Federal Practitioner

COVID-19 infection is significantly associated with chronically impaired cerebral vasoreactivity (CVR), results of a small study show.

In a small prospective study, participants who previously had COVID-19, even those with mild illness, had significantly decreased CVR, compared with never-infected individuals.

Results also showed cerebral blood flow (CBF) was greater in never-infected versus previously infected participants, and whole-brain CVR was lower in previously infected versus never-infected participants. Although CVR was also smaller in those with versus those without post-COVID neurologic conditions, the difference was not considered significant.

“It is important to remember that while our findings were statistically significant, we had a relatively small sample size – 25 total participants – and so we encourage future larger studies in this domain to see if these results are reproducible at a larger scale,” lead author Andrew Callen, MD, assistant professor of radiology, Neuroradiology Section, University of Colorado at Denver, Aurora, said in an interview.

“In a practical sense, it may encourage treating clinicians to be more aggressive with preventative neurovascular and cardiovascular health measures and/or screening in this patient population,” Dr. Callen said.

The findings were published online  in the American Journal of Roentgenology.
 

Endothelial dysfunction

The acute phase SARS-CoV-2 infection “is associated with strokes that have features of both vascular inflammation and thromboembolism,” the investigators note.

Moreover, following the acute phase of infection, up to three-quarters of patients “experience persistent neurologic symptoms not attributable to another diagnosis, including headache, difficulty concentrating, vision changes, disequilibrium, and fatigue,” they write.

Preliminary studies “suggest a potential role for endothelial and circulatory dysfunction” in these symptoms, they add.

The researchers note that vessel wall imaging is an MRI technique that can detect and characterize arterial vascular inflammation and may differentiate vasculitic arterial pathology from atherosclerotic pathology.

Dr. Callen conducted previous research assessing cerebral vasoreactivity in women living with HIV. He noted that this is a population at a much higher risk of stroke, compared with uninfected individuals with otherwise similar cardiovascular risk factors, even when their viral load is controlled with antiretroviral therapies.

Evidence has pointed to chronic endothelial dysfunction in these individuals, and endothelial function and dysfunction can be measured through vasoreactivity testing, Dr. Callen said.

“As the COVID pandemic progressed, not only did we observe an increased rate of stroke in individuals acutely infected with COVID, but histopathological evidence began to emerge which suggested that the COVID-19 virus had tropism to and often damaged the vascular endothelium,” he noted.

This emerging evidence prompted Dr. Callen to wonder whether “individuals previously infected with COVID might also demonstrate long-term impairment in cerebral vasoreactivity or if we might see abnormalities using high resolution vessel wall imaging.”

In the current study, 15 individuals with prior SARS-CoV-2 infection (11 women, 4 men; mean age, 43 years) were compared with 10 never-infected individuals (8 women, 2 men; mean age, 43 years) who functioned as the control group.

The previously infected individuals, of whom three had prior critical infection and 12 had prior mild infection, were assessed, on average, about 8 months after infection. Of this group, seven had various post-COVID neurologic conditions, including headache, memory impairment, insomnia, depression, disequilibrium, fatigue, personality change, phantosmias (detecting smells that aren’t present), dysgeusia (taste disorder), and tinnitus.

All participants underwent MRI and vessel wall imaging. The MRI included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure CBF and calculate CVR. The vessel wall imaging examinations used a contrast-enhanced black-blood 3D T1-weighted sequence.
 

Imaging data

Prior to acetazolamide administration, the mean whole-cortex CBF did not differ significantly between never-infected and previously infected participants. However, following the acetazolamide administration, the mean whole-cortex CBF was greater in never-infected participants (73.8 mL/100 g/min vs. 60.5 mL/100 g/min, respectively; P = .04).

Moreover, the mean whole-brain CVR was greater in never-infected participants, compared with previously infected participants (27.8 mL/100 g/min vs. 19.1 mL/100 g/min; P < .001).

After adjusting for age and sex, researchers found that prior infection was associated with a lower whole-brain CVR (–8.9 mL/100 g/min; 95% confidence interval, 4.6-13.3 ml/100g/min; P < .001).

Previously infected individuals also showed significantly lower CVR, even after the researchers excluded those with prior critical illness.

A nonsignificant difference was found in previously infected participants, with smaller CVR in participants with versus without post-COVID neurologic symptoms (16.9 vs. 21.0 mL/100 g/min; P = .22).

In addition, 40% of the previously infected participants versus 10% of the never-infected participants had at least one vessel wall imaging abnormality – but the difference was not deemed significant (P = .18). Notably, “all detected vessel wall imaging abnormalities were morphologically consistent with atherosclerosis rather than vasculitis,” the investigators said.

Dr. Callen said it is “unknown whether the lack of statistical significance in the differences in vasoreactivity impairment with those living with long COVID symptoms is due to a lack of a biomechanistic correlation or due to statistical underpowering.”

If it is the latter, “it may emphasize the role of vascular health in those living with long COVID symptoms and potentially all individuals living with COVID,” he added.
 

Independent risk factor?

Commenting on the study for this article, Jared Narvid, MD, associate professor of neuroradiology, University of California, San Francisco, said it “adds to the literature suggesting a correlation between COVID-19 infection and measures of cerebrovascular abnormality.”

Dr. Narvid, who was not involved with the research, added that “although it is a small case-control study, it is well executed and should encourage scientists to further study whether COVID-19 infection represents an independent risk factor for cerebrovascular disease.”

The investigators agree. “Future studies are needed to determine the clinical implications arising from SARS-CoV-2–associated CVR impairment,” they write.

The study was funded by a University of Colorado department of radiology Faculty Development Seed Grant. The investigators and Dr. Narvid report no relevant financial relationships.

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

COVID-19 infection is significantly associated with chronically impaired cerebral vasoreactivity (CVR), results of a small study show.

In a small prospective study, participants who previously had COVID-19, even those with mild illness, had significantly decreased CVR, compared with never-infected individuals.

Results also showed cerebral blood flow (CBF) was greater in never-infected versus previously infected participants, and whole-brain CVR was lower in previously infected versus never-infected participants. Although CVR was also smaller in those with versus those without post-COVID neurologic conditions, the difference was not considered significant.

“It is important to remember that while our findings were statistically significant, we had a relatively small sample size – 25 total participants – and so we encourage future larger studies in this domain to see if these results are reproducible at a larger scale,” lead author Andrew Callen, MD, assistant professor of radiology, Neuroradiology Section, University of Colorado at Denver, Aurora, said in an interview.

“In a practical sense, it may encourage treating clinicians to be more aggressive with preventative neurovascular and cardiovascular health measures and/or screening in this patient population,” Dr. Callen said.

The findings were published online  in the American Journal of Roentgenology.
 

Endothelial dysfunction

The acute phase SARS-CoV-2 infection “is associated with strokes that have features of both vascular inflammation and thromboembolism,” the investigators note.

Moreover, following the acute phase of infection, up to three-quarters of patients “experience persistent neurologic symptoms not attributable to another diagnosis, including headache, difficulty concentrating, vision changes, disequilibrium, and fatigue,” they write.

Preliminary studies “suggest a potential role for endothelial and circulatory dysfunction” in these symptoms, they add.

The researchers note that vessel wall imaging is an MRI technique that can detect and characterize arterial vascular inflammation and may differentiate vasculitic arterial pathology from atherosclerotic pathology.

Dr. Callen conducted previous research assessing cerebral vasoreactivity in women living with HIV. He noted that this is a population at a much higher risk of stroke, compared with uninfected individuals with otherwise similar cardiovascular risk factors, even when their viral load is controlled with antiretroviral therapies.

Evidence has pointed to chronic endothelial dysfunction in these individuals, and endothelial function and dysfunction can be measured through vasoreactivity testing, Dr. Callen said.

“As the COVID pandemic progressed, not only did we observe an increased rate of stroke in individuals acutely infected with COVID, but histopathological evidence began to emerge which suggested that the COVID-19 virus had tropism to and often damaged the vascular endothelium,” he noted.

This emerging evidence prompted Dr. Callen to wonder whether “individuals previously infected with COVID might also demonstrate long-term impairment in cerebral vasoreactivity or if we might see abnormalities using high resolution vessel wall imaging.”

In the current study, 15 individuals with prior SARS-CoV-2 infection (11 women, 4 men; mean age, 43 years) were compared with 10 never-infected individuals (8 women, 2 men; mean age, 43 years) who functioned as the control group.

The previously infected individuals, of whom three had prior critical infection and 12 had prior mild infection, were assessed, on average, about 8 months after infection. Of this group, seven had various post-COVID neurologic conditions, including headache, memory impairment, insomnia, depression, disequilibrium, fatigue, personality change, phantosmias (detecting smells that aren’t present), dysgeusia (taste disorder), and tinnitus.

All participants underwent MRI and vessel wall imaging. The MRI included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure CBF and calculate CVR. The vessel wall imaging examinations used a contrast-enhanced black-blood 3D T1-weighted sequence.
 

Imaging data

Prior to acetazolamide administration, the mean whole-cortex CBF did not differ significantly between never-infected and previously infected participants. However, following the acetazolamide administration, the mean whole-cortex CBF was greater in never-infected participants (73.8 mL/100 g/min vs. 60.5 mL/100 g/min, respectively; P = .04).

Moreover, the mean whole-brain CVR was greater in never-infected participants, compared with previously infected participants (27.8 mL/100 g/min vs. 19.1 mL/100 g/min; P < .001).

After adjusting for age and sex, researchers found that prior infection was associated with a lower whole-brain CVR (–8.9 mL/100 g/min; 95% confidence interval, 4.6-13.3 ml/100g/min; P < .001).

Previously infected individuals also showed significantly lower CVR, even after the researchers excluded those with prior critical illness.

A nonsignificant difference was found in previously infected participants, with smaller CVR in participants with versus without post-COVID neurologic symptoms (16.9 vs. 21.0 mL/100 g/min; P = .22).

In addition, 40% of the previously infected participants versus 10% of the never-infected participants had at least one vessel wall imaging abnormality – but the difference was not deemed significant (P = .18). Notably, “all detected vessel wall imaging abnormalities were morphologically consistent with atherosclerosis rather than vasculitis,” the investigators said.

Dr. Callen said it is “unknown whether the lack of statistical significance in the differences in vasoreactivity impairment with those living with long COVID symptoms is due to a lack of a biomechanistic correlation or due to statistical underpowering.”

If it is the latter, “it may emphasize the role of vascular health in those living with long COVID symptoms and potentially all individuals living with COVID,” he added.
 

Independent risk factor?

Commenting on the study for this article, Jared Narvid, MD, associate professor of neuroradiology, University of California, San Francisco, said it “adds to the literature suggesting a correlation between COVID-19 infection and measures of cerebrovascular abnormality.”

Dr. Narvid, who was not involved with the research, added that “although it is a small case-control study, it is well executed and should encourage scientists to further study whether COVID-19 infection represents an independent risk factor for cerebrovascular disease.”

The investigators agree. “Future studies are needed to determine the clinical implications arising from SARS-CoV-2–associated CVR impairment,” they write.

The study was funded by a University of Colorado department of radiology Faculty Development Seed Grant. The investigators and Dr. Narvid report no relevant financial relationships.

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

COVID-19 infection is significantly associated with chronically impaired cerebral vasoreactivity (CVR), results of a small study show.

In a small prospective study, participants who previously had COVID-19, even those with mild illness, had significantly decreased CVR, compared with never-infected individuals.

Results also showed cerebral blood flow (CBF) was greater in never-infected versus previously infected participants, and whole-brain CVR was lower in previously infected versus never-infected participants. Although CVR was also smaller in those with versus those without post-COVID neurologic conditions, the difference was not considered significant.

“It is important to remember that while our findings were statistically significant, we had a relatively small sample size – 25 total participants – and so we encourage future larger studies in this domain to see if these results are reproducible at a larger scale,” lead author Andrew Callen, MD, assistant professor of radiology, Neuroradiology Section, University of Colorado at Denver, Aurora, said in an interview.

“In a practical sense, it may encourage treating clinicians to be more aggressive with preventative neurovascular and cardiovascular health measures and/or screening in this patient population,” Dr. Callen said.

The findings were published online  in the American Journal of Roentgenology.
 

Endothelial dysfunction

The acute phase SARS-CoV-2 infection “is associated with strokes that have features of both vascular inflammation and thromboembolism,” the investigators note.

Moreover, following the acute phase of infection, up to three-quarters of patients “experience persistent neurologic symptoms not attributable to another diagnosis, including headache, difficulty concentrating, vision changes, disequilibrium, and fatigue,” they write.

Preliminary studies “suggest a potential role for endothelial and circulatory dysfunction” in these symptoms, they add.

The researchers note that vessel wall imaging is an MRI technique that can detect and characterize arterial vascular inflammation and may differentiate vasculitic arterial pathology from atherosclerotic pathology.

Dr. Callen conducted previous research assessing cerebral vasoreactivity in women living with HIV. He noted that this is a population at a much higher risk of stroke, compared with uninfected individuals with otherwise similar cardiovascular risk factors, even when their viral load is controlled with antiretroviral therapies.

Evidence has pointed to chronic endothelial dysfunction in these individuals, and endothelial function and dysfunction can be measured through vasoreactivity testing, Dr. Callen said.

“As the COVID pandemic progressed, not only did we observe an increased rate of stroke in individuals acutely infected with COVID, but histopathological evidence began to emerge which suggested that the COVID-19 virus had tropism to and often damaged the vascular endothelium,” he noted.

This emerging evidence prompted Dr. Callen to wonder whether “individuals previously infected with COVID might also demonstrate long-term impairment in cerebral vasoreactivity or if we might see abnormalities using high resolution vessel wall imaging.”

In the current study, 15 individuals with prior SARS-CoV-2 infection (11 women, 4 men; mean age, 43 years) were compared with 10 never-infected individuals (8 women, 2 men; mean age, 43 years) who functioned as the control group.

The previously infected individuals, of whom three had prior critical infection and 12 had prior mild infection, were assessed, on average, about 8 months after infection. Of this group, seven had various post-COVID neurologic conditions, including headache, memory impairment, insomnia, depression, disequilibrium, fatigue, personality change, phantosmias (detecting smells that aren’t present), dysgeusia (taste disorder), and tinnitus.

All participants underwent MRI and vessel wall imaging. The MRI included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure CBF and calculate CVR. The vessel wall imaging examinations used a contrast-enhanced black-blood 3D T1-weighted sequence.
 

Imaging data

Prior to acetazolamide administration, the mean whole-cortex CBF did not differ significantly between never-infected and previously infected participants. However, following the acetazolamide administration, the mean whole-cortex CBF was greater in never-infected participants (73.8 mL/100 g/min vs. 60.5 mL/100 g/min, respectively; P = .04).

Moreover, the mean whole-brain CVR was greater in never-infected participants, compared with previously infected participants (27.8 mL/100 g/min vs. 19.1 mL/100 g/min; P < .001).

After adjusting for age and sex, researchers found that prior infection was associated with a lower whole-brain CVR (–8.9 mL/100 g/min; 95% confidence interval, 4.6-13.3 ml/100g/min; P < .001).

Previously infected individuals also showed significantly lower CVR, even after the researchers excluded those with prior critical illness.

A nonsignificant difference was found in previously infected participants, with smaller CVR in participants with versus without post-COVID neurologic symptoms (16.9 vs. 21.0 mL/100 g/min; P = .22).

In addition, 40% of the previously infected participants versus 10% of the never-infected participants had at least one vessel wall imaging abnormality – but the difference was not deemed significant (P = .18). Notably, “all detected vessel wall imaging abnormalities were morphologically consistent with atherosclerosis rather than vasculitis,” the investigators said.

Dr. Callen said it is “unknown whether the lack of statistical significance in the differences in vasoreactivity impairment with those living with long COVID symptoms is due to a lack of a biomechanistic correlation or due to statistical underpowering.”

If it is the latter, “it may emphasize the role of vascular health in those living with long COVID symptoms and potentially all individuals living with COVID,” he added.
 

Independent risk factor?

Commenting on the study for this article, Jared Narvid, MD, associate professor of neuroradiology, University of California, San Francisco, said it “adds to the literature suggesting a correlation between COVID-19 infection and measures of cerebrovascular abnormality.”

Dr. Narvid, who was not involved with the research, added that “although it is a small case-control study, it is well executed and should encourage scientists to further study whether COVID-19 infection represents an independent risk factor for cerebrovascular disease.”

The investigators agree. “Future studies are needed to determine the clinical implications arising from SARS-CoV-2–associated CVR impairment,” they write.

The study was funded by a University of Colorado department of radiology Faculty Development Seed Grant. The investigators and Dr. Narvid report no relevant financial relationships.

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

“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.

Regardless of your opinion on BMI (body mass index), this conversation highlighted that the medical community needs to discuss the limitations of BMI and decide its future.

As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
 

BMI: From observational measurement to clinical use

Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.

The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.

Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.

In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.

By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
 

BMI as a tool to diagnose obesity

We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.

Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.

Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.

This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.

Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
 

Is it time to phase out BMI?

The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:

• Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
• Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
• Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.

The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.

Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.

Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.

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

“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.

Regardless of your opinion on BMI (body mass index), this conversation highlighted that the medical community needs to discuss the limitations of BMI and decide its future.

As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
 

BMI: From observational measurement to clinical use

Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.

The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.

Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.

In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.

By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
 

BMI as a tool to diagnose obesity

We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.

Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.

Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.

This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.

Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
 

Is it time to phase out BMI?

The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:

• Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
• Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
• Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.

The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.

Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.

Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.

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

“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.

Regardless of your opinion on BMI (body mass index), this conversation highlighted that the medical community needs to discuss the limitations of BMI and decide its future.

As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
 

BMI: From observational measurement to clinical use

Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.

The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.

Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.

In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.

By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
 

BMI as a tool to diagnose obesity

We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.

Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.

Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.

This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.

Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
 

Is it time to phase out BMI?

The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:

• Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
• Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
• Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.

The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.

Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.

Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.

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

PARIS – Adding cabozantinib (Cabometyx, Exelixis) to standard-of-care immunotherapy with nivolumab (Opdivo, Bristol Myers Squibb) plus ipilimumab (Yervoy) markedly improved progression-free survival (PFS) in advanced renal cell carcinoma (aRCC), particularly in intermediate-risk patients, suggest results from the COSMIC-313 trial.

At present, dual checkpoint inhibition with nivolumab and ipilimumab is a standard of care for first-line treatment of aRCC that is deemed to be of intermediate or poor risk on the International Metastatic RCC Database Consortium (IMDC) risk score.

Cabozantinib, a tyrosine kinase inhibitor (TKI), is also a standard of care in aRCC, both as a single agent and in combination with nivolumab.

The new study investigated the use of the three drugs together as upfront first-line treatment and suggests that this triplet may become a new standard of care, especially in patients with intermediate-risk disease.

The research was presented at the European Society for Medical Oncology Congress in Paris.

The trial involved 855 previously untreated patients with aRCC, all of whom received dual immunotherapy with nivolumab and ipilimumab, who were randomly assigned to also receive either cabozantinib or matched placebo.

Patients given the triplet therapy had a significant 27% reduction in the risk for progression versus the doublet in the overall patient population.

The difference increased to 37% in patients with intermediate-risk disease on the IMDC risk score.

However, patients with poor-risk disease appeared not to derive any benefit from adding cabozantinib to nivolumab plus ipilimumab.

In addition, grade 3 or 4 treatment-related adverse events were more common with the triplet therapy.

The results suggest that adding cabozantinib results in a “statistically significant and clinically meaningful” PFS benefit, study presenter Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, Boston, told a press conference.

He added that the safety profile of the triplet therapy was “generally manageable” and “consistent with the profiles of the treatment components.”

“The study will continue to the next analysis of overall survival, as this secondary endpoint was not met at first interim analysis,” Dr. Choueiri commented.

He told this news organization that, based on the current results, the triplet combination “may end up in intermediate-risk” patients, although it is not clear why there is a difference in response between risk groups, and the finding is “quite intriguing.”

Asked which therapy to choose now for first-line treatment of aRCC, given that there are now so many options, he said that there is now such “an embarrassment of riches of trials in the first-line” that it is perhaps easier to talk about which therapies “not to use.”

“We cannot use single TKIs anymore, so you have to use doublets and possibly now triplets,” he said.

“In my practice, patients that are progressing rapidly ... need a VEGF [vascular endothelial growth factor]–based combination. In patients that can wait and ... do not have a heavy disease burden, I still believe in nivolumab and ipilimumab, which has the longest follow-up, and the responses are durable.”

Approached for comment, Dominik Berthold, MD, Centre hospitalier universitaire vaudois, Lausanne, Switzerland, said that this is a “really important study” because it has a “modern” study comparator in the control arm.

He said in an interview, however, that the question now is “obviously” how much treatment should be escalated to triple therapy “upfront versus the sequencing of active drugs.” The answer, he said, is currently unclear, and overall survival data are awaited.

Alongside the potential “challenge” of the toxicity to patients of the triplet therapy, Dr. Berthold also highlighted that it is “currently a challenge for health systems to imagine giving such expensive combinations.”

So though it is “really interesting data” and potentially represents a “step forward” in the field, the combination of cabozantinib and nivolumab plus ipilimumab is “not for everybody.”

Dr. Choueiri said that he does “agree” that adding a third drug to an already expensive doublet therapy can mean that the costs end up being “exorbitant.”

However, he noted that in aRCC, “the paradigm is sequential, so if we’re able to delay the second line, and give drugs later, especially if there is some quality of life [benefit], I’m not sure it is more expensive” to give the three-drug combination.

Commenting for ESMO, Viktor Grünwald, MD, West German Cancer Center, University Hospital Essen, Germany, noted that this is the “first study” to report “successful treatment intensification” in metastatic RCC through the use of triple therapy.

“However, treatment intensification is rarely seen without additional risks. Patients experienced the benefit of superior disease control but also additional toxicities, treatment pauses and discontinuations,” he pointed out.

“The triplet may compete in the clinical landscape with recommended life-prolonging immune doublets but mature overall survival data is needed for it to become a novel standard of care,” Dr. Grünwald commented.
 

Details of the new results

The phase 3 COSMIC-313 trial enrolled intermediate- or poor-risk patients with aRCC and good performance status who had received no prior systemic therapy and had a clear cell component on histology, which, Dr. Choueiri noted, represents around 80% of patients.

They were randomly assigned to cabozantinib or a matched placebo against a background of four cycles of nivolumab plus ipilimumab followed by nivolumab for up to 2 years. No crossover was allowed between the two arms. Tumor assessment was performed every 8 weeks.

Overall, 855 patients were randomly assigned, 75% of whom had an intermediate risk on the IDMC risk score, and 25% had a poor risk. The median age of the patients was around 60 years, and between 73% and 76% were men. Prior nephrectomy had been performed in 65%.

The study met its primary endpoint of a significant improvement in PFS as assessed by blinded independent central review. The median PFS was not reached for the triplet versus 11.3 months for patients given the doublet, at a hazard ratio of 0.73 (P = 0.013).

At 12 months, 57% of patients in the triplet-therapy arm remained disease-free versus 49% of those on dual immunotherapy.

Moreover, there was a higher objective response rate with the triplet therapy, at 43% versus 36% for the doublet, and the median duration of response was not reached in either group.

Prespecified subgroup analysis suggested that most subgroups responded similarly to the overall patient population.

However, breaking the results down by IMDC risk group, Dr. Choueiri showed that PFS benefit was even greater in intermediate-risk patients, at an HR for the triplet versus the doublet therapy of 0.63 (95% confidence interval, 047-0.85), and a similar response rate as in the overall analysis.

But the benefit of adding cabozantinib to nivolumab plus ipilimumab appeared to be lost in poor-risk patients, at an HR for the triplet versus the doublet of 1.04 (95% CI, 0.65-1.69). And in this subgroup, the objective response rates were similar: 37% with the triplet and 38% with the doublet.

Also, the triplet had a higher rate of adverse events. Grade 3 or 4 treatment-related adverse events were observed in 73% of patients on the triplet versus 41% with the doublet; 1% of patients in each group had a grade 5 event.

Treatment-related adverse events leading to discontinuation of all treatment components occurred in 12% of patients receiving triplet therapy and in 5% of those assigned to placebo and nivolumab plus ipilimumab.

Dr. Choueiri highlighted that some adverse events, including elevated liver transaminases, diarrhea, and skin toxicity, were markedly more frequent with cabozantinib and nivolumab plus ipilimumab than with the doublet therapy. Discussing the study, Sumanta K. Pal, MD, co-director of the Kidney Cancer Program at City of Hope, Irvine, Calif., said that ESMO Congress 2022 has been a “high watermark” for trials in the RCC field and congratulated the researchers of COSMIC-313 for the number of “firsts” that it achieved.

However, he continued, the “elephant in the room” is the current lack of overall survival, and he pointed out that those hotly anticipated results could have a major impact on the future use of the triplet combination.

Dr. Pal questioned whether, in the meantime, it is even possible to make a decision about the combination and urged investigators of all trials to make overall survival data available sooner.

He also highlighted the high rates of elevated liver transaminases, and the apparent overlapping toxicities between the TKI and the immune checkpoint inhibitors, asking: “Does toxicity stand in the way of treatment?”

In conclusion, Dr. Pal acknowledged that the study did meet its PFS primary endpoint but asked whether a risk-adapted approach could be used to optimize delivery of triplet therapy.

He also called for investment into biomarker studies for regimens that are “actually used in the clinic” and wondered whether there could be a shift toward using drugs with novel modes of action that do not yield overlapping toxicities.

The study was funded by Exelixis.

Dr. Choueiri reports relationships with Bristol-Myers Squibb; Pfizer; Lilly; Merck; Exelixis; AstraZeneca; EMD Serono; Calithera; Ipsen; Infinity; Surface Oncology; Analysis Group; ww2.peerview.com; gotoper.com; researchtopractice.com; ResearchToPractice; National Association of Managed Care; Orien Network; Aptitude Health; Advent health; UAE Society of Onc; MJH life sciences; MDACC; Cancernet; Kidney Cancer Association; Springer; WebMed; ASiM, Caribou Publishing; Aravive; Roche, and others.

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

PARIS – Adding cabozantinib (Cabometyx, Exelixis) to standard-of-care immunotherapy with nivolumab (Opdivo, Bristol Myers Squibb) plus ipilimumab (Yervoy) markedly improved progression-free survival (PFS) in advanced renal cell carcinoma (aRCC), particularly in intermediate-risk patients, suggest results from the COSMIC-313 trial.

At present, dual checkpoint inhibition with nivolumab and ipilimumab is a standard of care for first-line treatment of aRCC that is deemed to be of intermediate or poor risk on the International Metastatic RCC Database Consortium (IMDC) risk score.

Cabozantinib, a tyrosine kinase inhibitor (TKI), is also a standard of care in aRCC, both as a single agent and in combination with nivolumab.

The new study investigated the use of the three drugs together as upfront first-line treatment and suggests that this triplet may become a new standard of care, especially in patients with intermediate-risk disease.

The research was presented at the European Society for Medical Oncology Congress in Paris.

The trial involved 855 previously untreated patients with aRCC, all of whom received dual immunotherapy with nivolumab and ipilimumab, who were randomly assigned to also receive either cabozantinib or matched placebo.

Patients given the triplet therapy had a significant 27% reduction in the risk for progression versus the doublet in the overall patient population.

The difference increased to 37% in patients with intermediate-risk disease on the IMDC risk score.

However, patients with poor-risk disease appeared not to derive any benefit from adding cabozantinib to nivolumab plus ipilimumab.

In addition, grade 3 or 4 treatment-related adverse events were more common with the triplet therapy.

The results suggest that adding cabozantinib results in a “statistically significant and clinically meaningful” PFS benefit, study presenter Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, Boston, told a press conference.

He added that the safety profile of the triplet therapy was “generally manageable” and “consistent with the profiles of the treatment components.”

“The study will continue to the next analysis of overall survival, as this secondary endpoint was not met at first interim analysis,” Dr. Choueiri commented.

He told this news organization that, based on the current results, the triplet combination “may end up in intermediate-risk” patients, although it is not clear why there is a difference in response between risk groups, and the finding is “quite intriguing.”

Asked which therapy to choose now for first-line treatment of aRCC, given that there are now so many options, he said that there is now such “an embarrassment of riches of trials in the first-line” that it is perhaps easier to talk about which therapies “not to use.”

“We cannot use single TKIs anymore, so you have to use doublets and possibly now triplets,” he said.

“In my practice, patients that are progressing rapidly ... need a VEGF [vascular endothelial growth factor]–based combination. In patients that can wait and ... do not have a heavy disease burden, I still believe in nivolumab and ipilimumab, which has the longest follow-up, and the responses are durable.”

Approached for comment, Dominik Berthold, MD, Centre hospitalier universitaire vaudois, Lausanne, Switzerland, said that this is a “really important study” because it has a “modern” study comparator in the control arm.

He said in an interview, however, that the question now is “obviously” how much treatment should be escalated to triple therapy “upfront versus the sequencing of active drugs.” The answer, he said, is currently unclear, and overall survival data are awaited.

Alongside the potential “challenge” of the toxicity to patients of the triplet therapy, Dr. Berthold also highlighted that it is “currently a challenge for health systems to imagine giving such expensive combinations.”

So though it is “really interesting data” and potentially represents a “step forward” in the field, the combination of cabozantinib and nivolumab plus ipilimumab is “not for everybody.”

Dr. Choueiri said that he does “agree” that adding a third drug to an already expensive doublet therapy can mean that the costs end up being “exorbitant.”

However, he noted that in aRCC, “the paradigm is sequential, so if we’re able to delay the second line, and give drugs later, especially if there is some quality of life [benefit], I’m not sure it is more expensive” to give the three-drug combination.

Commenting for ESMO, Viktor Grünwald, MD, West German Cancer Center, University Hospital Essen, Germany, noted that this is the “first study” to report “successful treatment intensification” in metastatic RCC through the use of triple therapy.

“However, treatment intensification is rarely seen without additional risks. Patients experienced the benefit of superior disease control but also additional toxicities, treatment pauses and discontinuations,” he pointed out.

“The triplet may compete in the clinical landscape with recommended life-prolonging immune doublets but mature overall survival data is needed for it to become a novel standard of care,” Dr. Grünwald commented.
 

Details of the new results

The phase 3 COSMIC-313 trial enrolled intermediate- or poor-risk patients with aRCC and good performance status who had received no prior systemic therapy and had a clear cell component on histology, which, Dr. Choueiri noted, represents around 80% of patients.

They were randomly assigned to cabozantinib or a matched placebo against a background of four cycles of nivolumab plus ipilimumab followed by nivolumab for up to 2 years. No crossover was allowed between the two arms. Tumor assessment was performed every 8 weeks.

Overall, 855 patients were randomly assigned, 75% of whom had an intermediate risk on the IDMC risk score, and 25% had a poor risk. The median age of the patients was around 60 years, and between 73% and 76% were men. Prior nephrectomy had been performed in 65%.

The study met its primary endpoint of a significant improvement in PFS as assessed by blinded independent central review. The median PFS was not reached for the triplet versus 11.3 months for patients given the doublet, at a hazard ratio of 0.73 (P = 0.013).

At 12 months, 57% of patients in the triplet-therapy arm remained disease-free versus 49% of those on dual immunotherapy.

Moreover, there was a higher objective response rate with the triplet therapy, at 43% versus 36% for the doublet, and the median duration of response was not reached in either group.

Prespecified subgroup analysis suggested that most subgroups responded similarly to the overall patient population.

However, breaking the results down by IMDC risk group, Dr. Choueiri showed that PFS benefit was even greater in intermediate-risk patients, at an HR for the triplet versus the doublet therapy of 0.63 (95% confidence interval, 047-0.85), and a similar response rate as in the overall analysis.

But the benefit of adding cabozantinib to nivolumab plus ipilimumab appeared to be lost in poor-risk patients, at an HR for the triplet versus the doublet of 1.04 (95% CI, 0.65-1.69). And in this subgroup, the objective response rates were similar: 37% with the triplet and 38% with the doublet.

Also, the triplet had a higher rate of adverse events. Grade 3 or 4 treatment-related adverse events were observed in 73% of patients on the triplet versus 41% with the doublet; 1% of patients in each group had a grade 5 event.

Treatment-related adverse events leading to discontinuation of all treatment components occurred in 12% of patients receiving triplet therapy and in 5% of those assigned to placebo and nivolumab plus ipilimumab.

Dr. Choueiri highlighted that some adverse events, including elevated liver transaminases, diarrhea, and skin toxicity, were markedly more frequent with cabozantinib and nivolumab plus ipilimumab than with the doublet therapy. Discussing the study, Sumanta K. Pal, MD, co-director of the Kidney Cancer Program at City of Hope, Irvine, Calif., said that ESMO Congress 2022 has been a “high watermark” for trials in the RCC field and congratulated the researchers of COSMIC-313 for the number of “firsts” that it achieved.

However, he continued, the “elephant in the room” is the current lack of overall survival, and he pointed out that those hotly anticipated results could have a major impact on the future use of the triplet combination.

Dr. Pal questioned whether, in the meantime, it is even possible to make a decision about the combination and urged investigators of all trials to make overall survival data available sooner.

He also highlighted the high rates of elevated liver transaminases, and the apparent overlapping toxicities between the TKI and the immune checkpoint inhibitors, asking: “Does toxicity stand in the way of treatment?”

In conclusion, Dr. Pal acknowledged that the study did meet its PFS primary endpoint but asked whether a risk-adapted approach could be used to optimize delivery of triplet therapy.

He also called for investment into biomarker studies for regimens that are “actually used in the clinic” and wondered whether there could be a shift toward using drugs with novel modes of action that do not yield overlapping toxicities.

The study was funded by Exelixis.

Dr. Choueiri reports relationships with Bristol-Myers Squibb; Pfizer; Lilly; Merck; Exelixis; AstraZeneca; EMD Serono; Calithera; Ipsen; Infinity; Surface Oncology; Analysis Group; ww2.peerview.com; gotoper.com; researchtopractice.com; ResearchToPractice; National Association of Managed Care; Orien Network; Aptitude Health; Advent health; UAE Society of Onc; MJH life sciences; MDACC; Cancernet; Kidney Cancer Association; Springer; WebMed; ASiM, Caribou Publishing; Aravive; Roche, and others.

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

PARIS – Adding cabozantinib (Cabometyx, Exelixis) to standard-of-care immunotherapy with nivolumab (Opdivo, Bristol Myers Squibb) plus ipilimumab (Yervoy) markedly improved progression-free survival (PFS) in advanced renal cell carcinoma (aRCC), particularly in intermediate-risk patients, suggest results from the COSMIC-313 trial.

At present, dual checkpoint inhibition with nivolumab and ipilimumab is a standard of care for first-line treatment of aRCC that is deemed to be of intermediate or poor risk on the International Metastatic RCC Database Consortium (IMDC) risk score.

Cabozantinib, a tyrosine kinase inhibitor (TKI), is also a standard of care in aRCC, both as a single agent and in combination with nivolumab.

The new study investigated the use of the three drugs together as upfront first-line treatment and suggests that this triplet may become a new standard of care, especially in patients with intermediate-risk disease.

The research was presented at the European Society for Medical Oncology Congress in Paris.

The trial involved 855 previously untreated patients with aRCC, all of whom received dual immunotherapy with nivolumab and ipilimumab, who were randomly assigned to also receive either cabozantinib or matched placebo.

Patients given the triplet therapy had a significant 27% reduction in the risk for progression versus the doublet in the overall patient population.

The difference increased to 37% in patients with intermediate-risk disease on the IMDC risk score.

However, patients with poor-risk disease appeared not to derive any benefit from adding cabozantinib to nivolumab plus ipilimumab.

In addition, grade 3 or 4 treatment-related adverse events were more common with the triplet therapy.

The results suggest that adding cabozantinib results in a “statistically significant and clinically meaningful” PFS benefit, study presenter Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, Boston, told a press conference.

He added that the safety profile of the triplet therapy was “generally manageable” and “consistent with the profiles of the treatment components.”

“The study will continue to the next analysis of overall survival, as this secondary endpoint was not met at first interim analysis,” Dr. Choueiri commented.

He told this news organization that, based on the current results, the triplet combination “may end up in intermediate-risk” patients, although it is not clear why there is a difference in response between risk groups, and the finding is “quite intriguing.”

Asked which therapy to choose now for first-line treatment of aRCC, given that there are now so many options, he said that there is now such “an embarrassment of riches of trials in the first-line” that it is perhaps easier to talk about which therapies “not to use.”

“We cannot use single TKIs anymore, so you have to use doublets and possibly now triplets,” he said.

“In my practice, patients that are progressing rapidly ... need a VEGF [vascular endothelial growth factor]–based combination. In patients that can wait and ... do not have a heavy disease burden, I still believe in nivolumab and ipilimumab, which has the longest follow-up, and the responses are durable.”

Approached for comment, Dominik Berthold, MD, Centre hospitalier universitaire vaudois, Lausanne, Switzerland, said that this is a “really important study” because it has a “modern” study comparator in the control arm.

He said in an interview, however, that the question now is “obviously” how much treatment should be escalated to triple therapy “upfront versus the sequencing of active drugs.” The answer, he said, is currently unclear, and overall survival data are awaited.

Alongside the potential “challenge” of the toxicity to patients of the triplet therapy, Dr. Berthold also highlighted that it is “currently a challenge for health systems to imagine giving such expensive combinations.”

So though it is “really interesting data” and potentially represents a “step forward” in the field, the combination of cabozantinib and nivolumab plus ipilimumab is “not for everybody.”

Dr. Choueiri said that he does “agree” that adding a third drug to an already expensive doublet therapy can mean that the costs end up being “exorbitant.”

However, he noted that in aRCC, “the paradigm is sequential, so if we’re able to delay the second line, and give drugs later, especially if there is some quality of life [benefit], I’m not sure it is more expensive” to give the three-drug combination.

Commenting for ESMO, Viktor Grünwald, MD, West German Cancer Center, University Hospital Essen, Germany, noted that this is the “first study” to report “successful treatment intensification” in metastatic RCC through the use of triple therapy.

“However, treatment intensification is rarely seen without additional risks. Patients experienced the benefit of superior disease control but also additional toxicities, treatment pauses and discontinuations,” he pointed out.

“The triplet may compete in the clinical landscape with recommended life-prolonging immune doublets but mature overall survival data is needed for it to become a novel standard of care,” Dr. Grünwald commented.
 

Details of the new results

The phase 3 COSMIC-313 trial enrolled intermediate- or poor-risk patients with aRCC and good performance status who had received no prior systemic therapy and had a clear cell component on histology, which, Dr. Choueiri noted, represents around 80% of patients.

They were randomly assigned to cabozantinib or a matched placebo against a background of four cycles of nivolumab plus ipilimumab followed by nivolumab for up to 2 years. No crossover was allowed between the two arms. Tumor assessment was performed every 8 weeks.

Overall, 855 patients were randomly assigned, 75% of whom had an intermediate risk on the IDMC risk score, and 25% had a poor risk. The median age of the patients was around 60 years, and between 73% and 76% were men. Prior nephrectomy had been performed in 65%.

The study met its primary endpoint of a significant improvement in PFS as assessed by blinded independent central review. The median PFS was not reached for the triplet versus 11.3 months for patients given the doublet, at a hazard ratio of 0.73 (P = 0.013).

At 12 months, 57% of patients in the triplet-therapy arm remained disease-free versus 49% of those on dual immunotherapy.

Moreover, there was a higher objective response rate with the triplet therapy, at 43% versus 36% for the doublet, and the median duration of response was not reached in either group.

Prespecified subgroup analysis suggested that most subgroups responded similarly to the overall patient population.

However, breaking the results down by IMDC risk group, Dr. Choueiri showed that PFS benefit was even greater in intermediate-risk patients, at an HR for the triplet versus the doublet therapy of 0.63 (95% confidence interval, 047-0.85), and a similar response rate as in the overall analysis.

But the benefit of adding cabozantinib to nivolumab plus ipilimumab appeared to be lost in poor-risk patients, at an HR for the triplet versus the doublet of 1.04 (95% CI, 0.65-1.69). And in this subgroup, the objective response rates were similar: 37% with the triplet and 38% with the doublet.

Also, the triplet had a higher rate of adverse events. Grade 3 or 4 treatment-related adverse events were observed in 73% of patients on the triplet versus 41% with the doublet; 1% of patients in each group had a grade 5 event.

Treatment-related adverse events leading to discontinuation of all treatment components occurred in 12% of patients receiving triplet therapy and in 5% of those assigned to placebo and nivolumab plus ipilimumab.

Dr. Choueiri highlighted that some adverse events, including elevated liver transaminases, diarrhea, and skin toxicity, were markedly more frequent with cabozantinib and nivolumab plus ipilimumab than with the doublet therapy. Discussing the study, Sumanta K. Pal, MD, co-director of the Kidney Cancer Program at City of Hope, Irvine, Calif., said that ESMO Congress 2022 has been a “high watermark” for trials in the RCC field and congratulated the researchers of COSMIC-313 for the number of “firsts” that it achieved.

However, he continued, the “elephant in the room” is the current lack of overall survival, and he pointed out that those hotly anticipated results could have a major impact on the future use of the triplet combination.

Dr. Pal questioned whether, in the meantime, it is even possible to make a decision about the combination and urged investigators of all trials to make overall survival data available sooner.

He also highlighted the high rates of elevated liver transaminases, and the apparent overlapping toxicities between the TKI and the immune checkpoint inhibitors, asking: “Does toxicity stand in the way of treatment?”

In conclusion, Dr. Pal acknowledged that the study did meet its PFS primary endpoint but asked whether a risk-adapted approach could be used to optimize delivery of triplet therapy.

He also called for investment into biomarker studies for regimens that are “actually used in the clinic” and wondered whether there could be a shift toward using drugs with novel modes of action that do not yield overlapping toxicities.

The study was funded by Exelixis.

Dr. Choueiri reports relationships with Bristol-Myers Squibb; Pfizer; Lilly; Merck; Exelixis; AstraZeneca; EMD Serono; Calithera; Ipsen; Infinity; Surface Oncology; Analysis Group; ww2.peerview.com; gotoper.com; researchtopractice.com; ResearchToPractice; National Association of Managed Care; Orien Network; Aptitude Health; Advent health; UAE Society of Onc; MJH life sciences; MDACC; Cancernet; Kidney Cancer Association; Springer; WebMed; ASiM, Caribou Publishing; Aravive; Roche, and others.

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

The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

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

The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

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

The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

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

New York Governor Kathy Hochul declared a state disaster emergency on Sept. 9 after the polio virus has been detected in another county. The order allows EMS workers, midwives, and pharmacists to administer the vaccine and permits physicians and nurse practitioners to issue standing orders for polio vaccines.

“On polio, we simply cannot roll the dice,” New York State Health Commissioner Dr. Mary T. Bassett said in a news release. “If you or your child are unvaccinated or not up to date with vaccinations, the risk of paralytic disease is real. I urge New Yorkers to not accept any risk at all.”

In July, an unvaccinated adult man in Rockland County, which is north of New York City, was diagnosed with polio virus. It was the first confirmed case of the virus in the United States since 2013.

New York state health officials have not announced any additional polio cases. Since as early as April, polio has also been detected in wastewater samples in New York City and in Rockland, Orange, and Sullivan counties. In August, the virus was detected in wastewater from Nassau County on Long Island.

New York’s statewide polio vaccination rate is 79%, and the New York State Department of Health is aiming for a rate over 90%, the announcement said. In some counties, vaccination rates are far below the state average, including Rockland County (60%), Orange County (59%), and Sullivan County (62%). Nassau County’s polio vaccination rate is similar to the state average.

“Polio immunization is safe and effective – protecting nearly all people against disease who receive the recommended doses,” Dr. Basset said; “Do not wait to vaccinate.”

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

New York Governor Kathy Hochul declared a state disaster emergency on Sept. 9 after the polio virus has been detected in another county. The order allows EMS workers, midwives, and pharmacists to administer the vaccine and permits physicians and nurse practitioners to issue standing orders for polio vaccines.

“On polio, we simply cannot roll the dice,” New York State Health Commissioner Dr. Mary T. Bassett said in a news release. “If you or your child are unvaccinated or not up to date with vaccinations, the risk of paralytic disease is real. I urge New Yorkers to not accept any risk at all.”

In July, an unvaccinated adult man in Rockland County, which is north of New York City, was diagnosed with polio virus. It was the first confirmed case of the virus in the United States since 2013.

New York state health officials have not announced any additional polio cases. Since as early as April, polio has also been detected in wastewater samples in New York City and in Rockland, Orange, and Sullivan counties. In August, the virus was detected in wastewater from Nassau County on Long Island.

New York’s statewide polio vaccination rate is 79%, and the New York State Department of Health is aiming for a rate over 90%, the announcement said. In some counties, vaccination rates are far below the state average, including Rockland County (60%), Orange County (59%), and Sullivan County (62%). Nassau County’s polio vaccination rate is similar to the state average.

“Polio immunization is safe and effective – protecting nearly all people against disease who receive the recommended doses,” Dr. Basset said; “Do not wait to vaccinate.”

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

New York Governor Kathy Hochul declared a state disaster emergency on Sept. 9 after the polio virus has been detected in another county. The order allows EMS workers, midwives, and pharmacists to administer the vaccine and permits physicians and nurse practitioners to issue standing orders for polio vaccines.

“On polio, we simply cannot roll the dice,” New York State Health Commissioner Dr. Mary T. Bassett said in a news release. “If you or your child are unvaccinated or not up to date with vaccinations, the risk of paralytic disease is real. I urge New Yorkers to not accept any risk at all.”

In July, an unvaccinated adult man in Rockland County, which is north of New York City, was diagnosed with polio virus. It was the first confirmed case of the virus in the United States since 2013.

New York state health officials have not announced any additional polio cases. Since as early as April, polio has also been detected in wastewater samples in New York City and in Rockland, Orange, and Sullivan counties. In August, the virus was detected in wastewater from Nassau County on Long Island.

New York’s statewide polio vaccination rate is 79%, and the New York State Department of Health is aiming for a rate over 90%, the announcement said. In some counties, vaccination rates are far below the state average, including Rockland County (60%), Orange County (59%), and Sullivan County (62%). Nassau County’s polio vaccination rate is similar to the state average.

“Polio immunization is safe and effective – protecting nearly all people against disease who receive the recommended doses,” Dr. Basset said; “Do not wait to vaccinate.”

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

An Italian study of women diagnosed with breast cancer reported that around 50% experienced body image disturbance and 20% noted a negative impact on their sex life. And while meeting with a specialist in psycho-oncology was universally viewed as an acceptable option, only one out of four patients considered consulting a sexologist. All these women should be encouraged to face and address issues related to sexuality so that they can truly regain a good quality of life, the study suggests.

The study, which was conducted at the breast unit of Santa Maria Goretti Hospital in Latina, Italy, enrolled 141 patients who had undergone breast cancer surgery. Participants were asked to complete a questionnaire that included questions regarding self-image, sexual activity, and sexual satisfaction, and it analyzed these aspects before and after treatment. The participants were then asked whether they felt that they needed to see a sexologist or a specialist in psycho-oncology.

The findings clearly showed a worsening in terms of body image perception. When the women were asked about the relationship they had with their body, femininity, and beauty prior to being diagnosed, 37.4% characterized it as very good and 58.9% as “normal,” with ups and downs but nothing that they would term “conflictual.” After diagnosis, 48.9% noted that the disease had an impact on their body image with a partial conditioning about their femininity and beauty. However, 7.2% had difficulty when it came to recognizing their own body, and their relationship with femininity also became difficult.

On the topic of sexuality, 71.2% of patients were completely satisfied with their sex life before they were diagnosed with breast cancer, 23.7% were partially satisfied, and 5.0% were unsatisfied. As for their sex life after diagnosis and surgery, 20.1% stated that it continued to be fulfilling and 55.4% said that it had gotten worse; 18.8% reported significant sexual dissatisfaction.

The participants were asked whether consulting a professional would be warranted, and whether that would provide useful support for overcoming the difficulties and challenges arising from the disease and the related treatments. In response, 97.1% said they would go to a specialist in psycho-oncology, but only 27.3% would seek help from a sexologist.

“Despite the negative impact on body image and on sexuality, few patients would seek the help of a sexologist; nearly all of the patients, however, would seek the help of a specialist in psycho-oncology. This was very surprising to us,” write the authors. They went on to note that they are carrying out another project to understand the reason for this disparity.

In addition, they advised clinicians to encourage communication about sexuality – a topic that is regularly overlooked and not included in discussions with patients, mostly because of cultural barriers. Often, physicians aren’t comfortable talking about sexuality, as they don’t feel they have the proper training to do so. Patients who are experiencing issues related to sexuality also often have difficulty asking for help. And so, in their conclusion, the authors point out that “collaborating together in the right direction is the basis of change and good communication.”

This article was translated from Univadis Italy and appeared on Medscape.com.

An Italian study of women diagnosed with breast cancer reported that around 50% experienced body image disturbance and 20% noted a negative impact on their sex life. And while meeting with a specialist in psycho-oncology was universally viewed as an acceptable option, only one out of four patients considered consulting a sexologist. All these women should be encouraged to face and address issues related to sexuality so that they can truly regain a good quality of life, the study suggests.

The study, which was conducted at the breast unit of Santa Maria Goretti Hospital in Latina, Italy, enrolled 141 patients who had undergone breast cancer surgery. Participants were asked to complete a questionnaire that included questions regarding self-image, sexual activity, and sexual satisfaction, and it analyzed these aspects before and after treatment. The participants were then asked whether they felt that they needed to see a sexologist or a specialist in psycho-oncology.

The findings clearly showed a worsening in terms of body image perception. When the women were asked about the relationship they had with their body, femininity, and beauty prior to being diagnosed, 37.4% characterized it as very good and 58.9% as “normal,” with ups and downs but nothing that they would term “conflictual.” After diagnosis, 48.9% noted that the disease had an impact on their body image with a partial conditioning about their femininity and beauty. However, 7.2% had difficulty when it came to recognizing their own body, and their relationship with femininity also became difficult.

On the topic of sexuality, 71.2% of patients were completely satisfied with their sex life before they were diagnosed with breast cancer, 23.7% were partially satisfied, and 5.0% were unsatisfied. As for their sex life after diagnosis and surgery, 20.1% stated that it continued to be fulfilling and 55.4% said that it had gotten worse; 18.8% reported significant sexual dissatisfaction.

The participants were asked whether consulting a professional would be warranted, and whether that would provide useful support for overcoming the difficulties and challenges arising from the disease and the related treatments. In response, 97.1% said they would go to a specialist in psycho-oncology, but only 27.3% would seek help from a sexologist.

“Despite the negative impact on body image and on sexuality, few patients would seek the help of a sexologist; nearly all of the patients, however, would seek the help of a specialist in psycho-oncology. This was very surprising to us,” write the authors. They went on to note that they are carrying out another project to understand the reason for this disparity.

In addition, they advised clinicians to encourage communication about sexuality – a topic that is regularly overlooked and not included in discussions with patients, mostly because of cultural barriers. Often, physicians aren’t comfortable talking about sexuality, as they don’t feel they have the proper training to do so. Patients who are experiencing issues related to sexuality also often have difficulty asking for help. And so, in their conclusion, the authors point out that “collaborating together in the right direction is the basis of change and good communication.”

This article was translated from Univadis Italy and appeared on Medscape.com.

An Italian study of women diagnosed with breast cancer reported that around 50% experienced body image disturbance and 20% noted a negative impact on their sex life. And while meeting with a specialist in psycho-oncology was universally viewed as an acceptable option, only one out of four patients considered consulting a sexologist. All these women should be encouraged to face and address issues related to sexuality so that they can truly regain a good quality of life, the study suggests.

The study, which was conducted at the breast unit of Santa Maria Goretti Hospital in Latina, Italy, enrolled 141 patients who had undergone breast cancer surgery. Participants were asked to complete a questionnaire that included questions regarding self-image, sexual activity, and sexual satisfaction, and it analyzed these aspects before and after treatment. The participants were then asked whether they felt that they needed to see a sexologist or a specialist in psycho-oncology.

The findings clearly showed a worsening in terms of body image perception. When the women were asked about the relationship they had with their body, femininity, and beauty prior to being diagnosed, 37.4% characterized it as very good and 58.9% as “normal,” with ups and downs but nothing that they would term “conflictual.” After diagnosis, 48.9% noted that the disease had an impact on their body image with a partial conditioning about their femininity and beauty. However, 7.2% had difficulty when it came to recognizing their own body, and their relationship with femininity also became difficult.

On the topic of sexuality, 71.2% of patients were completely satisfied with their sex life before they were diagnosed with breast cancer, 23.7% were partially satisfied, and 5.0% were unsatisfied. As for their sex life after diagnosis and surgery, 20.1% stated that it continued to be fulfilling and 55.4% said that it had gotten worse; 18.8% reported significant sexual dissatisfaction.

The participants were asked whether consulting a professional would be warranted, and whether that would provide useful support for overcoming the difficulties and challenges arising from the disease and the related treatments. In response, 97.1% said they would go to a specialist in psycho-oncology, but only 27.3% would seek help from a sexologist.

“Despite the negative impact on body image and on sexuality, few patients would seek the help of a sexologist; nearly all of the patients, however, would seek the help of a specialist in psycho-oncology. This was very surprising to us,” write the authors. They went on to note that they are carrying out another project to understand the reason for this disparity.

In addition, they advised clinicians to encourage communication about sexuality – a topic that is regularly overlooked and not included in discussions with patients, mostly because of cultural barriers. Often, physicians aren’t comfortable talking about sexuality, as they don’t feel they have the proper training to do so. Patients who are experiencing issues related to sexuality also often have difficulty asking for help. And so, in their conclusion, the authors point out that “collaborating together in the right direction is the basis of change and good communication.”

This article was translated from Univadis Italy and appeared on Medscape.com.

Psychedelics can produce positive changes in attitudes about death and dying – and may be a way to help ease anxiety and depression toward the end of life, new research suggests.

In a retrospective study of more than 3,000 participants, near-death experiences occurring naturally or via a psychedelic drug had a “remarkably” similar effect on attitudes about death and dying, with most participants reporting less fear and anxiety around death.

“Individuals with existential anxiety and depression at end of life account for substantial suffering and significantly increased health care expenses from desperate and often futile seeking of intensive and expensive medical treatments,” co-investigator Roland Griffiths, PhD, Center for Psychedelics and Consciousness Research at Johns Hopkins Medicine, Baltimore, told this news organization.

Direct comparisons

Both psychedelic drug experiences and near-death experiences can alter perspectives on death and dying, but there have been few direct comparisons of these phenomena, the investigators note.

In the current study, they directly compared psychedelic-occasioned and nondrug experiences, which altered individuals’ beliefs about death.

The researchers surveyed 3,192 mostly White adults from the United States, including 933 who had a natural, nondrug near-death experience and 2,259 who had psychedelic near-death experiences induced with lysergic acid diethylamide, psilocybin, ayahuasca, or N,N-dimethyltryptamine.

The psychedelic group had more men than women and tended to be younger at the time of the experience than was the nondrug group.

Nearly 90% of individuals in both groups said that they were less afraid of death than they were before their experiences.

About half of both groups said they’d encountered something they might call “God” during the experience.

Three-quarters of the psychedelic group and 85% of the nondrug group rated their experiences as among the top five most personally meaningful and spiritually significant events of their life.

Individuals in both groups also reported moderate- to strong-lasting positive changes in personal well-being and life purpose and meaning after their experiences. 

However, there were some differences between the groups.
 

More research needed

Compared with the psychedelic group, the nondrug group was more likely to report being unconscious, clinically dead, or that their life was in imminent danger.

The nonpsychedelic group was also more likely to report that their experience was very brief, lasting 5 minutes or less.

Both the psychedelic and nondrug participants showed robust increases on standardized measures of mystical and near-death experiences, but these measures were significantly greater in the psychedelic group.

The survey findings are in line with several recent clinical trials showing that a single treatment with the psychedelic psilocybin produced sustained decreases in anxiety and depression among patients with a life-threatening cancer diagnosis.

This includes a 2016 study by Dr. Griffiths and colleagues, which included 51 patients with late-stage cancer. As reported at the time, results showed a single, high dose of psilocybin had rapid, clinically significant, and lasting effects on mood and anxiety.

Limitations of the current survey cited by the researchers include the use of retrospective self-report to describe changes in death attitudes and the subjective features of the experiences. Also, respondents were a self-selected study population that may not be representative of all psychedelic or near-death experiences.

In addition, the study did not attempt to document worldview and other belief changes, such as increased belief in afterlife, that might help explain why death attitudes changed.

Looking ahead, the researchers note that future studies are needed to better understand the potential clinical use of psychedelics in ameliorating suffering related to fear of death.

Support through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation. Funding was also provided by the Y.C. Ho/Helen and Michael Chiang Foundation. The investigators have reported no relevant financial relationships.

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

Psychedelics can produce positive changes in attitudes about death and dying – and may be a way to help ease anxiety and depression toward the end of life, new research suggests.

In a retrospective study of more than 3,000 participants, near-death experiences occurring naturally or via a psychedelic drug had a “remarkably” similar effect on attitudes about death and dying, with most participants reporting less fear and anxiety around death.

“Individuals with existential anxiety and depression at end of life account for substantial suffering and significantly increased health care expenses from desperate and often futile seeking of intensive and expensive medical treatments,” co-investigator Roland Griffiths, PhD, Center for Psychedelics and Consciousness Research at Johns Hopkins Medicine, Baltimore, told this news organization.

Direct comparisons

Both psychedelic drug experiences and near-death experiences can alter perspectives on death and dying, but there have been few direct comparisons of these phenomena, the investigators note.

In the current study, they directly compared psychedelic-occasioned and nondrug experiences, which altered individuals’ beliefs about death.

The researchers surveyed 3,192 mostly White adults from the United States, including 933 who had a natural, nondrug near-death experience and 2,259 who had psychedelic near-death experiences induced with lysergic acid diethylamide, psilocybin, ayahuasca, or N,N-dimethyltryptamine.

The psychedelic group had more men than women and tended to be younger at the time of the experience than was the nondrug group.

Nearly 90% of individuals in both groups said that they were less afraid of death than they were before their experiences.

About half of both groups said they’d encountered something they might call “God” during the experience.

Three-quarters of the psychedelic group and 85% of the nondrug group rated their experiences as among the top five most personally meaningful and spiritually significant events of their life.

Individuals in both groups also reported moderate- to strong-lasting positive changes in personal well-being and life purpose and meaning after their experiences. 

However, there were some differences between the groups.
 

More research needed

Compared with the psychedelic group, the nondrug group was more likely to report being unconscious, clinically dead, or that their life was in imminent danger.

The nonpsychedelic group was also more likely to report that their experience was very brief, lasting 5 minutes or less.

Both the psychedelic and nondrug participants showed robust increases on standardized measures of mystical and near-death experiences, but these measures were significantly greater in the psychedelic group.

The survey findings are in line with several recent clinical trials showing that a single treatment with the psychedelic psilocybin produced sustained decreases in anxiety and depression among patients with a life-threatening cancer diagnosis.

This includes a 2016 study by Dr. Griffiths and colleagues, which included 51 patients with late-stage cancer. As reported at the time, results showed a single, high dose of psilocybin had rapid, clinically significant, and lasting effects on mood and anxiety.

Limitations of the current survey cited by the researchers include the use of retrospective self-report to describe changes in death attitudes and the subjective features of the experiences. Also, respondents were a self-selected study population that may not be representative of all psychedelic or near-death experiences.

In addition, the study did not attempt to document worldview and other belief changes, such as increased belief in afterlife, that might help explain why death attitudes changed.

Looking ahead, the researchers note that future studies are needed to better understand the potential clinical use of psychedelics in ameliorating suffering related to fear of death.

Support through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation. Funding was also provided by the Y.C. Ho/Helen and Michael Chiang Foundation. The investigators have reported no relevant financial relationships.

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

Psychedelics can produce positive changes in attitudes about death and dying – and may be a way to help ease anxiety and depression toward the end of life, new research suggests.

In a retrospective study of more than 3,000 participants, near-death experiences occurring naturally or via a psychedelic drug had a “remarkably” similar effect on attitudes about death and dying, with most participants reporting less fear and anxiety around death.

“Individuals with existential anxiety and depression at end of life account for substantial suffering and significantly increased health care expenses from desperate and often futile seeking of intensive and expensive medical treatments,” co-investigator Roland Griffiths, PhD, Center for Psychedelics and Consciousness Research at Johns Hopkins Medicine, Baltimore, told this news organization.

Direct comparisons

Both psychedelic drug experiences and near-death experiences can alter perspectives on death and dying, but there have been few direct comparisons of these phenomena, the investigators note.

In the current study, they directly compared psychedelic-occasioned and nondrug experiences, which altered individuals’ beliefs about death.

The researchers surveyed 3,192 mostly White adults from the United States, including 933 who had a natural, nondrug near-death experience and 2,259 who had psychedelic near-death experiences induced with lysergic acid diethylamide, psilocybin, ayahuasca, or N,N-dimethyltryptamine.

The psychedelic group had more men than women and tended to be younger at the time of the experience than was the nondrug group.

Nearly 90% of individuals in both groups said that they were less afraid of death than they were before their experiences.

About half of both groups said they’d encountered something they might call “God” during the experience.

Three-quarters of the psychedelic group and 85% of the nondrug group rated their experiences as among the top five most personally meaningful and spiritually significant events of their life.

Individuals in both groups also reported moderate- to strong-lasting positive changes in personal well-being and life purpose and meaning after their experiences. 

However, there were some differences between the groups.
 

More research needed

Compared with the psychedelic group, the nondrug group was more likely to report being unconscious, clinically dead, or that their life was in imminent danger.

The nonpsychedelic group was also more likely to report that their experience was very brief, lasting 5 minutes or less.

Both the psychedelic and nondrug participants showed robust increases on standardized measures of mystical and near-death experiences, but these measures were significantly greater in the psychedelic group.

The survey findings are in line with several recent clinical trials showing that a single treatment with the psychedelic psilocybin produced sustained decreases in anxiety and depression among patients with a life-threatening cancer diagnosis.

This includes a 2016 study by Dr. Griffiths and colleagues, which included 51 patients with late-stage cancer. As reported at the time, results showed a single, high dose of psilocybin had rapid, clinically significant, and lasting effects on mood and anxiety.

Limitations of the current survey cited by the researchers include the use of retrospective self-report to describe changes in death attitudes and the subjective features of the experiences. Also, respondents were a self-selected study population that may not be representative of all psychedelic or near-death experiences.

In addition, the study did not attempt to document worldview and other belief changes, such as increased belief in afterlife, that might help explain why death attitudes changed.

Looking ahead, the researchers note that future studies are needed to better understand the potential clinical use of psychedelics in ameliorating suffering related to fear of death.

Support through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation. Funding was also provided by the Y.C. Ho/Helen and Michael Chiang Foundation. The investigators have reported no relevant financial relationships.

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