Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through. 

Now, scientists hope to use this technology to develop more vaccines, with those at the University of Pennsylvania hoping to use that technology to pioneer yet another first: a universal flu vaccine that can protect us against all flu types, not just a select few. 

It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable. 

“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.” 

A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus. 

It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics. 

“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.” 

That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says. 

Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.

Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died. 

The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall. 

Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions. 

“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.

But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.

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

Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through. 

Now, scientists hope to use this technology to develop more vaccines, with those at the University of Pennsylvania hoping to use that technology to pioneer yet another first: a universal flu vaccine that can protect us against all flu types, not just a select few. 

It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable. 

“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.” 

A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus. 

It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics. 

“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.” 

That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says. 

Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.

Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died. 

The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall. 

Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions. 

“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.

But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.

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

Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through. 

Now, scientists hope to use this technology to develop more vaccines, with those at the University of Pennsylvania hoping to use that technology to pioneer yet another first: a universal flu vaccine that can protect us against all flu types, not just a select few. 

It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable. 

“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.” 

A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus. 

It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics. 

“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.” 

That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says. 

Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.

Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died. 

The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall. 

Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions. 

“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.

But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.

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

For many years, it has been believed that the aging process is inevitable and that age-related diseases cannot be prevented or reversed. For example, the U.S. Food and Drug Administration does not recognize aging as an indication for drug approval because there are no markers to determine whether possible treatments have a significant impact on the hallmarks of aging.

The field of geroscience aims to find ways to change this by delaying the onset of age-related diseases or by extending the life span. On May 19, 2021, experts in geroscience met virtually at a symposium of the New York Academy of Sciences. Presentations and discussions with experts in the field showed that remarkable advances have been made in understanding the mechanisms underlying biological aging. Those mechanisms contribute to the vulnerability of older adults. The presentations focused on identifying biomarkers of aging and on the search for interventions to prevent and treat age-related diseases.

Perspectives from this meeting were published in a report.
 

An abridged glossary

• Senescent cells: These are old cells with irreversibly damaged DNA; they strongly resist apoptosis. Thus, they are not eliminated and continue to secrete pathogenic proinflammatory molecules.
• Senolytics: This is a class of compounds that promote the removal of senescent cells from the body.
• Autophagy: This is a process that promotes protein degradation, which is attenuated with aging and that impedes the aggregation of proteins harmful to cell function, particularly those of the central nervous system.
• Proteostasis: This is the dynamic regulation of protein homeostasis.
• Epigenetics: This is the field of biology that studies phenotype changes that are not caused by changes in DNA sequencing and that continue to affect cellular division.
• Metabolome: This refers to small molecules that make up the building blocks of all organismal features, from cell membranes to metabolic cycles to genes and proteins.
• Translational research: This involves applying primary research results to clinical research and vice versa.

Possible research topics

Senescence not only occurs with age but also drives aging. At the meeting, evidence was provided that senescent cells may exacerbate the clinical course of older adults in cases of infections (for example, COVID-19) as they lead to cytokine storms.

Experiments on old mice that have undergone genetic modification of senescent cells or the administration of “senolytic cocktails” composed of dasatinib plus quercetin protected the animals from the effects of viral infections. This finding corroborates the idea that factors involved in biological aging increase vulnerability and could be modified through treatment.

Alzheimer’s disease is an example of the effects of cellular senescence. Senescent cells develop a senescence-associated secretory phenotype that can be toxic to neighboring healthy cells and can allow senescence to propagate within tissues. This effect makes Alzheimer’s disease an essential focal point when studying the use of senolytics. In addition, agents that stimulate autophagy may be of interest for treating degenerative diseases.
 

Assessing therapeutic effects

It may be possible to assess the therapeutic effects of drug candidates using the following biomarkers.

• Growth hormone and type 1 insulin-like growth factor (IGF-1): Older adults are often prescribed growth hormone. However, recent data suggest that doing so is not advantageous to this patient population, because it antagonizes proteostasis and other cell maintenance mechanisms in older age. Experimental studies and studies conducted on centenarians suggest that low growth hormone and IGF-1 levels contribute to longevity and may be therapeutic biomarkers.
• Epigenetics: DNA methylation is a method that offers an “epigenetic clock” to compare biological age with chronologic age. Higher epigenetic age was associated with increased mortality risk, breast cancer, and nonalcoholic fatty liver disease. Therefore, it could also be a therapeutic biomarker.
• Metabolomics: Studying metabolomes facilitates the identification of the link between genetic polymorphisms and longevity, as most polymorphisms explain less than 0.5% of longevity variations.
• New translational strategy: It is common practice to treat each age-related disease individually. An alternative strategy would be to target the hallmarks of biological aging to prevent these diseases from developing. The rate of biological aging correlates with the speed of damage accumulation at the macromolecular, organelle, and cellular levels. It also affects the capacity of the body to repair this damage. The assessment of biomarkers would make possibile research into the effects of short- and long-term treatments that minimize damage and enhance resilience related to diseases common with aging.

New translational research

The report highlights two translational research models: the in-depth study of centenarians and the analysis of how immune aging makes older adults vulnerable to COVID-19. The impact of impaired immunity on aging became particularly evident during the pandemic. However, to home in on immunity as a therapeutic target and to better understand immune resilience, the specific nature of immune and biological deficits still need to be defined.

Metformin is among the therapeutic agents under investigation in cutting-edge clinical research. Its effect on aging will be studied in the Targeting Aging with Metformin (TAME) clinical trial. This trial is the first to study aging outcomes. The goal is to create a regulatory framework that future therapies can follow to achieve FDA approval.

There are three promising therapeutic platforms among the cutting-edge research studies. The first aims to produce adenosine triphosphate, levels of which decline dramatically with aging. The second aims to promote autophagy to remove cellular waste to treat neurodegenerative diseases. The third reprograms the epigenome to a younger state.

Research on mitochondrial dysfunction is relevant because it is highly involved in age-related diseases. Mitochondrial-derived peptides could potentially serve as biomarkers of mitochondrial function in aging studies and become promising therapeutic targets in age-related diseases. One of these peptides, humanin, has been demonstrated to exert protective effects on the heart, brain, and liver. Researchers observed that mitochondrial proteins are age-dependent and are suppressed by growth hormone and IGF-1. They also found that humanin levels are correlated with endothelial function. Data from animal studies have shown that sustained humanin levels are positively linked to longevity; these findings are mirrored in data from centenarians and their offspring, who have higher levels of humanin.

The formation of a Translational Geroscience Network composed of several scientists from various institutions should accelerate the application of this understanding. Despite the ongoing investigational and clinical studies, senolytics should not be regarded as extending life span or treating certain conditions, because their full safety profiles have not yet been elucidated.
 

Conclusion

Geroscience faces challenges in dealing with age-related problems. It is hoped that these challenges will be overcome through investigational and clinical studies on the mechanisms involved in aging. In-depth study of the interactions of underlying mechanisms of aging are needed to answer the following questions:

• Is there a hierarchical relationship among these mechanisms?
• Are there organ or cell-type differences in the interactions among these mechanisms?
• Is it possible to achieve a synergistic effect through combined interventions targeting several of the processes that drive aging?

It is complicated, but researchers are starting to see the light at the end of the tunnel.

This article was translated from the Medscape Portuguese edition and a version appeared on Medscape.com.

For many years, it has been believed that the aging process is inevitable and that age-related diseases cannot be prevented or reversed. For example, the U.S. Food and Drug Administration does not recognize aging as an indication for drug approval because there are no markers to determine whether possible treatments have a significant impact on the hallmarks of aging.

The field of geroscience aims to find ways to change this by delaying the onset of age-related diseases or by extending the life span. On May 19, 2021, experts in geroscience met virtually at a symposium of the New York Academy of Sciences. Presentations and discussions with experts in the field showed that remarkable advances have been made in understanding the mechanisms underlying biological aging. Those mechanisms contribute to the vulnerability of older adults. The presentations focused on identifying biomarkers of aging and on the search for interventions to prevent and treat age-related diseases.

Perspectives from this meeting were published in a report.
 

An abridged glossary

• Senescent cells: These are old cells with irreversibly damaged DNA; they strongly resist apoptosis. Thus, they are not eliminated and continue to secrete pathogenic proinflammatory molecules.
• Senolytics: This is a class of compounds that promote the removal of senescent cells from the body.
• Autophagy: This is a process that promotes protein degradation, which is attenuated with aging and that impedes the aggregation of proteins harmful to cell function, particularly those of the central nervous system.
• Proteostasis: This is the dynamic regulation of protein homeostasis.
• Epigenetics: This is the field of biology that studies phenotype changes that are not caused by changes in DNA sequencing and that continue to affect cellular division.
• Metabolome: This refers to small molecules that make up the building blocks of all organismal features, from cell membranes to metabolic cycles to genes and proteins.
• Translational research: This involves applying primary research results to clinical research and vice versa.

Possible research topics

Senescence not only occurs with age but also drives aging. At the meeting, evidence was provided that senescent cells may exacerbate the clinical course of older adults in cases of infections (for example, COVID-19) as they lead to cytokine storms.

Experiments on old mice that have undergone genetic modification of senescent cells or the administration of “senolytic cocktails” composed of dasatinib plus quercetin protected the animals from the effects of viral infections. This finding corroborates the idea that factors involved in biological aging increase vulnerability and could be modified through treatment.

Alzheimer’s disease is an example of the effects of cellular senescence. Senescent cells develop a senescence-associated secretory phenotype that can be toxic to neighboring healthy cells and can allow senescence to propagate within tissues. This effect makes Alzheimer’s disease an essential focal point when studying the use of senolytics. In addition, agents that stimulate autophagy may be of interest for treating degenerative diseases.
 

Assessing therapeutic effects

It may be possible to assess the therapeutic effects of drug candidates using the following biomarkers.

• Growth hormone and type 1 insulin-like growth factor (IGF-1): Older adults are often prescribed growth hormone. However, recent data suggest that doing so is not advantageous to this patient population, because it antagonizes proteostasis and other cell maintenance mechanisms in older age. Experimental studies and studies conducted on centenarians suggest that low growth hormone and IGF-1 levels contribute to longevity and may be therapeutic biomarkers.
• Epigenetics: DNA methylation is a method that offers an “epigenetic clock” to compare biological age with chronologic age. Higher epigenetic age was associated with increased mortality risk, breast cancer, and nonalcoholic fatty liver disease. Therefore, it could also be a therapeutic biomarker.
• Metabolomics: Studying metabolomes facilitates the identification of the link between genetic polymorphisms and longevity, as most polymorphisms explain less than 0.5% of longevity variations.
• New translational strategy: It is common practice to treat each age-related disease individually. An alternative strategy would be to target the hallmarks of biological aging to prevent these diseases from developing. The rate of biological aging correlates with the speed of damage accumulation at the macromolecular, organelle, and cellular levels. It also affects the capacity of the body to repair this damage. The assessment of biomarkers would make possibile research into the effects of short- and long-term treatments that minimize damage and enhance resilience related to diseases common with aging.

New translational research

The report highlights two translational research models: the in-depth study of centenarians and the analysis of how immune aging makes older adults vulnerable to COVID-19. The impact of impaired immunity on aging became particularly evident during the pandemic. However, to home in on immunity as a therapeutic target and to better understand immune resilience, the specific nature of immune and biological deficits still need to be defined.

Metformin is among the therapeutic agents under investigation in cutting-edge clinical research. Its effect on aging will be studied in the Targeting Aging with Metformin (TAME) clinical trial. This trial is the first to study aging outcomes. The goal is to create a regulatory framework that future therapies can follow to achieve FDA approval.

There are three promising therapeutic platforms among the cutting-edge research studies. The first aims to produce adenosine triphosphate, levels of which decline dramatically with aging. The second aims to promote autophagy to remove cellular waste to treat neurodegenerative diseases. The third reprograms the epigenome to a younger state.

Research on mitochondrial dysfunction is relevant because it is highly involved in age-related diseases. Mitochondrial-derived peptides could potentially serve as biomarkers of mitochondrial function in aging studies and become promising therapeutic targets in age-related diseases. One of these peptides, humanin, has been demonstrated to exert protective effects on the heart, brain, and liver. Researchers observed that mitochondrial proteins are age-dependent and are suppressed by growth hormone and IGF-1. They also found that humanin levels are correlated with endothelial function. Data from animal studies have shown that sustained humanin levels are positively linked to longevity; these findings are mirrored in data from centenarians and their offspring, who have higher levels of humanin.

The formation of a Translational Geroscience Network composed of several scientists from various institutions should accelerate the application of this understanding. Despite the ongoing investigational and clinical studies, senolytics should not be regarded as extending life span or treating certain conditions, because their full safety profiles have not yet been elucidated.
 

Conclusion

Geroscience faces challenges in dealing with age-related problems. It is hoped that these challenges will be overcome through investigational and clinical studies on the mechanisms involved in aging. In-depth study of the interactions of underlying mechanisms of aging are needed to answer the following questions:

• Is there a hierarchical relationship among these mechanisms?
• Are there organ or cell-type differences in the interactions among these mechanisms?
• Is it possible to achieve a synergistic effect through combined interventions targeting several of the processes that drive aging?

It is complicated, but researchers are starting to see the light at the end of the tunnel.

This article was translated from the Medscape Portuguese edition and a version appeared on Medscape.com.

For many years, it has been believed that the aging process is inevitable and that age-related diseases cannot be prevented or reversed. For example, the U.S. Food and Drug Administration does not recognize aging as an indication for drug approval because there are no markers to determine whether possible treatments have a significant impact on the hallmarks of aging.

The field of geroscience aims to find ways to change this by delaying the onset of age-related diseases or by extending the life span. On May 19, 2021, experts in geroscience met virtually at a symposium of the New York Academy of Sciences. Presentations and discussions with experts in the field showed that remarkable advances have been made in understanding the mechanisms underlying biological aging. Those mechanisms contribute to the vulnerability of older adults. The presentations focused on identifying biomarkers of aging and on the search for interventions to prevent and treat age-related diseases.

Perspectives from this meeting were published in a report.
 

An abridged glossary

• Senescent cells: These are old cells with irreversibly damaged DNA; they strongly resist apoptosis. Thus, they are not eliminated and continue to secrete pathogenic proinflammatory molecules.
• Senolytics: This is a class of compounds that promote the removal of senescent cells from the body.
• Autophagy: This is a process that promotes protein degradation, which is attenuated with aging and that impedes the aggregation of proteins harmful to cell function, particularly those of the central nervous system.
• Proteostasis: This is the dynamic regulation of protein homeostasis.
• Epigenetics: This is the field of biology that studies phenotype changes that are not caused by changes in DNA sequencing and that continue to affect cellular division.
• Metabolome: This refers to small molecules that make up the building blocks of all organismal features, from cell membranes to metabolic cycles to genes and proteins.
• Translational research: This involves applying primary research results to clinical research and vice versa.

Possible research topics

Senescence not only occurs with age but also drives aging. At the meeting, evidence was provided that senescent cells may exacerbate the clinical course of older adults in cases of infections (for example, COVID-19) as they lead to cytokine storms.

Experiments on old mice that have undergone genetic modification of senescent cells or the administration of “senolytic cocktails” composed of dasatinib plus quercetin protected the animals from the effects of viral infections. This finding corroborates the idea that factors involved in biological aging increase vulnerability and could be modified through treatment.

Alzheimer’s disease is an example of the effects of cellular senescence. Senescent cells develop a senescence-associated secretory phenotype that can be toxic to neighboring healthy cells and can allow senescence to propagate within tissues. This effect makes Alzheimer’s disease an essential focal point when studying the use of senolytics. In addition, agents that stimulate autophagy may be of interest for treating degenerative diseases.
 

Assessing therapeutic effects

It may be possible to assess the therapeutic effects of drug candidates using the following biomarkers.

• Growth hormone and type 1 insulin-like growth factor (IGF-1): Older adults are often prescribed growth hormone. However, recent data suggest that doing so is not advantageous to this patient population, because it antagonizes proteostasis and other cell maintenance mechanisms in older age. Experimental studies and studies conducted on centenarians suggest that low growth hormone and IGF-1 levels contribute to longevity and may be therapeutic biomarkers.
• Epigenetics: DNA methylation is a method that offers an “epigenetic clock” to compare biological age with chronologic age. Higher epigenetic age was associated with increased mortality risk, breast cancer, and nonalcoholic fatty liver disease. Therefore, it could also be a therapeutic biomarker.
• Metabolomics: Studying metabolomes facilitates the identification of the link between genetic polymorphisms and longevity, as most polymorphisms explain less than 0.5% of longevity variations.
• New translational strategy: It is common practice to treat each age-related disease individually. An alternative strategy would be to target the hallmarks of biological aging to prevent these diseases from developing. The rate of biological aging correlates with the speed of damage accumulation at the macromolecular, organelle, and cellular levels. It also affects the capacity of the body to repair this damage. The assessment of biomarkers would make possibile research into the effects of short- and long-term treatments that minimize damage and enhance resilience related to diseases common with aging.

New translational research

The report highlights two translational research models: the in-depth study of centenarians and the analysis of how immune aging makes older adults vulnerable to COVID-19. The impact of impaired immunity on aging became particularly evident during the pandemic. However, to home in on immunity as a therapeutic target and to better understand immune resilience, the specific nature of immune and biological deficits still need to be defined.

Metformin is among the therapeutic agents under investigation in cutting-edge clinical research. Its effect on aging will be studied in the Targeting Aging with Metformin (TAME) clinical trial. This trial is the first to study aging outcomes. The goal is to create a regulatory framework that future therapies can follow to achieve FDA approval.

There are three promising therapeutic platforms among the cutting-edge research studies. The first aims to produce adenosine triphosphate, levels of which decline dramatically with aging. The second aims to promote autophagy to remove cellular waste to treat neurodegenerative diseases. The third reprograms the epigenome to a younger state.

Research on mitochondrial dysfunction is relevant because it is highly involved in age-related diseases. Mitochondrial-derived peptides could potentially serve as biomarkers of mitochondrial function in aging studies and become promising therapeutic targets in age-related diseases. One of these peptides, humanin, has been demonstrated to exert protective effects on the heart, brain, and liver. Researchers observed that mitochondrial proteins are age-dependent and are suppressed by growth hormone and IGF-1. They also found that humanin levels are correlated with endothelial function. Data from animal studies have shown that sustained humanin levels are positively linked to longevity; these findings are mirrored in data from centenarians and their offspring, who have higher levels of humanin.

The formation of a Translational Geroscience Network composed of several scientists from various institutions should accelerate the application of this understanding. Despite the ongoing investigational and clinical studies, senolytics should not be regarded as extending life span or treating certain conditions, because their full safety profiles have not yet been elucidated.
 

Conclusion

Geroscience faces challenges in dealing with age-related problems. It is hoped that these challenges will be overcome through investigational and clinical studies on the mechanisms involved in aging. In-depth study of the interactions of underlying mechanisms of aging are needed to answer the following questions:

• Is there a hierarchical relationship among these mechanisms?
• Are there organ or cell-type differences in the interactions among these mechanisms?
• Is it possible to achieve a synergistic effect through combined interventions targeting several of the processes that drive aging?

It is complicated, but researchers are starting to see the light at the end of the tunnel.

This article was translated from the Medscape Portuguese edition and a version appeared on Medscape.com.

More than a quarter of patients who were shot by assailants with guns had their injuries mislabeled as “unintentional” at hospital discharge, according to a review of more than 1,200 cases at three U.S. trauma centers.

These coding inaccuracies could distort our understanding of gun violence in the United States and make it seem like accidental shootings are more common than they really are, researchers reported in JAMA Network Open.

“The systematic error in intent classification is not widely known or acknowledged by researchers in this field,” Philip J. Cook, PhD, of Duke University, Durham, N.C., and Susan T. Parker, of the University of Michigan, Ann Arbor, wrote in an invited commentary about the new findings. “The bulk of all shootings, nonfatal and fatal together, are assaults, which is to say the result of one person intentionally shooting another. An accurate statistical portrait thus suggests that gun violence is predominantly a crime problem.”

In 2020, 79% of all homicides and 53% of all suicides involved firearms, the CDC reported. Gun violence is now the leading cause of death for children in the United States, government data show.

For the new study, Matthew Miller, MD, ScD, of Northeastern University and the Harvard Injury Control Research Center in Boston, and his colleagues examined how International Classification of Diseases (ICD) codes may misclassify the intent behind gunshot injuries.

Dr. Miller’s group looked at 1,227 incidents between 2008 and 2019 at three major trauma centers – Brigham and Women’s Hospital and Massachusetts General Hospital, both in Boston, and Harborview Medical Center in Seattle.

Of those shootings, 837 (68.2%) involved assaults, 168 (13.5%) were unintentional, 124 (9.9%) were deliberate self-harm, and 43 (3.4%) were instances of legal intervention, based on the researchers’ review of medical records.

ICD codes at discharge, however, labeled 581 cases (47.4%) as assaults and 432 (35.2%) as unintentional.

The researchers found that 234 of the 837 assaults (28%) and 9 of the 43 legal interventions (20.9%) were miscoded as unintentional. This problem occurred even when the “medical narrative explicitly indicated that the shooting was an act of interpersonal violence,” such as a drive-by shooting or an act of domestic violence, the researchers reported.

Hospital trauma registrars, who detail the circumstances surrounding injuries, were mostly in agreement with the researchers.

Medical coders “would likely have little trouble characterizing firearm injury intent accurately if incentives were created for them to do so,” the authors wrote.

Trends and interventions

Separately, researchers published studies showing that gun violence tends to affect various demographics differently, and that remediating abandoned houses could help reduce gun crime.

Lindsay Young, of the University of Cincinnati, and Henry Xiang, MD, PhD, director of the Center for Pediatric Trauma Research at Nationwide Children’s Hospital in Columbus, Ohio, analyzed rates of firearm deaths from 1981 to 2020.

They found that the rate of firearm-related homicide was five times higher among males than females, and the rate of suicide involving firearms was nearly seven times higher for men, they reported in PLOS ONE.

Black men were the group most affected by homicide, whereas White men were most affected by suicide, they found.

To see if fixing abandoned properties would improve health and reduce gun violence in low-income, Black neighborhoods in Philadelphia, Eugenia C. South, MD, of the University of Pennsylvania, Philadelphia, and colleagues conducted a randomized trial.

They randomly assigned abandoned properties in some areas to undergo full remediation (installing working windows and doors, cleaning trash, and weeding); trash cleanup and weeding only; or no intervention.

“Abandoned houses that were remediated showed substantial drops in nearby weapons violations (−8.43%), gun assaults (−13.12%), and to a lesser extent shootings (−6.96%),” the researchers reported.

The intervention targets effects of segregation that have resulted from “historical and ongoing government and private-sector policies” that lead to disinvestment in Black, urban communities, they wrote. Abandoned houses can be used to store firearms and for other illegal activity. They also can engender feelings of fear, neglect, and stress in communities, the researchers noted.

Dr. Miller’s study was funded by the National Collaborative on Gun Violence Research; coauthors disclosed corporate, government, and university grants. The full list of disclosures can be found with the original article. Editorialists Dr. Cook and Dr. Parker report no relevant financial relationships. Dr. South’s study was funded by the National Institutes of Health. Dr. South and some coauthors disclosed government grants.
 

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

More than a quarter of patients who were shot by assailants with guns had their injuries mislabeled as “unintentional” at hospital discharge, according to a review of more than 1,200 cases at three U.S. trauma centers.

These coding inaccuracies could distort our understanding of gun violence in the United States and make it seem like accidental shootings are more common than they really are, researchers reported in JAMA Network Open.

“The systematic error in intent classification is not widely known or acknowledged by researchers in this field,” Philip J. Cook, PhD, of Duke University, Durham, N.C., and Susan T. Parker, of the University of Michigan, Ann Arbor, wrote in an invited commentary about the new findings. “The bulk of all shootings, nonfatal and fatal together, are assaults, which is to say the result of one person intentionally shooting another. An accurate statistical portrait thus suggests that gun violence is predominantly a crime problem.”

In 2020, 79% of all homicides and 53% of all suicides involved firearms, the CDC reported. Gun violence is now the leading cause of death for children in the United States, government data show.

For the new study, Matthew Miller, MD, ScD, of Northeastern University and the Harvard Injury Control Research Center in Boston, and his colleagues examined how International Classification of Diseases (ICD) codes may misclassify the intent behind gunshot injuries.

Dr. Miller’s group looked at 1,227 incidents between 2008 and 2019 at three major trauma centers – Brigham and Women’s Hospital and Massachusetts General Hospital, both in Boston, and Harborview Medical Center in Seattle.

Of those shootings, 837 (68.2%) involved assaults, 168 (13.5%) were unintentional, 124 (9.9%) were deliberate self-harm, and 43 (3.4%) were instances of legal intervention, based on the researchers’ review of medical records.

ICD codes at discharge, however, labeled 581 cases (47.4%) as assaults and 432 (35.2%) as unintentional.

The researchers found that 234 of the 837 assaults (28%) and 9 of the 43 legal interventions (20.9%) were miscoded as unintentional. This problem occurred even when the “medical narrative explicitly indicated that the shooting was an act of interpersonal violence,” such as a drive-by shooting or an act of domestic violence, the researchers reported.

Hospital trauma registrars, who detail the circumstances surrounding injuries, were mostly in agreement with the researchers.

Medical coders “would likely have little trouble characterizing firearm injury intent accurately if incentives were created for them to do so,” the authors wrote.

Trends and interventions

Separately, researchers published studies showing that gun violence tends to affect various demographics differently, and that remediating abandoned houses could help reduce gun crime.

Lindsay Young, of the University of Cincinnati, and Henry Xiang, MD, PhD, director of the Center for Pediatric Trauma Research at Nationwide Children’s Hospital in Columbus, Ohio, analyzed rates of firearm deaths from 1981 to 2020.

They found that the rate of firearm-related homicide was five times higher among males than females, and the rate of suicide involving firearms was nearly seven times higher for men, they reported in PLOS ONE.

Black men were the group most affected by homicide, whereas White men were most affected by suicide, they found.

To see if fixing abandoned properties would improve health and reduce gun violence in low-income, Black neighborhoods in Philadelphia, Eugenia C. South, MD, of the University of Pennsylvania, Philadelphia, and colleagues conducted a randomized trial.

They randomly assigned abandoned properties in some areas to undergo full remediation (installing working windows and doors, cleaning trash, and weeding); trash cleanup and weeding only; or no intervention.

“Abandoned houses that were remediated showed substantial drops in nearby weapons violations (−8.43%), gun assaults (−13.12%), and to a lesser extent shootings (−6.96%),” the researchers reported.

The intervention targets effects of segregation that have resulted from “historical and ongoing government and private-sector policies” that lead to disinvestment in Black, urban communities, they wrote. Abandoned houses can be used to store firearms and for other illegal activity. They also can engender feelings of fear, neglect, and stress in communities, the researchers noted.

Dr. Miller’s study was funded by the National Collaborative on Gun Violence Research; coauthors disclosed corporate, government, and university grants. The full list of disclosures can be found with the original article. Editorialists Dr. Cook and Dr. Parker report no relevant financial relationships. Dr. South’s study was funded by the National Institutes of Health. Dr. South and some coauthors disclosed government grants.
 

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

More than a quarter of patients who were shot by assailants with guns had their injuries mislabeled as “unintentional” at hospital discharge, according to a review of more than 1,200 cases at three U.S. trauma centers.

These coding inaccuracies could distort our understanding of gun violence in the United States and make it seem like accidental shootings are more common than they really are, researchers reported in JAMA Network Open.

“The systematic error in intent classification is not widely known or acknowledged by researchers in this field,” Philip J. Cook, PhD, of Duke University, Durham, N.C., and Susan T. Parker, of the University of Michigan, Ann Arbor, wrote in an invited commentary about the new findings. “The bulk of all shootings, nonfatal and fatal together, are assaults, which is to say the result of one person intentionally shooting another. An accurate statistical portrait thus suggests that gun violence is predominantly a crime problem.”

In 2020, 79% of all homicides and 53% of all suicides involved firearms, the CDC reported. Gun violence is now the leading cause of death for children in the United States, government data show.

For the new study, Matthew Miller, MD, ScD, of Northeastern University and the Harvard Injury Control Research Center in Boston, and his colleagues examined how International Classification of Diseases (ICD) codes may misclassify the intent behind gunshot injuries.

Dr. Miller’s group looked at 1,227 incidents between 2008 and 2019 at three major trauma centers – Brigham and Women’s Hospital and Massachusetts General Hospital, both in Boston, and Harborview Medical Center in Seattle.

Of those shootings, 837 (68.2%) involved assaults, 168 (13.5%) were unintentional, 124 (9.9%) were deliberate self-harm, and 43 (3.4%) were instances of legal intervention, based on the researchers’ review of medical records.

ICD codes at discharge, however, labeled 581 cases (47.4%) as assaults and 432 (35.2%) as unintentional.

The researchers found that 234 of the 837 assaults (28%) and 9 of the 43 legal interventions (20.9%) were miscoded as unintentional. This problem occurred even when the “medical narrative explicitly indicated that the shooting was an act of interpersonal violence,” such as a drive-by shooting or an act of domestic violence, the researchers reported.

Hospital trauma registrars, who detail the circumstances surrounding injuries, were mostly in agreement with the researchers.

Medical coders “would likely have little trouble characterizing firearm injury intent accurately if incentives were created for them to do so,” the authors wrote.

Trends and interventions

Separately, researchers published studies showing that gun violence tends to affect various demographics differently, and that remediating abandoned houses could help reduce gun crime.

Lindsay Young, of the University of Cincinnati, and Henry Xiang, MD, PhD, director of the Center for Pediatric Trauma Research at Nationwide Children’s Hospital in Columbus, Ohio, analyzed rates of firearm deaths from 1981 to 2020.

They found that the rate of firearm-related homicide was five times higher among males than females, and the rate of suicide involving firearms was nearly seven times higher for men, they reported in PLOS ONE.

Black men were the group most affected by homicide, whereas White men were most affected by suicide, they found.

To see if fixing abandoned properties would improve health and reduce gun violence in low-income, Black neighborhoods in Philadelphia, Eugenia C. South, MD, of the University of Pennsylvania, Philadelphia, and colleagues conducted a randomized trial.

They randomly assigned abandoned properties in some areas to undergo full remediation (installing working windows and doors, cleaning trash, and weeding); trash cleanup and weeding only; or no intervention.

“Abandoned houses that were remediated showed substantial drops in nearby weapons violations (−8.43%), gun assaults (−13.12%), and to a lesser extent shootings (−6.96%),” the researchers reported.

The intervention targets effects of segregation that have resulted from “historical and ongoing government and private-sector policies” that lead to disinvestment in Black, urban communities, they wrote. Abandoned houses can be used to store firearms and for other illegal activity. They also can engender feelings of fear, neglect, and stress in communities, the researchers noted.

Dr. Miller’s study was funded by the National Collaborative on Gun Violence Research; coauthors disclosed corporate, government, and university grants. The full list of disclosures can be found with the original article. Editorialists Dr. Cook and Dr. Parker report no relevant financial relationships. Dr. South’s study was funded by the National Institutes of Health. Dr. South and some coauthors disclosed government grants.
 

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

The percentage of people in the U.S. getting the latest COVID-19 booster shot has crept up by single digits in the past couple months, despite health officials pleading for people to do so before the Christmas holiday. 

Now, a new poll shows why so few people are willing to roll up their sleeves again.

The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation. 

The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.

Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling. 

So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.

Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.

Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.

“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.

Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.

Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.

“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”

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

The percentage of people in the U.S. getting the latest COVID-19 booster shot has crept up by single digits in the past couple months, despite health officials pleading for people to do so before the Christmas holiday. 

Now, a new poll shows why so few people are willing to roll up their sleeves again.

The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation. 

The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.

Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling. 

So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.

Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.

Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.

“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.

Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.

Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.

“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”

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

The percentage of people in the U.S. getting the latest COVID-19 booster shot has crept up by single digits in the past couple months, despite health officials pleading for people to do so before the Christmas holiday. 

Now, a new poll shows why so few people are willing to roll up their sleeves again.

The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation. 

The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.

Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling. 

So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.

Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.

Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.

“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.

Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.

Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.

“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”

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

Patients who seek fracture care at a facility that treats a higher proportion of patients from racial or ethnic minorities or a higher number of uninsured patients are more likely to face a longer-than-recommended delay in treatment, according to new data.

Regardless of individual patient-level characteristics such as race, ethnicity, or insurance status, these patients were more likely to miss the recommended 24-hour benchmark for surgery.

“Institutions that treat a less diverse patient population appeared to be more resilient to the mix of insurance status in their patient population and were more likely to meet time-to-surgery benchmarks, regardless of patient insurance status or population-based insurance mix,” write study author Ida Leah Gitajn, MD, an orthopedic trauma surgeon at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and colleagues.

“While it is unsurprising that increased delays were associated with underfunded institutions, the association between institutional-level racial disparity and surgical delays implies structural health systems bias,” the authors wrote.

The study was published online  in JAMA Network Open.
 

Site performance varied

Racial inequalities in health care utilization and outcomes have been documented in many medical specialties, including orthopedic trauma, the study authors write. However, previous studies evaluating racial disparities in fracture care have been limited to patient-level associations rather than hospital-level factors.

The investigators conducted a secondary analysis of prospectively collected multicenter data for 2,565 patients with hip and femur fractures enrolled in two randomized trials at 23 sites in the United States and Canada. The researchers assessed whether disparities in meeting 24-hour time-to-surgery benchmarks exist at the patient level or at the institutional level, evaluating the association of race, ethnicity, and insurance status.

The cohort study used data from the Program of Randomized Trials to Evaluate Preoperative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT), which enrolled patients from 2018-2021 and followed them for 1 year. All patients with hip and femur fractures enrolled in the PREP-IT program were included in the analysis, which was conducted from April to September of this year.

The cohort included 2,565 patients with an average age of about 65 years. About 82% of patients were White, 13.4% were Black, 3.2% were Asian, and 1.1% were classified as another race or ethnicity. Among the study population, 32.5% of participants were employed, and 92.2% had health insurance. Nearly 40% had a femur fracture with an average injury severity score of 10.4.

Overall, 596 patients (23.2%) didn’t meet the 24-hour time-to-operating-room benchmark. Patients who didn’t meet the 24-hour surgical window were more likely to be older, women, and have a femur fracture. They were less likely to be employed.

The 23 sites had variability in meeting the 24-hour benchmark, race and ethnicity distribution, and population-based health insurance. Institutions met benchmarks at frequencies ranging from 45.2% (for 196 of 433 procedures) to 97.4% (37 of 38 procedures). Minority race and ethnicity distribution ranged from 0% (in 99 procedures) to 58.2% (in 53 of 91 procedures). The proportion of uninsured patients ranged from 0% (in 64 procedures) to 34.2% (in 13 of 38 procedures).

At the patient level, there was no association between missing the 24-hour benchmark and race or ethnicity, and there was no independent association between hospital population racial composition and surgical delay. In an analysis that controlled for patient-level characteristics, there was no association between missing the 24-hour benchmark and patient-level insurance status.

There was an independent association, however, between the hospital population insurance coverage and hospital population racial composition as an interaction term, suggesting a moderating effect (P = .03), the study authors write.

At low rates of uninsured patients, the probability of missing the 24-hour benchmark was 12.5%-14.6% when racial composition varied from 0%-50% minority patients. In contrast, at higher rates of uninsured patients, the risk of missing the 24-hour window was higher among more diverse populations. For instance, at 30% uninsured, the risk of missing the benchmark was 0.5% when the racial composition was low and 17.6% at 50% minority patients.

Additional studies are needed to understand the findings and how health system programs or structures play a role, the authors write. For instance, well-funded health systems that care for a higher proportion of insured patients likely have quality improvement programs and other support structures, such as operating room access, that ensure appropriate time-to-surgery benchmarks for time-sensitive fractures, they say.
 

Addressing inequalities

Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery, New York, said, “Despite these disparities being reported and well documented in recent years, unfortunately, not enough has been done to address them or understand their fundamental root causes.”

Dr. Amen, who wasn’t involved with this study, has researched racial and ethnic disparities in hip fracture surgery care across the United States. He and his colleagues found disparities in delayed time-to-surgery, particularly for Black patients.

“We live in a country and society where we want and strive for equality of care for patients regardless of race, ethnicity, gender, sexual orientation, or background,” he said. “We have a moral imperative to address these disparities as health care providers, not only among ourselves, but also in conjunction with lawmakers, hospital administrators, and health policy specialists.”

Uma Srikumaran, MD, an associate professor of orthopedic surgery at Johns Hopkins University, Baltimore, wasn’t involved with this study but has researched racial disparities in the timing of radiographic assessment and surgical treatment of hip fractures.

“Though we understand that racial disparities are pervasive in health care, we have a great deal left to understand about the extent of those disparities and all the various factors that contribute to them,” Dr. Srikumaran told this news organization.

Dr. Srikumaran and colleagues have found that Black patients had longer wait times for evaluation and surgery than White patients.

“We all want to get to the solutions, but those can be difficult to execute without an intricate understanding of the problem,” he said. “We should encourage this type of research all throughout health care in general but also very locally, as solutions are not likely to be one-size-fits-all.”

Dr. Srikumaran pointed to the need to measure the problem in specific pathologies, populations, geographies, hospital types, and other factors.

“Studying the trends of this issue will help us determine whether our national or local initiatives are making a difference and which interventions are most effective for a particular hospital, geographic location, or particular pathology,” he said. “Accordingly, if a particular hospital or health system isn’t looking at differences in the delivery of care by race, they are missing an opportunity to ensure equity and raise overall quality.”

The study was supported by funding from the Patient Centered Outcomes Research Institute. Dr. Gitajn reported receiving personal fees for consulting and teaching work from Stryker outside the submitted work. Dr. Amen and Dr. Srikumaran reported no relevant financial relationships.

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

Patients who seek fracture care at a facility that treats a higher proportion of patients from racial or ethnic minorities or a higher number of uninsured patients are more likely to face a longer-than-recommended delay in treatment, according to new data.

Regardless of individual patient-level characteristics such as race, ethnicity, or insurance status, these patients were more likely to miss the recommended 24-hour benchmark for surgery.

“Institutions that treat a less diverse patient population appeared to be more resilient to the mix of insurance status in their patient population and were more likely to meet time-to-surgery benchmarks, regardless of patient insurance status or population-based insurance mix,” write study author Ida Leah Gitajn, MD, an orthopedic trauma surgeon at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and colleagues.

“While it is unsurprising that increased delays were associated with underfunded institutions, the association between institutional-level racial disparity and surgical delays implies structural health systems bias,” the authors wrote.

The study was published online  in JAMA Network Open.
 

Site performance varied

Racial inequalities in health care utilization and outcomes have been documented in many medical specialties, including orthopedic trauma, the study authors write. However, previous studies evaluating racial disparities in fracture care have been limited to patient-level associations rather than hospital-level factors.

The investigators conducted a secondary analysis of prospectively collected multicenter data for 2,565 patients with hip and femur fractures enrolled in two randomized trials at 23 sites in the United States and Canada. The researchers assessed whether disparities in meeting 24-hour time-to-surgery benchmarks exist at the patient level or at the institutional level, evaluating the association of race, ethnicity, and insurance status.

The cohort study used data from the Program of Randomized Trials to Evaluate Preoperative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT), which enrolled patients from 2018-2021 and followed them for 1 year. All patients with hip and femur fractures enrolled in the PREP-IT program were included in the analysis, which was conducted from April to September of this year.

The cohort included 2,565 patients with an average age of about 65 years. About 82% of patients were White, 13.4% were Black, 3.2% were Asian, and 1.1% were classified as another race or ethnicity. Among the study population, 32.5% of participants were employed, and 92.2% had health insurance. Nearly 40% had a femur fracture with an average injury severity score of 10.4.

Overall, 596 patients (23.2%) didn’t meet the 24-hour time-to-operating-room benchmark. Patients who didn’t meet the 24-hour surgical window were more likely to be older, women, and have a femur fracture. They were less likely to be employed.

The 23 sites had variability in meeting the 24-hour benchmark, race and ethnicity distribution, and population-based health insurance. Institutions met benchmarks at frequencies ranging from 45.2% (for 196 of 433 procedures) to 97.4% (37 of 38 procedures). Minority race and ethnicity distribution ranged from 0% (in 99 procedures) to 58.2% (in 53 of 91 procedures). The proportion of uninsured patients ranged from 0% (in 64 procedures) to 34.2% (in 13 of 38 procedures).

At the patient level, there was no association between missing the 24-hour benchmark and race or ethnicity, and there was no independent association between hospital population racial composition and surgical delay. In an analysis that controlled for patient-level characteristics, there was no association between missing the 24-hour benchmark and patient-level insurance status.

There was an independent association, however, between the hospital population insurance coverage and hospital population racial composition as an interaction term, suggesting a moderating effect (P = .03), the study authors write.

At low rates of uninsured patients, the probability of missing the 24-hour benchmark was 12.5%-14.6% when racial composition varied from 0%-50% minority patients. In contrast, at higher rates of uninsured patients, the risk of missing the 24-hour window was higher among more diverse populations. For instance, at 30% uninsured, the risk of missing the benchmark was 0.5% when the racial composition was low and 17.6% at 50% minority patients.

Additional studies are needed to understand the findings and how health system programs or structures play a role, the authors write. For instance, well-funded health systems that care for a higher proportion of insured patients likely have quality improvement programs and other support structures, such as operating room access, that ensure appropriate time-to-surgery benchmarks for time-sensitive fractures, they say.
 

Addressing inequalities

Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery, New York, said, “Despite these disparities being reported and well documented in recent years, unfortunately, not enough has been done to address them or understand their fundamental root causes.”

Dr. Amen, who wasn’t involved with this study, has researched racial and ethnic disparities in hip fracture surgery care across the United States. He and his colleagues found disparities in delayed time-to-surgery, particularly for Black patients.

“We live in a country and society where we want and strive for equality of care for patients regardless of race, ethnicity, gender, sexual orientation, or background,” he said. “We have a moral imperative to address these disparities as health care providers, not only among ourselves, but also in conjunction with lawmakers, hospital administrators, and health policy specialists.”

Uma Srikumaran, MD, an associate professor of orthopedic surgery at Johns Hopkins University, Baltimore, wasn’t involved with this study but has researched racial disparities in the timing of radiographic assessment and surgical treatment of hip fractures.

“Though we understand that racial disparities are pervasive in health care, we have a great deal left to understand about the extent of those disparities and all the various factors that contribute to them,” Dr. Srikumaran told this news organization.

Dr. Srikumaran and colleagues have found that Black patients had longer wait times for evaluation and surgery than White patients.

“We all want to get to the solutions, but those can be difficult to execute without an intricate understanding of the problem,” he said. “We should encourage this type of research all throughout health care in general but also very locally, as solutions are not likely to be one-size-fits-all.”

Dr. Srikumaran pointed to the need to measure the problem in specific pathologies, populations, geographies, hospital types, and other factors.

“Studying the trends of this issue will help us determine whether our national or local initiatives are making a difference and which interventions are most effective for a particular hospital, geographic location, or particular pathology,” he said. “Accordingly, if a particular hospital or health system isn’t looking at differences in the delivery of care by race, they are missing an opportunity to ensure equity and raise overall quality.”

The study was supported by funding from the Patient Centered Outcomes Research Institute. Dr. Gitajn reported receiving personal fees for consulting and teaching work from Stryker outside the submitted work. Dr. Amen and Dr. Srikumaran reported no relevant financial relationships.

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

Patients who seek fracture care at a facility that treats a higher proportion of patients from racial or ethnic minorities or a higher number of uninsured patients are more likely to face a longer-than-recommended delay in treatment, according to new data.

Regardless of individual patient-level characteristics such as race, ethnicity, or insurance status, these patients were more likely to miss the recommended 24-hour benchmark for surgery.

“Institutions that treat a less diverse patient population appeared to be more resilient to the mix of insurance status in their patient population and were more likely to meet time-to-surgery benchmarks, regardless of patient insurance status or population-based insurance mix,” write study author Ida Leah Gitajn, MD, an orthopedic trauma surgeon at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and colleagues.

“While it is unsurprising that increased delays were associated with underfunded institutions, the association between institutional-level racial disparity and surgical delays implies structural health systems bias,” the authors wrote.

The study was published online  in JAMA Network Open.
 

Site performance varied

Racial inequalities in health care utilization and outcomes have been documented in many medical specialties, including orthopedic trauma, the study authors write. However, previous studies evaluating racial disparities in fracture care have been limited to patient-level associations rather than hospital-level factors.

The investigators conducted a secondary analysis of prospectively collected multicenter data for 2,565 patients with hip and femur fractures enrolled in two randomized trials at 23 sites in the United States and Canada. The researchers assessed whether disparities in meeting 24-hour time-to-surgery benchmarks exist at the patient level or at the institutional level, evaluating the association of race, ethnicity, and insurance status.

The cohort study used data from the Program of Randomized Trials to Evaluate Preoperative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT), which enrolled patients from 2018-2021 and followed them for 1 year. All patients with hip and femur fractures enrolled in the PREP-IT program were included in the analysis, which was conducted from April to September of this year.

The cohort included 2,565 patients with an average age of about 65 years. About 82% of patients were White, 13.4% were Black, 3.2% were Asian, and 1.1% were classified as another race or ethnicity. Among the study population, 32.5% of participants were employed, and 92.2% had health insurance. Nearly 40% had a femur fracture with an average injury severity score of 10.4.

Overall, 596 patients (23.2%) didn’t meet the 24-hour time-to-operating-room benchmark. Patients who didn’t meet the 24-hour surgical window were more likely to be older, women, and have a femur fracture. They were less likely to be employed.

The 23 sites had variability in meeting the 24-hour benchmark, race and ethnicity distribution, and population-based health insurance. Institutions met benchmarks at frequencies ranging from 45.2% (for 196 of 433 procedures) to 97.4% (37 of 38 procedures). Minority race and ethnicity distribution ranged from 0% (in 99 procedures) to 58.2% (in 53 of 91 procedures). The proportion of uninsured patients ranged from 0% (in 64 procedures) to 34.2% (in 13 of 38 procedures).

At the patient level, there was no association between missing the 24-hour benchmark and race or ethnicity, and there was no independent association between hospital population racial composition and surgical delay. In an analysis that controlled for patient-level characteristics, there was no association between missing the 24-hour benchmark and patient-level insurance status.

There was an independent association, however, between the hospital population insurance coverage and hospital population racial composition as an interaction term, suggesting a moderating effect (P = .03), the study authors write.

At low rates of uninsured patients, the probability of missing the 24-hour benchmark was 12.5%-14.6% when racial composition varied from 0%-50% minority patients. In contrast, at higher rates of uninsured patients, the risk of missing the 24-hour window was higher among more diverse populations. For instance, at 30% uninsured, the risk of missing the benchmark was 0.5% when the racial composition was low and 17.6% at 50% minority patients.

Additional studies are needed to understand the findings and how health system programs or structures play a role, the authors write. For instance, well-funded health systems that care for a higher proportion of insured patients likely have quality improvement programs and other support structures, such as operating room access, that ensure appropriate time-to-surgery benchmarks for time-sensitive fractures, they say.
 

Addressing inequalities

Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery, New York, said, “Despite these disparities being reported and well documented in recent years, unfortunately, not enough has been done to address them or understand their fundamental root causes.”

Dr. Amen, who wasn’t involved with this study, has researched racial and ethnic disparities in hip fracture surgery care across the United States. He and his colleagues found disparities in delayed time-to-surgery, particularly for Black patients.

“We live in a country and society where we want and strive for equality of care for patients regardless of race, ethnicity, gender, sexual orientation, or background,” he said. “We have a moral imperative to address these disparities as health care providers, not only among ourselves, but also in conjunction with lawmakers, hospital administrators, and health policy specialists.”

Uma Srikumaran, MD, an associate professor of orthopedic surgery at Johns Hopkins University, Baltimore, wasn’t involved with this study but has researched racial disparities in the timing of radiographic assessment and surgical treatment of hip fractures.

“Though we understand that racial disparities are pervasive in health care, we have a great deal left to understand about the extent of those disparities and all the various factors that contribute to them,” Dr. Srikumaran told this news organization.

Dr. Srikumaran and colleagues have found that Black patients had longer wait times for evaluation and surgery than White patients.

“We all want to get to the solutions, but those can be difficult to execute without an intricate understanding of the problem,” he said. “We should encourage this type of research all throughout health care in general but also very locally, as solutions are not likely to be one-size-fits-all.”

Dr. Srikumaran pointed to the need to measure the problem in specific pathologies, populations, geographies, hospital types, and other factors.

“Studying the trends of this issue will help us determine whether our national or local initiatives are making a difference and which interventions are most effective for a particular hospital, geographic location, or particular pathology,” he said. “Accordingly, if a particular hospital or health system isn’t looking at differences in the delivery of care by race, they are missing an opportunity to ensure equity and raise overall quality.”

The study was supported by funding from the Patient Centered Outcomes Research Institute. Dr. Gitajn reported receiving personal fees for consulting and teaching work from Stryker outside the submitted work. Dr. Amen and Dr. Srikumaran reported no relevant financial relationships.

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

“I could relate to many, many, many of the experiences and emotions that Charlie, which is Brendan Fraser’s character, was portraying,” Patricia Nece recalls after watching a preview copy of the new film “The Whale.”

A24

Much of the movie “rang true and hit home for me as things that I, too, had experienced,” Ms. Nece, the board of directors’ chair of the Obesity Action Coalition (OAC) and a person living with obesity, shares with this news organization.

In theaters as of December 9, The Whale chronicles the experience of a 600-lb, middle-aged man named Charlie. Throughout the film, Charlie seeks to rebuild his relationship with his estranged teenage daughter. Charlie had left his daughter and family to pursue a relationship with a man, who eventually died. As he navigates the pain surrounding his partner’s death and his lack of community, Charlie turns to food for comfort.

When the movie premiered at the Venice Film Festival, Mr. Fraser received a 6-minute standing ovation. However, activists criticized the movie for casting Fraser over an actor with obesity as well as its depiction of people with obesity.

Representatives from the National Association to Advance Fat Acceptance contend that casting an actor without obesity only contributes to ongoing bias against people of size. “Medical weight stigma and other socio-political determinants of health for people of all sizes cause far more harm to fat people than body fat does. Bias endangers fat people’s health. Anti-obesity organizations, such as those consulted with for this movie, contribute to stigma rather than reducing it as they claim,” NAAFA wrote in a statement to this news organization.

And they added that though the fat suit used in the movie may be superior to previous ones, it is still not an accurate depiction: “The creators of The Whale consider its CGI-generated fat suit to be superior to tactile fat suits, but we don’t. The issue with fat suits in Hollywood is not that they aren’t realistic enough. The issue is that they are used rather than using performers who actually live in bodies like the ones being depicted. If there is a 600-pound character in a movie, there should be a 600-pound human in that role. Rather than concentrate on the hype around the fake fat body created for The Whale, we want to see Hollywood create more opportunities for fat people across the size spectrum, both in front of the camera and behind the scenes.”
 

Prosthetics vs. reality?

Ms. Nece says she understands the controversy surrounding the use of fat suits but believes that it was not done in poor taste.

“OAC got involved with the movie after Brendan was already chosen for the part, and we never would have gotten involved with it had the prosthetics or fat suit been used to ridicule or make fun of people with obesity, which is usually the case,” she explains.

“But we knew from the start that that was never the intent of anyone involved with The Whale. And I think that’s shown by the fact that Brendan and Darren Aronofsky, the director, reached out to people who live with obesity on a daily basis to find out and learn more about it and to educate themselves about it,” Ms. Nece continues.

In a Daily Mail article, Mr. Fraser credited his son Griffin, who is autistic and obese, with helping him understand the struggles that people with obesity face.

Rachel Goldman, PhD, a clinical psychologist in private practice in New York and a professor in the psychology department at New York University, notes that there are other considerations that played into casting. “I know there was some pushback in terms of could, a say 600-lb individual, even be able to go to be on set every day and do this kind of work, and the answer is we don’t know.”

“I’m sure Darren chose Brendan for many reasons above and beyond just his body. I think that’s very important to keep in mind that just as much as representation is very important, I think it is also about finding the right person for the right role,” adds Dr. Goldman, who served as a consultant to the film.
 

Fat suits, extreme weight gains all to play a role

About 42% of adults in the United States have obesity, according to the 2017-2020 National Health and Nutrition Examination Survey, but that reality is not reflected in films or television.

A study of 1018 major television characters found that 24% of men and 14% of women had either overweight or obesity – far below the national average. And when characters with obesity are portrayed, actors often wear prosthetics, like Gwyneth Paltrow in Shallow Hal or Eddie Murphy in the Nutty Professor.

But unlike Mr. Fraser, some actors gain weight quickly instead.

This practice is unhealthy, says Jaime Almandoz, MD, an associate professor at the University of Texas Southwestern Medical Center, Dallas, and a nonsurgical weight management expert. In interviews, actors have shared how they increased calorie intake by drinking two milkshakes per day, going to fast food places regularly, or, in Mark Walhberg’s case, consuming 7,000 calories per day to gain 30 pounds for his role as boxer-turned-priest in the movie Father Stu.

This method provides their bodies with excess calories they are unable to burn off. “Then the amount of sugar and fat that streams into the blood as a result creates problems both directly and indirectly as your body tries to store it. It basically ends up using overflow warehouses for fat storage, like the liver for example, so we can create a condition called fatty liver, or in the muscle and other places, and this excess sugar and fat in the bloodstream cause several factors that are both insulin resistance causing,” Dr. Almandoz explains.

Though gaining weight helps the actor understand the character’s life experience, it may also be risky.

“To have an actor deliberately put his own health at risk and gain a certain amount of weight and whatever that might entail, one – that’s not necessarily the safest thing for that actor – but two, it’s also important to highlight the authentic experience of someone who has dealt with this chronic disease as well,” says Disha Narang, MD, a quadruple-board certified endocrinologist, obesity medicine, and culinary medicine specialist at Northwestern Medicine Lake Forest Hospital, Chicago.

These extreme fluctuations in weight may create problems. “It is typically not something we recommend because there could be metabolic damages as well as health concerns when patients are trying to gain weight quickly, just as we don’t want patients to lose weight quickly,” says Kurt Hong, MD, PhD, board-certified in internal medicine and clinical nutrition at the University of Southern California, Los Angeles.

Dr. Hong notes that it may be difficult for individuals to experience sudden weight gain because the body works hard to maintain a state of homeostasis.

“Similarly, to someone trying to gain weight you overeat, initially your body will try to again, maybe enhance its metabolic efficiency to hold the body stable,” Dr. Hong adds.

Dietary choices that may contribute to insulin resistance or promote high blood sugar can contribute to inflammation and a number of other adverse health outcomes, notes Dr. Almandoz. “The things that actors need to do in order to gain this magnitude of weight and they want to do it in the most time-effective manner is often not helpful for our bodies, it can be very problematic, the same thing goes for weight loss when actors need to lose significant amounts of weight for roles,” says Dr. Almandoz.

And Dr. Hong explained that for patients trying to lose weight, they may cut calories, but the body will try to compensate by slowing down the metabolism to keep their weight the same.
 

‘Your own worst bully’

In “The Whale,” Charlie appears to suffer from internalized weight bias, which is common to many people living with obesity, Ms. Nece says.

“Internalized weight bias is when the person of size takes all that negativity and turns it on themselves. The easiest way to describe that is to tell you that I became my own worst bully because I started believing all the negative things people said to me about my weight,” Ms. Nece adds.

Her hope is that the film will bring attention to the harm that this bias creates, especially when it derives from other people. “There’s no telling whether it will, but what Charlie experiences in bias and stigma from others clearly happens. It’s realistic. Those of us in large bodies have experienced what he is experiencing, so some people have said the movie is fat-phobic, but I see it as I can relate to those experiences because I have them too, so they are very realistic.”

Ms. Nece notes that it is important for clinicians to understand that obesity is a multifaceted and sensitive topic. “For those medical professionals who do not already know that obesity is complex, I hope the film will begin to open their eyes to the many different facets involved in obesity and their patients with obesity, I hope it will help them empathize and show compassion to their patients with obesity,” she concludes.

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

“I could relate to many, many, many of the experiences and emotions that Charlie, which is Brendan Fraser’s character, was portraying,” Patricia Nece recalls after watching a preview copy of the new film “The Whale.”

A24

Much of the movie “rang true and hit home for me as things that I, too, had experienced,” Ms. Nece, the board of directors’ chair of the Obesity Action Coalition (OAC) and a person living with obesity, shares with this news organization.

In theaters as of December 9, The Whale chronicles the experience of a 600-lb, middle-aged man named Charlie. Throughout the film, Charlie seeks to rebuild his relationship with his estranged teenage daughter. Charlie had left his daughter and family to pursue a relationship with a man, who eventually died. As he navigates the pain surrounding his partner’s death and his lack of community, Charlie turns to food for comfort.

When the movie premiered at the Venice Film Festival, Mr. Fraser received a 6-minute standing ovation. However, activists criticized the movie for casting Fraser over an actor with obesity as well as its depiction of people with obesity.

Representatives from the National Association to Advance Fat Acceptance contend that casting an actor without obesity only contributes to ongoing bias against people of size. “Medical weight stigma and other socio-political determinants of health for people of all sizes cause far more harm to fat people than body fat does. Bias endangers fat people’s health. Anti-obesity organizations, such as those consulted with for this movie, contribute to stigma rather than reducing it as they claim,” NAAFA wrote in a statement to this news organization.

And they added that though the fat suit used in the movie may be superior to previous ones, it is still not an accurate depiction: “The creators of The Whale consider its CGI-generated fat suit to be superior to tactile fat suits, but we don’t. The issue with fat suits in Hollywood is not that they aren’t realistic enough. The issue is that they are used rather than using performers who actually live in bodies like the ones being depicted. If there is a 600-pound character in a movie, there should be a 600-pound human in that role. Rather than concentrate on the hype around the fake fat body created for The Whale, we want to see Hollywood create more opportunities for fat people across the size spectrum, both in front of the camera and behind the scenes.”
 

Prosthetics vs. reality?

Ms. Nece says she understands the controversy surrounding the use of fat suits but believes that it was not done in poor taste.

“OAC got involved with the movie after Brendan was already chosen for the part, and we never would have gotten involved with it had the prosthetics or fat suit been used to ridicule or make fun of people with obesity, which is usually the case,” she explains.

“But we knew from the start that that was never the intent of anyone involved with The Whale. And I think that’s shown by the fact that Brendan and Darren Aronofsky, the director, reached out to people who live with obesity on a daily basis to find out and learn more about it and to educate themselves about it,” Ms. Nece continues.

In a Daily Mail article, Mr. Fraser credited his son Griffin, who is autistic and obese, with helping him understand the struggles that people with obesity face.

Rachel Goldman, PhD, a clinical psychologist in private practice in New York and a professor in the psychology department at New York University, notes that there are other considerations that played into casting. “I know there was some pushback in terms of could, a say 600-lb individual, even be able to go to be on set every day and do this kind of work, and the answer is we don’t know.”

“I’m sure Darren chose Brendan for many reasons above and beyond just his body. I think that’s very important to keep in mind that just as much as representation is very important, I think it is also about finding the right person for the right role,” adds Dr. Goldman, who served as a consultant to the film.
 

Fat suits, extreme weight gains all to play a role

About 42% of adults in the United States have obesity, according to the 2017-2020 National Health and Nutrition Examination Survey, but that reality is not reflected in films or television.

A study of 1018 major television characters found that 24% of men and 14% of women had either overweight or obesity – far below the national average. And when characters with obesity are portrayed, actors often wear prosthetics, like Gwyneth Paltrow in Shallow Hal or Eddie Murphy in the Nutty Professor.

But unlike Mr. Fraser, some actors gain weight quickly instead.

This practice is unhealthy, says Jaime Almandoz, MD, an associate professor at the University of Texas Southwestern Medical Center, Dallas, and a nonsurgical weight management expert. In interviews, actors have shared how they increased calorie intake by drinking two milkshakes per day, going to fast food places regularly, or, in Mark Walhberg’s case, consuming 7,000 calories per day to gain 30 pounds for his role as boxer-turned-priest in the movie Father Stu.

This method provides their bodies with excess calories they are unable to burn off. “Then the amount of sugar and fat that streams into the blood as a result creates problems both directly and indirectly as your body tries to store it. It basically ends up using overflow warehouses for fat storage, like the liver for example, so we can create a condition called fatty liver, or in the muscle and other places, and this excess sugar and fat in the bloodstream cause several factors that are both insulin resistance causing,” Dr. Almandoz explains.

Though gaining weight helps the actor understand the character’s life experience, it may also be risky.

“To have an actor deliberately put his own health at risk and gain a certain amount of weight and whatever that might entail, one – that’s not necessarily the safest thing for that actor – but two, it’s also important to highlight the authentic experience of someone who has dealt with this chronic disease as well,” says Disha Narang, MD, a quadruple-board certified endocrinologist, obesity medicine, and culinary medicine specialist at Northwestern Medicine Lake Forest Hospital, Chicago.

These extreme fluctuations in weight may create problems. “It is typically not something we recommend because there could be metabolic damages as well as health concerns when patients are trying to gain weight quickly, just as we don’t want patients to lose weight quickly,” says Kurt Hong, MD, PhD, board-certified in internal medicine and clinical nutrition at the University of Southern California, Los Angeles.

Dr. Hong notes that it may be difficult for individuals to experience sudden weight gain because the body works hard to maintain a state of homeostasis.

“Similarly, to someone trying to gain weight you overeat, initially your body will try to again, maybe enhance its metabolic efficiency to hold the body stable,” Dr. Hong adds.

Dietary choices that may contribute to insulin resistance or promote high blood sugar can contribute to inflammation and a number of other adverse health outcomes, notes Dr. Almandoz. “The things that actors need to do in order to gain this magnitude of weight and they want to do it in the most time-effective manner is often not helpful for our bodies, it can be very problematic, the same thing goes for weight loss when actors need to lose significant amounts of weight for roles,” says Dr. Almandoz.

And Dr. Hong explained that for patients trying to lose weight, they may cut calories, but the body will try to compensate by slowing down the metabolism to keep their weight the same.
 

‘Your own worst bully’

In “The Whale,” Charlie appears to suffer from internalized weight bias, which is common to many people living with obesity, Ms. Nece says.

“Internalized weight bias is when the person of size takes all that negativity and turns it on themselves. The easiest way to describe that is to tell you that I became my own worst bully because I started believing all the negative things people said to me about my weight,” Ms. Nece adds.

Her hope is that the film will bring attention to the harm that this bias creates, especially when it derives from other people. “There’s no telling whether it will, but what Charlie experiences in bias and stigma from others clearly happens. It’s realistic. Those of us in large bodies have experienced what he is experiencing, so some people have said the movie is fat-phobic, but I see it as I can relate to those experiences because I have them too, so they are very realistic.”

Ms. Nece notes that it is important for clinicians to understand that obesity is a multifaceted and sensitive topic. “For those medical professionals who do not already know that obesity is complex, I hope the film will begin to open their eyes to the many different facets involved in obesity and their patients with obesity, I hope it will help them empathize and show compassion to their patients with obesity,” she concludes.

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

“I could relate to many, many, many of the experiences and emotions that Charlie, which is Brendan Fraser’s character, was portraying,” Patricia Nece recalls after watching a preview copy of the new film “The Whale.”

A24

Much of the movie “rang true and hit home for me as things that I, too, had experienced,” Ms. Nece, the board of directors’ chair of the Obesity Action Coalition (OAC) and a person living with obesity, shares with this news organization.

In theaters as of December 9, The Whale chronicles the experience of a 600-lb, middle-aged man named Charlie. Throughout the film, Charlie seeks to rebuild his relationship with his estranged teenage daughter. Charlie had left his daughter and family to pursue a relationship with a man, who eventually died. As he navigates the pain surrounding his partner’s death and his lack of community, Charlie turns to food for comfort.

When the movie premiered at the Venice Film Festival, Mr. Fraser received a 6-minute standing ovation. However, activists criticized the movie for casting Fraser over an actor with obesity as well as its depiction of people with obesity.

Representatives from the National Association to Advance Fat Acceptance contend that casting an actor without obesity only contributes to ongoing bias against people of size. “Medical weight stigma and other socio-political determinants of health for people of all sizes cause far more harm to fat people than body fat does. Bias endangers fat people’s health. Anti-obesity organizations, such as those consulted with for this movie, contribute to stigma rather than reducing it as they claim,” NAAFA wrote in a statement to this news organization.

And they added that though the fat suit used in the movie may be superior to previous ones, it is still not an accurate depiction: “The creators of The Whale consider its CGI-generated fat suit to be superior to tactile fat suits, but we don’t. The issue with fat suits in Hollywood is not that they aren’t realistic enough. The issue is that they are used rather than using performers who actually live in bodies like the ones being depicted. If there is a 600-pound character in a movie, there should be a 600-pound human in that role. Rather than concentrate on the hype around the fake fat body created for The Whale, we want to see Hollywood create more opportunities for fat people across the size spectrum, both in front of the camera and behind the scenes.”
 

Prosthetics vs. reality?

Ms. Nece says she understands the controversy surrounding the use of fat suits but believes that it was not done in poor taste.

“OAC got involved with the movie after Brendan was already chosen for the part, and we never would have gotten involved with it had the prosthetics or fat suit been used to ridicule or make fun of people with obesity, which is usually the case,” she explains.

“But we knew from the start that that was never the intent of anyone involved with The Whale. And I think that’s shown by the fact that Brendan and Darren Aronofsky, the director, reached out to people who live with obesity on a daily basis to find out and learn more about it and to educate themselves about it,” Ms. Nece continues.

In a Daily Mail article, Mr. Fraser credited his son Griffin, who is autistic and obese, with helping him understand the struggles that people with obesity face.

Rachel Goldman, PhD, a clinical psychologist in private practice in New York and a professor in the psychology department at New York University, notes that there are other considerations that played into casting. “I know there was some pushback in terms of could, a say 600-lb individual, even be able to go to be on set every day and do this kind of work, and the answer is we don’t know.”

“I’m sure Darren chose Brendan for many reasons above and beyond just his body. I think that’s very important to keep in mind that just as much as representation is very important, I think it is also about finding the right person for the right role,” adds Dr. Goldman, who served as a consultant to the film.
 

Fat suits, extreme weight gains all to play a role

About 42% of adults in the United States have obesity, according to the 2017-2020 National Health and Nutrition Examination Survey, but that reality is not reflected in films or television.

A study of 1018 major television characters found that 24% of men and 14% of women had either overweight or obesity – far below the national average. And when characters with obesity are portrayed, actors often wear prosthetics, like Gwyneth Paltrow in Shallow Hal or Eddie Murphy in the Nutty Professor.

But unlike Mr. Fraser, some actors gain weight quickly instead.

This practice is unhealthy, says Jaime Almandoz, MD, an associate professor at the University of Texas Southwestern Medical Center, Dallas, and a nonsurgical weight management expert. In interviews, actors have shared how they increased calorie intake by drinking two milkshakes per day, going to fast food places regularly, or, in Mark Walhberg’s case, consuming 7,000 calories per day to gain 30 pounds for his role as boxer-turned-priest in the movie Father Stu.

This method provides their bodies with excess calories they are unable to burn off. “Then the amount of sugar and fat that streams into the blood as a result creates problems both directly and indirectly as your body tries to store it. It basically ends up using overflow warehouses for fat storage, like the liver for example, so we can create a condition called fatty liver, or in the muscle and other places, and this excess sugar and fat in the bloodstream cause several factors that are both insulin resistance causing,” Dr. Almandoz explains.

Though gaining weight helps the actor understand the character’s life experience, it may also be risky.

“To have an actor deliberately put his own health at risk and gain a certain amount of weight and whatever that might entail, one – that’s not necessarily the safest thing for that actor – but two, it’s also important to highlight the authentic experience of someone who has dealt with this chronic disease as well,” says Disha Narang, MD, a quadruple-board certified endocrinologist, obesity medicine, and culinary medicine specialist at Northwestern Medicine Lake Forest Hospital, Chicago.

These extreme fluctuations in weight may create problems. “It is typically not something we recommend because there could be metabolic damages as well as health concerns when patients are trying to gain weight quickly, just as we don’t want patients to lose weight quickly,” says Kurt Hong, MD, PhD, board-certified in internal medicine and clinical nutrition at the University of Southern California, Los Angeles.

Dr. Hong notes that it may be difficult for individuals to experience sudden weight gain because the body works hard to maintain a state of homeostasis.

“Similarly, to someone trying to gain weight you overeat, initially your body will try to again, maybe enhance its metabolic efficiency to hold the body stable,” Dr. Hong adds.

Dietary choices that may contribute to insulin resistance or promote high blood sugar can contribute to inflammation and a number of other adverse health outcomes, notes Dr. Almandoz. “The things that actors need to do in order to gain this magnitude of weight and they want to do it in the most time-effective manner is often not helpful for our bodies, it can be very problematic, the same thing goes for weight loss when actors need to lose significant amounts of weight for roles,” says Dr. Almandoz.

And Dr. Hong explained that for patients trying to lose weight, they may cut calories, but the body will try to compensate by slowing down the metabolism to keep their weight the same.
 

‘Your own worst bully’

In “The Whale,” Charlie appears to suffer from internalized weight bias, which is common to many people living with obesity, Ms. Nece says.

“Internalized weight bias is when the person of size takes all that negativity and turns it on themselves. The easiest way to describe that is to tell you that I became my own worst bully because I started believing all the negative things people said to me about my weight,” Ms. Nece adds.

Her hope is that the film will bring attention to the harm that this bias creates, especially when it derives from other people. “There’s no telling whether it will, but what Charlie experiences in bias and stigma from others clearly happens. It’s realistic. Those of us in large bodies have experienced what he is experiencing, so some people have said the movie is fat-phobic, but I see it as I can relate to those experiences because I have them too, so they are very realistic.”

Ms. Nece notes that it is important for clinicians to understand that obesity is a multifaceted and sensitive topic. “For those medical professionals who do not already know that obesity is complex, I hope the film will begin to open their eyes to the many different facets involved in obesity and their patients with obesity, I hope it will help them empathize and show compassion to their patients with obesity,” she concludes.

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

Colonoscopies with artificial intelligence demonstrate significantly better adenoma detection rates (ADRs) than most other endoscopic interventions, according to a new report.

AI-based tools appear to outperform other methods intended to increase ADRs, including distal attachment devices, dye-based/virtual chromoendoscopy, water-based techniques, and balloon-assisted devices, researchers found in a systematic review and meta-analysis.

“ADR is a very important quality metric. The higher the ADR, the less likely the chance of interval cancer,” first author Muhammad Aziz, MD, co-chief gastroenterology fellow at the University of Toledo (Ohio), told this news organization. Interval cancer refers to colorectal cancer that is diagnosed within 5 years of a patient’s undergoing a negative colonoscopy.

“Numerous interventions have been attempted and researched to see the impact on ADR,” he said. “The new kid on the block – AI-assisted colonoscopy – is a game-changer. I knew that AI was impactful in improving ADR, but I didn’t know it would be the best.”

The study was published online in the Journal of Clinical Gastroenterology.
 

Analyzing detection rates

Current guidelines set an ADR benchmark of 25% overall, with 30% for men and 20% for women undergoing screening colonoscopy. Every 1% increase in ADR results in a 3% reduction in colorectal cancer, Dr. Aziz and his co-authors write.

Several methods can improve ADR over standard colonoscopy. Computer-aided detection and AI methods, which have emerged in recent years, alert the endoscopist of potential lesions in real time with visual signals.

No direct comparative studies had been conducted, so to make an indirect comparison, Dr. Aziz and colleagues undertook a systematic review and network meta-analysis of 94 randomized controlled trials that included 61,172 patients and 20 different study interventions.

The research team assessed the impact of AI in comparison with other endoscopic methods, using relative risk for proportional outcomes and mean difference for continuous outcomes. About 63% of the colonoscopies were for screening and surveillance, and 37% were diagnostic. The effectiveness was ranked by P-score (the probability of being the best treatment).

Overall, AI had the highest P-score (0.96), signifying the best modality of all interventions for improving ADR, the study authors write. A sensitivity analysis using the fixed effects model did not significantly alter the effect measure.

The network meta-analysis showed significantly higher ADR for AI, compared with autofluorescence imaging (relative risk, 1.33), dye-based chromoendoscopy (RR, 1.22), Endocap (RR, 1.32), Endocuff (RR, 1.19), Endocuff Vision (RR, 1.26), EndoRings (RR, 1.30), flexible spectral imaging color enhancement (RR,1.26), full-spectrum endoscopy (RR, 1.40), high-definition (HD) colonoscopy (RR, 1.41), linked color imaging (1.21), narrow-band imaging (RR, 1.33), water exchange (RR, 1.22), and water immersion (RR, 1.47).

Among 34 studies of colonoscopies for screening or surveillance only, the ADR was significantly improved for linked color imaging (RR, 1.18), I-Scan with contrast and surface enhancement (RR, 1.25), Endocuff (RR, 1.20), Endocuff Vision (RR, 1.13), and water exchange (RR, 1.24), compared with HD colonoscopy. Only one AI study was included in this analysis, because the others had significantly more patients who underwent colonoscopy for diagnostic indications. In this case, AI did not improve ADR, compared with HD colonoscopy (RR, 1.44).

In addition, a significantly improved polyp detection rate (PDR) was noted for AI, compared with autofluorescence imaging (RR, 1.28), Endocap (RR, 1.18), Endocuff Vision (RR, 1.21), EndoRings (RR, 1.30), flexible spectral imaging color enhancement (RR, 1.21), full-spectrum endoscopy (RR, 1.39), HD colonoscopy (RR, 1.34), linked color imaging (RR, 1.19), and narrow-band imaging (RR, 1.21). Again, AI had the highest P-score (RR, 0.93).

Among 17 studies of colonoscopy for screening and surveillance, only one AI study was included for PDR. A significantly higher PDR was noted for AI, compared with HD colonoscopy (RR, 1.33). None of the other interventions improved PDR over HD colonoscopy.
 

No AI advantage for serrated polyps

Twenty-three studies evaluated detection for serrated polyps, including three AI studies. AI did not improve the serrated polyp detection rate (SPDR), compared with other interventions. However, several modalities did improve SPDR: G-EYE, compared with full-spectrum endoscopy (RR, 3.93), linked color imaging, compared with full-spectrum endoscopy (RR, 1.88), and HD colonoscopy (RR, 1.71), and Endocuff Vision, compared with HD colonoscopy (RR, 1.36). G-EYE had the highest P-score (0.93).

AI significantly improved adenomas per colonoscopy, compared with full-spectrum endoscopy (mean difference, 0.38), HD colonoscopy (MD, 0.18), and narrow-band imaging (MD, 0.13), the authors note. However, the number of adenomas detected per colonoscopy was significantly lower for AI, compared with Endocap (-0.13). Endocap had the highest P-score (0.92).

“The strengths of this study include the wide range of endoscopic add-ons included, the number of trials included, and the granularity of some of the reporting data,” Jeremy Glissen Brown, MD, a gastroenterologist and an assistant professor of medicine at Duke University, told this news organization.

Dr. Glissen Brown, who wasn’t involved with this study, researches AI tools for polyp detection. He and colleagues have found that AI decreases adenoma miss rates and increases the number of first-pass adenomas detected per colonoscopy.

“The limitations include significant heterogeneity among many of the comparisons, as well as a high risk of bias, as it is technically difficult to achieve blinding of provider participants in the device-based RCTs [randomized controlled trials] that this analysis was based on,” he said.
 

Additional considerations

Dr. Aziz and colleagues note the need for additional studies of AI-based detection, particularly for screening and surveillance. For widespread adoption into clinical practice, new systems must have higher specificity, sensitivity, accuracy, and efficiency, they write.

“AI technology needs further optimization, as there is still the aspect of having a lot of false positives – lesions detected but not necessarily adenomas that can turn into cancer,” Dr. Aziz said. “This decreases the efficiency of the colonoscopy and increases the anesthesia and sedation time. In addition, different AI systems have different diagnostic yield, as it all depends on the images that were fed to the system or algorithm.”

Dr. Glissen Brown also pointed to the low number of AI-based studies involving serrated polyp lesion detection. Future research could investigate whether computer-aided detection systems (CADe) decrease miss rates and increase detection rates for sessile serrated lesions, he said.

For practical clinical purposes, Dr. Glissen Brown highlighted the potential complementary nature of the various colonoscopy tools. When used together, for instance, AI and Endocuff may increase ADRs even further and decrease the number of missed polyps through different mechanisms, he said.

“It is also important in device research to interrogate the cost versus benefit of any intervention or combination of interventions,” he said. “I think with CADe this is still something that we are figuring out. We will need to find novel ways of making these technologies affordable, especially as the debate of which clinically meaningful outcomes we examine when it comes to AI continues to evolve.”

No funding source for the study was reported. Two authors have received grant support from or have consulted for several pharmaceutical and medical device companies. Dr. Glissen Brown has disclosed no relevant financial relationships.

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

Colonoscopies with artificial intelligence demonstrate significantly better adenoma detection rates (ADRs) than most other endoscopic interventions, according to a new report.

AI-based tools appear to outperform other methods intended to increase ADRs, including distal attachment devices, dye-based/virtual chromoendoscopy, water-based techniques, and balloon-assisted devices, researchers found in a systematic review and meta-analysis.

“ADR is a very important quality metric. The higher the ADR, the less likely the chance of interval cancer,” first author Muhammad Aziz, MD, co-chief gastroenterology fellow at the University of Toledo (Ohio), told this news organization. Interval cancer refers to colorectal cancer that is diagnosed within 5 years of a patient’s undergoing a negative colonoscopy.

“Numerous interventions have been attempted and researched to see the impact on ADR,” he said. “The new kid on the block – AI-assisted colonoscopy – is a game-changer. I knew that AI was impactful in improving ADR, but I didn’t know it would be the best.”

The study was published online in the Journal of Clinical Gastroenterology.
 

Analyzing detection rates

Current guidelines set an ADR benchmark of 25% overall, with 30% for men and 20% for women undergoing screening colonoscopy. Every 1% increase in ADR results in a 3% reduction in colorectal cancer, Dr. Aziz and his co-authors write.

Several methods can improve ADR over standard colonoscopy. Computer-aided detection and AI methods, which have emerged in recent years, alert the endoscopist of potential lesions in real time with visual signals.

No direct comparative studies had been conducted, so to make an indirect comparison, Dr. Aziz and colleagues undertook a systematic review and network meta-analysis of 94 randomized controlled trials that included 61,172 patients and 20 different study interventions.

The research team assessed the impact of AI in comparison with other endoscopic methods, using relative risk for proportional outcomes and mean difference for continuous outcomes. About 63% of the colonoscopies were for screening and surveillance, and 37% were diagnostic. The effectiveness was ranked by P-score (the probability of being the best treatment).

Overall, AI had the highest P-score (0.96), signifying the best modality of all interventions for improving ADR, the study authors write. A sensitivity analysis using the fixed effects model did not significantly alter the effect measure.

The network meta-analysis showed significantly higher ADR for AI, compared with autofluorescence imaging (relative risk, 1.33), dye-based chromoendoscopy (RR, 1.22), Endocap (RR, 1.32), Endocuff (RR, 1.19), Endocuff Vision (RR, 1.26), EndoRings (RR, 1.30), flexible spectral imaging color enhancement (RR,1.26), full-spectrum endoscopy (RR, 1.40), high-definition (HD) colonoscopy (RR, 1.41), linked color imaging (1.21), narrow-band imaging (RR, 1.33), water exchange (RR, 1.22), and water immersion (RR, 1.47).

Among 34 studies of colonoscopies for screening or surveillance only, the ADR was significantly improved for linked color imaging (RR, 1.18), I-Scan with contrast and surface enhancement (RR, 1.25), Endocuff (RR, 1.20), Endocuff Vision (RR, 1.13), and water exchange (RR, 1.24), compared with HD colonoscopy. Only one AI study was included in this analysis, because the others had significantly more patients who underwent colonoscopy for diagnostic indications. In this case, AI did not improve ADR, compared with HD colonoscopy (RR, 1.44).

In addition, a significantly improved polyp detection rate (PDR) was noted for AI, compared with autofluorescence imaging (RR, 1.28), Endocap (RR, 1.18), Endocuff Vision (RR, 1.21), EndoRings (RR, 1.30), flexible spectral imaging color enhancement (RR, 1.21), full-spectrum endoscopy (RR, 1.39), HD colonoscopy (RR, 1.34), linked color imaging (RR, 1.19), and narrow-band imaging (RR, 1.21). Again, AI had the highest P-score (RR, 0.93).

Among 17 studies of colonoscopy for screening and surveillance, only one AI study was included for PDR. A significantly higher PDR was noted for AI, compared with HD colonoscopy (RR, 1.33). None of the other interventions improved PDR over HD colonoscopy.
 

No AI advantage for serrated polyps

Twenty-three studies evaluated detection for serrated polyps, including three AI studies. AI did not improve the serrated polyp detection rate (SPDR), compared with other interventions. However, several modalities did improve SPDR: G-EYE, compared with full-spectrum endoscopy (RR, 3.93), linked color imaging, compared with full-spectrum endoscopy (RR, 1.88), and HD colonoscopy (RR, 1.71), and Endocuff Vision, compared with HD colonoscopy (RR, 1.36). G-EYE had the highest P-score (0.93).

AI significantly improved adenomas per colonoscopy, compared with full-spectrum endoscopy (mean difference, 0.38), HD colonoscopy (MD, 0.18), and narrow-band imaging (MD, 0.13), the authors note. However, the number of adenomas detected per colonoscopy was significantly lower for AI, compared with Endocap (-0.13). Endocap had the highest P-score (0.92).

“The strengths of this study include the wide range of endoscopic add-ons included, the number of trials included, and the granularity of some of the reporting data,” Jeremy Glissen Brown, MD, a gastroenterologist and an assistant professor of medicine at Duke University, told this news organization.

Dr. Glissen Brown, who wasn’t involved with this study, researches AI tools for polyp detection. He and colleagues have found that AI decreases adenoma miss rates and increases the number of first-pass adenomas detected per colonoscopy.

“The limitations include significant heterogeneity among many of the comparisons, as well as a high risk of bias, as it is technically difficult to achieve blinding of provider participants in the device-based RCTs [randomized controlled trials] that this analysis was based on,” he said.
 

Additional considerations

Dr. Aziz and colleagues note the need for additional studies of AI-based detection, particularly for screening and surveillance. For widespread adoption into clinical practice, new systems must have higher specificity, sensitivity, accuracy, and efficiency, they write.

“AI technology needs further optimization, as there is still the aspect of having a lot of false positives – lesions detected but not necessarily adenomas that can turn into cancer,” Dr. Aziz said. “This decreases the efficiency of the colonoscopy and increases the anesthesia and sedation time. In addition, different AI systems have different diagnostic yield, as it all depends on the images that were fed to the system or algorithm.”

Dr. Glissen Brown also pointed to the low number of AI-based studies involving serrated polyp lesion detection. Future research could investigate whether computer-aided detection systems (CADe) decrease miss rates and increase detection rates for sessile serrated lesions, he said.

For practical clinical purposes, Dr. Glissen Brown highlighted the potential complementary nature of the various colonoscopy tools. When used together, for instance, AI and Endocuff may increase ADRs even further and decrease the number of missed polyps through different mechanisms, he said.

“It is also important in device research to interrogate the cost versus benefit of any intervention or combination of interventions,” he said. “I think with CADe this is still something that we are figuring out. We will need to find novel ways of making these technologies affordable, especially as the debate of which clinically meaningful outcomes we examine when it comes to AI continues to evolve.”

No funding source for the study was reported. Two authors have received grant support from or have consulted for several pharmaceutical and medical device companies. Dr. Glissen Brown has disclosed no relevant financial relationships.

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

Colonoscopies with artificial intelligence demonstrate significantly better adenoma detection rates (ADRs) than most other endoscopic interventions, according to a new report.

AI-based tools appear to outperform other methods intended to increase ADRs, including distal attachment devices, dye-based/virtual chromoendoscopy, water-based techniques, and balloon-assisted devices, researchers found in a systematic review and meta-analysis.

“ADR is a very important quality metric. The higher the ADR, the less likely the chance of interval cancer,” first author Muhammad Aziz, MD, co-chief gastroenterology fellow at the University of Toledo (Ohio), told this news organization. Interval cancer refers to colorectal cancer that is diagnosed within 5 years of a patient’s undergoing a negative colonoscopy.

“Numerous interventions have been attempted and researched to see the impact on ADR,” he said. “The new kid on the block – AI-assisted colonoscopy – is a game-changer. I knew that AI was impactful in improving ADR, but I didn’t know it would be the best.”

The study was published online in the Journal of Clinical Gastroenterology.
 

Analyzing detection rates

Current guidelines set an ADR benchmark of 25% overall, with 30% for men and 20% for women undergoing screening colonoscopy. Every 1% increase in ADR results in a 3% reduction in colorectal cancer, Dr. Aziz and his co-authors write.

Several methods can improve ADR over standard colonoscopy. Computer-aided detection and AI methods, which have emerged in recent years, alert the endoscopist of potential lesions in real time with visual signals.

No direct comparative studies had been conducted, so to make an indirect comparison, Dr. Aziz and colleagues undertook a systematic review and network meta-analysis of 94 randomized controlled trials that included 61,172 patients and 20 different study interventions.

The research team assessed the impact of AI in comparison with other endoscopic methods, using relative risk for proportional outcomes and mean difference for continuous outcomes. About 63% of the colonoscopies were for screening and surveillance, and 37% were diagnostic. The effectiveness was ranked by P-score (the probability of being the best treatment).

Overall, AI had the highest P-score (0.96), signifying the best modality of all interventions for improving ADR, the study authors write. A sensitivity analysis using the fixed effects model did not significantly alter the effect measure.

The network meta-analysis showed significantly higher ADR for AI, compared with autofluorescence imaging (relative risk, 1.33), dye-based chromoendoscopy (RR, 1.22), Endocap (RR, 1.32), Endocuff (RR, 1.19), Endocuff Vision (RR, 1.26), EndoRings (RR, 1.30), flexible spectral imaging color enhancement (RR,1.26), full-spectrum endoscopy (RR, 1.40), high-definition (HD) colonoscopy (RR, 1.41), linked color imaging (1.21), narrow-band imaging (RR, 1.33), water exchange (RR, 1.22), and water immersion (RR, 1.47).

Among 34 studies of colonoscopies for screening or surveillance only, the ADR was significantly improved for linked color imaging (RR, 1.18), I-Scan with contrast and surface enhancement (RR, 1.25), Endocuff (RR, 1.20), Endocuff Vision (RR, 1.13), and water exchange (RR, 1.24), compared with HD colonoscopy. Only one AI study was included in this analysis, because the others had significantly more patients who underwent colonoscopy for diagnostic indications. In this case, AI did not improve ADR, compared with HD colonoscopy (RR, 1.44).

In addition, a significantly improved polyp detection rate (PDR) was noted for AI, compared with autofluorescence imaging (RR, 1.28), Endocap (RR, 1.18), Endocuff Vision (RR, 1.21), EndoRings (RR, 1.30), flexible spectral imaging color enhancement (RR, 1.21), full-spectrum endoscopy (RR, 1.39), HD colonoscopy (RR, 1.34), linked color imaging (RR, 1.19), and narrow-band imaging (RR, 1.21). Again, AI had the highest P-score (RR, 0.93).

Among 17 studies of colonoscopy for screening and surveillance, only one AI study was included for PDR. A significantly higher PDR was noted for AI, compared with HD colonoscopy (RR, 1.33). None of the other interventions improved PDR over HD colonoscopy.
 

No AI advantage for serrated polyps

Twenty-three studies evaluated detection for serrated polyps, including three AI studies. AI did not improve the serrated polyp detection rate (SPDR), compared with other interventions. However, several modalities did improve SPDR: G-EYE, compared with full-spectrum endoscopy (RR, 3.93), linked color imaging, compared with full-spectrum endoscopy (RR, 1.88), and HD colonoscopy (RR, 1.71), and Endocuff Vision, compared with HD colonoscopy (RR, 1.36). G-EYE had the highest P-score (0.93).

AI significantly improved adenomas per colonoscopy, compared with full-spectrum endoscopy (mean difference, 0.38), HD colonoscopy (MD, 0.18), and narrow-band imaging (MD, 0.13), the authors note. However, the number of adenomas detected per colonoscopy was significantly lower for AI, compared with Endocap (-0.13). Endocap had the highest P-score (0.92).

“The strengths of this study include the wide range of endoscopic add-ons included, the number of trials included, and the granularity of some of the reporting data,” Jeremy Glissen Brown, MD, a gastroenterologist and an assistant professor of medicine at Duke University, told this news organization.

Dr. Glissen Brown, who wasn’t involved with this study, researches AI tools for polyp detection. He and colleagues have found that AI decreases adenoma miss rates and increases the number of first-pass adenomas detected per colonoscopy.

“The limitations include significant heterogeneity among many of the comparisons, as well as a high risk of bias, as it is technically difficult to achieve blinding of provider participants in the device-based RCTs [randomized controlled trials] that this analysis was based on,” he said.
 

Additional considerations

Dr. Aziz and colleagues note the need for additional studies of AI-based detection, particularly for screening and surveillance. For widespread adoption into clinical practice, new systems must have higher specificity, sensitivity, accuracy, and efficiency, they write.

“AI technology needs further optimization, as there is still the aspect of having a lot of false positives – lesions detected but not necessarily adenomas that can turn into cancer,” Dr. Aziz said. “This decreases the efficiency of the colonoscopy and increases the anesthesia and sedation time. In addition, different AI systems have different diagnostic yield, as it all depends on the images that were fed to the system or algorithm.”

Dr. Glissen Brown also pointed to the low number of AI-based studies involving serrated polyp lesion detection. Future research could investigate whether computer-aided detection systems (CADe) decrease miss rates and increase detection rates for sessile serrated lesions, he said.

For practical clinical purposes, Dr. Glissen Brown highlighted the potential complementary nature of the various colonoscopy tools. When used together, for instance, AI and Endocuff may increase ADRs even further and decrease the number of missed polyps through different mechanisms, he said.

“It is also important in device research to interrogate the cost versus benefit of any intervention or combination of interventions,” he said. “I think with CADe this is still something that we are figuring out. We will need to find novel ways of making these technologies affordable, especially as the debate of which clinically meaningful outcomes we examine when it comes to AI continues to evolve.”

No funding source for the study was reported. Two authors have received grant support from or have consulted for several pharmaceutical and medical device companies. Dr. Glissen Brown has disclosed no relevant financial relationships.

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