Marilynn Larkin

Emerging evidence suggests that oral health, often overlooked by clinicians, is closely connected with overall health — and this connection has important consequences for individuals with type 2 diabetes (T2D). While most studies are observational and can’t prove cause and effect, the associations are robust enough for researchers to conclude that the connection is real.

Endocrinologists and other specialists, as well as primary care physicians, should ask about oral health, if not look in the mouth directly, experts say. “One of the most important things to ask people with diabetes is when their last dental visit was and if they have a follow-up,” said Robert Gabbay, MD, PhD, Chief Scientific and Medical Officer of the American Diabetes Association (ADA). The ADA advocates for attention to oral health through its 2024 standards of care.

Systemic Impact

“Periodontitis is a probable risk factor for various problems connected to the cardiovascular, pulmonary, endocrine, musculoskeletal, central nervous, and reproductive systems,” wrote the authors of a recent review on the effects of periodontitis on major organ systems. While not specific to the diabetes connection, the review pinpoints some of the latest evidence that “oral health affects overall health, and…dental health should never be considered a distinct, remote, and lower significant part of health.”

In line with this perspective, and looking specifically at T2D, a recent study of more than 17,000 patients with T2D participating in a screening program in Korea found that periodontitis and an increased number of teeth with cavities were independent risk factors for cerebral or myocardial infarction (adjusted hazard ratios, 1.17 and 1.67, respectively).

Dental disease and poor oral hygiene were also associated with an increased risk for heart failure among people with T2D in a large cohort study, and the authors suggested that managing oral health may prevent heart failure development.

A recent review suggested that periodontitis exacerbates and promotes the progression of chronic kidney disease, a disorder that affects 1 in 3 people with diabetes.

Studies also have shown that diabetes is associated with cognitive decline, and a review of oral health and dementia progression concluded, “collectively, experimental findings indicate that the connection between oral health and cognition cannot be underestimated.”

Bidirectional Effects

Research has shown that the association between periodontal disease and T2D is likely bidirectional, although there is little awareness of this two-way relationship among patients and providers.

A recent review of this bidirectional relationship focused on microvascular complications, oral microbiota, pro- and anti-inflammatory factors in T2D and periodontal disease and concluded that “these two diseases require specific/complementary therapeutic solutions when they occur in association, with new clinical trials and epidemiological research being necessary for better control of this interdependent pathogenic topic.”

Yet an Australian study showed that 54% of 241 participants in a survey never received any information regarding the bidirectional relationship between periodontal disease and diabetes and lacked understanding of the association.

What’s the Mechanism?

How does T2D affect the teeth and vice versa? “Basically, people with T2D have high blood sugar, and the sugar comes out in the saliva and that promotes bacterial growth in the mouth and plaque formation on the teeth and gum disease,” Samir Malkani, MD, clinical chief of endocrinology and diabetes at UMass Chan School of Medicine in Worcester, Massachusetts, told this news organization.

“Patients get gingivitis, they get periodontitis, and since the gums and the jaw are a single unit, if the gum disease gets very severe, then there’s loss of jawbone and the teeth could fall out,” he said. There’s also inflammation in the mouth, and “when you have generalized inflammation, it affects the whole body.”

Recent research in Europe suggested that “although the mechanisms behind these associations are partially unclear, poor oral health is probably sustaining systemic inflammation.” Common oral infections, periodontal disease, and cavities are associated with inflammatory metabolic profiles related to an increased risk for cardiometabolic diseases, and they predict future adverse changes in metabolic profiles, according to the authors.

Awareness, Accessibility, Collaboration

Despite the evidence, the connection between oral health and diabetes (any type) is not front of mind with clinicians or patients, Dr. Malkani said. He pointed to a systematic review that included 28 studies of close to 28,000 people in 14 countries. The review found that people with diabetes have “inadequate oral health knowledge, poor oral health attitudes, and fewer dental visits, [and] rarely receive oral health education and dental referrals from their care providers.”

Social determinants of health have a “huge impact” on whether people will develop T2D and its related complications, including poor oral health, according to the National Clinical Care Commission Report presented to the US Congress in 2022. The commission was charged with making recommendations for federal policies and programs that could more effectively prevent and control diabetes and its complications.

The commission “approached its charge through the lens of a socioecological and an expanded chronic care model,” the report authors wrote. “It was clear that diabetes in the US cannot simply be viewed as a medical or healthcare problem but also must be addressed as a societal problem that cuts across many sectors, including food, housing, commerce, transportation, and the environment.”

Diabetes also is associated with higher dental costs, another factor affecting an individual’s ability to obtain care.

A recent questionnaire-based study from Denmark found that people with T2D were more likely than those without diabetes to rate their oral health as poor, and that the risk for self-rated poor oral health increased with lower educational attainment. Highest educational attainment and disposable household income were indicators of a high socioeconomic position, and a lower likelihood of rating their oral health as poor, again pointing out inequities.

The authors concluded that “diabetes and dental care providers should engage in multidisciplinary collaboration across healthcare sectors to ensure coherent treatment and management of diabetes.”

But such collaborations are easier said than done. “One of the challenges is our fragmented health system, where oral health and medical care are separate,” Dr. Gabbay said.

For the most part, the two are separate, Dr. Malkani agreed. “When we’re dealing with most complications of diabetes, like involvement of the heart or eyes or kidneys, we can have interdisciplinary care — everyone is within the overall discipline of medicine, and if I refer to a colleague in ophthalmology or a cardiologist or a vascular surgeon, they can all be within the same network from an insurance point of view, as well.”

But for dental care, referrals are interprofessional, not interdisciplinary. “I have to make sure that the patient has a dentist because dentists are usually not part of medical networks, and if the patient doesn’t have dental insurance, then cost and access can be a challenge.”

A recent systematic review from Australia on interprofessional education and interprofessional collaborative care found that more than a third of medical professionals were “ignorant” of the relationship between oral health and T2D. Furthermore, only 30% reported ever referring their patients for an oral health assessment. And there was little, if any, interprofessional collaborative care between medical and dental professionals while managing patients with T2D.

Treat the Teeth

“We always talk to our T2D patients about the importance of getting an eye exam, a foot exam, and a kidney test,” Dr. Malkani said. “But we also need to make sure that they’re going to the dentist. Normally, people get their teeth cleaned twice a year. But if you have diabetes and poor oral health, you might need to get your teeth cleaned every three months, and insurance often will pay for that.”

Furthermore, in keeping with the bidirectional connection, treating periodontitis can help glycemic control. The authors of a 2022 update of a Cochrane review on treating periodontitis for glycemic control wrote that they “doubled the number of included studies and participants” from the 2015 update to 35 studies randomizing 3249 participants to periodontal treatment or control. This “led to a change in our conclusions about the primary outcome of glycemic control and in our level of certainty in this conclusion.”

“We now have moderate‐certainty evidence that periodontal treatment using subgingival instrumentation improves glycemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment vs no treatment/usual care are unlikely to change the overall conclusion reached in this review.”

“Dentists also have a responsibility,” Dr. Malkani added. “If they see someone with severe gum disease or cavities, especially at a younger age, they need to tell that person to get their blood sugar checked and make sure they don’t have T2D.”

In fact, a recent review found that complications of T2D such as xerostomia and periodontal problems adversely affect well-being, and that “dentists can play an essential role in the awareness of diabetic patients about these problems and improve their quality of life.”

Key Stats

The US Centers for Disease Control and Prevention highlighted these facts about diabetes and oral health:

• Adults aged 20 years or older with diabetes are 40% more likely to have untreated cavities than similar adults without diabetes.
• About 60% of US adults with diabetes had a medical visit in the past year but no dental visit.
• Expanding healthcare coverage for periodontal treatment among people with diabetes could save each person about $6000 (2019 US dollars) over their lifetimes.
• Adults aged 50 years or older with diabetes lack functional dentition (have fewer than 20 teeth) 46% more often and have severe tooth loss (eight or fewer teeth) 56% more often than those without diabetes.
• Adults aged 50 years or older with diabetes are more likely to report that they have a hard time eating because of dental problems.
• Annual dental expenditures for an adult with diabetes are $77 (2017 US dollars) higher than for an adult without diabetes. This cost translates to $1.9 billion for the United States.

A version of this article appeared on Medscape.com.

Emerging evidence suggests that oral health, often overlooked by clinicians, is closely connected with overall health — and this connection has important consequences for individuals with type 2 diabetes (T2D). While most studies are observational and can’t prove cause and effect, the associations are robust enough for researchers to conclude that the connection is real.

Endocrinologists and other specialists, as well as primary care physicians, should ask about oral health, if not look in the mouth directly, experts say. “One of the most important things to ask people with diabetes is when their last dental visit was and if they have a follow-up,” said Robert Gabbay, MD, PhD, Chief Scientific and Medical Officer of the American Diabetes Association (ADA). The ADA advocates for attention to oral health through its 2024 standards of care.

Systemic Impact

“Periodontitis is a probable risk factor for various problems connected to the cardiovascular, pulmonary, endocrine, musculoskeletal, central nervous, and reproductive systems,” wrote the authors of a recent review on the effects of periodontitis on major organ systems. While not specific to the diabetes connection, the review pinpoints some of the latest evidence that “oral health affects overall health, and…dental health should never be considered a distinct, remote, and lower significant part of health.”

In line with this perspective, and looking specifically at T2D, a recent study of more than 17,000 patients with T2D participating in a screening program in Korea found that periodontitis and an increased number of teeth with cavities were independent risk factors for cerebral or myocardial infarction (adjusted hazard ratios, 1.17 and 1.67, respectively).

Dental disease and poor oral hygiene were also associated with an increased risk for heart failure among people with T2D in a large cohort study, and the authors suggested that managing oral health may prevent heart failure development.

A recent review suggested that periodontitis exacerbates and promotes the progression of chronic kidney disease, a disorder that affects 1 in 3 people with diabetes.

Studies also have shown that diabetes is associated with cognitive decline, and a review of oral health and dementia progression concluded, “collectively, experimental findings indicate that the connection between oral health and cognition cannot be underestimated.”

Bidirectional Effects

Research has shown that the association between periodontal disease and T2D is likely bidirectional, although there is little awareness of this two-way relationship among patients and providers.

A recent review of this bidirectional relationship focused on microvascular complications, oral microbiota, pro- and anti-inflammatory factors in T2D and periodontal disease and concluded that “these two diseases require specific/complementary therapeutic solutions when they occur in association, with new clinical trials and epidemiological research being necessary for better control of this interdependent pathogenic topic.”

Yet an Australian study showed that 54% of 241 participants in a survey never received any information regarding the bidirectional relationship between periodontal disease and diabetes and lacked understanding of the association.

What’s the Mechanism?

How does T2D affect the teeth and vice versa? “Basically, people with T2D have high blood sugar, and the sugar comes out in the saliva and that promotes bacterial growth in the mouth and plaque formation on the teeth and gum disease,” Samir Malkani, MD, clinical chief of endocrinology and diabetes at UMass Chan School of Medicine in Worcester, Massachusetts, told this news organization.

“Patients get gingivitis, they get periodontitis, and since the gums and the jaw are a single unit, if the gum disease gets very severe, then there’s loss of jawbone and the teeth could fall out,” he said. There’s also inflammation in the mouth, and “when you have generalized inflammation, it affects the whole body.”

Recent research in Europe suggested that “although the mechanisms behind these associations are partially unclear, poor oral health is probably sustaining systemic inflammation.” Common oral infections, periodontal disease, and cavities are associated with inflammatory metabolic profiles related to an increased risk for cardiometabolic diseases, and they predict future adverse changes in metabolic profiles, according to the authors.

Awareness, Accessibility, Collaboration

Despite the evidence, the connection between oral health and diabetes (any type) is not front of mind with clinicians or patients, Dr. Malkani said. He pointed to a systematic review that included 28 studies of close to 28,000 people in 14 countries. The review found that people with diabetes have “inadequate oral health knowledge, poor oral health attitudes, and fewer dental visits, [and] rarely receive oral health education and dental referrals from their care providers.”

Social determinants of health have a “huge impact” on whether people will develop T2D and its related complications, including poor oral health, according to the National Clinical Care Commission Report presented to the US Congress in 2022. The commission was charged with making recommendations for federal policies and programs that could more effectively prevent and control diabetes and its complications.

The commission “approached its charge through the lens of a socioecological and an expanded chronic care model,” the report authors wrote. “It was clear that diabetes in the US cannot simply be viewed as a medical or healthcare problem but also must be addressed as a societal problem that cuts across many sectors, including food, housing, commerce, transportation, and the environment.”

Diabetes also is associated with higher dental costs, another factor affecting an individual’s ability to obtain care.

A recent questionnaire-based study from Denmark found that people with T2D were more likely than those without diabetes to rate their oral health as poor, and that the risk for self-rated poor oral health increased with lower educational attainment. Highest educational attainment and disposable household income were indicators of a high socioeconomic position, and a lower likelihood of rating their oral health as poor, again pointing out inequities.

The authors concluded that “diabetes and dental care providers should engage in multidisciplinary collaboration across healthcare sectors to ensure coherent treatment and management of diabetes.”

But such collaborations are easier said than done. “One of the challenges is our fragmented health system, where oral health and medical care are separate,” Dr. Gabbay said.

For the most part, the two are separate, Dr. Malkani agreed. “When we’re dealing with most complications of diabetes, like involvement of the heart or eyes or kidneys, we can have interdisciplinary care — everyone is within the overall discipline of medicine, and if I refer to a colleague in ophthalmology or a cardiologist or a vascular surgeon, they can all be within the same network from an insurance point of view, as well.”

But for dental care, referrals are interprofessional, not interdisciplinary. “I have to make sure that the patient has a dentist because dentists are usually not part of medical networks, and if the patient doesn’t have dental insurance, then cost and access can be a challenge.”

A recent systematic review from Australia on interprofessional education and interprofessional collaborative care found that more than a third of medical professionals were “ignorant” of the relationship between oral health and T2D. Furthermore, only 30% reported ever referring their patients for an oral health assessment. And there was little, if any, interprofessional collaborative care between medical and dental professionals while managing patients with T2D.

Treat the Teeth

“We always talk to our T2D patients about the importance of getting an eye exam, a foot exam, and a kidney test,” Dr. Malkani said. “But we also need to make sure that they’re going to the dentist. Normally, people get their teeth cleaned twice a year. But if you have diabetes and poor oral health, you might need to get your teeth cleaned every three months, and insurance often will pay for that.”

Furthermore, in keeping with the bidirectional connection, treating periodontitis can help glycemic control. The authors of a 2022 update of a Cochrane review on treating periodontitis for glycemic control wrote that they “doubled the number of included studies and participants” from the 2015 update to 35 studies randomizing 3249 participants to periodontal treatment or control. This “led to a change in our conclusions about the primary outcome of glycemic control and in our level of certainty in this conclusion.”

“We now have moderate‐certainty evidence that periodontal treatment using subgingival instrumentation improves glycemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment vs no treatment/usual care are unlikely to change the overall conclusion reached in this review.”

“Dentists also have a responsibility,” Dr. Malkani added. “If they see someone with severe gum disease or cavities, especially at a younger age, they need to tell that person to get their blood sugar checked and make sure they don’t have T2D.”

In fact, a recent review found that complications of T2D such as xerostomia and periodontal problems adversely affect well-being, and that “dentists can play an essential role in the awareness of diabetic patients about these problems and improve their quality of life.”

Key Stats

The US Centers for Disease Control and Prevention highlighted these facts about diabetes and oral health:

• Adults aged 20 years or older with diabetes are 40% more likely to have untreated cavities than similar adults without diabetes.
• About 60% of US adults with diabetes had a medical visit in the past year but no dental visit.
• Expanding healthcare coverage for periodontal treatment among people with diabetes could save each person about $6000 (2019 US dollars) over their lifetimes.
• Adults aged 50 years or older with diabetes lack functional dentition (have fewer than 20 teeth) 46% more often and have severe tooth loss (eight or fewer teeth) 56% more often than those without diabetes.
• Adults aged 50 years or older with diabetes are more likely to report that they have a hard time eating because of dental problems.
• Annual dental expenditures for an adult with diabetes are $77 (2017 US dollars) higher than for an adult without diabetes. This cost translates to $1.9 billion for the United States.

A version of this article appeared on Medscape.com.

Emerging evidence suggests that oral health, often overlooked by clinicians, is closely connected with overall health — and this connection has important consequences for individuals with type 2 diabetes (T2D). While most studies are observational and can’t prove cause and effect, the associations are robust enough for researchers to conclude that the connection is real.

Endocrinologists and other specialists, as well as primary care physicians, should ask about oral health, if not look in the mouth directly, experts say. “One of the most important things to ask people with diabetes is when their last dental visit was and if they have a follow-up,” said Robert Gabbay, MD, PhD, Chief Scientific and Medical Officer of the American Diabetes Association (ADA). The ADA advocates for attention to oral health through its 2024 standards of care.

Systemic Impact

“Periodontitis is a probable risk factor for various problems connected to the cardiovascular, pulmonary, endocrine, musculoskeletal, central nervous, and reproductive systems,” wrote the authors of a recent review on the effects of periodontitis on major organ systems. While not specific to the diabetes connection, the review pinpoints some of the latest evidence that “oral health affects overall health, and…dental health should never be considered a distinct, remote, and lower significant part of health.”

In line with this perspective, and looking specifically at T2D, a recent study of more than 17,000 patients with T2D participating in a screening program in Korea found that periodontitis and an increased number of teeth with cavities were independent risk factors for cerebral or myocardial infarction (adjusted hazard ratios, 1.17 and 1.67, respectively).

Dental disease and poor oral hygiene were also associated with an increased risk for heart failure among people with T2D in a large cohort study, and the authors suggested that managing oral health may prevent heart failure development.

A recent review suggested that periodontitis exacerbates and promotes the progression of chronic kidney disease, a disorder that affects 1 in 3 people with diabetes.

Studies also have shown that diabetes is associated with cognitive decline, and a review of oral health and dementia progression concluded, “collectively, experimental findings indicate that the connection between oral health and cognition cannot be underestimated.”

Bidirectional Effects

Research has shown that the association between periodontal disease and T2D is likely bidirectional, although there is little awareness of this two-way relationship among patients and providers.

A recent review of this bidirectional relationship focused on microvascular complications, oral microbiota, pro- and anti-inflammatory factors in T2D and periodontal disease and concluded that “these two diseases require specific/complementary therapeutic solutions when they occur in association, with new clinical trials and epidemiological research being necessary for better control of this interdependent pathogenic topic.”

Yet an Australian study showed that 54% of 241 participants in a survey never received any information regarding the bidirectional relationship between periodontal disease and diabetes and lacked understanding of the association.

What’s the Mechanism?

How does T2D affect the teeth and vice versa? “Basically, people with T2D have high blood sugar, and the sugar comes out in the saliva and that promotes bacterial growth in the mouth and plaque formation on the teeth and gum disease,” Samir Malkani, MD, clinical chief of endocrinology and diabetes at UMass Chan School of Medicine in Worcester, Massachusetts, told this news organization.

“Patients get gingivitis, they get periodontitis, and since the gums and the jaw are a single unit, if the gum disease gets very severe, then there’s loss of jawbone and the teeth could fall out,” he said. There’s also inflammation in the mouth, and “when you have generalized inflammation, it affects the whole body.”

Recent research in Europe suggested that “although the mechanisms behind these associations are partially unclear, poor oral health is probably sustaining systemic inflammation.” Common oral infections, periodontal disease, and cavities are associated with inflammatory metabolic profiles related to an increased risk for cardiometabolic diseases, and they predict future adverse changes in metabolic profiles, according to the authors.

Awareness, Accessibility, Collaboration

Despite the evidence, the connection between oral health and diabetes (any type) is not front of mind with clinicians or patients, Dr. Malkani said. He pointed to a systematic review that included 28 studies of close to 28,000 people in 14 countries. The review found that people with diabetes have “inadequate oral health knowledge, poor oral health attitudes, and fewer dental visits, [and] rarely receive oral health education and dental referrals from their care providers.”

Social determinants of health have a “huge impact” on whether people will develop T2D and its related complications, including poor oral health, according to the National Clinical Care Commission Report presented to the US Congress in 2022. The commission was charged with making recommendations for federal policies and programs that could more effectively prevent and control diabetes and its complications.

The commission “approached its charge through the lens of a socioecological and an expanded chronic care model,” the report authors wrote. “It was clear that diabetes in the US cannot simply be viewed as a medical or healthcare problem but also must be addressed as a societal problem that cuts across many sectors, including food, housing, commerce, transportation, and the environment.”

Diabetes also is associated with higher dental costs, another factor affecting an individual’s ability to obtain care.

A recent questionnaire-based study from Denmark found that people with T2D were more likely than those without diabetes to rate their oral health as poor, and that the risk for self-rated poor oral health increased with lower educational attainment. Highest educational attainment and disposable household income were indicators of a high socioeconomic position, and a lower likelihood of rating their oral health as poor, again pointing out inequities.

The authors concluded that “diabetes and dental care providers should engage in multidisciplinary collaboration across healthcare sectors to ensure coherent treatment and management of diabetes.”

But such collaborations are easier said than done. “One of the challenges is our fragmented health system, where oral health and medical care are separate,” Dr. Gabbay said.

For the most part, the two are separate, Dr. Malkani agreed. “When we’re dealing with most complications of diabetes, like involvement of the heart or eyes or kidneys, we can have interdisciplinary care — everyone is within the overall discipline of medicine, and if I refer to a colleague in ophthalmology or a cardiologist or a vascular surgeon, they can all be within the same network from an insurance point of view, as well.”

But for dental care, referrals are interprofessional, not interdisciplinary. “I have to make sure that the patient has a dentist because dentists are usually not part of medical networks, and if the patient doesn’t have dental insurance, then cost and access can be a challenge.”

A recent systematic review from Australia on interprofessional education and interprofessional collaborative care found that more than a third of medical professionals were “ignorant” of the relationship between oral health and T2D. Furthermore, only 30% reported ever referring their patients for an oral health assessment. And there was little, if any, interprofessional collaborative care between medical and dental professionals while managing patients with T2D.

Treat the Teeth

“We always talk to our T2D patients about the importance of getting an eye exam, a foot exam, and a kidney test,” Dr. Malkani said. “But we also need to make sure that they’re going to the dentist. Normally, people get their teeth cleaned twice a year. But if you have diabetes and poor oral health, you might need to get your teeth cleaned every three months, and insurance often will pay for that.”

Furthermore, in keeping with the bidirectional connection, treating periodontitis can help glycemic control. The authors of a 2022 update of a Cochrane review on treating periodontitis for glycemic control wrote that they “doubled the number of included studies and participants” from the 2015 update to 35 studies randomizing 3249 participants to periodontal treatment or control. This “led to a change in our conclusions about the primary outcome of glycemic control and in our level of certainty in this conclusion.”

“We now have moderate‐certainty evidence that periodontal treatment using subgingival instrumentation improves glycemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment vs no treatment/usual care are unlikely to change the overall conclusion reached in this review.”

“Dentists also have a responsibility,” Dr. Malkani added. “If they see someone with severe gum disease or cavities, especially at a younger age, they need to tell that person to get their blood sugar checked and make sure they don’t have T2D.”

In fact, a recent review found that complications of T2D such as xerostomia and periodontal problems adversely affect well-being, and that “dentists can play an essential role in the awareness of diabetic patients about these problems and improve their quality of life.”

Key Stats

The US Centers for Disease Control and Prevention highlighted these facts about diabetes and oral health:

• Adults aged 20 years or older with diabetes are 40% more likely to have untreated cavities than similar adults without diabetes.
• About 60% of US adults with diabetes had a medical visit in the past year but no dental visit.
• Expanding healthcare coverage for periodontal treatment among people with diabetes could save each person about $6000 (2019 US dollars) over their lifetimes.
• Adults aged 50 years or older with diabetes lack functional dentition (have fewer than 20 teeth) 46% more often and have severe tooth loss (eight or fewer teeth) 56% more often than those without diabetes.
• Adults aged 50 years or older with diabetes are more likely to report that they have a hard time eating because of dental problems.
• Annual dental expenditures for an adult with diabetes are $77 (2017 US dollars) higher than for an adult without diabetes. This cost translates to $1.9 billion for the United States.

A version of this article appeared on Medscape.com.

TOPLINE:

Specific microbes may distinguish the pathogenesis of young-onset colorectal cancer (yoCRC) from average-onset colorectal cancer (aoCRC) and could serve as preventive, diagnostic, and therapeutic targets.

METHODOLOGY:

• The study population was drawn from patients who underwent surgical resection of the primary colorectal tumor at a single center from 2000 to 2020.
• yoCRC was defined as CRC diagnosed before age 50 years, and aoCRC was defined as CRC diagnosed after age 60 years. Patients aged between 50 and 60 years at diagnosis were excluded to ensure two distinct cohorts for meaningful comparison.
• Researchers used various gene sequencing technologies to compare tissue samples from 136 patients with yoCRC against samples from 140 patients with aoCRC.

TAKEAWAY:

• Patients with yoCRC vs those with aoCRC were more likely to have left-sided (72.8% vs 54.3%), rectal (36.7% vs 25%), and stage IV (28% vs 15%) tumors.
• yoCRC and aoCRC tumors had distinct microbial profiles associated with tumor location, sidedness, and stage, and obesity.
• yoCRC tumors had significantly higher microbial alpha diversity and varied beta diversity than aoCRC tumors.
• yoCRC tumors were enriched with Akkermansia and Bacteroides, whereas aoCRC tumors showed greater relative abundances of Bacillus, Staphylococcus, Listeria, Enterococcus, Pseudomonas, Fusobacterium, and Escherichia/Shigella.
• In yoCRC, Fusobacterium and Akkermansia abundance correlated with overall survival.

IN PRACTICE:

“[O]ur findings help to comprehensively define the microbial community that may play a role in young-onset colorectal oncogenesis [and] should encourage the evaluation of environmental and lifestyle risk factors that might contribute to microbial dysbiosis in this patient population,” the authors wrote.

SOURCE:

The study, led by Shimoli V. Barot, MD, Cleveland Clinic, Ohio was published online in eBioMedicine.

LIMITATIONS:

The study had several limitations. It was a single-institution retrospective study with limited diversity in terms of race/ethnicity. Smoking and aspirin use were higher among older participants, whereas the yoCRC group had higher rates of neoadjuvant therapy and metastesectomy. Data on factors affecting the microbiome around the time of specimen collection, such as diet, stress, and antibiotic and probiotic use, were limited and not adjusted for in the analysis.

DISCLOSURES:

The study was funded by the Sondra and Stephen Hardis Chair in Oncology Research. Two coauthors report fees and research funding from industry. Barot and the other coauthors report no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Specific microbes may distinguish the pathogenesis of young-onset colorectal cancer (yoCRC) from average-onset colorectal cancer (aoCRC) and could serve as preventive, diagnostic, and therapeutic targets.

METHODOLOGY:

• The study population was drawn from patients who underwent surgical resection of the primary colorectal tumor at a single center from 2000 to 2020.
• yoCRC was defined as CRC diagnosed before age 50 years, and aoCRC was defined as CRC diagnosed after age 60 years. Patients aged between 50 and 60 years at diagnosis were excluded to ensure two distinct cohorts for meaningful comparison.
• Researchers used various gene sequencing technologies to compare tissue samples from 136 patients with yoCRC against samples from 140 patients with aoCRC.

TAKEAWAY:

• Patients with yoCRC vs those with aoCRC were more likely to have left-sided (72.8% vs 54.3%), rectal (36.7% vs 25%), and stage IV (28% vs 15%) tumors.
• yoCRC and aoCRC tumors had distinct microbial profiles associated with tumor location, sidedness, and stage, and obesity.
• yoCRC tumors had significantly higher microbial alpha diversity and varied beta diversity than aoCRC tumors.
• yoCRC tumors were enriched with Akkermansia and Bacteroides, whereas aoCRC tumors showed greater relative abundances of Bacillus, Staphylococcus, Listeria, Enterococcus, Pseudomonas, Fusobacterium, and Escherichia/Shigella.
• In yoCRC, Fusobacterium and Akkermansia abundance correlated with overall survival.

IN PRACTICE:

“[O]ur findings help to comprehensively define the microbial community that may play a role in young-onset colorectal oncogenesis [and] should encourage the evaluation of environmental and lifestyle risk factors that might contribute to microbial dysbiosis in this patient population,” the authors wrote.

SOURCE:

The study, led by Shimoli V. Barot, MD, Cleveland Clinic, Ohio was published online in eBioMedicine.

LIMITATIONS:

The study had several limitations. It was a single-institution retrospective study with limited diversity in terms of race/ethnicity. Smoking and aspirin use were higher among older participants, whereas the yoCRC group had higher rates of neoadjuvant therapy and metastesectomy. Data on factors affecting the microbiome around the time of specimen collection, such as diet, stress, and antibiotic and probiotic use, were limited and not adjusted for in the analysis.

DISCLOSURES:

The study was funded by the Sondra and Stephen Hardis Chair in Oncology Research. Two coauthors report fees and research funding from industry. Barot and the other coauthors report no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Specific microbes may distinguish the pathogenesis of young-onset colorectal cancer (yoCRC) from average-onset colorectal cancer (aoCRC) and could serve as preventive, diagnostic, and therapeutic targets.

METHODOLOGY:

• The study population was drawn from patients who underwent surgical resection of the primary colorectal tumor at a single center from 2000 to 2020.
• yoCRC was defined as CRC diagnosed before age 50 years, and aoCRC was defined as CRC diagnosed after age 60 years. Patients aged between 50 and 60 years at diagnosis were excluded to ensure two distinct cohorts for meaningful comparison.
• Researchers used various gene sequencing technologies to compare tissue samples from 136 patients with yoCRC against samples from 140 patients with aoCRC.

TAKEAWAY:

• Patients with yoCRC vs those with aoCRC were more likely to have left-sided (72.8% vs 54.3%), rectal (36.7% vs 25%), and stage IV (28% vs 15%) tumors.
• yoCRC and aoCRC tumors had distinct microbial profiles associated with tumor location, sidedness, and stage, and obesity.
• yoCRC tumors had significantly higher microbial alpha diversity and varied beta diversity than aoCRC tumors.
• yoCRC tumors were enriched with Akkermansia and Bacteroides, whereas aoCRC tumors showed greater relative abundances of Bacillus, Staphylococcus, Listeria, Enterococcus, Pseudomonas, Fusobacterium, and Escherichia/Shigella.
• In yoCRC, Fusobacterium and Akkermansia abundance correlated with overall survival.

IN PRACTICE:

“[O]ur findings help to comprehensively define the microbial community that may play a role in young-onset colorectal oncogenesis [and] should encourage the evaluation of environmental and lifestyle risk factors that might contribute to microbial dysbiosis in this patient population,” the authors wrote.

SOURCE:

The study, led by Shimoli V. Barot, MD, Cleveland Clinic, Ohio was published online in eBioMedicine.

LIMITATIONS:

The study had several limitations. It was a single-institution retrospective study with limited diversity in terms of race/ethnicity. Smoking and aspirin use were higher among older participants, whereas the yoCRC group had higher rates of neoadjuvant therapy and metastesectomy. Data on factors affecting the microbiome around the time of specimen collection, such as diet, stress, and antibiotic and probiotic use, were limited and not adjusted for in the analysis.

DISCLOSURES:

The study was funded by the Sondra and Stephen Hardis Chair in Oncology Research. Two coauthors report fees and research funding from industry. Barot and the other coauthors report no conflicts of interest.
 

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Women with steatotic liver disease (SLD) related to alcohol consumption are at greater risk of mortality than men with the same condition, new research suggested.

METHODOLOGY:

• Researchers analyzed data from the US National Health and Nutrition Examination Survey III (NHANES III, 1988-1994), which included standardized ultrasonographic measures of hepatic steatosis, assessment of cardiometabolic risk traits, and questionnaire data on alcohol intake.
• Among 10,007 participants aged 20 years and older (mean age, 42 years; 50.3% men) who were included and followed for a median of 26.7 years, 1461 had metabolic dysfunction–associated steatotic liver disease (MASLD), 105 alcohol-related liver disease (ALD), 225 metabolic dysfunction-associated and alcohol-related liver disease (MetALD), 180 other types of SLD, and 8036 no SLD.
• Researchers examined SLD-associated risks for all-cause mortality after adjustment for baseline age, smoking status, systolic blood pressure, antihypertensives, type 2 diabetes, diabetic medication use, body mass index, total cholesterol, high-density lipoprotein cholesterol, lipid-lowering therapy, race, and family income.

TAKEAWAY:

• In men, the prevalence of MASLD, MetALD, and ALD was 18.5%, 3.2%, and 1.7%, respectively, whereas the corresponding prevalence among women was 10.3%, 1.2%, and 0.3%, respectively.
• In multivariable-adjusted survival analyses, MASLD was not significantly associated with all-cause mortality for either sex compared with those without SLD.
• In contrast, MetALD was associated with an 83% higher hazard of all-cause mortality in women (hazard ratio [HR], 1.83), but not significantly associated with mortality in men.
• ALD was significantly associated with all-cause mortality in both sexes, with a greater magnitude in women than men (HRs, 3.49 vs 1.89, respectively) — the equivalent of about a 160% higher mortality risk for women.
• With regard to SLD severity, the trend across worsening phenotypes (ie, MASLD, MetALD, or ALD) was significant for sex differences in mortality but not in prevalence.

IN PRACTICE:

“Because alcohol consumption is modifiable, limiting alcohol intake particularly in women at risk for SLD could be critical as part of efforts to mitigate mortality risk in patients with SLD,” the authors wrote.

SOURCE:

The study, led by Hongwei Ji of Qingdao University, Qingdao, Shandong, China, and Susan Cheng, MD, Cedars-Sinai Medical Center, Los Angeles, was published in the February issue of Journal of Hepatology.

LIMITATIONS:

The study data came from NHANES III, which was conducted between 1988 and 1994. This is a potential limitation, as the prevalence of metabolic dysfunction and alcohol use may have changed since then.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China, the Taishan Scholar Program of Shandong Province, the Shandong Provincial Natural Science Foundation, the National Institutes of Health, and the NIH National Center for Advancing Translational Sciences UCLA Clinical and Translational Research Center. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with steatotic liver disease (SLD) related to alcohol consumption are at greater risk of mortality than men with the same condition, new research suggested.

METHODOLOGY:

• Researchers analyzed data from the US National Health and Nutrition Examination Survey III (NHANES III, 1988-1994), which included standardized ultrasonographic measures of hepatic steatosis, assessment of cardiometabolic risk traits, and questionnaire data on alcohol intake.
• Among 10,007 participants aged 20 years and older (mean age, 42 years; 50.3% men) who were included and followed for a median of 26.7 years, 1461 had metabolic dysfunction–associated steatotic liver disease (MASLD), 105 alcohol-related liver disease (ALD), 225 metabolic dysfunction-associated and alcohol-related liver disease (MetALD), 180 other types of SLD, and 8036 no SLD.
• Researchers examined SLD-associated risks for all-cause mortality after adjustment for baseline age, smoking status, systolic blood pressure, antihypertensives, type 2 diabetes, diabetic medication use, body mass index, total cholesterol, high-density lipoprotein cholesterol, lipid-lowering therapy, race, and family income.

TAKEAWAY:

• In men, the prevalence of MASLD, MetALD, and ALD was 18.5%, 3.2%, and 1.7%, respectively, whereas the corresponding prevalence among women was 10.3%, 1.2%, and 0.3%, respectively.
• In multivariable-adjusted survival analyses, MASLD was not significantly associated with all-cause mortality for either sex compared with those without SLD.
• In contrast, MetALD was associated with an 83% higher hazard of all-cause mortality in women (hazard ratio [HR], 1.83), but not significantly associated with mortality in men.
• ALD was significantly associated with all-cause mortality in both sexes, with a greater magnitude in women than men (HRs, 3.49 vs 1.89, respectively) — the equivalent of about a 160% higher mortality risk for women.
• With regard to SLD severity, the trend across worsening phenotypes (ie, MASLD, MetALD, or ALD) was significant for sex differences in mortality but not in prevalence.

IN PRACTICE:

“Because alcohol consumption is modifiable, limiting alcohol intake particularly in women at risk for SLD could be critical as part of efforts to mitigate mortality risk in patients with SLD,” the authors wrote.

SOURCE:

The study, led by Hongwei Ji of Qingdao University, Qingdao, Shandong, China, and Susan Cheng, MD, Cedars-Sinai Medical Center, Los Angeles, was published in the February issue of Journal of Hepatology.

LIMITATIONS:

The study data came from NHANES III, which was conducted between 1988 and 1994. This is a potential limitation, as the prevalence of metabolic dysfunction and alcohol use may have changed since then.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China, the Taishan Scholar Program of Shandong Province, the Shandong Provincial Natural Science Foundation, the National Institutes of Health, and the NIH National Center for Advancing Translational Sciences UCLA Clinical and Translational Research Center. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with steatotic liver disease (SLD) related to alcohol consumption are at greater risk of mortality than men with the same condition, new research suggested.

METHODOLOGY:

• Researchers analyzed data from the US National Health and Nutrition Examination Survey III (NHANES III, 1988-1994), which included standardized ultrasonographic measures of hepatic steatosis, assessment of cardiometabolic risk traits, and questionnaire data on alcohol intake.
• Among 10,007 participants aged 20 years and older (mean age, 42 years; 50.3% men) who were included and followed for a median of 26.7 years, 1461 had metabolic dysfunction–associated steatotic liver disease (MASLD), 105 alcohol-related liver disease (ALD), 225 metabolic dysfunction-associated and alcohol-related liver disease (MetALD), 180 other types of SLD, and 8036 no SLD.
• Researchers examined SLD-associated risks for all-cause mortality after adjustment for baseline age, smoking status, systolic blood pressure, antihypertensives, type 2 diabetes, diabetic medication use, body mass index, total cholesterol, high-density lipoprotein cholesterol, lipid-lowering therapy, race, and family income.

TAKEAWAY:

• In men, the prevalence of MASLD, MetALD, and ALD was 18.5%, 3.2%, and 1.7%, respectively, whereas the corresponding prevalence among women was 10.3%, 1.2%, and 0.3%, respectively.
• In multivariable-adjusted survival analyses, MASLD was not significantly associated with all-cause mortality for either sex compared with those without SLD.
• In contrast, MetALD was associated with an 83% higher hazard of all-cause mortality in women (hazard ratio [HR], 1.83), but not significantly associated with mortality in men.
• ALD was significantly associated with all-cause mortality in both sexes, with a greater magnitude in women than men (HRs, 3.49 vs 1.89, respectively) — the equivalent of about a 160% higher mortality risk for women.
• With regard to SLD severity, the trend across worsening phenotypes (ie, MASLD, MetALD, or ALD) was significant for sex differences in mortality but not in prevalence.

IN PRACTICE:

“Because alcohol consumption is modifiable, limiting alcohol intake particularly in women at risk for SLD could be critical as part of efforts to mitigate mortality risk in patients with SLD,” the authors wrote.

SOURCE:

The study, led by Hongwei Ji of Qingdao University, Qingdao, Shandong, China, and Susan Cheng, MD, Cedars-Sinai Medical Center, Los Angeles, was published in the February issue of Journal of Hepatology.

LIMITATIONS:

The study data came from NHANES III, which was conducted between 1988 and 1994. This is a potential limitation, as the prevalence of metabolic dysfunction and alcohol use may have changed since then.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China, the Taishan Scholar Program of Shandong Province, the Shandong Provincial Natural Science Foundation, the National Institutes of Health, and the NIH National Center for Advancing Translational Sciences UCLA Clinical and Translational Research Center. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Two breakdown products from excess niacin, called 2PY and 4PY, were strongly associated with myocardial infarction, stroke, and other adverse cardiac events, suggesting that niacin supplementation may require a more “nuanced, titrated approach,” researchers said.

METHODOLOGY:

• Investigators performed an untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort of 1162 individuals (36% women).
• Additional analyses were performed in a US validation cohort, including measurement of soluble vascular adhesion molecule-1 (sVCAM-1), and on archival fasting samples from patients in a European validation cohort undergoing diagnostic coronary angiography.
• Genetic analyses of samples from the UK Biobank were used to test the association with sVCAM-1 levels of a genetic variant, rs10496731, which was significantly associated with both N1-methyl-2-pyridone-5-carboxamide (2 PY) and N1-methyl-4-pyridone-3-carboxamide (4PY) levels.

TAKEAWAY:

• Niacin metabolism was associated with incident major adverse cardiovascular events (MACE).
• Plasma levels of the terminal metabolites of excess niacin, 2PY and 4PY, were associated with increased 3-year MACE risk in two validation cohorts (US: 2331 total, 33% women; European: 832 total, 30% women), with adjusted hazard ratios for 2PY of 1.64 and 2.02, respectively, and for 4PY, 1.89 and 1.99.
• The genetic variant rs10496731 was significantly associated with levels of sVCAM-1.
• Treatment with physiological levels of 4PY, but not 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice, suggesting an inflammation-dependent mechanism underlying the clinical association of 4PY, in particular, with MACE.
• In functional testing, a physiological level of 4PY, but not 2PY, provoked messenger RNA and protein expression of VCAM-1 on human endothelial cells.

IN PRACTICE:

“Total niacin consumption in the US averaged 48 mg/d from 2017 to 2020 — more than triple the Recommended Daily Allowance — and 2PY and 4PY were also increased by nicotinamideriboside and nicotinamide mononucleotide, both of which are commonly sold supplements with claimed antiaging benefits,” the authors noted.

“The present studies suggest that niacin pool supplementation may optimally require a more nuanced, titrated approach to achieve intended health benefits,” while not fostering excess 4PY generation.

SOURCE:

Stanley Hazen, MD, PhD, of Cleveland Clinic, Cleveland, Ohio, was the principal author of the study, published online in Nature Medicine.

LIMITATIONS:

Measurement of 2PY and 4PY in the validation cohorts was performed only once, whereas serial measures might have provided enhanced prognostic value for incident cardiovascular disease (CVD) risks. Cohorts were recruited at quaternary referral centers and showed a high prevalence of CVD and cardiometabolic disease risk factors. Although the meta-analysis of the community-based genomic (Biobank) studies showed a link between 4PY and VCAM-1 expression in multiple ethnic groups, the clinical studies linking 4PY to CVD events were based on high-risk European ancestry populations in the US and European cohorts.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health (NIH; both the National Heart, Lung, and Blood Institute and the Office of Dietary Supplements: A), Pilot Project Programs of the USC Center for Genetic Epidemiology and Southern California Environmental Health Sciences Center, and the Deutsche Forschungsgemeinschaft. One co-author was supported, in part, by NIH training grants; another was a participant in the BIH-Charité Advanced Clinician Scientist Program funded by Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. The LipidCardio study [validation cohort] was partially supported by Sanofi-Aventis Deutschland GmbH. The UK Biobank Resource provided access to their data. Dr. Hazen and a co-author reported being coinventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, and Dr. Hazen and two co-authors received funds from industry.

A version of the article appeared on Medscape.com.

TOPLINE:

Two breakdown products from excess niacin, called 2PY and 4PY, were strongly associated with myocardial infarction, stroke, and other adverse cardiac events, suggesting that niacin supplementation may require a more “nuanced, titrated approach,” researchers said.

METHODOLOGY:

• Investigators performed an untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort of 1162 individuals (36% women).
• Additional analyses were performed in a US validation cohort, including measurement of soluble vascular adhesion molecule-1 (sVCAM-1), and on archival fasting samples from patients in a European validation cohort undergoing diagnostic coronary angiography.
• Genetic analyses of samples from the UK Biobank were used to test the association with sVCAM-1 levels of a genetic variant, rs10496731, which was significantly associated with both N1-methyl-2-pyridone-5-carboxamide (2 PY) and N1-methyl-4-pyridone-3-carboxamide (4PY) levels.

TAKEAWAY:

• Niacin metabolism was associated with incident major adverse cardiovascular events (MACE).
• Plasma levels of the terminal metabolites of excess niacin, 2PY and 4PY, were associated with increased 3-year MACE risk in two validation cohorts (US: 2331 total, 33% women; European: 832 total, 30% women), with adjusted hazard ratios for 2PY of 1.64 and 2.02, respectively, and for 4PY, 1.89 and 1.99.
• The genetic variant rs10496731 was significantly associated with levels of sVCAM-1.
• Treatment with physiological levels of 4PY, but not 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice, suggesting an inflammation-dependent mechanism underlying the clinical association of 4PY, in particular, with MACE.
• In functional testing, a physiological level of 4PY, but not 2PY, provoked messenger RNA and protein expression of VCAM-1 on human endothelial cells.

IN PRACTICE:

“Total niacin consumption in the US averaged 48 mg/d from 2017 to 2020 — more than triple the Recommended Daily Allowance — and 2PY and 4PY were also increased by nicotinamideriboside and nicotinamide mononucleotide, both of which are commonly sold supplements with claimed antiaging benefits,” the authors noted.

“The present studies suggest that niacin pool supplementation may optimally require a more nuanced, titrated approach to achieve intended health benefits,” while not fostering excess 4PY generation.

SOURCE:

Stanley Hazen, MD, PhD, of Cleveland Clinic, Cleveland, Ohio, was the principal author of the study, published online in Nature Medicine.

LIMITATIONS:

Measurement of 2PY and 4PY in the validation cohorts was performed only once, whereas serial measures might have provided enhanced prognostic value for incident cardiovascular disease (CVD) risks. Cohorts were recruited at quaternary referral centers and showed a high prevalence of CVD and cardiometabolic disease risk factors. Although the meta-analysis of the community-based genomic (Biobank) studies showed a link between 4PY and VCAM-1 expression in multiple ethnic groups, the clinical studies linking 4PY to CVD events were based on high-risk European ancestry populations in the US and European cohorts.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health (NIH; both the National Heart, Lung, and Blood Institute and the Office of Dietary Supplements: A), Pilot Project Programs of the USC Center for Genetic Epidemiology and Southern California Environmental Health Sciences Center, and the Deutsche Forschungsgemeinschaft. One co-author was supported, in part, by NIH training grants; another was a participant in the BIH-Charité Advanced Clinician Scientist Program funded by Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. The LipidCardio study [validation cohort] was partially supported by Sanofi-Aventis Deutschland GmbH. The UK Biobank Resource provided access to their data. Dr. Hazen and a co-author reported being coinventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, and Dr. Hazen and two co-authors received funds from industry.

A version of the article appeared on Medscape.com.

TOPLINE:

Two breakdown products from excess niacin, called 2PY and 4PY, were strongly associated with myocardial infarction, stroke, and other adverse cardiac events, suggesting that niacin supplementation may require a more “nuanced, titrated approach,” researchers said.

METHODOLOGY:

• Investigators performed an untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort of 1162 individuals (36% women).
• Additional analyses were performed in a US validation cohort, including measurement of soluble vascular adhesion molecule-1 (sVCAM-1), and on archival fasting samples from patients in a European validation cohort undergoing diagnostic coronary angiography.
• Genetic analyses of samples from the UK Biobank were used to test the association with sVCAM-1 levels of a genetic variant, rs10496731, which was significantly associated with both N1-methyl-2-pyridone-5-carboxamide (2 PY) and N1-methyl-4-pyridone-3-carboxamide (4PY) levels.

TAKEAWAY:

• Niacin metabolism was associated with incident major adverse cardiovascular events (MACE).
• Plasma levels of the terminal metabolites of excess niacin, 2PY and 4PY, were associated with increased 3-year MACE risk in two validation cohorts (US: 2331 total, 33% women; European: 832 total, 30% women), with adjusted hazard ratios for 2PY of 1.64 and 2.02, respectively, and for 4PY, 1.89 and 1.99.
• The genetic variant rs10496731 was significantly associated with levels of sVCAM-1.
• Treatment with physiological levels of 4PY, but not 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice, suggesting an inflammation-dependent mechanism underlying the clinical association of 4PY, in particular, with MACE.
• In functional testing, a physiological level of 4PY, but not 2PY, provoked messenger RNA and protein expression of VCAM-1 on human endothelial cells.

IN PRACTICE:

“Total niacin consumption in the US averaged 48 mg/d from 2017 to 2020 — more than triple the Recommended Daily Allowance — and 2PY and 4PY were also increased by nicotinamideriboside and nicotinamide mononucleotide, both of which are commonly sold supplements with claimed antiaging benefits,” the authors noted.

“The present studies suggest that niacin pool supplementation may optimally require a more nuanced, titrated approach to achieve intended health benefits,” while not fostering excess 4PY generation.

SOURCE:

Stanley Hazen, MD, PhD, of Cleveland Clinic, Cleveland, Ohio, was the principal author of the study, published online in Nature Medicine.

LIMITATIONS:

Measurement of 2PY and 4PY in the validation cohorts was performed only once, whereas serial measures might have provided enhanced prognostic value for incident cardiovascular disease (CVD) risks. Cohorts were recruited at quaternary referral centers and showed a high prevalence of CVD and cardiometabolic disease risk factors. Although the meta-analysis of the community-based genomic (Biobank) studies showed a link between 4PY and VCAM-1 expression in multiple ethnic groups, the clinical studies linking 4PY to CVD events were based on high-risk European ancestry populations in the US and European cohorts.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health (NIH; both the National Heart, Lung, and Blood Institute and the Office of Dietary Supplements: A), Pilot Project Programs of the USC Center for Genetic Epidemiology and Southern California Environmental Health Sciences Center, and the Deutsche Forschungsgemeinschaft. One co-author was supported, in part, by NIH training grants; another was a participant in the BIH-Charité Advanced Clinician Scientist Program funded by Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. The LipidCardio study [validation cohort] was partially supported by Sanofi-Aventis Deutschland GmbH. The UK Biobank Resource provided access to their data. Dr. Hazen and a co-author reported being coinventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, and Dr. Hazen and two co-authors received funds from industry.

A version of the article appeared on Medscape.com.

Cognitive impairment in some US veterans may be due to treatable hepatic encephalopathy (HE) rather than dementia, new research suggested.

From 5%-10% of veterans diagnosed with dementia had possible undiagnosed cirrhosis, implicating HE as a contributor to cognitive impairment, found the study by Jasmohan S. Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Virginia, and colleagues.

The research was prompted, in part, by an earlier case study by Dr. Bajaj and colleagues that showed that two older men diagnosed with dementia and Parkinson’s disease actually had HE, meaning their symptoms were due to advanced but treatable liver disease.

“Once they were properly diagnosed, whatever had been considered dementia was gone,” Dr. Bajaj said. “The spouse of one man said, ‘My husband is a different person now.’ It’s not that clinicians don’t know how to treat HE; the problem was that they did not suspect it.”

Among veterans with cirrhosis, concomitant dementia is common and is difficult to distinguish from HE, but the extent to which patients with dementia also have undiagnosed cirrhosis and HE is unknown, the authors of the current study wrote. “Undiagnosed cirrhosis among veterans with dementia could raise the possibility that part of their cognitive impairment may be due to reversible HE,” they added.

To investigate, the researchers examined the prevalence and risk factors of undiagnosed cirrhosis — and therefore, possible HE — among US veterans.

The study was published online in JAMA Network Open.
 

Dementia or Cirrhosis?

Using the VHA Corporate Data Warehouse, researchers analyzed medical records of 177,422 US veterans diagnosed with dementia but not cirrhosis between 2009 and 2019 and with sufficient laboratory test results to calculate their Fibrosis-4 (FIB-4) scores. The mean age was 78.35 years, 97.1% were men, and 80.7% were White individuals.

The FIB-4 score for each patient was calculated using the most recent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels or values and platelet values that were closest to the index date during the two years after the index dementia date.

Age is in the numerator of the FIB-4 score calculation; hence, higher age could lead to an erroneously high FIB-4 score, the authors noted. Therefore, for patients older than 65 years, the researchers entered 65 years as an input variable, rather than the actual age.

A FIB-4 score > 2.67 was suggestive of advanced fibrosis, whereas a score > 3.25 was suggestive of cirrhosis. 

A total of 18,390 (10.3%) veterans had a FIB-4 score > 2.67, and 9373 (5.3%) had a FIB-4 score > 3.25.

In multivariable logistic regression models, a FIB-4 score > 3.25 was associated with older age (odds ratio [OR], 1.07), male sex (OR, 1.43), congestive heart failure (OR, 1.48), viral hepatitis (OR, 1.79), an Alcohol Use Disorders Identification Test score showing problem drinking (OR, 1.56), and chronic kidney disease (OR, 1.11).

In contrast, a FIB-4 score > 3.25 was inversely associated with the White race (OR, 0.79), diabetes (OR, 0.78), hyperlipidemia (OR, 0.84), stroke (OR, 0.85), tobacco use disorder (OR, 0.78), and rural residence (OR, 0.92).

Similar findings were associated with the FIB-4 greater than 2.67 threshold.

In a follow-up validation study among 89 veterans diagnosed with dementia at a single center, the researchers found similar results: 4.4%-11.2% of participants had high FIB-4 scores, suggestive of HE.

After investigating further, they concluded that 5% of patients in that cohort had reasons other than cirrhosis for their high FIB-4 scores. The remaining patients (95%) had evidence of cirrhosis, had risk factors, and/or had no other explanation for their high FIB-4 scores.

“The combination of high FIB-4 scores and other risk factors for liver disease in patients with dementia raises the possibility that reversible HE could be a factor associated with cognitive impairment,” the authors wrote. “These findings highlight the potential to enhance cognitive function and quality of life by increasing awareness of risk factors and diagnostic indicators of advanced liver disease that may be associated with HE as a factor or as a differential diagnosis of dementia among clinicians other than liver specialists.”
 

FIB-4 Screening Advised

“An elderly patient with cirrhosis used to be an oxymoron, because we never used to have people who lived this long or were diagnosed this late with cirrhosis,” Dr. Bajaj told this news organization. “It’s a good problem to have because people are now living longer, but it also means that we need to have every single person who is taking care of patients with what is deemed to be dementia know that the patient could also have an element of encephalopathy.”

Increased awareness is important because, unlike dementia, encephalopathy is very easily treated, Dr. Bajaj said. “The biggest, easiest, correctable cause is to figure out if they have severe liver disease, and if that’s the case, your friendly neighborhood gastroenterologist is waiting for you,” he added.

The finding that cirrhosis was present in 95% of patients in the validation cohort is “very impressive, as they had excluded from the consideration all those with obvious cirrhosis before the FIB-4 was done,” said William Carey, MD, acting hepatology section head in the Department of Gastroenterology, Hepatology and Nutrition at Cleveland Clinic’s Digestive Disease Institute in Ohio. “This validates FIB-4 as a powerful tool for cirrhosis case-finding.” 

Ordering a FIB-4 “is within the skill set of every healthcare provider,” Dr. Carey, who was not involved in the study, told this news organization. “Patients with altered mental status, including suspected or proven dementia, should be screened for possible cirrhosis, as future management will change. Those with elevated FIB-4 results should also be tested for possible HE and treated if it is present.”

The study was partly funded by VA Merit Review grants to Dr. Bajaj. Dr. Bajaj reported receiving grants from Bausch, Grifols, Sequana, and Mallinckrodt outside the submitted work. Dr. Carey reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Cognitive impairment in some US veterans may be due to treatable hepatic encephalopathy (HE) rather than dementia, new research suggested.

From 5%-10% of veterans diagnosed with dementia had possible undiagnosed cirrhosis, implicating HE as a contributor to cognitive impairment, found the study by Jasmohan S. Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Virginia, and colleagues.

The research was prompted, in part, by an earlier case study by Dr. Bajaj and colleagues that showed that two older men diagnosed with dementia and Parkinson’s disease actually had HE, meaning their symptoms were due to advanced but treatable liver disease.

“Once they were properly diagnosed, whatever had been considered dementia was gone,” Dr. Bajaj said. “The spouse of one man said, ‘My husband is a different person now.’ It’s not that clinicians don’t know how to treat HE; the problem was that they did not suspect it.”

Among veterans with cirrhosis, concomitant dementia is common and is difficult to distinguish from HE, but the extent to which patients with dementia also have undiagnosed cirrhosis and HE is unknown, the authors of the current study wrote. “Undiagnosed cirrhosis among veterans with dementia could raise the possibility that part of their cognitive impairment may be due to reversible HE,” they added.

To investigate, the researchers examined the prevalence and risk factors of undiagnosed cirrhosis — and therefore, possible HE — among US veterans.

The study was published online in JAMA Network Open.
 

Dementia or Cirrhosis?

Using the VHA Corporate Data Warehouse, researchers analyzed medical records of 177,422 US veterans diagnosed with dementia but not cirrhosis between 2009 and 2019 and with sufficient laboratory test results to calculate their Fibrosis-4 (FIB-4) scores. The mean age was 78.35 years, 97.1% were men, and 80.7% were White individuals.

The FIB-4 score for each patient was calculated using the most recent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels or values and platelet values that were closest to the index date during the two years after the index dementia date.

Age is in the numerator of the FIB-4 score calculation; hence, higher age could lead to an erroneously high FIB-4 score, the authors noted. Therefore, for patients older than 65 years, the researchers entered 65 years as an input variable, rather than the actual age.

A FIB-4 score > 2.67 was suggestive of advanced fibrosis, whereas a score > 3.25 was suggestive of cirrhosis. 

A total of 18,390 (10.3%) veterans had a FIB-4 score > 2.67, and 9373 (5.3%) had a FIB-4 score > 3.25.

In multivariable logistic regression models, a FIB-4 score > 3.25 was associated with older age (odds ratio [OR], 1.07), male sex (OR, 1.43), congestive heart failure (OR, 1.48), viral hepatitis (OR, 1.79), an Alcohol Use Disorders Identification Test score showing problem drinking (OR, 1.56), and chronic kidney disease (OR, 1.11).

In contrast, a FIB-4 score > 3.25 was inversely associated with the White race (OR, 0.79), diabetes (OR, 0.78), hyperlipidemia (OR, 0.84), stroke (OR, 0.85), tobacco use disorder (OR, 0.78), and rural residence (OR, 0.92).

Similar findings were associated with the FIB-4 greater than 2.67 threshold.

In a follow-up validation study among 89 veterans diagnosed with dementia at a single center, the researchers found similar results: 4.4%-11.2% of participants had high FIB-4 scores, suggestive of HE.

After investigating further, they concluded that 5% of patients in that cohort had reasons other than cirrhosis for their high FIB-4 scores. The remaining patients (95%) had evidence of cirrhosis, had risk factors, and/or had no other explanation for their high FIB-4 scores.

“The combination of high FIB-4 scores and other risk factors for liver disease in patients with dementia raises the possibility that reversible HE could be a factor associated with cognitive impairment,” the authors wrote. “These findings highlight the potential to enhance cognitive function and quality of life by increasing awareness of risk factors and diagnostic indicators of advanced liver disease that may be associated with HE as a factor or as a differential diagnosis of dementia among clinicians other than liver specialists.”
 

FIB-4 Screening Advised

“An elderly patient with cirrhosis used to be an oxymoron, because we never used to have people who lived this long or were diagnosed this late with cirrhosis,” Dr. Bajaj told this news organization. “It’s a good problem to have because people are now living longer, but it also means that we need to have every single person who is taking care of patients with what is deemed to be dementia know that the patient could also have an element of encephalopathy.”

Increased awareness is important because, unlike dementia, encephalopathy is very easily treated, Dr. Bajaj said. “The biggest, easiest, correctable cause is to figure out if they have severe liver disease, and if that’s the case, your friendly neighborhood gastroenterologist is waiting for you,” he added.

The finding that cirrhosis was present in 95% of patients in the validation cohort is “very impressive, as they had excluded from the consideration all those with obvious cirrhosis before the FIB-4 was done,” said William Carey, MD, acting hepatology section head in the Department of Gastroenterology, Hepatology and Nutrition at Cleveland Clinic’s Digestive Disease Institute in Ohio. “This validates FIB-4 as a powerful tool for cirrhosis case-finding.” 

Ordering a FIB-4 “is within the skill set of every healthcare provider,” Dr. Carey, who was not involved in the study, told this news organization. “Patients with altered mental status, including suspected or proven dementia, should be screened for possible cirrhosis, as future management will change. Those with elevated FIB-4 results should also be tested for possible HE and treated if it is present.”

The study was partly funded by VA Merit Review grants to Dr. Bajaj. Dr. Bajaj reported receiving grants from Bausch, Grifols, Sequana, and Mallinckrodt outside the submitted work. Dr. Carey reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Cognitive impairment in some US veterans may be due to treatable hepatic encephalopathy (HE) rather than dementia, new research suggested.

From 5%-10% of veterans diagnosed with dementia had possible undiagnosed cirrhosis, implicating HE as a contributor to cognitive impairment, found the study by Jasmohan S. Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Virginia, and colleagues.

The research was prompted, in part, by an earlier case study by Dr. Bajaj and colleagues that showed that two older men diagnosed with dementia and Parkinson’s disease actually had HE, meaning their symptoms were due to advanced but treatable liver disease.

“Once they were properly diagnosed, whatever had been considered dementia was gone,” Dr. Bajaj said. “The spouse of one man said, ‘My husband is a different person now.’ It’s not that clinicians don’t know how to treat HE; the problem was that they did not suspect it.”

Among veterans with cirrhosis, concomitant dementia is common and is difficult to distinguish from HE, but the extent to which patients with dementia also have undiagnosed cirrhosis and HE is unknown, the authors of the current study wrote. “Undiagnosed cirrhosis among veterans with dementia could raise the possibility that part of their cognitive impairment may be due to reversible HE,” they added.

To investigate, the researchers examined the prevalence and risk factors of undiagnosed cirrhosis — and therefore, possible HE — among US veterans.

The study was published online in JAMA Network Open.
 

Dementia or Cirrhosis?

Using the VHA Corporate Data Warehouse, researchers analyzed medical records of 177,422 US veterans diagnosed with dementia but not cirrhosis between 2009 and 2019 and with sufficient laboratory test results to calculate their Fibrosis-4 (FIB-4) scores. The mean age was 78.35 years, 97.1% were men, and 80.7% were White individuals.

The FIB-4 score for each patient was calculated using the most recent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels or values and platelet values that were closest to the index date during the two years after the index dementia date.

Age is in the numerator of the FIB-4 score calculation; hence, higher age could lead to an erroneously high FIB-4 score, the authors noted. Therefore, for patients older than 65 years, the researchers entered 65 years as an input variable, rather than the actual age.

A FIB-4 score > 2.67 was suggestive of advanced fibrosis, whereas a score > 3.25 was suggestive of cirrhosis. 

A total of 18,390 (10.3%) veterans had a FIB-4 score > 2.67, and 9373 (5.3%) had a FIB-4 score > 3.25.

In multivariable logistic regression models, a FIB-4 score > 3.25 was associated with older age (odds ratio [OR], 1.07), male sex (OR, 1.43), congestive heart failure (OR, 1.48), viral hepatitis (OR, 1.79), an Alcohol Use Disorders Identification Test score showing problem drinking (OR, 1.56), and chronic kidney disease (OR, 1.11).

In contrast, a FIB-4 score > 3.25 was inversely associated with the White race (OR, 0.79), diabetes (OR, 0.78), hyperlipidemia (OR, 0.84), stroke (OR, 0.85), tobacco use disorder (OR, 0.78), and rural residence (OR, 0.92).

Similar findings were associated with the FIB-4 greater than 2.67 threshold.

In a follow-up validation study among 89 veterans diagnosed with dementia at a single center, the researchers found similar results: 4.4%-11.2% of participants had high FIB-4 scores, suggestive of HE.

After investigating further, they concluded that 5% of patients in that cohort had reasons other than cirrhosis for their high FIB-4 scores. The remaining patients (95%) had evidence of cirrhosis, had risk factors, and/or had no other explanation for their high FIB-4 scores.

“The combination of high FIB-4 scores and other risk factors for liver disease in patients with dementia raises the possibility that reversible HE could be a factor associated with cognitive impairment,” the authors wrote. “These findings highlight the potential to enhance cognitive function and quality of life by increasing awareness of risk factors and diagnostic indicators of advanced liver disease that may be associated with HE as a factor or as a differential diagnosis of dementia among clinicians other than liver specialists.”
 

FIB-4 Screening Advised

“An elderly patient with cirrhosis used to be an oxymoron, because we never used to have people who lived this long or were diagnosed this late with cirrhosis,” Dr. Bajaj told this news organization. “It’s a good problem to have because people are now living longer, but it also means that we need to have every single person who is taking care of patients with what is deemed to be dementia know that the patient could also have an element of encephalopathy.”

Increased awareness is important because, unlike dementia, encephalopathy is very easily treated, Dr. Bajaj said. “The biggest, easiest, correctable cause is to figure out if they have severe liver disease, and if that’s the case, your friendly neighborhood gastroenterologist is waiting for you,” he added.

The finding that cirrhosis was present in 95% of patients in the validation cohort is “very impressive, as they had excluded from the consideration all those with obvious cirrhosis before the FIB-4 was done,” said William Carey, MD, acting hepatology section head in the Department of Gastroenterology, Hepatology and Nutrition at Cleveland Clinic’s Digestive Disease Institute in Ohio. “This validates FIB-4 as a powerful tool for cirrhosis case-finding.” 

Ordering a FIB-4 “is within the skill set of every healthcare provider,” Dr. Carey, who was not involved in the study, told this news organization. “Patients with altered mental status, including suspected or proven dementia, should be screened for possible cirrhosis, as future management will change. Those with elevated FIB-4 results should also be tested for possible HE and treated if it is present.”

The study was partly funded by VA Merit Review grants to Dr. Bajaj. Dr. Bajaj reported receiving grants from Bausch, Grifols, Sequana, and Mallinckrodt outside the submitted work. Dr. Carey reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Implementing strategies to optimize electronic health record (EHR) use can save time, improve the doctor-patient relationship, and reduce burnout, a new practice management article suggests.

Michelle Kang Kim, MD, PhD, AGAF, chair of gastroenterology at Cleveland Clinic, Ohio, and colleagues provide EHR improvement strategies and examples that can be adapted for use in a variety of gastroenterology clinic settings. 

Kim_Michelle_K_NEW YORK_web.jpg

Their article, which was published online in Clinical Gastroenterology and Hepatology , includes the following suggestions, among others:

• Develop optimization teams. An example is SPRINT, a short, intensive team-based intervention at the University of Colorado Health, Aurora, Colorado, that developed specialty-specific tools, provided EHR efficiency training, and helped streamline workflows. The optimization project increased EHR satisfaction scores and reduced documentation time.
• Reroute low-acuity messages. Low-risk medication refills or appointment requests can be handled by nurses and medical assistants. This strategy has helped reduce the inbox burden.
• Create order sets for complex treatment dosing. One example is Cleveland Clinic’s Helicobacter pylori order set, which enables clinicians to quickly place orders with built-in dosages.
• Personalize EHR drop-down menus. Incorporate inflammatory bowel disease (IBD) severity scores, biopsy sampling, resection protocols, specimen container numbering, and other workflow-specific documentation into the EHR.
• Employ medical scribes. These professionals can serve as personal assistants, supporting care teams and reducing clinician documentation time. Alternatively, clinical support staff, such as nurses, can assist with documentation and messages, helping to reduce physician burnout. “These models could be particularly useful in GI specialties that require a multidisciplinary approach, for example, IBD and hepatology,” the authors write.
• Provide real-time training on best practices. There is no widely accepted EHR training curriculum for students, and experienced physicians face time constraints in learning new practices. Real-time training can help clinicians at all levels optimize their time outside the clinic.

In addition, the authors addressed novel tools and strategies that have been recently deployed and/or are in development, which are based largely on artificial intelligence (AI), natural language processing, and speech recognition. For now, these tools are digitizing data to help automate some EHR tasks, supporting communications with patients, and assisting in clinical decision making.

However, the authors note that although current optimization tools are promising, “there is still a lack of knowledge about their usability and effects on provider and patient well-being. More research is needed to evaluate current methodologies and design intelligent tools for the future that will help GI providers overcome the EHR-related obstacles specific to our field and harness the enormous potential of AI in optimizing the busy GI practice.”

This work received no external funding, and the authors disclosed no conflicts. 

A version of this article appeared on Medscape.com.

Implementing strategies to optimize electronic health record (EHR) use can save time, improve the doctor-patient relationship, and reduce burnout, a new practice management article suggests.

Michelle Kang Kim, MD, PhD, AGAF, chair of gastroenterology at Cleveland Clinic, Ohio, and colleagues provide EHR improvement strategies and examples that can be adapted for use in a variety of gastroenterology clinic settings. 

Kim_Michelle_K_NEW YORK_web.jpg

Their article, which was published online in Clinical Gastroenterology and Hepatology , includes the following suggestions, among others:

• Develop optimization teams. An example is SPRINT, a short, intensive team-based intervention at the University of Colorado Health, Aurora, Colorado, that developed specialty-specific tools, provided EHR efficiency training, and helped streamline workflows. The optimization project increased EHR satisfaction scores and reduced documentation time.
• Reroute low-acuity messages. Low-risk medication refills or appointment requests can be handled by nurses and medical assistants. This strategy has helped reduce the inbox burden.
• Create order sets for complex treatment dosing. One example is Cleveland Clinic’s Helicobacter pylori order set, which enables clinicians to quickly place orders with built-in dosages.
• Personalize EHR drop-down menus. Incorporate inflammatory bowel disease (IBD) severity scores, biopsy sampling, resection protocols, specimen container numbering, and other workflow-specific documentation into the EHR.
• Employ medical scribes. These professionals can serve as personal assistants, supporting care teams and reducing clinician documentation time. Alternatively, clinical support staff, such as nurses, can assist with documentation and messages, helping to reduce physician burnout. “These models could be particularly useful in GI specialties that require a multidisciplinary approach, for example, IBD and hepatology,” the authors write.
• Provide real-time training on best practices. There is no widely accepted EHR training curriculum for students, and experienced physicians face time constraints in learning new practices. Real-time training can help clinicians at all levels optimize their time outside the clinic.

In addition, the authors addressed novel tools and strategies that have been recently deployed and/or are in development, which are based largely on artificial intelligence (AI), natural language processing, and speech recognition. For now, these tools are digitizing data to help automate some EHR tasks, supporting communications with patients, and assisting in clinical decision making.

However, the authors note that although current optimization tools are promising, “there is still a lack of knowledge about their usability and effects on provider and patient well-being. More research is needed to evaluate current methodologies and design intelligent tools for the future that will help GI providers overcome the EHR-related obstacles specific to our field and harness the enormous potential of AI in optimizing the busy GI practice.”

This work received no external funding, and the authors disclosed no conflicts. 

A version of this article appeared on Medscape.com.

Implementing strategies to optimize electronic health record (EHR) use can save time, improve the doctor-patient relationship, and reduce burnout, a new practice management article suggests.

Michelle Kang Kim, MD, PhD, AGAF, chair of gastroenterology at Cleveland Clinic, Ohio, and colleagues provide EHR improvement strategies and examples that can be adapted for use in a variety of gastroenterology clinic settings. 

Kim_Michelle_K_NEW YORK_web.jpg

Their article, which was published online in Clinical Gastroenterology and Hepatology , includes the following suggestions, among others:

• Develop optimization teams. An example is SPRINT, a short, intensive team-based intervention at the University of Colorado Health, Aurora, Colorado, that developed specialty-specific tools, provided EHR efficiency training, and helped streamline workflows. The optimization project increased EHR satisfaction scores and reduced documentation time.
• Reroute low-acuity messages. Low-risk medication refills or appointment requests can be handled by nurses and medical assistants. This strategy has helped reduce the inbox burden.
• Create order sets for complex treatment dosing. One example is Cleveland Clinic’s Helicobacter pylori order set, which enables clinicians to quickly place orders with built-in dosages.
• Personalize EHR drop-down menus. Incorporate inflammatory bowel disease (IBD) severity scores, biopsy sampling, resection protocols, specimen container numbering, and other workflow-specific documentation into the EHR.
• Employ medical scribes. These professionals can serve as personal assistants, supporting care teams and reducing clinician documentation time. Alternatively, clinical support staff, such as nurses, can assist with documentation and messages, helping to reduce physician burnout. “These models could be particularly useful in GI specialties that require a multidisciplinary approach, for example, IBD and hepatology,” the authors write.
• Provide real-time training on best practices. There is no widely accepted EHR training curriculum for students, and experienced physicians face time constraints in learning new practices. Real-time training can help clinicians at all levels optimize their time outside the clinic.

In addition, the authors addressed novel tools and strategies that have been recently deployed and/or are in development, which are based largely on artificial intelligence (AI), natural language processing, and speech recognition. For now, these tools are digitizing data to help automate some EHR tasks, supporting communications with patients, and assisting in clinical decision making.

However, the authors note that although current optimization tools are promising, “there is still a lack of knowledge about their usability and effects on provider and patient well-being. More research is needed to evaluate current methodologies and design intelligent tools for the future that will help GI providers overcome the EHR-related obstacles specific to our field and harness the enormous potential of AI in optimizing the busy GI practice.”

This work received no external funding, and the authors disclosed no conflicts. 

A version of this article appeared on Medscape.com.

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

About one-quarter of all adult day services center (ADSC) participants have dementia, and the prevalence of dementia in ADSCs that specialize in the disorder is more than 40%, a new US National Health Statistics Report revealed.

ADSCs are a growing sector of the US home- and community-based long-term care delivery system, providing daytime services to adults with disabilities who often have multiple chronic conditions, including various types of dementia, according to report authors Priyanka Singha, MPH, and colleagues at the US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics in Bethesda, Maryland.

Dementia often leads to the transition to receiving long-term care services, such as nursing home care. Delaying institutionalization is a primary goal of ADSCs, so they also try to meet the needs of a growing population of community-dwelling adults with dementia.

Survey responses from 1800 ADSCs across the United States showed that overall, 42.2% of participants had dementia in ADSCs specializing in dementia care, while 22.7% of participants in nonspecialized ADSCs also had dementia.

Dementia was more prevalent in the Midwest and West, where nearly one half of participants in specialized centers had dementia.

Nevertheless, the overall prevalence of dementia in ADSCs was similar across US regions, with a slightly lower percentage in the West.
 

Positive Outcomes

The new report used data from the ADSC component of the 2020 National Post-acute and Long-term Care Study collected from January 2020 through mid-July 2021. About 1800 ADSCs from a census of 5500 ADSCs were included and weighted to be nationally representative.

The authors compared dementia prevalence among participants in ADSCs that provide specialized care for dementia with other ADSCs by census region, metropolitan statistical area (MSA) status, chain affiliation, and ownership type.

MSA is a core urban area population of 50,000 or more. ADSCs that specialize in dementia care have specially trained staff, activities, and facilities. They offer social activities, including art and music therapy, dementia-appropriate games, and group exercises, as well as respite care for unpaid caregivers. The survey found that 14% of ADSCs reported specializing in dementia.

The investigators also found that the percentage of ADSC participants with dementia, regardless of center specialization, was higher in the Midwest (32.1%), Northeast (28.5%), and South (24.5%) than in the West (21.1%).

The percentage of participants with dementia in specialized centers was higher in the Midwest (49.5%) and West (48.8%) than in the Northeast (31.9%) and in nonchain centers (50.5%) than in chain-affiliated centers (30.4%).

In addition, the percentage of participants with dementia, regardless of specialization, was higher in nonchain ADSCs (25%) than in chain-affiliated centers (20.1%). In addition, the percentage of participants with dementia in nonspecialized centers was higher in nonchain centers (25%) than in chain-affiliated centers (20.1%).

Finally, the research revealed that the percentage of participants with dementia, regardless of specialization, was higher in nonprofit ADSCs (28.7%) than for-profit centers (21%).

“These findings indicate that ADSCs in MSAs, nonprofit organizations, and nonchain centers provide services to a higher proportion of participants with dementia, particularly among centers that specialize in dementia care,” the investigators wrote.

Whereas “caregivers manage prescription medications, help with activities of daily living, and offer nutritional diets, exercise, and social engagement, ADSCs play a role in providing this type of care for people with dementia while also offering respite for their unpaid caregivers,” they noted.

Overall, they concluded that ADSCs provide positive outcomes for both family caregivers and people with dementia.

They noted that the study’s limitations include the use of cross-sectional data, which cannot show effectiveness for participants receiving care in specialized centers or be used to analyze relationships between other participant-level sociodemographic or health characteristics and specialized dementia care.
 

A version of this article appeared on Medscape.com.

About one-quarter of all adult day services center (ADSC) participants have dementia, and the prevalence of dementia in ADSCs that specialize in the disorder is more than 40%, a new US National Health Statistics Report revealed.

ADSCs are a growing sector of the US home- and community-based long-term care delivery system, providing daytime services to adults with disabilities who often have multiple chronic conditions, including various types of dementia, according to report authors Priyanka Singha, MPH, and colleagues at the US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics in Bethesda, Maryland.

Dementia often leads to the transition to receiving long-term care services, such as nursing home care. Delaying institutionalization is a primary goal of ADSCs, so they also try to meet the needs of a growing population of community-dwelling adults with dementia.

Survey responses from 1800 ADSCs across the United States showed that overall, 42.2% of participants had dementia in ADSCs specializing in dementia care, while 22.7% of participants in nonspecialized ADSCs also had dementia.

Dementia was more prevalent in the Midwest and West, where nearly one half of participants in specialized centers had dementia.

Nevertheless, the overall prevalence of dementia in ADSCs was similar across US regions, with a slightly lower percentage in the West.
 

Positive Outcomes

The new report used data from the ADSC component of the 2020 National Post-acute and Long-term Care Study collected from January 2020 through mid-July 2021. About 1800 ADSCs from a census of 5500 ADSCs were included and weighted to be nationally representative.

The authors compared dementia prevalence among participants in ADSCs that provide specialized care for dementia with other ADSCs by census region, metropolitan statistical area (MSA) status, chain affiliation, and ownership type.

MSA is a core urban area population of 50,000 or more. ADSCs that specialize in dementia care have specially trained staff, activities, and facilities. They offer social activities, including art and music therapy, dementia-appropriate games, and group exercises, as well as respite care for unpaid caregivers. The survey found that 14% of ADSCs reported specializing in dementia.

The investigators also found that the percentage of ADSC participants with dementia, regardless of center specialization, was higher in the Midwest (32.1%), Northeast (28.5%), and South (24.5%) than in the West (21.1%).

The percentage of participants with dementia in specialized centers was higher in the Midwest (49.5%) and West (48.8%) than in the Northeast (31.9%) and in nonchain centers (50.5%) than in chain-affiliated centers (30.4%).

In addition, the percentage of participants with dementia, regardless of specialization, was higher in nonchain ADSCs (25%) than in chain-affiliated centers (20.1%). In addition, the percentage of participants with dementia in nonspecialized centers was higher in nonchain centers (25%) than in chain-affiliated centers (20.1%).

Finally, the research revealed that the percentage of participants with dementia, regardless of specialization, was higher in nonprofit ADSCs (28.7%) than for-profit centers (21%).

“These findings indicate that ADSCs in MSAs, nonprofit organizations, and nonchain centers provide services to a higher proportion of participants with dementia, particularly among centers that specialize in dementia care,” the investigators wrote.

Whereas “caregivers manage prescription medications, help with activities of daily living, and offer nutritional diets, exercise, and social engagement, ADSCs play a role in providing this type of care for people with dementia while also offering respite for their unpaid caregivers,” they noted.

Overall, they concluded that ADSCs provide positive outcomes for both family caregivers and people with dementia.

They noted that the study’s limitations include the use of cross-sectional data, which cannot show effectiveness for participants receiving care in specialized centers or be used to analyze relationships between other participant-level sociodemographic or health characteristics and specialized dementia care.
 

A version of this article appeared on Medscape.com.

About one-quarter of all adult day services center (ADSC) participants have dementia, and the prevalence of dementia in ADSCs that specialize in the disorder is more than 40%, a new US National Health Statistics Report revealed.

ADSCs are a growing sector of the US home- and community-based long-term care delivery system, providing daytime services to adults with disabilities who often have multiple chronic conditions, including various types of dementia, according to report authors Priyanka Singha, MPH, and colleagues at the US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics in Bethesda, Maryland.

Dementia often leads to the transition to receiving long-term care services, such as nursing home care. Delaying institutionalization is a primary goal of ADSCs, so they also try to meet the needs of a growing population of community-dwelling adults with dementia.

Survey responses from 1800 ADSCs across the United States showed that overall, 42.2% of participants had dementia in ADSCs specializing in dementia care, while 22.7% of participants in nonspecialized ADSCs also had dementia.

Dementia was more prevalent in the Midwest and West, where nearly one half of participants in specialized centers had dementia.

Nevertheless, the overall prevalence of dementia in ADSCs was similar across US regions, with a slightly lower percentage in the West.
 

Positive Outcomes

The new report used data from the ADSC component of the 2020 National Post-acute and Long-term Care Study collected from January 2020 through mid-July 2021. About 1800 ADSCs from a census of 5500 ADSCs were included and weighted to be nationally representative.

The authors compared dementia prevalence among participants in ADSCs that provide specialized care for dementia with other ADSCs by census region, metropolitan statistical area (MSA) status, chain affiliation, and ownership type.

MSA is a core urban area population of 50,000 or more. ADSCs that specialize in dementia care have specially trained staff, activities, and facilities. They offer social activities, including art and music therapy, dementia-appropriate games, and group exercises, as well as respite care for unpaid caregivers. The survey found that 14% of ADSCs reported specializing in dementia.

The investigators also found that the percentage of ADSC participants with dementia, regardless of center specialization, was higher in the Midwest (32.1%), Northeast (28.5%), and South (24.5%) than in the West (21.1%).

The percentage of participants with dementia in specialized centers was higher in the Midwest (49.5%) and West (48.8%) than in the Northeast (31.9%) and in nonchain centers (50.5%) than in chain-affiliated centers (30.4%).

In addition, the percentage of participants with dementia, regardless of specialization, was higher in nonchain ADSCs (25%) than in chain-affiliated centers (20.1%). In addition, the percentage of participants with dementia in nonspecialized centers was higher in nonchain centers (25%) than in chain-affiliated centers (20.1%).

Finally, the research revealed that the percentage of participants with dementia, regardless of specialization, was higher in nonprofit ADSCs (28.7%) than for-profit centers (21%).

“These findings indicate that ADSCs in MSAs, nonprofit organizations, and nonchain centers provide services to a higher proportion of participants with dementia, particularly among centers that specialize in dementia care,” the investigators wrote.

Whereas “caregivers manage prescription medications, help with activities of daily living, and offer nutritional diets, exercise, and social engagement, ADSCs play a role in providing this type of care for people with dementia while also offering respite for their unpaid caregivers,” they noted.

Overall, they concluded that ADSCs provide positive outcomes for both family caregivers and people with dementia.

They noted that the study’s limitations include the use of cross-sectional data, which cannot show effectiveness for participants receiving care in specialized centers or be used to analyze relationships between other participant-level sociodemographic or health characteristics and specialized dementia care.
 

A version of this article appeared on Medscape.com.

If someone has been in cardiac arrest for 10 minutes, the brain is permanently damaged and there’s nothing to do, right?

Not so according to emerging evidence that suggests that the brain shows signs of electrical recovery for as long as an hour into ongoing cardiopulmonary resuscitation (CPR). This time between cardiac arrest and awakening can be a period of vivid experiences for the dying patient before they return to life — a phenomenon known as “recalled death.”

This should be an impetus to increase the use of devices that measure the quality of CPR and to find new treatments to restart the heart or prevent brain injury, experts advised. Cardiologists and critical care clinicians are among those who will need to manage patients in the aftermath.

“If people who go into cardiac arrest receive good quality chest compressions that restore blood flow to the brain, then consciousness is restored, as well, said Jasmeet Soar, MD, consultant in Anesthetics & Intensive Care Medicine, North Bristol NHS Trust, Bristol, England, and an editor of the journal Resuscitation.

“We know that because if chest compressions are stopped, the person becomes unconscious again,” he said. “This CPR-induced consciousness has become more common when professionals do the CPR because resuscitation guidelines now place a much bigger focus on high-quality CPR — ‘push hard, push fast.’ ” 

“People are giving up too soon on trying to revive individuals, and they should be trying more modern strategies, such as extracorporeal membrane oxygenation,” said Sam Parnia, MD, PhD, associate professor in the Department of Medicine at NYU Langone Health and director of critical care and resuscitation research at NYU Langone, New York City.

Brain Activity, Heightened Experiences

Two types of brain activity may occur when CPR works. The first, called CPR-induced consciousness, is when an individual recovers consciousness while in cardiac arrest. Signs of consciousness include combativeness, groaning, and eye-opening, Soar explained.

The second type is a perception of lucidity with recall of events, he said. “Patients who experience this may form memories that they can recall. We’re not sure whether that happens during CPR or while the patient is waking up during intensive care, or how the brain creates these memories, or if they’re real memories or coincidental, but it’s clear the brain does form them during the dying and recovery process.”

This latter phenomenon was explored in detail in a recent study led by Dr. Parnia.

In that study of 567 in-hospital patients with cardiac arrest from 25 centers in the United States and United Kingdom, 53 survived, 28 of those survivors were interviewed, and 11 reported memories or perceptions suggestive of consciousness.

Four types of experiences occurred:

• Recalled experiences of death: “I thought I heard my grandma [who had passed] saying ‘you need to go back.’”
• Emergence from coma during CPR/CPR-induced consciousness: “I remember when I came back and they were putting those two electrodes to my chest, and I remember the shock.”
• Emergence from coma in the post-resuscitation period: “I heard my partner saying [patient’s name] and my son saying ‘mom.’”
• Dreams and dream-like experiences: “[I] felt as though someone was holding my hand. It was very black; I couldn’t see anything.”

In a complementary cross-sectional study, 126 community cardiac arrest survivors reported similar experiences plus a fifth type, “delusions,” or “misattribution of medical events,” for example, “I heard my name, over and over again. All around me were things like demons and monsters. It felt like they were trying to tear off my body parts.”

“Many people label recalled experiences of death as ‘near-death’ experiences, but they’re not,” Dr. Parnia said. “Medically speaking, being near to death means your heart is about to stop. But the whole point is that these people are not near death. They actually died and came back from it.”

One of the big implications of the study, he said, is that “a lot of physicians are taught that somehow after, say, 3-5 minutes of oxygen deprivation, the brain dies. Our study showed this is not true. It showed that the brain may not be functioning, which is why they flatline. But if you’re able to resuscitate them appropriately, you can restore activity up to an hour later.”

Because some clinicians questioned or dismissed previous work in this area by Dr. Parnia and others, the latest study used EEG monitoring in a subset of 53 patients. Among those with evaluable EEG data, brain activity returned to normal or near-normal after flatlining in about 40% of images; spikes were seen in the delta (22%), theta (12%), alpha (6%), and beta (1%) waves associated with higher mental function.

“The team recorded what was happening in the brain during real-time CPR using various tests of consciousness, including EEG measurements and tests of visual and auditory awareness using a tablet with a special app and a Bluetooth headphone.”

“Incredibly, we found that even though the brain flatlines, which is what we expect when the heart stops, with professionally given CPR even up to about an hour after this, the brainwaves changed into normal to near-normal patterns,” Dr. Parnia said. “We were able to identify these brain waves in patients while they were being resuscitated, which confirms the fact that people can have lucid consciousness even though they appear to be unconscious.”

Asked what implications, if any, his work has for current definitions of brain death and cardiac death, Dr. Parnia said that the problem is that these are based on the concept of “a permanent irreversible loss of function,” but “that’s only relative to what medical treatments are developed at a given time.”

Potential Mechanism

Dr. Parnia and his team proposed a potential mechanism for recalled experiences of death. Essentially, when the brain flatlines, the dying brain removes natural inhibitory (braking) systems that are needed to support daily functioning. This disinhibition may open access to “new dimensions of reality, including lucid recall of stored memories from early childhood to death,” he said.

From a clinical perspective, he noted, “although the brain stops working when it flatlines, it does not die within 5 or 10 minutes of oxygen deprivation.”

This is contrary to what many doctors believe, and because of that, he said, “nobody has tried to find treatments or new ways to restart the heart or prevent brain injury. They think it’s futile. So, with this work, we’ve opened up the window to developing cocktails of drugs that could be given to patients who have technically gone through death to bring them back to life again.”

Probe Patients or Leave Well Enough Alone?

The findings have ramifications for clinicians who may be caring for patients who survive cardiac arrest, said Lance B. Becker, MD, professor and chair, Department of Emergency Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York, and chair, Department of Emergency Medicine at North Shore University Hospital, Manhasset, and Long Island Jewish Medical Center, Queens, New York.

“I’ve talked with a lot of patients who have had some kind of recalled experience around cardiac arrest and some who have had zero recall, as well, like in the paper,” he told this news organization. “The ones who do have an experience are sometimes mystified by it and have questions. And very often, clinicians don’t want to listen, don’t think it’s important, and downplay it.”

“I think it is important, and when people have important things happen to them, it’s really imperative that doctors listen, learn, and respond,” he said. “When I started in this field a long time ago, there were so few survivors that there wasn’t even a concept of survivorship,” he said.

Dr. Becker noted that it’s not uncommon for cardiac arrest survivors to have depression, problems with executive function, or a small brain injury they need to recover from. “Now survivorship organizations are springing up that these people can turn to, but clinicians still need to become more aware and sensitive to this.”

Not all are. “I had a number of patients who said I was the only doctor who ever asked them about what they experienced,” he recalled. “I was a young doctor at the time and didn’t exactly know what to say to them, but they were just happy to have a doctor who would listen to them and not be afraid to hear what they had to say.”

Recognizing that support is an issue, the American Heart Association released a scientific statement in 2020 on sudden cardiac arrest survivorship, which “expands the cardiac arrest resuscitation system of care to include patients, caregivers, and rehabilitative healthcare partnerships, which are central to cardiac survivorship.”

Soar has a more nuanced view of survivorship support, however. “I suspect some people are very glad to be alive, and that trying to dig deep and bring things out may actually be harmful,” he said. “It’s not as clear cut as everybody thinks.”

He noted that follow-up and rehabilitation should be an option for people who specifically need it who would need to be identified. “But human beings are resilient, and while some people will require help, not everybody will,” he said.

Better CPR, New Treatments

Experts in emergency and intensive care medicine studying survival after cardiac arrest hope to find ways to save patients before too much damage is done to the brain and other organs from loss of oxygen, Dr. Parnia said. He is the lead author in a recent multidisciplinary consensus statement on guidelines and standards for the study of death and recalled experiences of death.

“One of my bugbears is that our survival outcomes from cardiac arrest resuscitation have not changed very much for 60 years because we haven’t developed new treatments and innovative methods,” he said. “Unlike the rest of medicine, we’re living in the past.”

Currently, his team is developing cocktails of treatments. These include hypothermic circulatory arrest — cooling the body to stop blood circulation and brain function for up to 40 minutes — and giving magnesium, a brain-protective treatment, to people whose hearts stop.

Dr. Becker would like to see optimal care of patients with cardiac arrest. “The first step is to increase blood flow with good CPR and then measure whether CPR is working,” he said. Adding that despite the availability of devices that provide feedback on the quality of CPR, they’re rarely used. He cited ultrasound devices that measure the blood flow generated during CPR, compression meter devices that go between the patient’s chest and the rescuer’s hands that gauge the rate and depth of compression, and invasive devices that measure blood pressure during CPR.

His group is trying to design even better devices, he said. “An example would be a little probe that you could pop on the neck that would study blood flow to the brain with ultrasound, so that while you were pumping on the person, you could see if you’re making them better or not.”

“We also have some preliminary data showing that the American Heart Association recommended position on the chest for doing CPR is not the perfect place for everybody,” he said. The 2020 AHA guidelines recommended the center of the lower half of the sternum. At the 2023 American College of Emergency Physicians meeting, Dr. Becker›s team at Hofstra/Northwell presented data on 175 video-recorded adult cardiac arrests in their emergency department over more than 2 years, 22 of which involved at least one change of compression location (for a total of 29 location changes). They found that 41% of compression location changes were associated with return of spontaneous circulation.

For about a third of people, the hands need to be repositioned slightly. “This is not anything that is taught to the public because you can only figure it out if you have some kind of sensor that will let you know how you’re doing. That’s very achievable. We could have that in the future on every ambulance and even in people’s homes.”

When the person arrives at the hospital, he said, “we can make it easier and more likely that they can be put on extracorporeal membrane oxygenation (ECMO). We do that on selected patients in our hospital, even though it’s very difficult to do, because we know that when it’s done properly, it can change survival rates dramatically, from maybe 10%-50%.”

Dr. Dr. Becker, like Dr. Parnia, also favors the development of drug cocktails, and his team has been experimenting with various combinations in animal models. “We think those two things together — ECMO and a drug cocktail — would be a very powerful one to two knock out for cardiac arrest,” he said. “We have a long way to go — 10 or 20 years. But most people around the world working in this area believe that will be the future.”

Dr. Parnia’s study on recalled death was supported by The John Templeton Foundation, Resuscitation Council (UK), and New York University Grossman School of Medicine, with research support staff provided by the UK’s National Institutes for Health Research. Soar is the editor of the journal Resuscitation and receives payment from the publisher Elsevier. Dr. Becker’s institute has received grants from Philips Medical Systems, NIH, Zoll Medical Corp, Nihon Kohden, PCORI, BrainCool, and United Therapeutics. He has received advisory/consultancy honoraria from NIH, Nihon Kohden, HP, and Philips, and he holds several patents in hypothermia induction and reperfusion therapies and several pending patents involving the use of medical slurries as human coolant devices to create reperfusion cocktails and measurement of respiratory quotient.

A version of this article appeared on Medscape.com.

If someone has been in cardiac arrest for 10 minutes, the brain is permanently damaged and there’s nothing to do, right?

Not so according to emerging evidence that suggests that the brain shows signs of electrical recovery for as long as an hour into ongoing cardiopulmonary resuscitation (CPR). This time between cardiac arrest and awakening can be a period of vivid experiences for the dying patient before they return to life — a phenomenon known as “recalled death.”

This should be an impetus to increase the use of devices that measure the quality of CPR and to find new treatments to restart the heart or prevent brain injury, experts advised. Cardiologists and critical care clinicians are among those who will need to manage patients in the aftermath.

“If people who go into cardiac arrest receive good quality chest compressions that restore blood flow to the brain, then consciousness is restored, as well, said Jasmeet Soar, MD, consultant in Anesthetics & Intensive Care Medicine, North Bristol NHS Trust, Bristol, England, and an editor of the journal Resuscitation.

“We know that because if chest compressions are stopped, the person becomes unconscious again,” he said. “This CPR-induced consciousness has become more common when professionals do the CPR because resuscitation guidelines now place a much bigger focus on high-quality CPR — ‘push hard, push fast.’ ” 

“People are giving up too soon on trying to revive individuals, and they should be trying more modern strategies, such as extracorporeal membrane oxygenation,” said Sam Parnia, MD, PhD, associate professor in the Department of Medicine at NYU Langone Health and director of critical care and resuscitation research at NYU Langone, New York City.

Brain Activity, Heightened Experiences

Two types of brain activity may occur when CPR works. The first, called CPR-induced consciousness, is when an individual recovers consciousness while in cardiac arrest. Signs of consciousness include combativeness, groaning, and eye-opening, Soar explained.

The second type is a perception of lucidity with recall of events, he said. “Patients who experience this may form memories that they can recall. We’re not sure whether that happens during CPR or while the patient is waking up during intensive care, or how the brain creates these memories, or if they’re real memories or coincidental, but it’s clear the brain does form them during the dying and recovery process.”

This latter phenomenon was explored in detail in a recent study led by Dr. Parnia.

In that study of 567 in-hospital patients with cardiac arrest from 25 centers in the United States and United Kingdom, 53 survived, 28 of those survivors were interviewed, and 11 reported memories or perceptions suggestive of consciousness.

Four types of experiences occurred:

• Recalled experiences of death: “I thought I heard my grandma [who had passed] saying ‘you need to go back.’”
• Emergence from coma during CPR/CPR-induced consciousness: “I remember when I came back and they were putting those two electrodes to my chest, and I remember the shock.”
• Emergence from coma in the post-resuscitation period: “I heard my partner saying [patient’s name] and my son saying ‘mom.’”
• Dreams and dream-like experiences: “[I] felt as though someone was holding my hand. It was very black; I couldn’t see anything.”

In a complementary cross-sectional study, 126 community cardiac arrest survivors reported similar experiences plus a fifth type, “delusions,” or “misattribution of medical events,” for example, “I heard my name, over and over again. All around me were things like demons and monsters. It felt like they were trying to tear off my body parts.”

“Many people label recalled experiences of death as ‘near-death’ experiences, but they’re not,” Dr. Parnia said. “Medically speaking, being near to death means your heart is about to stop. But the whole point is that these people are not near death. They actually died and came back from it.”

One of the big implications of the study, he said, is that “a lot of physicians are taught that somehow after, say, 3-5 minutes of oxygen deprivation, the brain dies. Our study showed this is not true. It showed that the brain may not be functioning, which is why they flatline. But if you’re able to resuscitate them appropriately, you can restore activity up to an hour later.”

Because some clinicians questioned or dismissed previous work in this area by Dr. Parnia and others, the latest study used EEG monitoring in a subset of 53 patients. Among those with evaluable EEG data, brain activity returned to normal or near-normal after flatlining in about 40% of images; spikes were seen in the delta (22%), theta (12%), alpha (6%), and beta (1%) waves associated with higher mental function.

“The team recorded what was happening in the brain during real-time CPR using various tests of consciousness, including EEG measurements and tests of visual and auditory awareness using a tablet with a special app and a Bluetooth headphone.”

“Incredibly, we found that even though the brain flatlines, which is what we expect when the heart stops, with professionally given CPR even up to about an hour after this, the brainwaves changed into normal to near-normal patterns,” Dr. Parnia said. “We were able to identify these brain waves in patients while they were being resuscitated, which confirms the fact that people can have lucid consciousness even though they appear to be unconscious.”

Asked what implications, if any, his work has for current definitions of brain death and cardiac death, Dr. Parnia said that the problem is that these are based on the concept of “a permanent irreversible loss of function,” but “that’s only relative to what medical treatments are developed at a given time.”

Potential Mechanism

Dr. Parnia and his team proposed a potential mechanism for recalled experiences of death. Essentially, when the brain flatlines, the dying brain removes natural inhibitory (braking) systems that are needed to support daily functioning. This disinhibition may open access to “new dimensions of reality, including lucid recall of stored memories from early childhood to death,” he said.

From a clinical perspective, he noted, “although the brain stops working when it flatlines, it does not die within 5 or 10 minutes of oxygen deprivation.”

This is contrary to what many doctors believe, and because of that, he said, “nobody has tried to find treatments or new ways to restart the heart or prevent brain injury. They think it’s futile. So, with this work, we’ve opened up the window to developing cocktails of drugs that could be given to patients who have technically gone through death to bring them back to life again.”

Probe Patients or Leave Well Enough Alone?

The findings have ramifications for clinicians who may be caring for patients who survive cardiac arrest, said Lance B. Becker, MD, professor and chair, Department of Emergency Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York, and chair, Department of Emergency Medicine at North Shore University Hospital, Manhasset, and Long Island Jewish Medical Center, Queens, New York.

“I’ve talked with a lot of patients who have had some kind of recalled experience around cardiac arrest and some who have had zero recall, as well, like in the paper,” he told this news organization. “The ones who do have an experience are sometimes mystified by it and have questions. And very often, clinicians don’t want to listen, don’t think it’s important, and downplay it.”

“I think it is important, and when people have important things happen to them, it’s really imperative that doctors listen, learn, and respond,” he said. “When I started in this field a long time ago, there were so few survivors that there wasn’t even a concept of survivorship,” he said.

Dr. Becker noted that it’s not uncommon for cardiac arrest survivors to have depression, problems with executive function, or a small brain injury they need to recover from. “Now survivorship organizations are springing up that these people can turn to, but clinicians still need to become more aware and sensitive to this.”

Not all are. “I had a number of patients who said I was the only doctor who ever asked them about what they experienced,” he recalled. “I was a young doctor at the time and didn’t exactly know what to say to them, but they were just happy to have a doctor who would listen to them and not be afraid to hear what they had to say.”

Recognizing that support is an issue, the American Heart Association released a scientific statement in 2020 on sudden cardiac arrest survivorship, which “expands the cardiac arrest resuscitation system of care to include patients, caregivers, and rehabilitative healthcare partnerships, which are central to cardiac survivorship.”

Soar has a more nuanced view of survivorship support, however. “I suspect some people are very glad to be alive, and that trying to dig deep and bring things out may actually be harmful,” he said. “It’s not as clear cut as everybody thinks.”

He noted that follow-up and rehabilitation should be an option for people who specifically need it who would need to be identified. “But human beings are resilient, and while some people will require help, not everybody will,” he said.

Better CPR, New Treatments

Experts in emergency and intensive care medicine studying survival after cardiac arrest hope to find ways to save patients before too much damage is done to the brain and other organs from loss of oxygen, Dr. Parnia said. He is the lead author in a recent multidisciplinary consensus statement on guidelines and standards for the study of death and recalled experiences of death.

“One of my bugbears is that our survival outcomes from cardiac arrest resuscitation have not changed very much for 60 years because we haven’t developed new treatments and innovative methods,” he said. “Unlike the rest of medicine, we’re living in the past.”

Currently, his team is developing cocktails of treatments. These include hypothermic circulatory arrest — cooling the body to stop blood circulation and brain function for up to 40 minutes — and giving magnesium, a brain-protective treatment, to people whose hearts stop.

Dr. Becker would like to see optimal care of patients with cardiac arrest. “The first step is to increase blood flow with good CPR and then measure whether CPR is working,” he said. Adding that despite the availability of devices that provide feedback on the quality of CPR, they’re rarely used. He cited ultrasound devices that measure the blood flow generated during CPR, compression meter devices that go between the patient’s chest and the rescuer’s hands that gauge the rate and depth of compression, and invasive devices that measure blood pressure during CPR.

His group is trying to design even better devices, he said. “An example would be a little probe that you could pop on the neck that would study blood flow to the brain with ultrasound, so that while you were pumping on the person, you could see if you’re making them better or not.”

“We also have some preliminary data showing that the American Heart Association recommended position on the chest for doing CPR is not the perfect place for everybody,” he said. The 2020 AHA guidelines recommended the center of the lower half of the sternum. At the 2023 American College of Emergency Physicians meeting, Dr. Becker›s team at Hofstra/Northwell presented data on 175 video-recorded adult cardiac arrests in their emergency department over more than 2 years, 22 of which involved at least one change of compression location (for a total of 29 location changes). They found that 41% of compression location changes were associated with return of spontaneous circulation.

For about a third of people, the hands need to be repositioned slightly. “This is not anything that is taught to the public because you can only figure it out if you have some kind of sensor that will let you know how you’re doing. That’s very achievable. We could have that in the future on every ambulance and even in people’s homes.”

When the person arrives at the hospital, he said, “we can make it easier and more likely that they can be put on extracorporeal membrane oxygenation (ECMO). We do that on selected patients in our hospital, even though it’s very difficult to do, because we know that when it’s done properly, it can change survival rates dramatically, from maybe 10%-50%.”

Dr. Dr. Becker, like Dr. Parnia, also favors the development of drug cocktails, and his team has been experimenting with various combinations in animal models. “We think those two things together — ECMO and a drug cocktail — would be a very powerful one to two knock out for cardiac arrest,” he said. “We have a long way to go — 10 or 20 years. But most people around the world working in this area believe that will be the future.”

Dr. Parnia’s study on recalled death was supported by The John Templeton Foundation, Resuscitation Council (UK), and New York University Grossman School of Medicine, with research support staff provided by the UK’s National Institutes for Health Research. Soar is the editor of the journal Resuscitation and receives payment from the publisher Elsevier. Dr. Becker’s institute has received grants from Philips Medical Systems, NIH, Zoll Medical Corp, Nihon Kohden, PCORI, BrainCool, and United Therapeutics. He has received advisory/consultancy honoraria from NIH, Nihon Kohden, HP, and Philips, and he holds several patents in hypothermia induction and reperfusion therapies and several pending patents involving the use of medical slurries as human coolant devices to create reperfusion cocktails and measurement of respiratory quotient.

A version of this article appeared on Medscape.com.

If someone has been in cardiac arrest for 10 minutes, the brain is permanently damaged and there’s nothing to do, right?

Not so according to emerging evidence that suggests that the brain shows signs of electrical recovery for as long as an hour into ongoing cardiopulmonary resuscitation (CPR). This time between cardiac arrest and awakening can be a period of vivid experiences for the dying patient before they return to life — a phenomenon known as “recalled death.”

This should be an impetus to increase the use of devices that measure the quality of CPR and to find new treatments to restart the heart or prevent brain injury, experts advised. Cardiologists and critical care clinicians are among those who will need to manage patients in the aftermath.

“If people who go into cardiac arrest receive good quality chest compressions that restore blood flow to the brain, then consciousness is restored, as well, said Jasmeet Soar, MD, consultant in Anesthetics & Intensive Care Medicine, North Bristol NHS Trust, Bristol, England, and an editor of the journal Resuscitation.

“We know that because if chest compressions are stopped, the person becomes unconscious again,” he said. “This CPR-induced consciousness has become more common when professionals do the CPR because resuscitation guidelines now place a much bigger focus on high-quality CPR — ‘push hard, push fast.’ ” 

“People are giving up too soon on trying to revive individuals, and they should be trying more modern strategies, such as extracorporeal membrane oxygenation,” said Sam Parnia, MD, PhD, associate professor in the Department of Medicine at NYU Langone Health and director of critical care and resuscitation research at NYU Langone, New York City.

Brain Activity, Heightened Experiences

Two types of brain activity may occur when CPR works. The first, called CPR-induced consciousness, is when an individual recovers consciousness while in cardiac arrest. Signs of consciousness include combativeness, groaning, and eye-opening, Soar explained.

The second type is a perception of lucidity with recall of events, he said. “Patients who experience this may form memories that they can recall. We’re not sure whether that happens during CPR or while the patient is waking up during intensive care, or how the brain creates these memories, or if they’re real memories or coincidental, but it’s clear the brain does form them during the dying and recovery process.”

This latter phenomenon was explored in detail in a recent study led by Dr. Parnia.

In that study of 567 in-hospital patients with cardiac arrest from 25 centers in the United States and United Kingdom, 53 survived, 28 of those survivors were interviewed, and 11 reported memories or perceptions suggestive of consciousness.

Four types of experiences occurred:

• Recalled experiences of death: “I thought I heard my grandma [who had passed] saying ‘you need to go back.’”
• Emergence from coma during CPR/CPR-induced consciousness: “I remember when I came back and they were putting those two electrodes to my chest, and I remember the shock.”
• Emergence from coma in the post-resuscitation period: “I heard my partner saying [patient’s name] and my son saying ‘mom.’”
• Dreams and dream-like experiences: “[I] felt as though someone was holding my hand. It was very black; I couldn’t see anything.”

In a complementary cross-sectional study, 126 community cardiac arrest survivors reported similar experiences plus a fifth type, “delusions,” or “misattribution of medical events,” for example, “I heard my name, over and over again. All around me were things like demons and monsters. It felt like they were trying to tear off my body parts.”

“Many people label recalled experiences of death as ‘near-death’ experiences, but they’re not,” Dr. Parnia said. “Medically speaking, being near to death means your heart is about to stop. But the whole point is that these people are not near death. They actually died and came back from it.”

One of the big implications of the study, he said, is that “a lot of physicians are taught that somehow after, say, 3-5 minutes of oxygen deprivation, the brain dies. Our study showed this is not true. It showed that the brain may not be functioning, which is why they flatline. But if you’re able to resuscitate them appropriately, you can restore activity up to an hour later.”

Because some clinicians questioned or dismissed previous work in this area by Dr. Parnia and others, the latest study used EEG monitoring in a subset of 53 patients. Among those with evaluable EEG data, brain activity returned to normal or near-normal after flatlining in about 40% of images; spikes were seen in the delta (22%), theta (12%), alpha (6%), and beta (1%) waves associated with higher mental function.

“The team recorded what was happening in the brain during real-time CPR using various tests of consciousness, including EEG measurements and tests of visual and auditory awareness using a tablet with a special app and a Bluetooth headphone.”

“Incredibly, we found that even though the brain flatlines, which is what we expect when the heart stops, with professionally given CPR even up to about an hour after this, the brainwaves changed into normal to near-normal patterns,” Dr. Parnia said. “We were able to identify these brain waves in patients while they were being resuscitated, which confirms the fact that people can have lucid consciousness even though they appear to be unconscious.”

Asked what implications, if any, his work has for current definitions of brain death and cardiac death, Dr. Parnia said that the problem is that these are based on the concept of “a permanent irreversible loss of function,” but “that’s only relative to what medical treatments are developed at a given time.”

Potential Mechanism

Dr. Parnia and his team proposed a potential mechanism for recalled experiences of death. Essentially, when the brain flatlines, the dying brain removes natural inhibitory (braking) systems that are needed to support daily functioning. This disinhibition may open access to “new dimensions of reality, including lucid recall of stored memories from early childhood to death,” he said.

From a clinical perspective, he noted, “although the brain stops working when it flatlines, it does not die within 5 or 10 minutes of oxygen deprivation.”

This is contrary to what many doctors believe, and because of that, he said, “nobody has tried to find treatments or new ways to restart the heart or prevent brain injury. They think it’s futile. So, with this work, we’ve opened up the window to developing cocktails of drugs that could be given to patients who have technically gone through death to bring them back to life again.”

Probe Patients or Leave Well Enough Alone?

The findings have ramifications for clinicians who may be caring for patients who survive cardiac arrest, said Lance B. Becker, MD, professor and chair, Department of Emergency Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York, and chair, Department of Emergency Medicine at North Shore University Hospital, Manhasset, and Long Island Jewish Medical Center, Queens, New York.

“I’ve talked with a lot of patients who have had some kind of recalled experience around cardiac arrest and some who have had zero recall, as well, like in the paper,” he told this news organization. “The ones who do have an experience are sometimes mystified by it and have questions. And very often, clinicians don’t want to listen, don’t think it’s important, and downplay it.”

“I think it is important, and when people have important things happen to them, it’s really imperative that doctors listen, learn, and respond,” he said. “When I started in this field a long time ago, there were so few survivors that there wasn’t even a concept of survivorship,” he said.

Dr. Becker noted that it’s not uncommon for cardiac arrest survivors to have depression, problems with executive function, or a small brain injury they need to recover from. “Now survivorship organizations are springing up that these people can turn to, but clinicians still need to become more aware and sensitive to this.”

Not all are. “I had a number of patients who said I was the only doctor who ever asked them about what they experienced,” he recalled. “I was a young doctor at the time and didn’t exactly know what to say to them, but they were just happy to have a doctor who would listen to them and not be afraid to hear what they had to say.”

Recognizing that support is an issue, the American Heart Association released a scientific statement in 2020 on sudden cardiac arrest survivorship, which “expands the cardiac arrest resuscitation system of care to include patients, caregivers, and rehabilitative healthcare partnerships, which are central to cardiac survivorship.”

Soar has a more nuanced view of survivorship support, however. “I suspect some people are very glad to be alive, and that trying to dig deep and bring things out may actually be harmful,” he said. “It’s not as clear cut as everybody thinks.”

He noted that follow-up and rehabilitation should be an option for people who specifically need it who would need to be identified. “But human beings are resilient, and while some people will require help, not everybody will,” he said.

Better CPR, New Treatments

Experts in emergency and intensive care medicine studying survival after cardiac arrest hope to find ways to save patients before too much damage is done to the brain and other organs from loss of oxygen, Dr. Parnia said. He is the lead author in a recent multidisciplinary consensus statement on guidelines and standards for the study of death and recalled experiences of death.

“One of my bugbears is that our survival outcomes from cardiac arrest resuscitation have not changed very much for 60 years because we haven’t developed new treatments and innovative methods,” he said. “Unlike the rest of medicine, we’re living in the past.”

Currently, his team is developing cocktails of treatments. These include hypothermic circulatory arrest — cooling the body to stop blood circulation and brain function for up to 40 minutes — and giving magnesium, a brain-protective treatment, to people whose hearts stop.

Dr. Becker would like to see optimal care of patients with cardiac arrest. “The first step is to increase blood flow with good CPR and then measure whether CPR is working,” he said. Adding that despite the availability of devices that provide feedback on the quality of CPR, they’re rarely used. He cited ultrasound devices that measure the blood flow generated during CPR, compression meter devices that go between the patient’s chest and the rescuer’s hands that gauge the rate and depth of compression, and invasive devices that measure blood pressure during CPR.

His group is trying to design even better devices, he said. “An example would be a little probe that you could pop on the neck that would study blood flow to the brain with ultrasound, so that while you were pumping on the person, you could see if you’re making them better or not.”

“We also have some preliminary data showing that the American Heart Association recommended position on the chest for doing CPR is not the perfect place for everybody,” he said. The 2020 AHA guidelines recommended the center of the lower half of the sternum. At the 2023 American College of Emergency Physicians meeting, Dr. Becker›s team at Hofstra/Northwell presented data on 175 video-recorded adult cardiac arrests in their emergency department over more than 2 years, 22 of which involved at least one change of compression location (for a total of 29 location changes). They found that 41% of compression location changes were associated with return of spontaneous circulation.

For about a third of people, the hands need to be repositioned slightly. “This is not anything that is taught to the public because you can only figure it out if you have some kind of sensor that will let you know how you’re doing. That’s very achievable. We could have that in the future on every ambulance and even in people’s homes.”

When the person arrives at the hospital, he said, “we can make it easier and more likely that they can be put on extracorporeal membrane oxygenation (ECMO). We do that on selected patients in our hospital, even though it’s very difficult to do, because we know that when it’s done properly, it can change survival rates dramatically, from maybe 10%-50%.”

Dr. Dr. Becker, like Dr. Parnia, also favors the development of drug cocktails, and his team has been experimenting with various combinations in animal models. “We think those two things together — ECMO and a drug cocktail — would be a very powerful one to two knock out for cardiac arrest,” he said. “We have a long way to go — 10 or 20 years. But most people around the world working in this area believe that will be the future.”

Dr. Parnia’s study on recalled death was supported by The John Templeton Foundation, Resuscitation Council (UK), and New York University Grossman School of Medicine, with research support staff provided by the UK’s National Institutes for Health Research. Soar is the editor of the journal Resuscitation and receives payment from the publisher Elsevier. Dr. Becker’s institute has received grants from Philips Medical Systems, NIH, Zoll Medical Corp, Nihon Kohden, PCORI, BrainCool, and United Therapeutics. He has received advisory/consultancy honoraria from NIH, Nihon Kohden, HP, and Philips, and he holds several patents in hypothermia induction and reperfusion therapies and several pending patents involving the use of medical slurries as human coolant devices to create reperfusion cocktails and measurement of respiratory quotient.

A version of this article appeared on Medscape.com.