Clinician Reviews

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

Hospital-acquired adverse events or conditions including falls and infections increased by approximately 25% after hospitals’ acquisition by private equity compared with control hospitals, on the basis of a study of Medicare claims for more than 4,500,000 hospitalizations.

“Prior research on private equity in health care showed that acquisition is associated with higher charges, prices, and spending; however, the implications for quality of care and patient outcomes remained less understood,” corresponding author Zirui Song, MD, of Harvard Medical School, Boston, said in an interview. “This was particularly true for measures of clinical quality that were less susceptible to changes in patient mix or coding behavior, such as hospital-acquired adverse events.”

In the study, published in JAMA, the researchers compared data from 100% Medicare Part A claims for 662,095 hospitalizations at 51 hospitals acquired by private equities and 4,160,720 hospitalizations at 259 control hospitals. The hospitalizations occurred between 2009 and 2019. The researchers also used a difference-in-differences design to evaluate hospitalizations from 3 years before to 3 years after acquisition, controlling for patient and hospital attributes.

Hospital-acquired adverse events as defined by the US Centers for Medicare & Medicaid Services included falls, infections, stage III or IV pressure ulcers, foreign objects retained after surgery, air embolism, and blood incompatibility.

Overall, Medicare patients in private equity hospitals experienced a 25.4% increase in hospital-acquired conditions compared with those in control hospitals through a period of up to 3 years after acquisition, with a difference of 4.6 additional hospital-acquired conditions per 10,000 hospitalizations (P = .004). Central line-associated bloodstream infections accounted for 37.7% of the increase (P = .04), despite a 16.2% decrease in placement of central lines, and falls accounted for 27.3% (P = .02).

Notably, the incidence of surgical site infections increased from 10.8 per 10,000 hospitalizations before acquisition to 21.6 per 10,000 hospitalizations after acquisition, despite a reduction of 8.1% in surgical volume. By contrast, surgical site infections decreased at control hospitals over the study period.

In-hospital mortality decreased slightly at private equity hospitals compared with the control hospitals, but there was no differential change in mortality by 30 days after hospital discharge. The slight difference might be caused by the trend in slightly younger Medicare beneficiaries treated at private equity hospitals; these patients were less likely to be eligible for both Medicaid and Medicare and were more likely to be transferred to other hospitals, the researchers noted.

The findings were limited by several factors including the lack of generalizability to all private equity-acquired hospitals and to non-Medicare patients, the researchers noted. Other limitations include the use of the International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes that might have failed to capture all hospital-acquired conditions and the inability to account for all confounding factors.

However, the results suggest that private equity acquisition was associated with increased hospital-acquired adverse events and highlight concerns about the impact of private equity ownership on healthcare delivery, the researchers concluded.

In a related story published in July 2023, this news organization described a report showing an association between private equity ownership of medical practices and increased consumer prices for multiple medical specialties.

“Medicare patients admitted to private equity-owned hospitals experienced, on average, an 25% increase in hospital-acquired adverse events after the hospital was bought compared to similar patients at hospitals not acquired by private equity firms. We were surprised by the extent of this change relative to the comparison (non-private equity) hospitals, including the sizable increase in central line-associated bloodstream infections and the doubling of surgical site infections at private equity hospitals — both of which went down at the comparison hospitals during the same period,” Dr. Song said in an interview.

“A key implication is that patients, providers, and policymakers might be more attuned to the potential clinical impact of private equity ownership in the delivery system. Given that a plausible explanation for these findings is reductions in clinician staffing, clinical organizations and policymakers might also be more aware of cost-cutting strategies after acquisition,” Dr. Song said. “Prior research has shown that hospitals, nursing homes, and physician practices experience staffing cuts after private equity acquisition, which is a common way to reduce operating costs and boost the profitability of acquired entities,” he noted.

“More research is needed to understand the impact of private equity acquisitions across health care settings and the potential effects of policy levers that aim to protect patients and societal resources,” said Dr. Song, who coauthored an article outlining a policy framework for addressing private equity in healthcare, published in JAMA in April 2023. “Potential regulatory remedies include minimum staffing ratios, antitrust enforcement, mitigating the financial risk of such acquisitions, increasing the transparency of these acquisitions, and protecting patients and society from the higher prices of care attributed to this model of provider ownership,” he said.
 

Patients Pay the Price of Private Equity Acquisition

“The exponential growth in private equity ownership in hospital and physician practices in the past few decades has left a majority of health care providers disillusioned with cost-cutting practices resulting in staffing reductions and ratios that sacrifice patient care as part of their approach to running clinical operations ‘lean,’ ” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, NY, said in an interview.

“While private equity companies argue that such practices are essential to meet their bottom line and increase operating margins, it doesn’t translate into ideal care for patients; lean practices in staffing which focus on profits at the expense of patient safety and quality of care.

“When you look at patient outcomes, it is the patients who ultimately pay the price — not the shareholders,” Dr. Glatter said. “This translates to higher risks of hospital-acquired complications including falls and blood-borne infections, including surgical site infections, as noted by the authors of the current study when private equity took over operations in hospitals.

Dr. Glatter said he was not surprised by the findings. “In my world, patient care and safety come first. Period,” he said. “Would you want your family’s health and well-being sacrificed in the name of company profits? I think it’s a rhetorical question, but one that every health care provider who works in a hospital or practice run by private equity must consider.”

Despite a decline in utilization at private equity hospitals as noted in the current study, hospital-acquired infections and adverse outcomes still increased, illustrating a decline in quality of care, said Dr. Glatter. “While these disparities were not evident when looking at 30-day outcomes, they demonstrate how operational changes impact patient outcomes in the near term. Having younger and healthier patients, and fewer Medicare and Medicaid patients combined with more hospital transfers to non–private equity run hospitals, resulted in lower in-hospital mortality in the near term, which was not apparent at 30 days post discharge,” he said.

“The explosion of hospital mergers and consolidation in the past several decades has led to skyrocketing health care costs at the expense of patient satisfaction, but also health care providers’ autonomy to manage and maintain quality care for their patients,” Dr. Glatter said.

“It’s important to understand that private equity’s interests are primarily aligned with their shareholder’s interests, as opposed to patients’ outcomes and interests,” Dr. Glatter told this news organization. “Within 5-7 years, the goal is to increase operating margins and profits and then sell a practice or hospital, which is ultimately part of a ‘health care portfolio,’ ” he said.

Additional research is needed to examine whether other hospital-acquired conditions including pressure sores, catheter-associated UTIs, methicillin-resistant Staphylococcus aureus infections, Clostridium difficile infections, and nosocomial pneumonia have increased in hospitals following private equity acquisition, given the overall national decline in these events, he said.

“At the same time, it is vital to also look at management and readmission rates for patients with strokes, heart attacks, and congestive heart failure in hospitals that are run by private equity,” Dr. Glatter noted. “These are important benchmarks of care monitored by CMS that reflect the quality of care that payers ultimately factor into reimbursement.”

Examining the metrics associated with these diagnoses will help in understanding whether private equity-managed facilities are leading to adverse outcomes and mortality, increased length of stay, hospital readmissions, and increased nosocomial infections, apart from other aspects of patient experience, Dr. Glatter added.

The study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and Arnold Ventures. The researchers had no financial conflicts to disclose. Dr. Glatter had no financial conflicts to disclose and serves on the Medscape Emergency Medicine Editorial Board.
 

A version of this article appeared on Medscape.com.

Hospital-acquired adverse events or conditions including falls and infections increased by approximately 25% after hospitals’ acquisition by private equity compared with control hospitals, on the basis of a study of Medicare claims for more than 4,500,000 hospitalizations.

“Prior research on private equity in health care showed that acquisition is associated with higher charges, prices, and spending; however, the implications for quality of care and patient outcomes remained less understood,” corresponding author Zirui Song, MD, of Harvard Medical School, Boston, said in an interview. “This was particularly true for measures of clinical quality that were less susceptible to changes in patient mix or coding behavior, such as hospital-acquired adverse events.”

In the study, published in JAMA, the researchers compared data from 100% Medicare Part A claims for 662,095 hospitalizations at 51 hospitals acquired by private equities and 4,160,720 hospitalizations at 259 control hospitals. The hospitalizations occurred between 2009 and 2019. The researchers also used a difference-in-differences design to evaluate hospitalizations from 3 years before to 3 years after acquisition, controlling for patient and hospital attributes.

Hospital-acquired adverse events as defined by the US Centers for Medicare & Medicaid Services included falls, infections, stage III or IV pressure ulcers, foreign objects retained after surgery, air embolism, and blood incompatibility.

Overall, Medicare patients in private equity hospitals experienced a 25.4% increase in hospital-acquired conditions compared with those in control hospitals through a period of up to 3 years after acquisition, with a difference of 4.6 additional hospital-acquired conditions per 10,000 hospitalizations (P = .004). Central line-associated bloodstream infections accounted for 37.7% of the increase (P = .04), despite a 16.2% decrease in placement of central lines, and falls accounted for 27.3% (P = .02).

Notably, the incidence of surgical site infections increased from 10.8 per 10,000 hospitalizations before acquisition to 21.6 per 10,000 hospitalizations after acquisition, despite a reduction of 8.1% in surgical volume. By contrast, surgical site infections decreased at control hospitals over the study period.

In-hospital mortality decreased slightly at private equity hospitals compared with the control hospitals, but there was no differential change in mortality by 30 days after hospital discharge. The slight difference might be caused by the trend in slightly younger Medicare beneficiaries treated at private equity hospitals; these patients were less likely to be eligible for both Medicaid and Medicare and were more likely to be transferred to other hospitals, the researchers noted.

The findings were limited by several factors including the lack of generalizability to all private equity-acquired hospitals and to non-Medicare patients, the researchers noted. Other limitations include the use of the International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes that might have failed to capture all hospital-acquired conditions and the inability to account for all confounding factors.

However, the results suggest that private equity acquisition was associated with increased hospital-acquired adverse events and highlight concerns about the impact of private equity ownership on healthcare delivery, the researchers concluded.

In a related story published in July 2023, this news organization described a report showing an association between private equity ownership of medical practices and increased consumer prices for multiple medical specialties.

“Medicare patients admitted to private equity-owned hospitals experienced, on average, an 25% increase in hospital-acquired adverse events after the hospital was bought compared to similar patients at hospitals not acquired by private equity firms. We were surprised by the extent of this change relative to the comparison (non-private equity) hospitals, including the sizable increase in central line-associated bloodstream infections and the doubling of surgical site infections at private equity hospitals — both of which went down at the comparison hospitals during the same period,” Dr. Song said in an interview.

“A key implication is that patients, providers, and policymakers might be more attuned to the potential clinical impact of private equity ownership in the delivery system. Given that a plausible explanation for these findings is reductions in clinician staffing, clinical organizations and policymakers might also be more aware of cost-cutting strategies after acquisition,” Dr. Song said. “Prior research has shown that hospitals, nursing homes, and physician practices experience staffing cuts after private equity acquisition, which is a common way to reduce operating costs and boost the profitability of acquired entities,” he noted.

“More research is needed to understand the impact of private equity acquisitions across health care settings and the potential effects of policy levers that aim to protect patients and societal resources,” said Dr. Song, who coauthored an article outlining a policy framework for addressing private equity in healthcare, published in JAMA in April 2023. “Potential regulatory remedies include minimum staffing ratios, antitrust enforcement, mitigating the financial risk of such acquisitions, increasing the transparency of these acquisitions, and protecting patients and society from the higher prices of care attributed to this model of provider ownership,” he said.
 

Patients Pay the Price of Private Equity Acquisition

“The exponential growth in private equity ownership in hospital and physician practices in the past few decades has left a majority of health care providers disillusioned with cost-cutting practices resulting in staffing reductions and ratios that sacrifice patient care as part of their approach to running clinical operations ‘lean,’ ” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, NY, said in an interview.

“While private equity companies argue that such practices are essential to meet their bottom line and increase operating margins, it doesn’t translate into ideal care for patients; lean practices in staffing which focus on profits at the expense of patient safety and quality of care.

“When you look at patient outcomes, it is the patients who ultimately pay the price — not the shareholders,” Dr. Glatter said. “This translates to higher risks of hospital-acquired complications including falls and blood-borne infections, including surgical site infections, as noted by the authors of the current study when private equity took over operations in hospitals.

Dr. Glatter said he was not surprised by the findings. “In my world, patient care and safety come first. Period,” he said. “Would you want your family’s health and well-being sacrificed in the name of company profits? I think it’s a rhetorical question, but one that every health care provider who works in a hospital or practice run by private equity must consider.”

Despite a decline in utilization at private equity hospitals as noted in the current study, hospital-acquired infections and adverse outcomes still increased, illustrating a decline in quality of care, said Dr. Glatter. “While these disparities were not evident when looking at 30-day outcomes, they demonstrate how operational changes impact patient outcomes in the near term. Having younger and healthier patients, and fewer Medicare and Medicaid patients combined with more hospital transfers to non–private equity run hospitals, resulted in lower in-hospital mortality in the near term, which was not apparent at 30 days post discharge,” he said.

“The explosion of hospital mergers and consolidation in the past several decades has led to skyrocketing health care costs at the expense of patient satisfaction, but also health care providers’ autonomy to manage and maintain quality care for their patients,” Dr. Glatter said.

“It’s important to understand that private equity’s interests are primarily aligned with their shareholder’s interests, as opposed to patients’ outcomes and interests,” Dr. Glatter told this news organization. “Within 5-7 years, the goal is to increase operating margins and profits and then sell a practice or hospital, which is ultimately part of a ‘health care portfolio,’ ” he said.

Additional research is needed to examine whether other hospital-acquired conditions including pressure sores, catheter-associated UTIs, methicillin-resistant Staphylococcus aureus infections, Clostridium difficile infections, and nosocomial pneumonia have increased in hospitals following private equity acquisition, given the overall national decline in these events, he said.

“At the same time, it is vital to also look at management and readmission rates for patients with strokes, heart attacks, and congestive heart failure in hospitals that are run by private equity,” Dr. Glatter noted. “These are important benchmarks of care monitored by CMS that reflect the quality of care that payers ultimately factor into reimbursement.”

Examining the metrics associated with these diagnoses will help in understanding whether private equity-managed facilities are leading to adverse outcomes and mortality, increased length of stay, hospital readmissions, and increased nosocomial infections, apart from other aspects of patient experience, Dr. Glatter added.

The study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and Arnold Ventures. The researchers had no financial conflicts to disclose. Dr. Glatter had no financial conflicts to disclose and serves on the Medscape Emergency Medicine Editorial Board.
 

A version of this article appeared on Medscape.com.

Hospital-acquired adverse events or conditions including falls and infections increased by approximately 25% after hospitals’ acquisition by private equity compared with control hospitals, on the basis of a study of Medicare claims for more than 4,500,000 hospitalizations.

“Prior research on private equity in health care showed that acquisition is associated with higher charges, prices, and spending; however, the implications for quality of care and patient outcomes remained less understood,” corresponding author Zirui Song, MD, of Harvard Medical School, Boston, said in an interview. “This was particularly true for measures of clinical quality that were less susceptible to changes in patient mix or coding behavior, such as hospital-acquired adverse events.”

In the study, published in JAMA, the researchers compared data from 100% Medicare Part A claims for 662,095 hospitalizations at 51 hospitals acquired by private equities and 4,160,720 hospitalizations at 259 control hospitals. The hospitalizations occurred between 2009 and 2019. The researchers also used a difference-in-differences design to evaluate hospitalizations from 3 years before to 3 years after acquisition, controlling for patient and hospital attributes.

Hospital-acquired adverse events as defined by the US Centers for Medicare & Medicaid Services included falls, infections, stage III or IV pressure ulcers, foreign objects retained after surgery, air embolism, and blood incompatibility.

Overall, Medicare patients in private equity hospitals experienced a 25.4% increase in hospital-acquired conditions compared with those in control hospitals through a period of up to 3 years after acquisition, with a difference of 4.6 additional hospital-acquired conditions per 10,000 hospitalizations (P = .004). Central line-associated bloodstream infections accounted for 37.7% of the increase (P = .04), despite a 16.2% decrease in placement of central lines, and falls accounted for 27.3% (P = .02).

Notably, the incidence of surgical site infections increased from 10.8 per 10,000 hospitalizations before acquisition to 21.6 per 10,000 hospitalizations after acquisition, despite a reduction of 8.1% in surgical volume. By contrast, surgical site infections decreased at control hospitals over the study period.

In-hospital mortality decreased slightly at private equity hospitals compared with the control hospitals, but there was no differential change in mortality by 30 days after hospital discharge. The slight difference might be caused by the trend in slightly younger Medicare beneficiaries treated at private equity hospitals; these patients were less likely to be eligible for both Medicaid and Medicare and were more likely to be transferred to other hospitals, the researchers noted.

The findings were limited by several factors including the lack of generalizability to all private equity-acquired hospitals and to non-Medicare patients, the researchers noted. Other limitations include the use of the International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes that might have failed to capture all hospital-acquired conditions and the inability to account for all confounding factors.

However, the results suggest that private equity acquisition was associated with increased hospital-acquired adverse events and highlight concerns about the impact of private equity ownership on healthcare delivery, the researchers concluded.

In a related story published in July 2023, this news organization described a report showing an association between private equity ownership of medical practices and increased consumer prices for multiple medical specialties.

“Medicare patients admitted to private equity-owned hospitals experienced, on average, an 25% increase in hospital-acquired adverse events after the hospital was bought compared to similar patients at hospitals not acquired by private equity firms. We were surprised by the extent of this change relative to the comparison (non-private equity) hospitals, including the sizable increase in central line-associated bloodstream infections and the doubling of surgical site infections at private equity hospitals — both of which went down at the comparison hospitals during the same period,” Dr. Song said in an interview.

“A key implication is that patients, providers, and policymakers might be more attuned to the potential clinical impact of private equity ownership in the delivery system. Given that a plausible explanation for these findings is reductions in clinician staffing, clinical organizations and policymakers might also be more aware of cost-cutting strategies after acquisition,” Dr. Song said. “Prior research has shown that hospitals, nursing homes, and physician practices experience staffing cuts after private equity acquisition, which is a common way to reduce operating costs and boost the profitability of acquired entities,” he noted.

“More research is needed to understand the impact of private equity acquisitions across health care settings and the potential effects of policy levers that aim to protect patients and societal resources,” said Dr. Song, who coauthored an article outlining a policy framework for addressing private equity in healthcare, published in JAMA in April 2023. “Potential regulatory remedies include minimum staffing ratios, antitrust enforcement, mitigating the financial risk of such acquisitions, increasing the transparency of these acquisitions, and protecting patients and society from the higher prices of care attributed to this model of provider ownership,” he said.
 

Patients Pay the Price of Private Equity Acquisition

“The exponential growth in private equity ownership in hospital and physician practices in the past few decades has left a majority of health care providers disillusioned with cost-cutting practices resulting in staffing reductions and ratios that sacrifice patient care as part of their approach to running clinical operations ‘lean,’ ” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, NY, said in an interview.

“While private equity companies argue that such practices are essential to meet their bottom line and increase operating margins, it doesn’t translate into ideal care for patients; lean practices in staffing which focus on profits at the expense of patient safety and quality of care.

“When you look at patient outcomes, it is the patients who ultimately pay the price — not the shareholders,” Dr. Glatter said. “This translates to higher risks of hospital-acquired complications including falls and blood-borne infections, including surgical site infections, as noted by the authors of the current study when private equity took over operations in hospitals.

Dr. Glatter said he was not surprised by the findings. “In my world, patient care and safety come first. Period,” he said. “Would you want your family’s health and well-being sacrificed in the name of company profits? I think it’s a rhetorical question, but one that every health care provider who works in a hospital or practice run by private equity must consider.”

Despite a decline in utilization at private equity hospitals as noted in the current study, hospital-acquired infections and adverse outcomes still increased, illustrating a decline in quality of care, said Dr. Glatter. “While these disparities were not evident when looking at 30-day outcomes, they demonstrate how operational changes impact patient outcomes in the near term. Having younger and healthier patients, and fewer Medicare and Medicaid patients combined with more hospital transfers to non–private equity run hospitals, resulted in lower in-hospital mortality in the near term, which was not apparent at 30 days post discharge,” he said.

“The explosion of hospital mergers and consolidation in the past several decades has led to skyrocketing health care costs at the expense of patient satisfaction, but also health care providers’ autonomy to manage and maintain quality care for their patients,” Dr. Glatter said.

“It’s important to understand that private equity’s interests are primarily aligned with their shareholder’s interests, as opposed to patients’ outcomes and interests,” Dr. Glatter told this news organization. “Within 5-7 years, the goal is to increase operating margins and profits and then sell a practice or hospital, which is ultimately part of a ‘health care portfolio,’ ” he said.

Additional research is needed to examine whether other hospital-acquired conditions including pressure sores, catheter-associated UTIs, methicillin-resistant Staphylococcus aureus infections, Clostridium difficile infections, and nosocomial pneumonia have increased in hospitals following private equity acquisition, given the overall national decline in these events, he said.

“At the same time, it is vital to also look at management and readmission rates for patients with strokes, heart attacks, and congestive heart failure in hospitals that are run by private equity,” Dr. Glatter noted. “These are important benchmarks of care monitored by CMS that reflect the quality of care that payers ultimately factor into reimbursement.”

Examining the metrics associated with these diagnoses will help in understanding whether private equity-managed facilities are leading to adverse outcomes and mortality, increased length of stay, hospital readmissions, and increased nosocomial infections, apart from other aspects of patient experience, Dr. Glatter added.

The study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and Arnold Ventures. The researchers had no financial conflicts to disclose. Dr. Glatter had no financial conflicts to disclose and serves on the Medscape Emergency Medicine Editorial Board.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Consuming nonsugar sweeteners (NSS) leads to significant changes in both stool and duodenal microbial diversity and composition and levels of circulating inflammatory markers.

METHODOLOGY:

• Researchers analyzed samples from the REIMAGINE (Revealing the Entire Intestinal Microbiota and its Associations with the Genetic, Immunologic, and Neuroendocrine Ecosystem) study to assess the potential effects of NSS consumption on the duodenal luminal microbiome.
• They analyzed subjects consuming non-aspartame nonsugar sweeteners (NANS; n = 35) and aspartame only (ASP; n = 9), who were compared with 55 control participants matched for age, sex, and body mass index.
• A subset of 40 participants provided stool samples for additional analysis.

TAKEAWAY:

• Duodenal alpha diversity was lower in NANS consumers vs controls.
• Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella was lower in both NANS and ASP vs controls, whereas stool RA of these phylum Proteobacteria was increased in both NANS and ASP.
• Compared with controls, NANS and ASP differed in how they altered predicted duodenal microbial metabolic pathways, with NANS impacting polysaccharides biosynthesis and D-galactose degradation and ASP significantly enriching biosynthesis of cylindrospermopsin, a potential cancer-causing agent known to adversely impact the liver and nervous system.
• Circulating levels of interleukin (IL)-1b, a pro-inflammatory cytokine that plays a key role in the immune response, were significantly decreased in NANS vs controls, whereas IL-6 and IL-10, two cytokines with protective properties, were decreased in the ASP group vs controls.

IN PRACTICE:

“Given the crucial role played by small intestinal microbes in digestion, nutrient absorption, immune regulation, and endocrine functions, coupled with the substantial prevalence of NSS consumption among US adults (estimated at 41.4%), our findings have potential implications for metabolic and gastrointestinal health in a considerable proportion of the American adult population.”

SOURCE:

The study, conducted by Ava Hosseini, MPH, and colleagues at Cedars-Sinai, Los Angeles, was published online on November 22, 2023, in iScience.

LIMITATIONS:

The study population may not be representative of healthy individuals as they underwent upper endoscopy for various reasons (eg, evaluation of intestinal complaints). After exclusions, the duodenal sample size for the aspartame group was small. Samples were collected at a single timepoint, limiting the ability to establish causal relationships.

DISCLOSURES:

This research was supported by Frank Lee, the Monica Lester Charitable Trust, and the Elias, Genevieve, and Georgianna Atol Charitable Trust through their support of the Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Consuming nonsugar sweeteners (NSS) leads to significant changes in both stool and duodenal microbial diversity and composition and levels of circulating inflammatory markers.

METHODOLOGY:

• Researchers analyzed samples from the REIMAGINE (Revealing the Entire Intestinal Microbiota and its Associations with the Genetic, Immunologic, and Neuroendocrine Ecosystem) study to assess the potential effects of NSS consumption on the duodenal luminal microbiome.
• They analyzed subjects consuming non-aspartame nonsugar sweeteners (NANS; n = 35) and aspartame only (ASP; n = 9), who were compared with 55 control participants matched for age, sex, and body mass index.
• A subset of 40 participants provided stool samples for additional analysis.

TAKEAWAY:

• Duodenal alpha diversity was lower in NANS consumers vs controls.
• Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella was lower in both NANS and ASP vs controls, whereas stool RA of these phylum Proteobacteria was increased in both NANS and ASP.
• Compared with controls, NANS and ASP differed in how they altered predicted duodenal microbial metabolic pathways, with NANS impacting polysaccharides biosynthesis and D-galactose degradation and ASP significantly enriching biosynthesis of cylindrospermopsin, a potential cancer-causing agent known to adversely impact the liver and nervous system.
• Circulating levels of interleukin (IL)-1b, a pro-inflammatory cytokine that plays a key role in the immune response, were significantly decreased in NANS vs controls, whereas IL-6 and IL-10, two cytokines with protective properties, were decreased in the ASP group vs controls.

IN PRACTICE:

“Given the crucial role played by small intestinal microbes in digestion, nutrient absorption, immune regulation, and endocrine functions, coupled with the substantial prevalence of NSS consumption among US adults (estimated at 41.4%), our findings have potential implications for metabolic and gastrointestinal health in a considerable proportion of the American adult population.”

SOURCE:

The study, conducted by Ava Hosseini, MPH, and colleagues at Cedars-Sinai, Los Angeles, was published online on November 22, 2023, in iScience.

LIMITATIONS:

The study population may not be representative of healthy individuals as they underwent upper endoscopy for various reasons (eg, evaluation of intestinal complaints). After exclusions, the duodenal sample size for the aspartame group was small. Samples were collected at a single timepoint, limiting the ability to establish causal relationships.

DISCLOSURES:

This research was supported by Frank Lee, the Monica Lester Charitable Trust, and the Elias, Genevieve, and Georgianna Atol Charitable Trust through their support of the Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Consuming nonsugar sweeteners (NSS) leads to significant changes in both stool and duodenal microbial diversity and composition and levels of circulating inflammatory markers.

METHODOLOGY:

• Researchers analyzed samples from the REIMAGINE (Revealing the Entire Intestinal Microbiota and its Associations with the Genetic, Immunologic, and Neuroendocrine Ecosystem) study to assess the potential effects of NSS consumption on the duodenal luminal microbiome.
• They analyzed subjects consuming non-aspartame nonsugar sweeteners (NANS; n = 35) and aspartame only (ASP; n = 9), who were compared with 55 control participants matched for age, sex, and body mass index.
• A subset of 40 participants provided stool samples for additional analysis.

TAKEAWAY:

• Duodenal alpha diversity was lower in NANS consumers vs controls.
• Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella was lower in both NANS and ASP vs controls, whereas stool RA of these phylum Proteobacteria was increased in both NANS and ASP.
• Compared with controls, NANS and ASP differed in how they altered predicted duodenal microbial metabolic pathways, with NANS impacting polysaccharides biosynthesis and D-galactose degradation and ASP significantly enriching biosynthesis of cylindrospermopsin, a potential cancer-causing agent known to adversely impact the liver and nervous system.
• Circulating levels of interleukin (IL)-1b, a pro-inflammatory cytokine that plays a key role in the immune response, were significantly decreased in NANS vs controls, whereas IL-6 and IL-10, two cytokines with protective properties, were decreased in the ASP group vs controls.

IN PRACTICE:

“Given the crucial role played by small intestinal microbes in digestion, nutrient absorption, immune regulation, and endocrine functions, coupled with the substantial prevalence of NSS consumption among US adults (estimated at 41.4%), our findings have potential implications for metabolic and gastrointestinal health in a considerable proportion of the American adult population.”

SOURCE:

The study, conducted by Ava Hosseini, MPH, and colleagues at Cedars-Sinai, Los Angeles, was published online on November 22, 2023, in iScience.

LIMITATIONS:

The study population may not be representative of healthy individuals as they underwent upper endoscopy for various reasons (eg, evaluation of intestinal complaints). After exclusions, the duodenal sample size for the aspartame group was small. Samples were collected at a single timepoint, limiting the ability to establish causal relationships.

DISCLOSURES:

This research was supported by Frank Lee, the Monica Lester Charitable Trust, and the Elias, Genevieve, and Georgianna Atol Charitable Trust through their support of the Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Older adults (aged ≥ 65 years) with diabetes who received insulin may have an increased risk for serious hypoglycemic events in extreme heat.

METHODOLOGY:

• Thermoregulatory response is often compromised in older adults with diabetes, making them vulnerable to extreme heat.
• Researchers evaluated the association between ambient heat and risk for hypoglycemia in about 2 million and about 283,000 patients aged 65-100 years with diabetes from the United States and Taiwan, respectively, who received insulin.
• A serious hypoglycemic event was defined as a primary emergency department (ED) visit or an unplanned inpatient admission for hypoglycemia from June 1 to September 30.
• Medication use was determined by at least one prescription dispensing insulin within 90 days of the index event.
• The average heat index (HI), a combination of ambient temperature and humidity exposure, was calculated by ZIP code and grouped into percentiles: ≥ 99th, 95-98th, 85-94th, 76-84th, 25-74th, and < 25th.

TAKEAWAY:

• Among insulin users overall, 32,461 and 10,162 older adults from the United States and Taiwan, respectively, experienced a hypoglycemic event.
• The risk for a serious hypoglycemic event was about 40% higher among insulin users on days with a HI of ≥ 99th percentile than 25-74th percentile (unadjusted odds ratio, 1.38; 95% CI, 1.28-1.48).
• Conversely, on days with a low HI (< 25th percentile), the risk for hypoglycemia among insulin users decreased.
• No substantial differences were observed in the risk for hypoglycemic events and HI by climate region in either country, such as between the US Northeast and Southwest.

IN PRACTICE:

“Our finding of elevated risk of hypoglycemia-related ED visits in older adults using insulin and exposed to extreme heat underscores the need for patients and providers to be aware and cautious that extreme heat may increase the risk of hypoglycemia,” the authors wrote.

SOURCE:

The study was conducted by first author Aayush Visaria, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, and coauthors. The study was published online on December 7, 2023, in Diabetes Care.

LIMITATIONS:

• The individuals with hypoglycemia were older, were more frequently non-Hispanic Black in the United States, and had more comorbidities, so caution should be used before the results can be generalized to broader populations.
• The authors were unable to capture variables that can alter the risk for serious hypoglycemia, such as outdoor activity, exercise, and diet.
• Prescriptions may not reflect actual insulin use and adherence.

DISCLOSURES:

This study was funded by the US National Institutes of Health/National Institute on Aging. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Older adults (aged ≥ 65 years) with diabetes who received insulin may have an increased risk for serious hypoglycemic events in extreme heat.

METHODOLOGY:

• Thermoregulatory response is often compromised in older adults with diabetes, making them vulnerable to extreme heat.
• Researchers evaluated the association between ambient heat and risk for hypoglycemia in about 2 million and about 283,000 patients aged 65-100 years with diabetes from the United States and Taiwan, respectively, who received insulin.
• A serious hypoglycemic event was defined as a primary emergency department (ED) visit or an unplanned inpatient admission for hypoglycemia from June 1 to September 30.
• Medication use was determined by at least one prescription dispensing insulin within 90 days of the index event.
• The average heat index (HI), a combination of ambient temperature and humidity exposure, was calculated by ZIP code and grouped into percentiles: ≥ 99th, 95-98th, 85-94th, 76-84th, 25-74th, and < 25th.

TAKEAWAY:

• Among insulin users overall, 32,461 and 10,162 older adults from the United States and Taiwan, respectively, experienced a hypoglycemic event.
• The risk for a serious hypoglycemic event was about 40% higher among insulin users on days with a HI of ≥ 99th percentile than 25-74th percentile (unadjusted odds ratio, 1.38; 95% CI, 1.28-1.48).
• Conversely, on days with a low HI (< 25th percentile), the risk for hypoglycemia among insulin users decreased.
• No substantial differences were observed in the risk for hypoglycemic events and HI by climate region in either country, such as between the US Northeast and Southwest.

IN PRACTICE:

“Our finding of elevated risk of hypoglycemia-related ED visits in older adults using insulin and exposed to extreme heat underscores the need for patients and providers to be aware and cautious that extreme heat may increase the risk of hypoglycemia,” the authors wrote.

SOURCE:

The study was conducted by first author Aayush Visaria, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, and coauthors. The study was published online on December 7, 2023, in Diabetes Care.

LIMITATIONS:

• The individuals with hypoglycemia were older, were more frequently non-Hispanic Black in the United States, and had more comorbidities, so caution should be used before the results can be generalized to broader populations.
• The authors were unable to capture variables that can alter the risk for serious hypoglycemia, such as outdoor activity, exercise, and diet.
• Prescriptions may not reflect actual insulin use and adherence.

DISCLOSURES:

This study was funded by the US National Institutes of Health/National Institute on Aging. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Older adults (aged ≥ 65 years) with diabetes who received insulin may have an increased risk for serious hypoglycemic events in extreme heat.

METHODOLOGY:

• Thermoregulatory response is often compromised in older adults with diabetes, making them vulnerable to extreme heat.
• Researchers evaluated the association between ambient heat and risk for hypoglycemia in about 2 million and about 283,000 patients aged 65-100 years with diabetes from the United States and Taiwan, respectively, who received insulin.
• A serious hypoglycemic event was defined as a primary emergency department (ED) visit or an unplanned inpatient admission for hypoglycemia from June 1 to September 30.
• Medication use was determined by at least one prescription dispensing insulin within 90 days of the index event.
• The average heat index (HI), a combination of ambient temperature and humidity exposure, was calculated by ZIP code and grouped into percentiles: ≥ 99th, 95-98th, 85-94th, 76-84th, 25-74th, and < 25th.

TAKEAWAY:

• Among insulin users overall, 32,461 and 10,162 older adults from the United States and Taiwan, respectively, experienced a hypoglycemic event.
• The risk for a serious hypoglycemic event was about 40% higher among insulin users on days with a HI of ≥ 99th percentile than 25-74th percentile (unadjusted odds ratio, 1.38; 95% CI, 1.28-1.48).
• Conversely, on days with a low HI (< 25th percentile), the risk for hypoglycemia among insulin users decreased.
• No substantial differences were observed in the risk for hypoglycemic events and HI by climate region in either country, such as between the US Northeast and Southwest.

IN PRACTICE:

“Our finding of elevated risk of hypoglycemia-related ED visits in older adults using insulin and exposed to extreme heat underscores the need for patients and providers to be aware and cautious that extreme heat may increase the risk of hypoglycemia,” the authors wrote.

SOURCE:

The study was conducted by first author Aayush Visaria, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, and coauthors. The study was published online on December 7, 2023, in Diabetes Care.

LIMITATIONS:

• The individuals with hypoglycemia were older, were more frequently non-Hispanic Black in the United States, and had more comorbidities, so caution should be used before the results can be generalized to broader populations.
• The authors were unable to capture variables that can alter the risk for serious hypoglycemia, such as outdoor activity, exercise, and diet.
• Prescriptions may not reflect actual insulin use and adherence.

DISCLOSURES:

This study was funded by the US National Institutes of Health/National Institute on Aging. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Neuroinflammation expert Jarred Younger, PhD, disputes a recent study commentary calling for clinicians to stop prescribing low-dose naltrexone for people with fibromyalgia.

Naltrexone is a nonselective µ-opioid receptor antagonist approved by the US Food and Drug Administration (FDA) at doses of 50-100 mg/day to treat opioid and alcohol dependence. Lower doses, typically 1-5 mg, can produce an analgesic effect via antagonism of receptors on microglial cells that lead to neuroinflammation. The low-dose version, available at compounding pharmacies, is not FDA-approved, but for many years it has been used off-label to treat fibromyalgia and related conditions.

Results from earlier small clinical trials have conflicted, but two conducted by Dr. Younger using doses of 4.5 mg/day showed benefit in reducing pain and other fibromyalgia symptoms. However, a new study from Denmark on 6 mg low-dose naltrexone versus placebo among 99 women with fibromyalgia demonstrated no significant difference in the primary outcome of change in pain intensity from baseline to 12 weeks.

On the other hand, there was a significant improvement in memory, and there were no differences in adverse events or safety, the authors reported in The Lancet Rheumatology.

Nonetheless, an accompanying commentary called the study a “resoundingly negative trial” and advised that while off-label use of low-dose naltrexone could continue for patients already taking it, clinicians should not initiate it for patients who have not previously used it, pending additional data.

Dr. Younger, director of the Neuroinflammation, Pain and Fatigue Laboratory at the University of Alabama, Birmingham, was speaking on December 13, 2023, at a National Institutes of Health meeting about myalgic encephalomyelitis/chronic fatigue syndrome about the potential use of low-dose naltrexone for that patient population. He had checked the literature in preparation for his talk and saw the new study, which had just been published December 5, 2023. 

During his talk, Dr. Younger said, “It looks like the study was very well done, and all the decisions made sense to me, so I don’t doubt the quality of their data or the statistics.”

But as for the commentary, he said, “I strongly disagree, and I believe the physicians at this conference strongly disagree with that as well. I know plenty of physicians who would say that is not good advice because this drug is so helpful for so many people.”

Indeed, Anthony L. Komaroff, MD, who heard Dr. Younger’s talk but hadn’t seen the new study, told this news organization that he is a “fan” of low-dose naltrexone based on his own experience with one patient who had a “clearly beneficial response” and that of other clinicians he’s spoken with about it. “My colleagues say it doesn’t work for everyone because the disease is so heterogeneous ... but it definitely works for some patients.”

Dr. Younger noted that the proportion of people in the Danish study who reported a clinically significant, that is 30% reduction, in pain scores was 45% versus 28% with placebo, not far from the 50% he found in his studies. “If they’d had 40 to 60 more people, they would have had statistically significant difference,” Dr. Younger said.

Indeed, the authors themselves pointed this out in their discussion, noting, “Our study was not powered to detect a significant difference regarding responder indices ... Subgroups of patients with fibromyalgia might respond differently to low-dose naltrexone treatment, and we intend to conduct a responder analysis based on levels of inflammatory biomarkers and specific biomarkers of glial activation, hypothesising that an inflammatory subgroup might benefit from the treatment. Results will be published in subsequent papers.”

The commentary authors responded to that, saying that they “appreciate” the intention to conduct that subgroup analysis, but that it is “probable that the current sample size will preclude robust statistical comparisons but could be a step to generate hypotheses.”

Those authors noted that a systematic review has described both pro-inflammatory (tumor necrosis factor, interleukin [IL]-6, and IL-8) and anti-inflammatory (IL-10) cytokines as peripheral inflammatory biomarkers in patients with fibromyalgia. “The specific peripheral biomarkers of glial activation are yet to be identified. The neuroinflammation hypothesis of fibromyalgia could be supported if a reduction of central nervous system inflammation would predict improvement of fibromyalgia symptoms. Subsequent work in this area is eagerly awaited.”

In the meantime, Dr. Younger said, “I do not think this should stop us from looking at low-dose naltrexone [or that] we shouldn’t try it. I’ve talked to over a thousand people over the last 10 years. It would be a very bad thing to give up on low-dose naltrexone now.”

Dr. Younger’s work is funded by the National Institutes of Health, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Komaroff has no disclosures.

A version of this article appeared on Medscape.com.

Neuroinflammation expert Jarred Younger, PhD, disputes a recent study commentary calling for clinicians to stop prescribing low-dose naltrexone for people with fibromyalgia.

Naltrexone is a nonselective µ-opioid receptor antagonist approved by the US Food and Drug Administration (FDA) at doses of 50-100 mg/day to treat opioid and alcohol dependence. Lower doses, typically 1-5 mg, can produce an analgesic effect via antagonism of receptors on microglial cells that lead to neuroinflammation. The low-dose version, available at compounding pharmacies, is not FDA-approved, but for many years it has been used off-label to treat fibromyalgia and related conditions.

Results from earlier small clinical trials have conflicted, but two conducted by Dr. Younger using doses of 4.5 mg/day showed benefit in reducing pain and other fibromyalgia symptoms. However, a new study from Denmark on 6 mg low-dose naltrexone versus placebo among 99 women with fibromyalgia demonstrated no significant difference in the primary outcome of change in pain intensity from baseline to 12 weeks.

On the other hand, there was a significant improvement in memory, and there were no differences in adverse events or safety, the authors reported in The Lancet Rheumatology.

Nonetheless, an accompanying commentary called the study a “resoundingly negative trial” and advised that while off-label use of low-dose naltrexone could continue for patients already taking it, clinicians should not initiate it for patients who have not previously used it, pending additional data.

Dr. Younger, director of the Neuroinflammation, Pain and Fatigue Laboratory at the University of Alabama, Birmingham, was speaking on December 13, 2023, at a National Institutes of Health meeting about myalgic encephalomyelitis/chronic fatigue syndrome about the potential use of low-dose naltrexone for that patient population. He had checked the literature in preparation for his talk and saw the new study, which had just been published December 5, 2023. 

During his talk, Dr. Younger said, “It looks like the study was very well done, and all the decisions made sense to me, so I don’t doubt the quality of their data or the statistics.”

But as for the commentary, he said, “I strongly disagree, and I believe the physicians at this conference strongly disagree with that as well. I know plenty of physicians who would say that is not good advice because this drug is so helpful for so many people.”

Indeed, Anthony L. Komaroff, MD, who heard Dr. Younger’s talk but hadn’t seen the new study, told this news organization that he is a “fan” of low-dose naltrexone based on his own experience with one patient who had a “clearly beneficial response” and that of other clinicians he’s spoken with about it. “My colleagues say it doesn’t work for everyone because the disease is so heterogeneous ... but it definitely works for some patients.”

Dr. Younger noted that the proportion of people in the Danish study who reported a clinically significant, that is 30% reduction, in pain scores was 45% versus 28% with placebo, not far from the 50% he found in his studies. “If they’d had 40 to 60 more people, they would have had statistically significant difference,” Dr. Younger said.

Indeed, the authors themselves pointed this out in their discussion, noting, “Our study was not powered to detect a significant difference regarding responder indices ... Subgroups of patients with fibromyalgia might respond differently to low-dose naltrexone treatment, and we intend to conduct a responder analysis based on levels of inflammatory biomarkers and specific biomarkers of glial activation, hypothesising that an inflammatory subgroup might benefit from the treatment. Results will be published in subsequent papers.”

The commentary authors responded to that, saying that they “appreciate” the intention to conduct that subgroup analysis, but that it is “probable that the current sample size will preclude robust statistical comparisons but could be a step to generate hypotheses.”

Those authors noted that a systematic review has described both pro-inflammatory (tumor necrosis factor, interleukin [IL]-6, and IL-8) and anti-inflammatory (IL-10) cytokines as peripheral inflammatory biomarkers in patients with fibromyalgia. “The specific peripheral biomarkers of glial activation are yet to be identified. The neuroinflammation hypothesis of fibromyalgia could be supported if a reduction of central nervous system inflammation would predict improvement of fibromyalgia symptoms. Subsequent work in this area is eagerly awaited.”

In the meantime, Dr. Younger said, “I do not think this should stop us from looking at low-dose naltrexone [or that] we shouldn’t try it. I’ve talked to over a thousand people over the last 10 years. It would be a very bad thing to give up on low-dose naltrexone now.”

Dr. Younger’s work is funded by the National Institutes of Health, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Komaroff has no disclosures.

A version of this article appeared on Medscape.com.

Neuroinflammation expert Jarred Younger, PhD, disputes a recent study commentary calling for clinicians to stop prescribing low-dose naltrexone for people with fibromyalgia.

Naltrexone is a nonselective µ-opioid receptor antagonist approved by the US Food and Drug Administration (FDA) at doses of 50-100 mg/day to treat opioid and alcohol dependence. Lower doses, typically 1-5 mg, can produce an analgesic effect via antagonism of receptors on microglial cells that lead to neuroinflammation. The low-dose version, available at compounding pharmacies, is not FDA-approved, but for many years it has been used off-label to treat fibromyalgia and related conditions.

Results from earlier small clinical trials have conflicted, but two conducted by Dr. Younger using doses of 4.5 mg/day showed benefit in reducing pain and other fibromyalgia symptoms. However, a new study from Denmark on 6 mg low-dose naltrexone versus placebo among 99 women with fibromyalgia demonstrated no significant difference in the primary outcome of change in pain intensity from baseline to 12 weeks.

On the other hand, there was a significant improvement in memory, and there were no differences in adverse events or safety, the authors reported in The Lancet Rheumatology.

Nonetheless, an accompanying commentary called the study a “resoundingly negative trial” and advised that while off-label use of low-dose naltrexone could continue for patients already taking it, clinicians should not initiate it for patients who have not previously used it, pending additional data.

Dr. Younger, director of the Neuroinflammation, Pain and Fatigue Laboratory at the University of Alabama, Birmingham, was speaking on December 13, 2023, at a National Institutes of Health meeting about myalgic encephalomyelitis/chronic fatigue syndrome about the potential use of low-dose naltrexone for that patient population. He had checked the literature in preparation for his talk and saw the new study, which had just been published December 5, 2023. 

During his talk, Dr. Younger said, “It looks like the study was very well done, and all the decisions made sense to me, so I don’t doubt the quality of their data or the statistics.”

But as for the commentary, he said, “I strongly disagree, and I believe the physicians at this conference strongly disagree with that as well. I know plenty of physicians who would say that is not good advice because this drug is so helpful for so many people.”

Indeed, Anthony L. Komaroff, MD, who heard Dr. Younger’s talk but hadn’t seen the new study, told this news organization that he is a “fan” of low-dose naltrexone based on his own experience with one patient who had a “clearly beneficial response” and that of other clinicians he’s spoken with about it. “My colleagues say it doesn’t work for everyone because the disease is so heterogeneous ... but it definitely works for some patients.”

Dr. Younger noted that the proportion of people in the Danish study who reported a clinically significant, that is 30% reduction, in pain scores was 45% versus 28% with placebo, not far from the 50% he found in his studies. “If they’d had 40 to 60 more people, they would have had statistically significant difference,” Dr. Younger said.

Indeed, the authors themselves pointed this out in their discussion, noting, “Our study was not powered to detect a significant difference regarding responder indices ... Subgroups of patients with fibromyalgia might respond differently to low-dose naltrexone treatment, and we intend to conduct a responder analysis based on levels of inflammatory biomarkers and specific biomarkers of glial activation, hypothesising that an inflammatory subgroup might benefit from the treatment. Results will be published in subsequent papers.”

The commentary authors responded to that, saying that they “appreciate” the intention to conduct that subgroup analysis, but that it is “probable that the current sample size will preclude robust statistical comparisons but could be a step to generate hypotheses.”

Those authors noted that a systematic review has described both pro-inflammatory (tumor necrosis factor, interleukin [IL]-6, and IL-8) and anti-inflammatory (IL-10) cytokines as peripheral inflammatory biomarkers in patients with fibromyalgia. “The specific peripheral biomarkers of glial activation are yet to be identified. The neuroinflammation hypothesis of fibromyalgia could be supported if a reduction of central nervous system inflammation would predict improvement of fibromyalgia symptoms. Subsequent work in this area is eagerly awaited.”

In the meantime, Dr. Younger said, “I do not think this should stop us from looking at low-dose naltrexone [or that] we shouldn’t try it. I’ve talked to over a thousand people over the last 10 years. It would be a very bad thing to give up on low-dose naltrexone now.”

Dr. Younger’s work is funded by the National Institutes of Health, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Komaroff has no disclosures.

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.