid commented on the use of PD-L1 expression to select patients for enrollment, acknowledging that PD-L1 is not the best biomarker.

“Its expression is very dynamic and can change rapidly,” he said. He added, however, that it is currently the most suitable biomarker for patient selection for treatment with anti–PD-1/PD-L1 agents.

Sara M. Tolaney, MD, MPH, added that, because patients were selected based on PD-L1 expression, it is unclear whether this combination therapy would show anti-tumor activity in patients with PD-L1–negative tumors. Dr. Tolaney, a medical oncologist at the Dana-Farber Cancer Institute who was not involved in the study, served as a discussant, providing her expert opinion on the findings presented by Dr. Schmid.
 

Promising Anti-tumor Activity

The combination of atezolizumab and sacituzumab govitecan demonstrated promising anti-tumor activity as initial treatment for this patient population. The interim analysis at 18 weeks showed an objective response rate of 76.7% (95% CI, 57.7-90.1; n = 23, including five complete responses) in the atezolizumab plus sacituzumab govitecan arm, versus 66.7% (95% CI, 29.9-92.5; n = 6, all of which were partial responses) in the control arm.

“The 66% response rate in the control arm aligns with what we see in historical data from patients treated with immunotherapy plus chemotherapy,” noted Dr. Schmid during his talk.

The clinical benefit rate, which includes complete and partial responses as well as stable disease, was also encouraging at 83.3% (95% CI, 65.3-94.4) with the dual immunotherapy regimen versus 66.7% (95% CI, 29.9-92.5) with standard therapy.

Commenting on the potential mechanisms of the synergistic effect of this combination therapy, Dr. Tolaney said, “In addition to delivering chemotherapy payloads to cancer cells, antibody-drug conjugates can lead to dendritic cell activation, T-cell activation, and immune cell infiltration.”

She added that antibody-drug conjugates can cause Fc activation in NK cells, thereby enhancing antibody-dependent cytotoxicity.
 

Encouraging survival trends

Interim survival data showed trends favoring atezolizumab plus sacituzumab govitecan over the control arm of atezolizumab plus nab-paclitaxel chemotherapy. The median progression-free survival (PFS) was 12.2 months (95% CI, 7.4-not estimable) in the immunotherapy combination group versus 5.9 months (95% CI, 4.1-8.7) in the control group, yielding a hazard ratio of 0.29 (95% CI, 0.11-0.70). The overall survival data are still immature.

During the discussion session, Dr. Schmid cautioned that, although the benefit of this combination therapy in terms of PFS seems promising, the validity of the hazard ratio is limited because of the small cohort size. He added, “The survival data is still immature, and longer follow-up is needed.”

These encouraging response and PFS rates need to be confirmed in larger studies of this immunotherapy combination as a potential new first-line standard for PD-L1–positive TNBC, according to Dr. Schmid.
 

Relationship between biomarker expression and response

The MORPHEUS-pan BC trial enrolled only patients with PD-L1–positive tumors at baseline, defined as PD-L1 expression in at least 1% of immune cells infiltrating the tumor. Tumors at baseline were also tested for Trop-2 expression, CD8 immune phenotype, and stromal tumor-infiltrating lymphocytes (TILs).

“We wanted to get an idea of whether these biomarkers are associated with treatment response,” Dr. Schmid explained during his talk.

Although the benefit of sacituzumab govitecan treatment was observed across all Trop-2 expression levels, preliminary analyses suggest that high Trop-2 expression, CD8 immune phenotype, and stromal TILs may be associated with response to atezolizumab plus sacituzumab govitecan. However, Dr. Schmid noted that validation of these associations in larger cohorts is required.
 

Safety of combination treatment

The side effect profile of atezolizumab plus sacituzumab govitecan appeared consistent with that expected from the two individual drugs, with no new toxicity signals.

All patients in both treatment arms experienced at least one adverse event; however, there were no fatal adverse events. Grade 3-4 adverse events were more common in the experimental arm (70.0%) than in the control arm (44.4%), while serious adverse events were more common in the control group (44.4% versus 23.3%). Immune-related adverse events were considerably more common in the atezolizumab plus sacituzumab govitecan group than in the control group (80.0% versus 55.6%).

The most common adverse events in patients treated with atezolizumab plus sacituzumab govitecan were nausea, alopecia, diarrhea, and neutropenia. Dr. Schmid emphasized in his presentation that this toxicity profile was dominated by adverse events that are common in patients treated with chemotherapy.

“These safety data are significant as they suggest that the combination therapy does not introduce additional risks beyond those already associated with each drug,” he added.
 

Looking Ahead

Dr. Tolaney highlighted that the cohort size of this study was small and the follow-up time was insufficient to draw conclusions about survival outcomes. Larger studies with long-term follow-up are needed to confirm the efficacy of first-line atezolizumab plus sacituzumab govitecan, she said.

“While this was a small study, the response data is very intriguing, with 17% of patients experiencing complete responses. The PFS data are also impressive, and there seems to be an interesting trend towards better response in patients with high Trop-2 expression and those with high levels of stromal TILs,” she added.

Dr. Tolaney also noted that the response rates and PFS data presented are similar to those of one of the treatment arms in the BEGONIA trial (NCT03742102), which investigated different combinations of immunotherapy in patients with metastatic TNBC. Like MORPHEUS-pan BC (NCT03424005), this study evaluated the efficacy of a different antibody-drug conjugate with chemotherapy. Patients in the study arm of the BEGONIA trial she was referring to received durvalumab (an anti-PD-L1 agent) and datopotamab deruxtecan (an antibody-drug conjugate).

Dr. Schmid said that biomarker analyses are ongoing to assess whether there is a correlation between Trop-2 expression levels and the benefits of sacituzumab govitecan. Studies are also needed to determine whether this combination can improve pathologic complete response rates in early-stage TNBC.

Dr. Tolaney echoed the importance of evaluating the efficacy of antibody-drug conjugates plus immune checkpoint inhibitors in different settings, including patients with PD-L1–negative or immunologically cold tumors and those with early-stage disease. “Ultimately, we want this combination treatment to move forward to early-stage TNBC to see if we could cure more patients,” she said, during the discussion.

Dr. Schmid reported financial relationships with Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (consulting or advisory roles); Pfizer, AstraZeneca, Novartis, Gilead, Roche, Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, and Puma (honoraria); and AstraZeneca, Genentech, Roche, Oncogenex, Novartis, Astellas, and Medivation (research funding). Dr. Tolaney reported financial relationships with Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., Beyond Spring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, and Jazz Pharmaceuticals (consulting or advisory roles); Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Nanostring, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, Cyclacel, Sanofi, and Seattle Genetics (research funding).

Lipoid proteinosis, or Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis with a global prevalence of less than 500 reported cases, with an equal distribution across genders and ethnicities.¹ It is caused by mutations in the ECM1 gene² on chromosome 1q21. This leads to the abnormal deposition of hyaline material in various tissues across different organ systems, with the classic manifestations known as the “string of pearls” sign and a hoarse cry or voice.

The rarity of lipoid proteinosis often leads to challenges in diagnosis. Particularly when deviating from the common association with consanguinity, the potential for de novo mutations or a broader genetic variability in disease expression is highlighted. Our patient presents with symptoms that are pathognomonic to LP with moniliform blepharosis and hoarseness of the voice, in addition to scarring of the extremities. 

Other common clinical manifestations in patients with LP include cobblestoning of the mucosa; hyperkeratosis of the elbows, knees, and hands; and calcification of the amygdala with neuroimaging.³

Genetic testing that identifies a loss-of-function mutation in ECM1 offers diagnostic confirmation. Patients often need multidisciplinary care involving dermatology; ear, nose, throat; neurology; and genetics. Treatment of LP is mostly symptomatic with unsatisfactory resolution of cutaneous changes, with retinoids such as acitretin used as the first-line option and surgery as a consideration for laryngeal hyaline deposits.² Although LP can affect different organ systems, patients tend to have a normal lifespan.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Mcgrath JA. Handb Clin Neurol. 2015:132:317-22. doi: 10.1016/B978-0-444-62702-5.00023-8.

2. Hamada Tet al. Hum Mol Genet. 2002 Apr 1;11(7):833-40. doi: 10.1093/hmg/11.7.833.

3. Frenkel B et al. Clin Oral Investig. 2017 Sep;21(7):2245-51 doi: 10.1007/s00784-016-2017-7.

Lipoid proteinosis, or Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis with a global prevalence of less than 500 reported cases, with an equal distribution across genders and ethnicities.¹ It is caused by mutations in the ECM1 gene² on chromosome 1q21. This leads to the abnormal deposition of hyaline material in various tissues across different organ systems, with the classic manifestations known as the “string of pearls” sign and a hoarse cry or voice.

The rarity of lipoid proteinosis often leads to challenges in diagnosis. Particularly when deviating from the common association with consanguinity, the potential for de novo mutations or a broader genetic variability in disease expression is highlighted. Our patient presents with symptoms that are pathognomonic to LP with moniliform blepharosis and hoarseness of the voice, in addition to scarring of the extremities. 

Other common clinical manifestations in patients with LP include cobblestoning of the mucosa; hyperkeratosis of the elbows, knees, and hands; and calcification of the amygdala with neuroimaging.³

Genetic testing that identifies a loss-of-function mutation in ECM1 offers diagnostic confirmation. Patients often need multidisciplinary care involving dermatology; ear, nose, throat; neurology; and genetics. Treatment of LP is mostly symptomatic with unsatisfactory resolution of cutaneous changes, with retinoids such as acitretin used as the first-line option and surgery as a consideration for laryngeal hyaline deposits.² Although LP can affect different organ systems, patients tend to have a normal lifespan.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Mcgrath JA. Handb Clin Neurol. 2015:132:317-22. doi: 10.1016/B978-0-444-62702-5.00023-8.

2. Hamada Tet al. Hum Mol Genet. 2002 Apr 1;11(7):833-40. doi: 10.1093/hmg/11.7.833.

3. Frenkel B et al. Clin Oral Investig. 2017 Sep;21(7):2245-51 doi: 10.1007/s00784-016-2017-7.

Lipoid proteinosis, or Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis with a global prevalence of less than 500 reported cases, with an equal distribution across genders and ethnicities.¹ It is caused by mutations in the ECM1 gene² on chromosome 1q21. This leads to the abnormal deposition of hyaline material in various tissues across different organ systems, with the classic manifestations known as the “string of pearls” sign and a hoarse cry or voice.

The rarity of lipoid proteinosis often leads to challenges in diagnosis. Particularly when deviating from the common association with consanguinity, the potential for de novo mutations or a broader genetic variability in disease expression is highlighted. Our patient presents with symptoms that are pathognomonic to LP with moniliform blepharosis and hoarseness of the voice, in addition to scarring of the extremities. 

Other common clinical manifestations in patients with LP include cobblestoning of the mucosa; hyperkeratosis of the elbows, knees, and hands; and calcification of the amygdala with neuroimaging.³

Genetic testing that identifies a loss-of-function mutation in ECM1 offers diagnostic confirmation. Patients often need multidisciplinary care involving dermatology; ear, nose, throat; neurology; and genetics. Treatment of LP is mostly symptomatic with unsatisfactory resolution of cutaneous changes, with retinoids such as acitretin used as the first-line option and surgery as a consideration for laryngeal hyaline deposits.² Although LP can affect different organ systems, patients tend to have a normal lifespan.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Mcgrath JA. Handb Clin Neurol. 2015:132:317-22. doi: 10.1016/B978-0-444-62702-5.00023-8.

2. Hamada Tet al. Hum Mol Genet. 2002 Apr 1;11(7):833-40. doi: 10.1093/hmg/11.7.833.

3. Frenkel B et al. Clin Oral Investig. 2017 Sep;21(7):2245-51 doi: 10.1007/s00784-016-2017-7.

Seniors are increasingly targeted in ever-sophisticated online financial cybercrimes, but mental health clinicians can play a key role in protecting their patients.

Elizabeth J. Santos, MD, clinical chief, Division of Geriatric Mental Health & Memory Care, and associate professor of psychiatry, neurology & medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, provided tips to attendees of the American Psychiatric Association (APA) 2024 Annual Meeting, and elaborated on these for this news organization.

Cybercrimes targeting seniors are common. A 2023 University of Michigan National Poll on Healthy Aging found 75% of adults aged 50-80 years experienced a fraud attempt either online or by phone, text, email, or mail in the past 2 years.

The poll found about 30% of respondents reported experiencing financial fraud, which could involve compromising credit cards, hacking bank accounts, or identity theft.

Older age is a risk factor for cybercrime. Seniors may have lower cognitive functioning and/or impaired decision-making. In addition, they are often socially isolated, dependent on others, and have poor health and financial literacy.
 

Romance Scams Common

Romance scams are another common financial fraud. Stephanie Garayalde, MD, a geriatric psychiatrist at the University of Florida, Gainesville, Florida, and another presenter at the APA session, used the example of Mr. L, a 74-year-old outpatient under treatment for depression who was unable to pay his rent.

Mr. L was giving money to his “girlfriend” he met online. Their relationship was totally virtual; she always had constant excuses for not meeting in person. He was funneling increasing funds to pay what he believed were medical bills and to bail her out of various other emergencies.

Once the fraud was discovered, Mr. L not only felt the loneliness of a lost romantic connection but also grappled with feelings of embarrassment and guilt.

“I see older patients who have been scammed who feel ashamed that they haven’t left enough money for their families,” said Dr. Santos.

Another well-known scam targets grandparents. Fraudsters sometimes use an artificial intelligence–generated voice mimicking a young family member and pretend to need money right away for bail or another problem.

In such situations, Dr. Santos advises patients to “hang up and call your family” to verify the call “no matter what the person says or who they sound like.”

Scammers may impersonate government officials to try to get social insurance information. Dr. Santos stresses the importance of never giving out this information. “If someone says they’re from your bank or a government agency like the IRS, hang up and call the bank or agency yourself.”

Evidence suggests this and other cybercrimes are on the rise. The Federal Bureau of Investigation’s Internet Crime Complaint Center received 888,000 complaints in 2023, a 10% increase from 2022, and losses of about $12.5 billion, which is a 22% increase over 2022.

It’s not that uncommon for the same older person to be scammed by numerous people and fall for it again and again, said Dr. Santos.

To mitigate the risk to this vulnerable group, researchers at the University of Central Florida, Orlando, Florida, are developing a scam screener for the elderly that will provide tools to help doctors screen older adults. The screen will focus on identifying factors that make victims most vulnerable, including seniors’ ability to think critically, a necessary skill for guarding against cybercrime.
 

Red Flags

In the meantime, Dr. Santos identified red flags for clinicians. Patients may show deviations in their typical behaviors; for example, they may seem sadder, more subdued, or more withdrawn than usual.

As loneliness and isolation can be a signal of victimization, “ask patients about their connectedness and be suspicious if the connectedness is all virtual,” she said.

Learning about the quality of their relationships is also important. “Instead of asking the superficial question of ‘Do you have friends’, ask ‘How do you talk to your friends? Are you actually getting out and meeting them?’”

If patients report they have never actually seen these so-called friends in-person, it should raise a red flag.

Another clue something may be amiss is “needing to be on their device or be home to get a call at a certain time.” Dr. Santos recalled a patient whose cell phone rang constantly during an evaluation, even after she had changed her phone number several times. “The scammers kept tracking her down,” she said.

Patients who are victims of cybercrime may stop taking their medications, fail to follow up on ordered tests, or miss paying for medical services.

Dr. Santos recommended screening for conditions known to be linked to cybercrime victimization such as depression. One of her patients was attending her memory clinic, but their cognitive issues were due to depression, not dementia.

It is important to identify subtle cognitive impairments. Dr. Santos recommended using the Saint Louis University Mental Status Examination, which she says is easier to use than the Montreal Cognitive Assessment.
 

Avoid Shaming

When managing patients who are potential cybercrime victims, she also suggests doctors be careful about their tone and their attitude. “Don’t shame someone for becoming a victim because it happens to everyone.”

When patients show signs of victimization, physicians could consider asking about their Internet use, social media practices, and general safety surrounding their finances.

They should emphasize the importance of protecting accounts through strong passwords, multifactor authentication when possible, and avoidance of sharing personal information with anyone who calls, emails, or texts.

Clinicians might also consider asking patients to review bills for new or unusual charges, check their bank account statements for withdrawals they didn’t make, and review credit reports for accounts in their name they don’t recognize.

Clinicians should also encourage patients to have a healthcare proxy, power of attorney, and advanced directives and recommend resources that can help victims. These include:

Federal Trade Commission (to report identity theft): https://reportfraud.ftc.gov;  https://www.identitytheft.gov

Federal Bureau of Investigation – Internet Crime and Complaint Center https://www.ic3.gov

National Elder Fraud Hotline (1-833-372-8311) or 1-833-FRAUD-11

http://ovc.ojp.gov/program/stop-elder-fraud/providing-help-restoring-hope

A version of this article appeared on Medscape.com.

Seniors are increasingly targeted in ever-sophisticated online financial cybercrimes, but mental health clinicians can play a key role in protecting their patients.

Elizabeth J. Santos, MD, clinical chief, Division of Geriatric Mental Health & Memory Care, and associate professor of psychiatry, neurology & medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, provided tips to attendees of the American Psychiatric Association (APA) 2024 Annual Meeting, and elaborated on these for this news organization.

Cybercrimes targeting seniors are common. A 2023 University of Michigan National Poll on Healthy Aging found 75% of adults aged 50-80 years experienced a fraud attempt either online or by phone, text, email, or mail in the past 2 years.

The poll found about 30% of respondents reported experiencing financial fraud, which could involve compromising credit cards, hacking bank accounts, or identity theft.

Older age is a risk factor for cybercrime. Seniors may have lower cognitive functioning and/or impaired decision-making. In addition, they are often socially isolated, dependent on others, and have poor health and financial literacy.
 

Romance Scams Common

Romance scams are another common financial fraud. Stephanie Garayalde, MD, a geriatric psychiatrist at the University of Florida, Gainesville, Florida, and another presenter at the APA session, used the example of Mr. L, a 74-year-old outpatient under treatment for depression who was unable to pay his rent.

Mr. L was giving money to his “girlfriend” he met online. Their relationship was totally virtual; she always had constant excuses for not meeting in person. He was funneling increasing funds to pay what he believed were medical bills and to bail her out of various other emergencies.

Once the fraud was discovered, Mr. L not only felt the loneliness of a lost romantic connection but also grappled with feelings of embarrassment and guilt.

“I see older patients who have been scammed who feel ashamed that they haven’t left enough money for their families,” said Dr. Santos.

Another well-known scam targets grandparents. Fraudsters sometimes use an artificial intelligence–generated voice mimicking a young family member and pretend to need money right away for bail or another problem.

In such situations, Dr. Santos advises patients to “hang up and call your family” to verify the call “no matter what the person says or who they sound like.”

Scammers may impersonate government officials to try to get social insurance information. Dr. Santos stresses the importance of never giving out this information. “If someone says they’re from your bank or a government agency like the IRS, hang up and call the bank or agency yourself.”

Evidence suggests this and other cybercrimes are on the rise. The Federal Bureau of Investigation’s Internet Crime Complaint Center received 888,000 complaints in 2023, a 10% increase from 2022, and losses of about $12.5 billion, which is a 22% increase over 2022.

It’s not that uncommon for the same older person to be scammed by numerous people and fall for it again and again, said Dr. Santos.

To mitigate the risk to this vulnerable group, researchers at the University of Central Florida, Orlando, Florida, are developing a scam screener for the elderly that will provide tools to help doctors screen older adults. The screen will focus on identifying factors that make victims most vulnerable, including seniors’ ability to think critically, a necessary skill for guarding against cybercrime.
 

Red Flags

In the meantime, Dr. Santos identified red flags for clinicians. Patients may show deviations in their typical behaviors; for example, they may seem sadder, more subdued, or more withdrawn than usual.

As loneliness and isolation can be a signal of victimization, “ask patients about their connectedness and be suspicious if the connectedness is all virtual,” she said.

Learning about the quality of their relationships is also important. “Instead of asking the superficial question of ‘Do you have friends’, ask ‘How do you talk to your friends? Are you actually getting out and meeting them?’”

If patients report they have never actually seen these so-called friends in-person, it should raise a red flag.

Another clue something may be amiss is “needing to be on their device or be home to get a call at a certain time.” Dr. Santos recalled a patient whose cell phone rang constantly during an evaluation, even after she had changed her phone number several times. “The scammers kept tracking her down,” she said.

Patients who are victims of cybercrime may stop taking their medications, fail to follow up on ordered tests, or miss paying for medical services.

Dr. Santos recommended screening for conditions known to be linked to cybercrime victimization such as depression. One of her patients was attending her memory clinic, but their cognitive issues were due to depression, not dementia.

It is important to identify subtle cognitive impairments. Dr. Santos recommended using the Saint Louis University Mental Status Examination, which she says is easier to use than the Montreal Cognitive Assessment.
 

Avoid Shaming

When managing patients who are potential cybercrime victims, she also suggests doctors be careful about their tone and their attitude. “Don’t shame someone for becoming a victim because it happens to everyone.”

When patients show signs of victimization, physicians could consider asking about their Internet use, social media practices, and general safety surrounding their finances.

They should emphasize the importance of protecting accounts through strong passwords, multifactor authentication when possible, and avoidance of sharing personal information with anyone who calls, emails, or texts.

Clinicians might also consider asking patients to review bills for new or unusual charges, check their bank account statements for withdrawals they didn’t make, and review credit reports for accounts in their name they don’t recognize.

Clinicians should also encourage patients to have a healthcare proxy, power of attorney, and advanced directives and recommend resources that can help victims. These include:

Federal Trade Commission (to report identity theft): https://reportfraud.ftc.gov;  https://www.identitytheft.gov

Federal Bureau of Investigation – Internet Crime and Complaint Center https://www.ic3.gov

National Elder Fraud Hotline (1-833-372-8311) or 1-833-FRAUD-11

http://ovc.ojp.gov/program/stop-elder-fraud/providing-help-restoring-hope

A version of this article appeared on Medscape.com.

Seniors are increasingly targeted in ever-sophisticated online financial cybercrimes, but mental health clinicians can play a key role in protecting their patients.

Elizabeth J. Santos, MD, clinical chief, Division of Geriatric Mental Health & Memory Care, and associate professor of psychiatry, neurology & medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, provided tips to attendees of the American Psychiatric Association (APA) 2024 Annual Meeting, and elaborated on these for this news organization.

Cybercrimes targeting seniors are common. A 2023 University of Michigan National Poll on Healthy Aging found 75% of adults aged 50-80 years experienced a fraud attempt either online or by phone, text, email, or mail in the past 2 years.

The poll found about 30% of respondents reported experiencing financial fraud, which could involve compromising credit cards, hacking bank accounts, or identity theft.

Older age is a risk factor for cybercrime. Seniors may have lower cognitive functioning and/or impaired decision-making. In addition, they are often socially isolated, dependent on others, and have poor health and financial literacy.
 

Romance Scams Common

Romance scams are another common financial fraud. Stephanie Garayalde, MD, a geriatric psychiatrist at the University of Florida, Gainesville, Florida, and another presenter at the APA session, used the example of Mr. L, a 74-year-old outpatient under treatment for depression who was unable to pay his rent.

Mr. L was giving money to his “girlfriend” he met online. Their relationship was totally virtual; she always had constant excuses for not meeting in person. He was funneling increasing funds to pay what he believed were medical bills and to bail her out of various other emergencies.

Once the fraud was discovered, Mr. L not only felt the loneliness of a lost romantic connection but also grappled with feelings of embarrassment and guilt.

“I see older patients who have been scammed who feel ashamed that they haven’t left enough money for their families,” said Dr. Santos.

Another well-known scam targets grandparents. Fraudsters sometimes use an artificial intelligence–generated voice mimicking a young family member and pretend to need money right away for bail or another problem.

In such situations, Dr. Santos advises patients to “hang up and call your family” to verify the call “no matter what the person says or who they sound like.”

Scammers may impersonate government officials to try to get social insurance information. Dr. Santos stresses the importance of never giving out this information. “If someone says they’re from your bank or a government agency like the IRS, hang up and call the bank or agency yourself.”

Evidence suggests this and other cybercrimes are on the rise. The Federal Bureau of Investigation’s Internet Crime Complaint Center received 888,000 complaints in 2023, a 10% increase from 2022, and losses of about $12.5 billion, which is a 22% increase over 2022.

It’s not that uncommon for the same older person to be scammed by numerous people and fall for it again and again, said Dr. Santos.

To mitigate the risk to this vulnerable group, researchers at the University of Central Florida, Orlando, Florida, are developing a scam screener for the elderly that will provide tools to help doctors screen older adults. The screen will focus on identifying factors that make victims most vulnerable, including seniors’ ability to think critically, a necessary skill for guarding against cybercrime.
 

Red Flags

In the meantime, Dr. Santos identified red flags for clinicians. Patients may show deviations in their typical behaviors; for example, they may seem sadder, more subdued, or more withdrawn than usual.

As loneliness and isolation can be a signal of victimization, “ask patients about their connectedness and be suspicious if the connectedness is all virtual,” she said.

Learning about the quality of their relationships is also important. “Instead of asking the superficial question of ‘Do you have friends’, ask ‘How do you talk to your friends? Are you actually getting out and meeting them?’”

If patients report they have never actually seen these so-called friends in-person, it should raise a red flag.

Another clue something may be amiss is “needing to be on their device or be home to get a call at a certain time.” Dr. Santos recalled a patient whose cell phone rang constantly during an evaluation, even after she had changed her phone number several times. “The scammers kept tracking her down,” she said.

Patients who are victims of cybercrime may stop taking their medications, fail to follow up on ordered tests, or miss paying for medical services.

Dr. Santos recommended screening for conditions known to be linked to cybercrime victimization such as depression. One of her patients was attending her memory clinic, but their cognitive issues were due to depression, not dementia.

It is important to identify subtle cognitive impairments. Dr. Santos recommended using the Saint Louis University Mental Status Examination, which she says is easier to use than the Montreal Cognitive Assessment.
 

Avoid Shaming

When managing patients who are potential cybercrime victims, she also suggests doctors be careful about their tone and their attitude. “Don’t shame someone for becoming a victim because it happens to everyone.”

When patients show signs of victimization, physicians could consider asking about their Internet use, social media practices, and general safety surrounding their finances.

They should emphasize the importance of protecting accounts through strong passwords, multifactor authentication when possible, and avoidance of sharing personal information with anyone who calls, emails, or texts.

Clinicians might also consider asking patients to review bills for new or unusual charges, check their bank account statements for withdrawals they didn’t make, and review credit reports for accounts in their name they don’t recognize.

Clinicians should also encourage patients to have a healthcare proxy, power of attorney, and advanced directives and recommend resources that can help victims. These include:

Federal Trade Commission (to report identity theft): https://reportfraud.ftc.gov;  https://www.identitytheft.gov

Federal Bureau of Investigation – Internet Crime and Complaint Center https://www.ic3.gov

National Elder Fraud Hotline (1-833-372-8311) or 1-833-FRAUD-11

http://ovc.ojp.gov/program/stop-elder-fraud/providing-help-restoring-hope

A version of this article appeared on Medscape.com.