Extraverts and individuals who are disciplined are less likely to experience cognitive decline later in life, whereas those with neuroticism have an increased risk for cognitive dysfunction, new research shows.

Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.

Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.

Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.

“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.

“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.

The study was published online in the Journal of Personality and Social Psychology.
 

Competing risk factors

Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.

“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.

Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”

Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”  

For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.

To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
 

Cognitive healthspan

By the end of the study, over half of the sample (54%) had died.

Most transitions showed “relative stability in cognitive status across measurement occasions.”

• NCI to NCI (n = 7,368)
• MCI to MCI (n = 1,244)
• Dementia to dementia (n = 876)

There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.

There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”

After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.

Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).

Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.

Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.

“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.

Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.

In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.

The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.

Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
 

‘Invaluable window’

In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”

“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.

Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.

Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”

The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.

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

Extraverts and individuals who are disciplined are less likely to experience cognitive decline later in life, whereas those with neuroticism have an increased risk for cognitive dysfunction, new research shows.

Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.

Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.

Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.

“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.

“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.

The study was published online in the Journal of Personality and Social Psychology.
 

Competing risk factors

Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.

“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.

Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”

Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”  

For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.

To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
 

Cognitive healthspan

By the end of the study, over half of the sample (54%) had died.

Most transitions showed “relative stability in cognitive status across measurement occasions.”

• NCI to NCI (n = 7,368)
• MCI to MCI (n = 1,244)
• Dementia to dementia (n = 876)

There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.

There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”

After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.

Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).

Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.

Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.

“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.

Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.

In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.

The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.

Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
 

‘Invaluable window’

In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”

“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.

Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.

Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”

The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.

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

Extraverts and individuals who are disciplined are less likely to experience cognitive decline later in life, whereas those with neuroticism have an increased risk for cognitive dysfunction, new research shows.

Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.

Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.

Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.

“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.

“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.

The study was published online in the Journal of Personality and Social Psychology.
 

Competing risk factors

Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.

“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.

Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”

Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”  

For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.

To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
 

Cognitive healthspan

By the end of the study, over half of the sample (54%) had died.

Most transitions showed “relative stability in cognitive status across measurement occasions.”

• NCI to NCI (n = 7,368)
• MCI to MCI (n = 1,244)
• Dementia to dementia (n = 876)

There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.

There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”

After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.

Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).

Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.

Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.

“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.

Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.

In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.

The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.

Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
 

‘Invaluable window’

In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”

“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.

Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.

Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”

The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.

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

Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.

Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.

Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.

The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.

Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.

“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.

Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”

The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.

Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.

When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.

Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.

“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”

“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”

For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.

For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.

“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”

Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.

“We need more information on what drives this in older adults,” she said.

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

Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.

Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.

Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.

The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.

Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.

“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.

Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”

The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.

Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.

When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.

Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.

“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”

“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”

For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.

For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.

“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”

Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.

“We need more information on what drives this in older adults,” she said.

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

Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.

Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.

Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.

The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.

Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.

“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.

Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”

The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.

Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.

When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.

Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.

“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”

“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”

For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.

For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.

“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”

Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.

“We need more information on what drives this in older adults,” she said.

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

In an unprecedented murder case about end-of-life care, a physician accused of killing 14 critically ill patients with opioid overdoses in a Columbus, Ohio, hospital ICU over a period of 4 years was found not guilty by a jury April 20.

The jury, after a 7-week trial featuring more than 50 witnesses in the Franklin County Court of Common Pleas, declared William Husel, DO, not guilty on 14 counts of murder and attempted murder.

In a news conference after the verdict was announced, lead defense attorney Jose Baez said Dr. Husel, whom he called a “great doctor,” hopes to practice medicine again in the future. The verdict, he argued, offers an encouraging sign that physicians and other providers won’t face prosecution for providing “comfort care” to patients suffering pain. “They don’t need to be looking over their shoulders worrying about whether they’ll get charged with crimes,” he said.

The prosecutors in the case declined to comment, other than to say they “accept” the verdict.

Legal experts said it’s highly unlikely that Ohio or any other state would restore Dr. Husel’s suspended medical license. “I doubt he could ever work in medicine again,” said Mark Schumacher, a Columbus medical malpractice defense attorney who retired in 2020 after practicing for 39 years. Mr. Schumacher followed the trial closely.

The trial raised the specific issue of what constitutes a medically justifiable dose of opioid painkillers during the end-of-life procedure known as palliative extubation, in which critically ill patients are withdrawn from the ventilator when they are expected to die. Under medicine’s so-called double-effect principle, physicians must weigh the benefits and risks of ordering potentially lethal doses of painkillers and sedatives to provide comfort care for critically ill patients.

To many observers, however, the case really centered on the largely hidden debate over whether it’s acceptable to hasten the deaths of dying patients who haven’t chosen that path. That’s called euthanasia, which is illegal in the United States. In contrast, 10 states plus the District of Columbia allow physicians to prescribe lethal drugs to terminally ill, mentally competent adults who can self-administer them. That’s called medical aid in dying, or physician-assisted dying or suicide.

“Maybe this is a wake-up call that people believe this is the right thing to do,” said Lewis Nelson, MD, chair of emergency medicine at New Jersey Medical School in Newark. “The medical community has a sense that we often prolong life unnecessarily. But a physician cannot unilaterally decide it’s time for someone to die. It sounds like [Dr. Husel] took that decision into his own hands.”

The case also exposed major gaps in the patient safety culture at Mount Carmel West Hospital in Columbus, which is owned by the Catholic chain Trinity Health. Experts say failures by hospital staff to question physicians’ orders and raise patient safety concerns, as happened at Mount Carmel, occur at many hospitals around the country. Experts say the Husel case offers vital lessons for health care professionals about improving safety procedures.

“This is an extreme example, that everyone should learn from, about what not to do,” said Michael Cohen, RPh, founder and president emeritus of the Institute for Safe Medication Practices. “Husel was giving massive overdoses of drugs, people knew it was problematic, and someone didn’t put their foot down. You’ve got to have a process in place to address these situations where there is disagreement over the safety of a medication order.”

Dr. Husel was charged with killing the 14 patients from 2015 through 2018 by ordering single large doses of the painkiller fentanyl – from 500 to 2,000 micrograms – often in combination with other opioids and sedatives, while working as the solo physician on the overnight shift in the ICU at Mount Carmel West Hospital and at Mount Carmel St. Ann’s Hospital in Westerville, Ohio.

Dr. Husel ordered administration of the drugs while his patients were having an endotracheal tube removed as part of palliative extubation. There was conflicting testimony during the trial about whether the patients were showing signs of pain or were even capable of feeling pain.

Prosecutors argued that Dr. Husel, who did a residency and fellowship in critical care medicine at Cleveland Clinic and started working at Mount Carmel in 2013 in his first job as a full-fledged physician, intended to kill the patients or hasten their deaths. They contended that the inexperienced nurses in the ICU went along with his large drug doses because they were “in thrall” to him because of his prestigious background at the Cleveland Clinic and his willingness to take the time to teach them.

“With his training in anesthesiology, he knew what those drugs do,” assistant prosecutor David Zeyen said in closing arguments. “This isn’t negligence. This is on purpose ... Euthanizing animals with the intent to kill is fine in veterinary medicine. It’s not fine in the ICU at Mount Carmel or anywhere.”

The defense team argued that Dr. Husel was a caring and compassionate physician who ordered the drugs to relieve the patients’ pain and discomfort during the extubation process. He did not testify.

“Common sense says Dr Husel had no motive to harm patients,” defense attorney Baez said in his closing. “He dedicated his life to taking care of patients and saving lives, not taking them. ... Why would this man risk his family, career, and 17 years of trying to be a doctor to hasten someone’s death or kill them?”

There were 35 Mount Carmel patients who died in the ICU under Dr. Husel’s care after receiving large fentanyl doses during palliative extubation. The state originally charged him with murder in 25 of those cases, then reduced that to 14.

Many of Dr. Husel’s drug orders were given verbally instead of through the regular process of being entered into the electronic health record. He and the nurses on duty also skipped the standard nonemergency process of getting approval from the pharmacist on duty, instead using the override function on Mount Carmel’s automated Pyxis drug dispensing system.

Dr. Husel’s unusual dosing patterns were first reported to Mount Carmel officials by pharmacists in October 2018, spurring an investigation. The hospital system let him go in December 2018, after concluding that the opioid dosages he used were “significantly excessive and potentially fatal” and “went beyond providing comfort.”

Nearly two dozen RNs and two pharmacists involved in these cases have faced state disciplinary action, mostly license suspension. Federal and state agencies have cited the Mount Carmel system for faults in its patient safety processes and culture that were exposed by the Husel cases.

The Mount Carmel CEO; the chief clinical officer; other physician, nursing, and pharmacy leaders; and dozens of nurses and pharmacists were forced out following the Husel investigation.

In 2019, the Centers for Medicare & Medicaid  Services, after threatening to cut off federal reimbursements to Mount Carmel, accepted the hospital system’s correction plan restricting the use of verbal drug orders and prohibiting Pyxis system overrides for opioids except in life-threatening emergencies. The Ohio Board of Pharmacy hit Mount Carmel with $477,000 in fines and costs for pharmacy rules violations.

Mount Carmel and Trinity have settled a number of civil wrongful death lawsuits filed by the families of Dr. Husel’s patients for nearly $20 million, with many more suits pending. Gerry Leeseberg, a Columbus medical malpractice plaintiff attorney who is representing 17 of the families, said a number of the cases are set for trial starting in June.

During the trial, family members of many of the 14 patients whom Dr. Husel allegedly murdered testified that Dr. Husel told them their loved ones were dying. Some said they felt rushed into making a decision to extubate the person.

Before performing a palliative extubation, physicians commonly administer opioids and/or sedatives to ease pain and discomfort, and spare family members from witnessing their loved ones gasping for breath. But most medical experts – including the state’s two physician expert witnesses – say the fentanyl doses Dr. Husel ordered were 5-20 times larger than doses normally used in palliative extubation. Such doses, they say, will quickly kill most patients – except those with high opioid tolerance – by stopping their breathing.

Physicians say they typically give much smaller doses of fentanyl or morphine, then administer more as needed if they observe the patient experiencing pain or distress. Mount Carmel’s 2016 guidelines for IV administration of fentanyl specified a dosage range of 50-100 micrograms for relieving pain, and its 2018 guidelines reduced that to 25-50 micrograms.

The doses Dr. Husel ordered are lethal, even for most patients with some tolerance to opioids, said Rutgers EM chair Dr. Nelson, who practices medical toxicology and addiction medicine. “Those are doses to provide euthanasia, not to relieve pain.”

At trial, the prosecutors had to overcome two big challenges to win murder convictions against Dr. Husel: They had to prove beyond a reasonable doubt that the drugs Dr. Husel ordered are what directly caused these critically ill patients to die, and that he intended to kill them.

Late in the trial, at the state’s request, the judge ruled to allow the jury to also consider attempted murder charges, which require proof of intent but not that the defendant’s actions directly caused the deaths.

Another challenge was that physicians have certain legal protections for administering drugs to patients for the purpose of relieving pain and suffering, even if the drugs hasten the patients’ deaths – as long the intent was not to cause death and the drugs were properly used. This is known as the double-effect principle. In contrast, intentional killing to relieve pain and suffering is called euthanasia. That’s what prosecutors accused Dr. Husel of doing.

“If you hasten a person’s death, even if their death is as sure as the sun is going to rise in the morning ... you have caused their death in the eyes of the law,” assistant prosecutor Mr. Zeyen said in his closing. “You don’t get a pass for killing a dying man ...”

Mr. Leeseberg said it was always going to be extremely hard to convince a jury to convict a physician of murder, with the potential of life in prison, in a case where the physician’s acts occurred openly over 4 years in a hospital setting where no one did anything to stop him. It would have been much easier to convince a jury to convict him of reckless homicide, a lesser offense with a shorter prison term. That would have required proving that he acted in reckless disregard for his patients’ health and safety.

In post-verdict comments to the news media, Judge Michael Holbrook said jurors told him that the procedures for the dispensing of fentanyl and other drugs at Mount Carmel weren’t properly explained to them during the trial, and that they were confused by the large number of prosecution witnesses. He also said they were confused that no one had stated a maximum dosage for fentanyl.

Mr. Schumacher, the retired malpractice defense lawyer who followed the trial, disagreed with defense attorney Baez’s takeaway about the impact of the case on pain-relief practices. In his view, the case likely will heighten rather than reduce the anxiety of physicians and nurses about administering opioids, even when the dosages are clearly needed and appropriate. He doesn’t think Dr. Husel’s dosages can be justified, however. 

“Physicians have a naive overreaction to any legal development, and overgeneralize from a particular case to everyday practice,” he said.

There is only one known prior case that’s somewhat comparable of a physician tried for murder or attempted murder for giving a critically ill patient opioids for pain relief. In 1996, a Kansas jury convicted Lloyd Stanley Naramore, DO, of attempted murder in the death of a patient to whom he gave an opioid, and of second-degree murder for removing a patient from a ventilator. After Dr. Naramore served 6 months in prison, an appellate court reversed the convictions for lack of evidence.

In March, RaDonda Vaught, a nurse who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted of criminal neglect and negligent homicide for mistakenly administering a fatal dose of the paralyzing drug vecuronium, instead of the prescribed drug Versed (midazolam), to a patient. Providers around the country were alarmed by her criminal prosecution for what was clearly an unintentional error.

But legal and medical experts said Dr. Husel’s case was sharply different from Vaught’s and Dr. Naramore’s because he deliberately and repeatedly ordered large doses of fentanyl and other drugs that he knew or should have known were potentially lethal. “You don’t need 2,000 micrograms of fentanyl plus other drugs for comfort care, and repeat that again and again for patient after patient,” said Mr. Cohen, of the Institute for Safe Medication Practices. “No one gives that to patients. You’ll knock them off.”

During the trial, prosecutors said repeatedly that no one except Dr. Husel knows what he was thinking when he ordered those huge drug dosages for his ICU patients. Judge Holbrook told the jury the state did not have to prove motive, only intent. But many observers still have wondered what his motives were.

Dr. Husel’s own view of his care in these cases soon will become public. Immediately after the April 20 verdict, Mr. Leeseberg filed a notice requesting a May 9 deposition of Dr. Husel, who will no longer be able to claim the Fifth Amendment right against self-incrimination. He predicted the deposition will last about a week, and then the transcript will be publicly available.

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

In an unprecedented murder case about end-of-life care, a physician accused of killing 14 critically ill patients with opioid overdoses in a Columbus, Ohio, hospital ICU over a period of 4 years was found not guilty by a jury April 20.

The jury, after a 7-week trial featuring more than 50 witnesses in the Franklin County Court of Common Pleas, declared William Husel, DO, not guilty on 14 counts of murder and attempted murder.

In a news conference after the verdict was announced, lead defense attorney Jose Baez said Dr. Husel, whom he called a “great doctor,” hopes to practice medicine again in the future. The verdict, he argued, offers an encouraging sign that physicians and other providers won’t face prosecution for providing “comfort care” to patients suffering pain. “They don’t need to be looking over their shoulders worrying about whether they’ll get charged with crimes,” he said.

The prosecutors in the case declined to comment, other than to say they “accept” the verdict.

Legal experts said it’s highly unlikely that Ohio or any other state would restore Dr. Husel’s suspended medical license. “I doubt he could ever work in medicine again,” said Mark Schumacher, a Columbus medical malpractice defense attorney who retired in 2020 after practicing for 39 years. Mr. Schumacher followed the trial closely.

The trial raised the specific issue of what constitutes a medically justifiable dose of opioid painkillers during the end-of-life procedure known as palliative extubation, in which critically ill patients are withdrawn from the ventilator when they are expected to die. Under medicine’s so-called double-effect principle, physicians must weigh the benefits and risks of ordering potentially lethal doses of painkillers and sedatives to provide comfort care for critically ill patients.

To many observers, however, the case really centered on the largely hidden debate over whether it’s acceptable to hasten the deaths of dying patients who haven’t chosen that path. That’s called euthanasia, which is illegal in the United States. In contrast, 10 states plus the District of Columbia allow physicians to prescribe lethal drugs to terminally ill, mentally competent adults who can self-administer them. That’s called medical aid in dying, or physician-assisted dying or suicide.

“Maybe this is a wake-up call that people believe this is the right thing to do,” said Lewis Nelson, MD, chair of emergency medicine at New Jersey Medical School in Newark. “The medical community has a sense that we often prolong life unnecessarily. But a physician cannot unilaterally decide it’s time for someone to die. It sounds like [Dr. Husel] took that decision into his own hands.”

The case also exposed major gaps in the patient safety culture at Mount Carmel West Hospital in Columbus, which is owned by the Catholic chain Trinity Health. Experts say failures by hospital staff to question physicians’ orders and raise patient safety concerns, as happened at Mount Carmel, occur at many hospitals around the country. Experts say the Husel case offers vital lessons for health care professionals about improving safety procedures.

“This is an extreme example, that everyone should learn from, about what not to do,” said Michael Cohen, RPh, founder and president emeritus of the Institute for Safe Medication Practices. “Husel was giving massive overdoses of drugs, people knew it was problematic, and someone didn’t put their foot down. You’ve got to have a process in place to address these situations where there is disagreement over the safety of a medication order.”

Dr. Husel was charged with killing the 14 patients from 2015 through 2018 by ordering single large doses of the painkiller fentanyl – from 500 to 2,000 micrograms – often in combination with other opioids and sedatives, while working as the solo physician on the overnight shift in the ICU at Mount Carmel West Hospital and at Mount Carmel St. Ann’s Hospital in Westerville, Ohio.

Dr. Husel ordered administration of the drugs while his patients were having an endotracheal tube removed as part of palliative extubation. There was conflicting testimony during the trial about whether the patients were showing signs of pain or were even capable of feeling pain.

Prosecutors argued that Dr. Husel, who did a residency and fellowship in critical care medicine at Cleveland Clinic and started working at Mount Carmel in 2013 in his first job as a full-fledged physician, intended to kill the patients or hasten their deaths. They contended that the inexperienced nurses in the ICU went along with his large drug doses because they were “in thrall” to him because of his prestigious background at the Cleveland Clinic and his willingness to take the time to teach them.

“With his training in anesthesiology, he knew what those drugs do,” assistant prosecutor David Zeyen said in closing arguments. “This isn’t negligence. This is on purpose ... Euthanizing animals with the intent to kill is fine in veterinary medicine. It’s not fine in the ICU at Mount Carmel or anywhere.”

The defense team argued that Dr. Husel was a caring and compassionate physician who ordered the drugs to relieve the patients’ pain and discomfort during the extubation process. He did not testify.

“Common sense says Dr Husel had no motive to harm patients,” defense attorney Baez said in his closing. “He dedicated his life to taking care of patients and saving lives, not taking them. ... Why would this man risk his family, career, and 17 years of trying to be a doctor to hasten someone’s death or kill them?”

There were 35 Mount Carmel patients who died in the ICU under Dr. Husel’s care after receiving large fentanyl doses during palliative extubation. The state originally charged him with murder in 25 of those cases, then reduced that to 14.

Many of Dr. Husel’s drug orders were given verbally instead of through the regular process of being entered into the electronic health record. He and the nurses on duty also skipped the standard nonemergency process of getting approval from the pharmacist on duty, instead using the override function on Mount Carmel’s automated Pyxis drug dispensing system.

Dr. Husel’s unusual dosing patterns were first reported to Mount Carmel officials by pharmacists in October 2018, spurring an investigation. The hospital system let him go in December 2018, after concluding that the opioid dosages he used were “significantly excessive and potentially fatal” and “went beyond providing comfort.”

Nearly two dozen RNs and two pharmacists involved in these cases have faced state disciplinary action, mostly license suspension. Federal and state agencies have cited the Mount Carmel system for faults in its patient safety processes and culture that were exposed by the Husel cases.

The Mount Carmel CEO; the chief clinical officer; other physician, nursing, and pharmacy leaders; and dozens of nurses and pharmacists were forced out following the Husel investigation.

In 2019, the Centers for Medicare & Medicaid  Services, after threatening to cut off federal reimbursements to Mount Carmel, accepted the hospital system’s correction plan restricting the use of verbal drug orders and prohibiting Pyxis system overrides for opioids except in life-threatening emergencies. The Ohio Board of Pharmacy hit Mount Carmel with $477,000 in fines and costs for pharmacy rules violations.

Mount Carmel and Trinity have settled a number of civil wrongful death lawsuits filed by the families of Dr. Husel’s patients for nearly $20 million, with many more suits pending. Gerry Leeseberg, a Columbus medical malpractice plaintiff attorney who is representing 17 of the families, said a number of the cases are set for trial starting in June.

During the trial, family members of many of the 14 patients whom Dr. Husel allegedly murdered testified that Dr. Husel told them their loved ones were dying. Some said they felt rushed into making a decision to extubate the person.

Before performing a palliative extubation, physicians commonly administer opioids and/or sedatives to ease pain and discomfort, and spare family members from witnessing their loved ones gasping for breath. But most medical experts – including the state’s two physician expert witnesses – say the fentanyl doses Dr. Husel ordered were 5-20 times larger than doses normally used in palliative extubation. Such doses, they say, will quickly kill most patients – except those with high opioid tolerance – by stopping their breathing.

Physicians say they typically give much smaller doses of fentanyl or morphine, then administer more as needed if they observe the patient experiencing pain or distress. Mount Carmel’s 2016 guidelines for IV administration of fentanyl specified a dosage range of 50-100 micrograms for relieving pain, and its 2018 guidelines reduced that to 25-50 micrograms.

The doses Dr. Husel ordered are lethal, even for most patients with some tolerance to opioids, said Rutgers EM chair Dr. Nelson, who practices medical toxicology and addiction medicine. “Those are doses to provide euthanasia, not to relieve pain.”

At trial, the prosecutors had to overcome two big challenges to win murder convictions against Dr. Husel: They had to prove beyond a reasonable doubt that the drugs Dr. Husel ordered are what directly caused these critically ill patients to die, and that he intended to kill them.

Late in the trial, at the state’s request, the judge ruled to allow the jury to also consider attempted murder charges, which require proof of intent but not that the defendant’s actions directly caused the deaths.

Another challenge was that physicians have certain legal protections for administering drugs to patients for the purpose of relieving pain and suffering, even if the drugs hasten the patients’ deaths – as long the intent was not to cause death and the drugs were properly used. This is known as the double-effect principle. In contrast, intentional killing to relieve pain and suffering is called euthanasia. That’s what prosecutors accused Dr. Husel of doing.

“If you hasten a person’s death, even if their death is as sure as the sun is going to rise in the morning ... you have caused their death in the eyes of the law,” assistant prosecutor Mr. Zeyen said in his closing. “You don’t get a pass for killing a dying man ...”

Mr. Leeseberg said it was always going to be extremely hard to convince a jury to convict a physician of murder, with the potential of life in prison, in a case where the physician’s acts occurred openly over 4 years in a hospital setting where no one did anything to stop him. It would have been much easier to convince a jury to convict him of reckless homicide, a lesser offense with a shorter prison term. That would have required proving that he acted in reckless disregard for his patients’ health and safety.

In post-verdict comments to the news media, Judge Michael Holbrook said jurors told him that the procedures for the dispensing of fentanyl and other drugs at Mount Carmel weren’t properly explained to them during the trial, and that they were confused by the large number of prosecution witnesses. He also said they were confused that no one had stated a maximum dosage for fentanyl.

Mr. Schumacher, the retired malpractice defense lawyer who followed the trial, disagreed with defense attorney Baez’s takeaway about the impact of the case on pain-relief practices. In his view, the case likely will heighten rather than reduce the anxiety of physicians and nurses about administering opioids, even when the dosages are clearly needed and appropriate. He doesn’t think Dr. Husel’s dosages can be justified, however. 

“Physicians have a naive overreaction to any legal development, and overgeneralize from a particular case to everyday practice,” he said.

There is only one known prior case that’s somewhat comparable of a physician tried for murder or attempted murder for giving a critically ill patient opioids for pain relief. In 1996, a Kansas jury convicted Lloyd Stanley Naramore, DO, of attempted murder in the death of a patient to whom he gave an opioid, and of second-degree murder for removing a patient from a ventilator. After Dr. Naramore served 6 months in prison, an appellate court reversed the convictions for lack of evidence.

In March, RaDonda Vaught, a nurse who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted of criminal neglect and negligent homicide for mistakenly administering a fatal dose of the paralyzing drug vecuronium, instead of the prescribed drug Versed (midazolam), to a patient. Providers around the country were alarmed by her criminal prosecution for what was clearly an unintentional error.

But legal and medical experts said Dr. Husel’s case was sharply different from Vaught’s and Dr. Naramore’s because he deliberately and repeatedly ordered large doses of fentanyl and other drugs that he knew or should have known were potentially lethal. “You don’t need 2,000 micrograms of fentanyl plus other drugs for comfort care, and repeat that again and again for patient after patient,” said Mr. Cohen, of the Institute for Safe Medication Practices. “No one gives that to patients. You’ll knock them off.”

During the trial, prosecutors said repeatedly that no one except Dr. Husel knows what he was thinking when he ordered those huge drug dosages for his ICU patients. Judge Holbrook told the jury the state did not have to prove motive, only intent. But many observers still have wondered what his motives were.

Dr. Husel’s own view of his care in these cases soon will become public. Immediately after the April 20 verdict, Mr. Leeseberg filed a notice requesting a May 9 deposition of Dr. Husel, who will no longer be able to claim the Fifth Amendment right against self-incrimination. He predicted the deposition will last about a week, and then the transcript will be publicly available.

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

In an unprecedented murder case about end-of-life care, a physician accused of killing 14 critically ill patients with opioid overdoses in a Columbus, Ohio, hospital ICU over a period of 4 years was found not guilty by a jury April 20.

The jury, after a 7-week trial featuring more than 50 witnesses in the Franklin County Court of Common Pleas, declared William Husel, DO, not guilty on 14 counts of murder and attempted murder.

In a news conference after the verdict was announced, lead defense attorney Jose Baez said Dr. Husel, whom he called a “great doctor,” hopes to practice medicine again in the future. The verdict, he argued, offers an encouraging sign that physicians and other providers won’t face prosecution for providing “comfort care” to patients suffering pain. “They don’t need to be looking over their shoulders worrying about whether they’ll get charged with crimes,” he said.

The prosecutors in the case declined to comment, other than to say they “accept” the verdict.

Legal experts said it’s highly unlikely that Ohio or any other state would restore Dr. Husel’s suspended medical license. “I doubt he could ever work in medicine again,” said Mark Schumacher, a Columbus medical malpractice defense attorney who retired in 2020 after practicing for 39 years. Mr. Schumacher followed the trial closely.

The trial raised the specific issue of what constitutes a medically justifiable dose of opioid painkillers during the end-of-life procedure known as palliative extubation, in which critically ill patients are withdrawn from the ventilator when they are expected to die. Under medicine’s so-called double-effect principle, physicians must weigh the benefits and risks of ordering potentially lethal doses of painkillers and sedatives to provide comfort care for critically ill patients.

To many observers, however, the case really centered on the largely hidden debate over whether it’s acceptable to hasten the deaths of dying patients who haven’t chosen that path. That’s called euthanasia, which is illegal in the United States. In contrast, 10 states plus the District of Columbia allow physicians to prescribe lethal drugs to terminally ill, mentally competent adults who can self-administer them. That’s called medical aid in dying, or physician-assisted dying or suicide.

“Maybe this is a wake-up call that people believe this is the right thing to do,” said Lewis Nelson, MD, chair of emergency medicine at New Jersey Medical School in Newark. “The medical community has a sense that we often prolong life unnecessarily. But a physician cannot unilaterally decide it’s time for someone to die. It sounds like [Dr. Husel] took that decision into his own hands.”

The case also exposed major gaps in the patient safety culture at Mount Carmel West Hospital in Columbus, which is owned by the Catholic chain Trinity Health. Experts say failures by hospital staff to question physicians’ orders and raise patient safety concerns, as happened at Mount Carmel, occur at many hospitals around the country. Experts say the Husel case offers vital lessons for health care professionals about improving safety procedures.

“This is an extreme example, that everyone should learn from, about what not to do,” said Michael Cohen, RPh, founder and president emeritus of the Institute for Safe Medication Practices. “Husel was giving massive overdoses of drugs, people knew it was problematic, and someone didn’t put their foot down. You’ve got to have a process in place to address these situations where there is disagreement over the safety of a medication order.”

Dr. Husel was charged with killing the 14 patients from 2015 through 2018 by ordering single large doses of the painkiller fentanyl – from 500 to 2,000 micrograms – often in combination with other opioids and sedatives, while working as the solo physician on the overnight shift in the ICU at Mount Carmel West Hospital and at Mount Carmel St. Ann’s Hospital in Westerville, Ohio.

Dr. Husel ordered administration of the drugs while his patients were having an endotracheal tube removed as part of palliative extubation. There was conflicting testimony during the trial about whether the patients were showing signs of pain or were even capable of feeling pain.

Prosecutors argued that Dr. Husel, who did a residency and fellowship in critical care medicine at Cleveland Clinic and started working at Mount Carmel in 2013 in his first job as a full-fledged physician, intended to kill the patients or hasten their deaths. They contended that the inexperienced nurses in the ICU went along with his large drug doses because they were “in thrall” to him because of his prestigious background at the Cleveland Clinic and his willingness to take the time to teach them.

“With his training in anesthesiology, he knew what those drugs do,” assistant prosecutor David Zeyen said in closing arguments. “This isn’t negligence. This is on purpose ... Euthanizing animals with the intent to kill is fine in veterinary medicine. It’s not fine in the ICU at Mount Carmel or anywhere.”

The defense team argued that Dr. Husel was a caring and compassionate physician who ordered the drugs to relieve the patients’ pain and discomfort during the extubation process. He did not testify.

“Common sense says Dr Husel had no motive to harm patients,” defense attorney Baez said in his closing. “He dedicated his life to taking care of patients and saving lives, not taking them. ... Why would this man risk his family, career, and 17 years of trying to be a doctor to hasten someone’s death or kill them?”

There were 35 Mount Carmel patients who died in the ICU under Dr. Husel’s care after receiving large fentanyl doses during palliative extubation. The state originally charged him with murder in 25 of those cases, then reduced that to 14.

Many of Dr. Husel’s drug orders were given verbally instead of through the regular process of being entered into the electronic health record. He and the nurses on duty also skipped the standard nonemergency process of getting approval from the pharmacist on duty, instead using the override function on Mount Carmel’s automated Pyxis drug dispensing system.

Dr. Husel’s unusual dosing patterns were first reported to Mount Carmel officials by pharmacists in October 2018, spurring an investigation. The hospital system let him go in December 2018, after concluding that the opioid dosages he used were “significantly excessive and potentially fatal” and “went beyond providing comfort.”

Nearly two dozen RNs and two pharmacists involved in these cases have faced state disciplinary action, mostly license suspension. Federal and state agencies have cited the Mount Carmel system for faults in its patient safety processes and culture that were exposed by the Husel cases.

The Mount Carmel CEO; the chief clinical officer; other physician, nursing, and pharmacy leaders; and dozens of nurses and pharmacists were forced out following the Husel investigation.

In 2019, the Centers for Medicare & Medicaid  Services, after threatening to cut off federal reimbursements to Mount Carmel, accepted the hospital system’s correction plan restricting the use of verbal drug orders and prohibiting Pyxis system overrides for opioids except in life-threatening emergencies. The Ohio Board of Pharmacy hit Mount Carmel with $477,000 in fines and costs for pharmacy rules violations.

Mount Carmel and Trinity have settled a number of civil wrongful death lawsuits filed by the families of Dr. Husel’s patients for nearly $20 million, with many more suits pending. Gerry Leeseberg, a Columbus medical malpractice plaintiff attorney who is representing 17 of the families, said a number of the cases are set for trial starting in June.

During the trial, family members of many of the 14 patients whom Dr. Husel allegedly murdered testified that Dr. Husel told them their loved ones were dying. Some said they felt rushed into making a decision to extubate the person.

Before performing a palliative extubation, physicians commonly administer opioids and/or sedatives to ease pain and discomfort, and spare family members from witnessing their loved ones gasping for breath. But most medical experts – including the state’s two physician expert witnesses – say the fentanyl doses Dr. Husel ordered were 5-20 times larger than doses normally used in palliative extubation. Such doses, they say, will quickly kill most patients – except those with high opioid tolerance – by stopping their breathing.

Physicians say they typically give much smaller doses of fentanyl or morphine, then administer more as needed if they observe the patient experiencing pain or distress. Mount Carmel’s 2016 guidelines for IV administration of fentanyl specified a dosage range of 50-100 micrograms for relieving pain, and its 2018 guidelines reduced that to 25-50 micrograms.

The doses Dr. Husel ordered are lethal, even for most patients with some tolerance to opioids, said Rutgers EM chair Dr. Nelson, who practices medical toxicology and addiction medicine. “Those are doses to provide euthanasia, not to relieve pain.”

At trial, the prosecutors had to overcome two big challenges to win murder convictions against Dr. Husel: They had to prove beyond a reasonable doubt that the drugs Dr. Husel ordered are what directly caused these critically ill patients to die, and that he intended to kill them.

Late in the trial, at the state’s request, the judge ruled to allow the jury to also consider attempted murder charges, which require proof of intent but not that the defendant’s actions directly caused the deaths.

Another challenge was that physicians have certain legal protections for administering drugs to patients for the purpose of relieving pain and suffering, even if the drugs hasten the patients’ deaths – as long the intent was not to cause death and the drugs were properly used. This is known as the double-effect principle. In contrast, intentional killing to relieve pain and suffering is called euthanasia. That’s what prosecutors accused Dr. Husel of doing.

“If you hasten a person’s death, even if their death is as sure as the sun is going to rise in the morning ... you have caused their death in the eyes of the law,” assistant prosecutor Mr. Zeyen said in his closing. “You don’t get a pass for killing a dying man ...”

Mr. Leeseberg said it was always going to be extremely hard to convince a jury to convict a physician of murder, with the potential of life in prison, in a case where the physician’s acts occurred openly over 4 years in a hospital setting where no one did anything to stop him. It would have been much easier to convince a jury to convict him of reckless homicide, a lesser offense with a shorter prison term. That would have required proving that he acted in reckless disregard for his patients’ health and safety.

In post-verdict comments to the news media, Judge Michael Holbrook said jurors told him that the procedures for the dispensing of fentanyl and other drugs at Mount Carmel weren’t properly explained to them during the trial, and that they were confused by the large number of prosecution witnesses. He also said they were confused that no one had stated a maximum dosage for fentanyl.

Mr. Schumacher, the retired malpractice defense lawyer who followed the trial, disagreed with defense attorney Baez’s takeaway about the impact of the case on pain-relief practices. In his view, the case likely will heighten rather than reduce the anxiety of physicians and nurses about administering opioids, even when the dosages are clearly needed and appropriate. He doesn’t think Dr. Husel’s dosages can be justified, however. 

“Physicians have a naive overreaction to any legal development, and overgeneralize from a particular case to everyday practice,” he said.

There is only one known prior case that’s somewhat comparable of a physician tried for murder or attempted murder for giving a critically ill patient opioids for pain relief. In 1996, a Kansas jury convicted Lloyd Stanley Naramore, DO, of attempted murder in the death of a patient to whom he gave an opioid, and of second-degree murder for removing a patient from a ventilator. After Dr. Naramore served 6 months in prison, an appellate court reversed the convictions for lack of evidence.

In March, RaDonda Vaught, a nurse who worked at Vanderbilt University Medical Center in Nashville, Tenn., was convicted of criminal neglect and negligent homicide for mistakenly administering a fatal dose of the paralyzing drug vecuronium, instead of the prescribed drug Versed (midazolam), to a patient. Providers around the country were alarmed by her criminal prosecution for what was clearly an unintentional error.

But legal and medical experts said Dr. Husel’s case was sharply different from Vaught’s and Dr. Naramore’s because he deliberately and repeatedly ordered large doses of fentanyl and other drugs that he knew or should have known were potentially lethal. “You don’t need 2,000 micrograms of fentanyl plus other drugs for comfort care, and repeat that again and again for patient after patient,” said Mr. Cohen, of the Institute for Safe Medication Practices. “No one gives that to patients. You’ll knock them off.”

During the trial, prosecutors said repeatedly that no one except Dr. Husel knows what he was thinking when he ordered those huge drug dosages for his ICU patients. Judge Holbrook told the jury the state did not have to prove motive, only intent. But many observers still have wondered what his motives were.

Dr. Husel’s own view of his care in these cases soon will become public. Immediately after the April 20 verdict, Mr. Leeseberg filed a notice requesting a May 9 deposition of Dr. Husel, who will no longer be able to claim the Fifth Amendment right against self-incrimination. He predicted the deposition will last about a week, and then the transcript will be publicly available.

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

Disulfiram, a U.S. Food and Drug Administration–approved medication for the treatment of chronic alcohol dependence, shows promise as a potential anxiolytic, early research suggests.

Japanese researchers, headed by Akiyoshi Saitoh, PhD, professor in the department of pharmacy, Tokyo University of Science, compared the reactions of mice that received a classic anxiolytic agent (diazepam) to those that received disulfiram while performing a maze task and found comparable reductions in anxiety in both groups of mice.

Moreover, unlike diazepam, disulfiram caused no sedation, amnesia, or impairments in coordination.

“These results indicate that disulfiram can be used safely by elderly patients suffering from anxiety and insomnia and has the potential to become a breakthrough psychotropic drug,” Dr. Saitoh said in a press release.

The study was published online in Frontiers in Pharmacology.
 

Inhibitory function

Disulfiram inhibits the enzyme aldehyde dehydrogenase (ALDH), which is responsible for alcohol metabolism. Recent research suggests that disulfiram may have broader inhibitory functions.

In particular, it inhibits the cytoplasmic protein FROUNT, preventing it from interacting with two chemokine receptors (CCR2 and CCRs) that are involved in cellular signaling pathways and are associated with regulating behaviors, including anxiety, in rodents, the authors write.

“Although the functions of FROUNT-chemokines signaling in the immune system are well documented, the potential role of CNS-expressed FROUNT chemokine–related molecules as neuromodulators remains largely unknown,” they write.

The researchers had been conducting preclinical research on the secondary pharmacologic properties of disulfiram and “coincidentally discovered” its “anxiolytic-like effects.” They investigated these effects further because currently used anxiolytics – i.e., benzodiazepines – have unwanted side effects.

The researchers utilized an elevated plus-maze (EPM) test to investigate the effects of disulfiram in mice. The EPM apparatus consists of four arms set in a cross pattern and are connected to a central square. Of these, two arms are protected by vertical boundaries, while the other two have unprotected edges. Typically, mice with anxiety prefer to spend time in the closed arms. The mice also underwent other tests of coordination and the ability to navigate a Y-maze.

Some mice received disulfiram, others received a benzodiazepine, and others received merely a “vehicle,” which served as a control.

Disulfiram “significantly and dose-dependently” increased the time spent in the open arms of the EPM, compared with the vehicle-treated group, at 30 minutes after administration (F [3, 30] = 16.64; P < .0001), suggesting less anxiety. The finding was confirmed by a Bonferroni analysis that showed a significant effect of disulfiram, compared with the vehicle-treated group, at all three doses (20 mg/kg: t = 0.9894; P > .05; 40 mg/kg: t = 3.863; P < .01; 80 mg/kg: t = 6.417; P < .001).

A Student’s t-test analysis showed that diazepam likewise had a significant effect, compared to the vehicle (t = 5.038; P < .001).

Disulfiram also “significantly and dose-dependently” increased the percentage of open-arm entries (F [3, 30] = 14.24; P < .0001). The Bonferroni analysis showed this effect at all three doses (20 mg/kg: t = 0.3999; P > .05; 40 mg/kg: t = 2.693; P > .05; 80 mg/kg: t = 5.864; P < .001).

Diazepam similarly showed a significant effect, compared to the vehicle condition (t = 3.733; P < .005).

In particular, the 40 mg/kg dose of disulfiram significantly increased the percentage of time spent in the open arms at 15, 30, and 60 minutes after administration, with the peak effect occurring at 30 minutes.

The researchers examined the effect of cyanamide, another ALDH inhibitor, on the anxiety behaviors of mice and found no effect on the number of open-arm entries or percentage of time the mice spent in the open arm, compared with the vehicle condition.

In contrast to diazepam, disulfiram had no effect on the amount of spontaneous locomotor activity, time spent on the rotarod, or activity on the Y-maze test displayed by the mice, “suggesting that there were no apparent sedative effects at the dosages used.” Moreover, unlike the mice treated with diazepam, there were no increases in the number of falls the mice experienced on the rotarod.

Glutamate levels in the prelimbic-prefrontal cortex (PL-PFC) “play an important role in the development of anxiety-like behavior in mice,” the authors state. Disulfiram “significantly and completely attenuated increased extracellular glutamate levels in the PL-PFC during stress exposure” on the EPM.

“We propose that DSF inhibits FROUNT protein and the chemokine signaling pathways under its influence, which may suppress presynaptic glutamatergic transmission in the brain,” said Dr. Saitoh. “This, in turn, attenuates the levels of glutamate in the brain, reducing overall anxiety.”
 

Humanity’s most common affliction

Commenting for this news organization, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, noted that there is a “renewed interest in psychiatry in excitatory and inhibitory balance – for example, ketamine represents a treatment that facilitates excitatory activity, while neurosteroids are candidate medicines now for inhibitory activity.”

Dr. McIntyre, who is the chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, and was not involved with the study, said it is believed “that the excitatory-inhibitory balance may be relevant to brain health and disease.”

Dr. McIntyre also pointed out that the study “highlights not only the repurposing of a well-known medicine but also exploit[s] the potential brain therapeutic effects of immune targets that indirectly affect inhibitory systems, resulting in potentially a safer treatment for anxiety – the most common affliction of humanity.”

Also commenting for this article, Wilfrid Noel Raby, MD, PhD, a psychiatrist in private practice in Teaneck, N.J., called disulfiram “grossly underused for alcohol use disorders and even more so when people use alcohol and cocaine.”

Dr. Raby, who was not involved with the study, has found that patients withdrawing from cocaine, cannabis, or stimulants “can respond very well to disulfiram [not only] in terms of their cravings but also in terms of mood stabilization and anxiolysis.”

He has also found that for patients with bipolar disorder or attention-deficit/hyperactivity disorder with depression disulfiram and low-dose lithium “can provide anxiolysis and mood stabilization, especially if a rapid effect is required, usually within a week.”

However, Dr. Raby cautioned that “it is probably not advisable to maintain patients on disulfiram for periods long than 3 months consecutively because there is a risk of neuropathy and hepatopathology that are not common but are seen often enough.” He usually interrupts treatment for a month and then resumes if necessary.

The research was partially supported by the Tsukuba Clinical Research and Development Organization from the Japan Agency for Medical Research and Development. The authors and Dr. Raby have disclosed no relevant financial relationships. Dr. McIntyre reports receiving research grant support from CIHR/GACD/National Natural Science Foundation of China; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, AbbVie, and Atai Life Sciences. Dr. McIntyre is CEO of Braxia Scientific.

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

Disulfiram, a U.S. Food and Drug Administration–approved medication for the treatment of chronic alcohol dependence, shows promise as a potential anxiolytic, early research suggests.

Japanese researchers, headed by Akiyoshi Saitoh, PhD, professor in the department of pharmacy, Tokyo University of Science, compared the reactions of mice that received a classic anxiolytic agent (diazepam) to those that received disulfiram while performing a maze task and found comparable reductions in anxiety in both groups of mice.

Moreover, unlike diazepam, disulfiram caused no sedation, amnesia, or impairments in coordination.

“These results indicate that disulfiram can be used safely by elderly patients suffering from anxiety and insomnia and has the potential to become a breakthrough psychotropic drug,” Dr. Saitoh said in a press release.

The study was published online in Frontiers in Pharmacology.
 

Inhibitory function

Disulfiram inhibits the enzyme aldehyde dehydrogenase (ALDH), which is responsible for alcohol metabolism. Recent research suggests that disulfiram may have broader inhibitory functions.

In particular, it inhibits the cytoplasmic protein FROUNT, preventing it from interacting with two chemokine receptors (CCR2 and CCRs) that are involved in cellular signaling pathways and are associated with regulating behaviors, including anxiety, in rodents, the authors write.

“Although the functions of FROUNT-chemokines signaling in the immune system are well documented, the potential role of CNS-expressed FROUNT chemokine–related molecules as neuromodulators remains largely unknown,” they write.

The researchers had been conducting preclinical research on the secondary pharmacologic properties of disulfiram and “coincidentally discovered” its “anxiolytic-like effects.” They investigated these effects further because currently used anxiolytics – i.e., benzodiazepines – have unwanted side effects.

The researchers utilized an elevated plus-maze (EPM) test to investigate the effects of disulfiram in mice. The EPM apparatus consists of four arms set in a cross pattern and are connected to a central square. Of these, two arms are protected by vertical boundaries, while the other two have unprotected edges. Typically, mice with anxiety prefer to spend time in the closed arms. The mice also underwent other tests of coordination and the ability to navigate a Y-maze.

Some mice received disulfiram, others received a benzodiazepine, and others received merely a “vehicle,” which served as a control.

Disulfiram “significantly and dose-dependently” increased the time spent in the open arms of the EPM, compared with the vehicle-treated group, at 30 minutes after administration (F [3, 30] = 16.64; P < .0001), suggesting less anxiety. The finding was confirmed by a Bonferroni analysis that showed a significant effect of disulfiram, compared with the vehicle-treated group, at all three doses (20 mg/kg: t = 0.9894; P > .05; 40 mg/kg: t = 3.863; P < .01; 80 mg/kg: t = 6.417; P < .001).

A Student’s t-test analysis showed that diazepam likewise had a significant effect, compared to the vehicle (t = 5.038; P < .001).

Disulfiram also “significantly and dose-dependently” increased the percentage of open-arm entries (F [3, 30] = 14.24; P < .0001). The Bonferroni analysis showed this effect at all three doses (20 mg/kg: t = 0.3999; P > .05; 40 mg/kg: t = 2.693; P > .05; 80 mg/kg: t = 5.864; P < .001).

Diazepam similarly showed a significant effect, compared to the vehicle condition (t = 3.733; P < .005).

In particular, the 40 mg/kg dose of disulfiram significantly increased the percentage of time spent in the open arms at 15, 30, and 60 minutes after administration, with the peak effect occurring at 30 minutes.

The researchers examined the effect of cyanamide, another ALDH inhibitor, on the anxiety behaviors of mice and found no effect on the number of open-arm entries or percentage of time the mice spent in the open arm, compared with the vehicle condition.

In contrast to diazepam, disulfiram had no effect on the amount of spontaneous locomotor activity, time spent on the rotarod, or activity on the Y-maze test displayed by the mice, “suggesting that there were no apparent sedative effects at the dosages used.” Moreover, unlike the mice treated with diazepam, there were no increases in the number of falls the mice experienced on the rotarod.

Glutamate levels in the prelimbic-prefrontal cortex (PL-PFC) “play an important role in the development of anxiety-like behavior in mice,” the authors state. Disulfiram “significantly and completely attenuated increased extracellular glutamate levels in the PL-PFC during stress exposure” on the EPM.

“We propose that DSF inhibits FROUNT protein and the chemokine signaling pathways under its influence, which may suppress presynaptic glutamatergic transmission in the brain,” said Dr. Saitoh. “This, in turn, attenuates the levels of glutamate in the brain, reducing overall anxiety.”
 

Humanity’s most common affliction

Commenting for this news organization, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, noted that there is a “renewed interest in psychiatry in excitatory and inhibitory balance – for example, ketamine represents a treatment that facilitates excitatory activity, while neurosteroids are candidate medicines now for inhibitory activity.”

Dr. McIntyre, who is the chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, and was not involved with the study, said it is believed “that the excitatory-inhibitory balance may be relevant to brain health and disease.”

Dr. McIntyre also pointed out that the study “highlights not only the repurposing of a well-known medicine but also exploit[s] the potential brain therapeutic effects of immune targets that indirectly affect inhibitory systems, resulting in potentially a safer treatment for anxiety – the most common affliction of humanity.”

Also commenting for this article, Wilfrid Noel Raby, MD, PhD, a psychiatrist in private practice in Teaneck, N.J., called disulfiram “grossly underused for alcohol use disorders and even more so when people use alcohol and cocaine.”

Dr. Raby, who was not involved with the study, has found that patients withdrawing from cocaine, cannabis, or stimulants “can respond very well to disulfiram [not only] in terms of their cravings but also in terms of mood stabilization and anxiolysis.”

He has also found that for patients with bipolar disorder or attention-deficit/hyperactivity disorder with depression disulfiram and low-dose lithium “can provide anxiolysis and mood stabilization, especially if a rapid effect is required, usually within a week.”

However, Dr. Raby cautioned that “it is probably not advisable to maintain patients on disulfiram for periods long than 3 months consecutively because there is a risk of neuropathy and hepatopathology that are not common but are seen often enough.” He usually interrupts treatment for a month and then resumes if necessary.

The research was partially supported by the Tsukuba Clinical Research and Development Organization from the Japan Agency for Medical Research and Development. The authors and Dr. Raby have disclosed no relevant financial relationships. Dr. McIntyre reports receiving research grant support from CIHR/GACD/National Natural Science Foundation of China; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, AbbVie, and Atai Life Sciences. Dr. McIntyre is CEO of Braxia Scientific.

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

Disulfiram, a U.S. Food and Drug Administration–approved medication for the treatment of chronic alcohol dependence, shows promise as a potential anxiolytic, early research suggests.

Japanese researchers, headed by Akiyoshi Saitoh, PhD, professor in the department of pharmacy, Tokyo University of Science, compared the reactions of mice that received a classic anxiolytic agent (diazepam) to those that received disulfiram while performing a maze task and found comparable reductions in anxiety in both groups of mice.

Moreover, unlike diazepam, disulfiram caused no sedation, amnesia, or impairments in coordination.

“These results indicate that disulfiram can be used safely by elderly patients suffering from anxiety and insomnia and has the potential to become a breakthrough psychotropic drug,” Dr. Saitoh said in a press release.

The study was published online in Frontiers in Pharmacology.
 

Inhibitory function

Disulfiram inhibits the enzyme aldehyde dehydrogenase (ALDH), which is responsible for alcohol metabolism. Recent research suggests that disulfiram may have broader inhibitory functions.

In particular, it inhibits the cytoplasmic protein FROUNT, preventing it from interacting with two chemokine receptors (CCR2 and CCRs) that are involved in cellular signaling pathways and are associated with regulating behaviors, including anxiety, in rodents, the authors write.

“Although the functions of FROUNT-chemokines signaling in the immune system are well documented, the potential role of CNS-expressed FROUNT chemokine–related molecules as neuromodulators remains largely unknown,” they write.

The researchers had been conducting preclinical research on the secondary pharmacologic properties of disulfiram and “coincidentally discovered” its “anxiolytic-like effects.” They investigated these effects further because currently used anxiolytics – i.e., benzodiazepines – have unwanted side effects.

The researchers utilized an elevated plus-maze (EPM) test to investigate the effects of disulfiram in mice. The EPM apparatus consists of four arms set in a cross pattern and are connected to a central square. Of these, two arms are protected by vertical boundaries, while the other two have unprotected edges. Typically, mice with anxiety prefer to spend time in the closed arms. The mice also underwent other tests of coordination and the ability to navigate a Y-maze.

Some mice received disulfiram, others received a benzodiazepine, and others received merely a “vehicle,” which served as a control.

Disulfiram “significantly and dose-dependently” increased the time spent in the open arms of the EPM, compared with the vehicle-treated group, at 30 minutes after administration (F [3, 30] = 16.64; P < .0001), suggesting less anxiety. The finding was confirmed by a Bonferroni analysis that showed a significant effect of disulfiram, compared with the vehicle-treated group, at all three doses (20 mg/kg: t = 0.9894; P > .05; 40 mg/kg: t = 3.863; P < .01; 80 mg/kg: t = 6.417; P < .001).

A Student’s t-test analysis showed that diazepam likewise had a significant effect, compared to the vehicle (t = 5.038; P < .001).

Disulfiram also “significantly and dose-dependently” increased the percentage of open-arm entries (F [3, 30] = 14.24; P < .0001). The Bonferroni analysis showed this effect at all three doses (20 mg/kg: t = 0.3999; P > .05; 40 mg/kg: t = 2.693; P > .05; 80 mg/kg: t = 5.864; P < .001).

Diazepam similarly showed a significant effect, compared to the vehicle condition (t = 3.733; P < .005).

In particular, the 40 mg/kg dose of disulfiram significantly increased the percentage of time spent in the open arms at 15, 30, and 60 minutes after administration, with the peak effect occurring at 30 minutes.

The researchers examined the effect of cyanamide, another ALDH inhibitor, on the anxiety behaviors of mice and found no effect on the number of open-arm entries or percentage of time the mice spent in the open arm, compared with the vehicle condition.

In contrast to diazepam, disulfiram had no effect on the amount of spontaneous locomotor activity, time spent on the rotarod, or activity on the Y-maze test displayed by the mice, “suggesting that there were no apparent sedative effects at the dosages used.” Moreover, unlike the mice treated with diazepam, there were no increases in the number of falls the mice experienced on the rotarod.

Glutamate levels in the prelimbic-prefrontal cortex (PL-PFC) “play an important role in the development of anxiety-like behavior in mice,” the authors state. Disulfiram “significantly and completely attenuated increased extracellular glutamate levels in the PL-PFC during stress exposure” on the EPM.

“We propose that DSF inhibits FROUNT protein and the chemokine signaling pathways under its influence, which may suppress presynaptic glutamatergic transmission in the brain,” said Dr. Saitoh. “This, in turn, attenuates the levels of glutamate in the brain, reducing overall anxiety.”
 

Humanity’s most common affliction

Commenting for this news organization, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, noted that there is a “renewed interest in psychiatry in excitatory and inhibitory balance – for example, ketamine represents a treatment that facilitates excitatory activity, while neurosteroids are candidate medicines now for inhibitory activity.”

Dr. McIntyre, who is the chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, and was not involved with the study, said it is believed “that the excitatory-inhibitory balance may be relevant to brain health and disease.”

Dr. McIntyre also pointed out that the study “highlights not only the repurposing of a well-known medicine but also exploit[s] the potential brain therapeutic effects of immune targets that indirectly affect inhibitory systems, resulting in potentially a safer treatment for anxiety – the most common affliction of humanity.”

Also commenting for this article, Wilfrid Noel Raby, MD, PhD, a psychiatrist in private practice in Teaneck, N.J., called disulfiram “grossly underused for alcohol use disorders and even more so when people use alcohol and cocaine.”

Dr. Raby, who was not involved with the study, has found that patients withdrawing from cocaine, cannabis, or stimulants “can respond very well to disulfiram [not only] in terms of their cravings but also in terms of mood stabilization and anxiolysis.”

He has also found that for patients with bipolar disorder or attention-deficit/hyperactivity disorder with depression disulfiram and low-dose lithium “can provide anxiolysis and mood stabilization, especially if a rapid effect is required, usually within a week.”

However, Dr. Raby cautioned that “it is probably not advisable to maintain patients on disulfiram for periods long than 3 months consecutively because there is a risk of neuropathy and hepatopathology that are not common but are seen often enough.” He usually interrupts treatment for a month and then resumes if necessary.

The research was partially supported by the Tsukuba Clinical Research and Development Organization from the Japan Agency for Medical Research and Development. The authors and Dr. Raby have disclosed no relevant financial relationships. Dr. McIntyre reports receiving research grant support from CIHR/GACD/National Natural Science Foundation of China; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, AbbVie, and Atai Life Sciences. Dr. McIntyre is CEO of Braxia Scientific.

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

Approximately one-third of critical care workers reported some degree of depression, anxiety, or somatic symptoms in the early phase of the COVID-19 pandemic, based on survey results from 939 health care professionals.

The emotional response of professionals in a critical care setting in the early phase of the COVID-19 pandemic has not been well studied, Robyn Branca, PhD, and Paul Branca, MD, of Carson Newman University and the University of Tennessee Medical Center, both in Knoxville, wrote in an abstract presented at the virtual Critical Care Congress sponsored by the Society of Critical Care Medicine.

The prevalence of depression, anxiety, and somatization is low in the general population overall, but the researchers predicted that these conditions increased among workers in critical care settings early in the pandemic.

To assess the prevalence of psychological problems during that time, they sent an email survey on April 7, 2020, to members of the Society of Critical Care Medicine. The survey collected data on demographics, perceived caseload, and potential course of the pandemic. The survey also collected responses to assessments for depression (using the Patient Health Questionnaire–9), anxiety (using the Generalized Anxiety Disorder [GAD] Scale–7), and symptom somatization (using the PHQ-15).

Of the 939 survey respondents, 37% were male, 61.4% were female, and 1.4% gave another or no response.

Overall, 32.3% reported encountering 0-50 COVID-19 cases, 31.1% had encountered 51-200 cases, 12.5% had encountered 201-500 cases, 9.4% had encountered 501-1000 cases, and 13.7% had encountered more than 1,000 cases.

Based on the PHQ-9 depression scale, 44.9% of the respondents had minimal symptoms, 31.1% mild symptoms, 14.3% moderate symptoms, and 9.7% met criteria for severe depressive symptoms. Based on the GAD-7 anxiety scale, 35.5% had minimal symptoms, 32.9% mild, 16.8% moderate, and 14.8% had severe symptoms. Based on the PHQ-15 somatization scale, 39.6% of respondents showed minimal symptoms, whereas 38.2% showed mild symptoms, 17.3% moderate symptoms, and 4.9% had a severe degree of somatic symptoms.

The study findings were limited by the reliance on self-reports; however, the results indicate that a high percentage of critical care workers experienced significant, diagnosable levels of depression, anxiety, and somatic symptoms, the researchers said.

The standard guidance is to pursue individual intervention for anyone with scores of moderate or severe on the scales used in the survey, the researchers said.

Therefore, the findings represent “an alarming degree of mental health impact,” they emphasized. “Immediate mitigation efforts are needed to preserve the health of our ICU workforce.”

The study is important at this time because clinician fatigue and occupational stress are at endemic levels, Bernard Chang, MD, of Columbia University Irving Medical Center, New York City, said in an interview. “It is vital that we take stock of how frontline workers in critical care settings are doing overall,” said Dr. Chang.  

Dr. Chang, who was not involved with the study but has conducted research on mental health in frontline health care workers during the pandemic, said he was not surprised by the findings. “This work builds on the growing body of literature in the pandemic noting high levels of stress, fatigue, and depression/anxiety symptoms across many frontline workers, from emergency department staff, first responders and others. These are all data points highlighting the urgent need for a broad safety net, not only for patients but the providers serving them.”

The takeaway message: “Clinicians are often so focused on providing care for their patients that they may overlook the need to care for their own well-being and mental health,” said Dr. Chang.

As for additional research, “we need to now take this important data and build on creating and identifying tangible solutions to improve the morale of the acute care/health care workforce to ensure career longevity, professional satisfaction, and overall well-being,” Dr. Chang emphasized. Mental health and morale affect not only health care workers, but also the patients they care for. Well–cared for health care providers can be at their best to provide the optimal care for their patients.

The study received no outside funding. The researchers and Dr. Chang disclosed no relevant financial relationships.

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

Approximately one-third of critical care workers reported some degree of depression, anxiety, or somatic symptoms in the early phase of the COVID-19 pandemic, based on survey results from 939 health care professionals.

The emotional response of professionals in a critical care setting in the early phase of the COVID-19 pandemic has not been well studied, Robyn Branca, PhD, and Paul Branca, MD, of Carson Newman University and the University of Tennessee Medical Center, both in Knoxville, wrote in an abstract presented at the virtual Critical Care Congress sponsored by the Society of Critical Care Medicine.

The prevalence of depression, anxiety, and somatization is low in the general population overall, but the researchers predicted that these conditions increased among workers in critical care settings early in the pandemic.

To assess the prevalence of psychological problems during that time, they sent an email survey on April 7, 2020, to members of the Society of Critical Care Medicine. The survey collected data on demographics, perceived caseload, and potential course of the pandemic. The survey also collected responses to assessments for depression (using the Patient Health Questionnaire–9), anxiety (using the Generalized Anxiety Disorder [GAD] Scale–7), and symptom somatization (using the PHQ-15).

Of the 939 survey respondents, 37% were male, 61.4% were female, and 1.4% gave another or no response.

Overall, 32.3% reported encountering 0-50 COVID-19 cases, 31.1% had encountered 51-200 cases, 12.5% had encountered 201-500 cases, 9.4% had encountered 501-1000 cases, and 13.7% had encountered more than 1,000 cases.

Based on the PHQ-9 depression scale, 44.9% of the respondents had minimal symptoms, 31.1% mild symptoms, 14.3% moderate symptoms, and 9.7% met criteria for severe depressive symptoms. Based on the GAD-7 anxiety scale, 35.5% had minimal symptoms, 32.9% mild, 16.8% moderate, and 14.8% had severe symptoms. Based on the PHQ-15 somatization scale, 39.6% of respondents showed minimal symptoms, whereas 38.2% showed mild symptoms, 17.3% moderate symptoms, and 4.9% had a severe degree of somatic symptoms.

The study findings were limited by the reliance on self-reports; however, the results indicate that a high percentage of critical care workers experienced significant, diagnosable levels of depression, anxiety, and somatic symptoms, the researchers said.

The standard guidance is to pursue individual intervention for anyone with scores of moderate or severe on the scales used in the survey, the researchers said.

Therefore, the findings represent “an alarming degree of mental health impact,” they emphasized. “Immediate mitigation efforts are needed to preserve the health of our ICU workforce.”

The study is important at this time because clinician fatigue and occupational stress are at endemic levels, Bernard Chang, MD, of Columbia University Irving Medical Center, New York City, said in an interview. “It is vital that we take stock of how frontline workers in critical care settings are doing overall,” said Dr. Chang.  

Dr. Chang, who was not involved with the study but has conducted research on mental health in frontline health care workers during the pandemic, said he was not surprised by the findings. “This work builds on the growing body of literature in the pandemic noting high levels of stress, fatigue, and depression/anxiety symptoms across many frontline workers, from emergency department staff, first responders and others. These are all data points highlighting the urgent need for a broad safety net, not only for patients but the providers serving them.”

The takeaway message: “Clinicians are often so focused on providing care for their patients that they may overlook the need to care for their own well-being and mental health,” said Dr. Chang.

As for additional research, “we need to now take this important data and build on creating and identifying tangible solutions to improve the morale of the acute care/health care workforce to ensure career longevity, professional satisfaction, and overall well-being,” Dr. Chang emphasized. Mental health and morale affect not only health care workers, but also the patients they care for. Well–cared for health care providers can be at their best to provide the optimal care for their patients.

The study received no outside funding. The researchers and Dr. Chang disclosed no relevant financial relationships.

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

Approximately one-third of critical care workers reported some degree of depression, anxiety, or somatic symptoms in the early phase of the COVID-19 pandemic, based on survey results from 939 health care professionals.

The emotional response of professionals in a critical care setting in the early phase of the COVID-19 pandemic has not been well studied, Robyn Branca, PhD, and Paul Branca, MD, of Carson Newman University and the University of Tennessee Medical Center, both in Knoxville, wrote in an abstract presented at the virtual Critical Care Congress sponsored by the Society of Critical Care Medicine.

The prevalence of depression, anxiety, and somatization is low in the general population overall, but the researchers predicted that these conditions increased among workers in critical care settings early in the pandemic.

To assess the prevalence of psychological problems during that time, they sent an email survey on April 7, 2020, to members of the Society of Critical Care Medicine. The survey collected data on demographics, perceived caseload, and potential course of the pandemic. The survey also collected responses to assessments for depression (using the Patient Health Questionnaire–9), anxiety (using the Generalized Anxiety Disorder [GAD] Scale–7), and symptom somatization (using the PHQ-15).

Of the 939 survey respondents, 37% were male, 61.4% were female, and 1.4% gave another or no response.

Overall, 32.3% reported encountering 0-50 COVID-19 cases, 31.1% had encountered 51-200 cases, 12.5% had encountered 201-500 cases, 9.4% had encountered 501-1000 cases, and 13.7% had encountered more than 1,000 cases.

Based on the PHQ-9 depression scale, 44.9% of the respondents had minimal symptoms, 31.1% mild symptoms, 14.3% moderate symptoms, and 9.7% met criteria for severe depressive symptoms. Based on the GAD-7 anxiety scale, 35.5% had minimal symptoms, 32.9% mild, 16.8% moderate, and 14.8% had severe symptoms. Based on the PHQ-15 somatization scale, 39.6% of respondents showed minimal symptoms, whereas 38.2% showed mild symptoms, 17.3% moderate symptoms, and 4.9% had a severe degree of somatic symptoms.

The study findings were limited by the reliance on self-reports; however, the results indicate that a high percentage of critical care workers experienced significant, diagnosable levels of depression, anxiety, and somatic symptoms, the researchers said.

The standard guidance is to pursue individual intervention for anyone with scores of moderate or severe on the scales used in the survey, the researchers said.

Therefore, the findings represent “an alarming degree of mental health impact,” they emphasized. “Immediate mitigation efforts are needed to preserve the health of our ICU workforce.”

The study is important at this time because clinician fatigue and occupational stress are at endemic levels, Bernard Chang, MD, of Columbia University Irving Medical Center, New York City, said in an interview. “It is vital that we take stock of how frontline workers in critical care settings are doing overall,” said Dr. Chang.  

Dr. Chang, who was not involved with the study but has conducted research on mental health in frontline health care workers during the pandemic, said he was not surprised by the findings. “This work builds on the growing body of literature in the pandemic noting high levels of stress, fatigue, and depression/anxiety symptoms across many frontline workers, from emergency department staff, first responders and others. These are all data points highlighting the urgent need for a broad safety net, not only for patients but the providers serving them.”

The takeaway message: “Clinicians are often so focused on providing care for their patients that they may overlook the need to care for their own well-being and mental health,” said Dr. Chang.

As for additional research, “we need to now take this important data and build on creating and identifying tangible solutions to improve the morale of the acute care/health care workforce to ensure career longevity, professional satisfaction, and overall well-being,” Dr. Chang emphasized. Mental health and morale affect not only health care workers, but also the patients they care for. Well–cared for health care providers can be at their best to provide the optimal care for their patients.

The study received no outside funding. The researchers and Dr. Chang disclosed no relevant financial relationships.

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

On the basis of the patient's history and presentation, the likely diagnosis is extensive UC. Extensive colitis is defined by the presence of disease activity proximal to the splenic flexure. Because disease activity in UC is dynamic, up to half of patients who present with proctitis and 70% of those who present with left-sided colitis go on to develop extensive colitis on follow-up. 

On the basis of the workup, it appears that this patient's UC has transitioned from left-sided to extensive disease, given the loss of treatment response. Endoscopic evaluation of patients with loss of treatment response may reveal patchiness of the histologic activity, as seen in this case. 

Extensive colitis is a poor prognostic factor in UC, as is systemic steroid requirement, young age at diagnosis, and an elevated C-reactive protein level or erythrocyte sedimentation rate, all of which are associated with higher rates of colectomy. Over time, patients living with extensive ulcerative colitis develop an increased risk for colorectal cancer. Routine colonoscopic screening and surveillance are recommended for these high-risk patients.

UC most often presents as a continuously inflamed segment involving the distal rectum and extending proximally. Endoscopic features of inflammation include loss of vascular markings; granularity and friability of the mucosa; erosions; and, in the setting of severe inflammation, ulcerations and spontaneous bleeding. The diagnosis of UC involves both a lower gastrointestinal endoscopic examination and histologic confirmation. In general, a complete colonoscopy including examination of the terminal ileum should be performed, allowing clinicians to assess the full extent of the disease while ruling out distal ileal involvement, which is characteristic of Crohn's disease.

Evaluation of UC during relapses should include assessment of symptom severity and potential triggers, including enteric infections, use of nonsteroidal anti-inflammatory drugs, and recent smoking cessation. Nonadherence to therapy is common in patients with UC and may lead to relapse. 

To treat a patient like the one represented here, the American College of Gastroenterology guidelines recommend oral 5-ASA at a dose of at least 2 g/d to induce remission. However, because this patient lost response to this treatment, the next step in the guidelines are appropriate oral systemic corticosteroids.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships

On the basis of the patient's history and presentation, the likely diagnosis is extensive UC. Extensive colitis is defined by the presence of disease activity proximal to the splenic flexure. Because disease activity in UC is dynamic, up to half of patients who present with proctitis and 70% of those who present with left-sided colitis go on to develop extensive colitis on follow-up. 

On the basis of the workup, it appears that this patient's UC has transitioned from left-sided to extensive disease, given the loss of treatment response. Endoscopic evaluation of patients with loss of treatment response may reveal patchiness of the histologic activity, as seen in this case. 

Extensive colitis is a poor prognostic factor in UC, as is systemic steroid requirement, young age at diagnosis, and an elevated C-reactive protein level or erythrocyte sedimentation rate, all of which are associated with higher rates of colectomy. Over time, patients living with extensive ulcerative colitis develop an increased risk for colorectal cancer. Routine colonoscopic screening and surveillance are recommended for these high-risk patients.

UC most often presents as a continuously inflamed segment involving the distal rectum and extending proximally. Endoscopic features of inflammation include loss of vascular markings; granularity and friability of the mucosa; erosions; and, in the setting of severe inflammation, ulcerations and spontaneous bleeding. The diagnosis of UC involves both a lower gastrointestinal endoscopic examination and histologic confirmation. In general, a complete colonoscopy including examination of the terminal ileum should be performed, allowing clinicians to assess the full extent of the disease while ruling out distal ileal involvement, which is characteristic of Crohn's disease.

Evaluation of UC during relapses should include assessment of symptom severity and potential triggers, including enteric infections, use of nonsteroidal anti-inflammatory drugs, and recent smoking cessation. Nonadherence to therapy is common in patients with UC and may lead to relapse. 

To treat a patient like the one represented here, the American College of Gastroenterology guidelines recommend oral 5-ASA at a dose of at least 2 g/d to induce remission. However, because this patient lost response to this treatment, the next step in the guidelines are appropriate oral systemic corticosteroids.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships

On the basis of the patient's history and presentation, the likely diagnosis is extensive UC. Extensive colitis is defined by the presence of disease activity proximal to the splenic flexure. Because disease activity in UC is dynamic, up to half of patients who present with proctitis and 70% of those who present with left-sided colitis go on to develop extensive colitis on follow-up. 

On the basis of the workup, it appears that this patient's UC has transitioned from left-sided to extensive disease, given the loss of treatment response. Endoscopic evaluation of patients with loss of treatment response may reveal patchiness of the histologic activity, as seen in this case. 

Extensive colitis is a poor prognostic factor in UC, as is systemic steroid requirement, young age at diagnosis, and an elevated C-reactive protein level or erythrocyte sedimentation rate, all of which are associated with higher rates of colectomy. Over time, patients living with extensive ulcerative colitis develop an increased risk for colorectal cancer. Routine colonoscopic screening and surveillance are recommended for these high-risk patients.

UC most often presents as a continuously inflamed segment involving the distal rectum and extending proximally. Endoscopic features of inflammation include loss of vascular markings; granularity and friability of the mucosa; erosions; and, in the setting of severe inflammation, ulcerations and spontaneous bleeding. The diagnosis of UC involves both a lower gastrointestinal endoscopic examination and histologic confirmation. In general, a complete colonoscopy including examination of the terminal ileum should be performed, allowing clinicians to assess the full extent of the disease while ruling out distal ileal involvement, which is characteristic of Crohn's disease.

Evaluation of UC during relapses should include assessment of symptom severity and potential triggers, including enteric infections, use of nonsteroidal anti-inflammatory drugs, and recent smoking cessation. Nonadherence to therapy is common in patients with UC and may lead to relapse. 

To treat a patient like the one represented here, the American College of Gastroenterology guidelines recommend oral 5-ASA at a dose of at least 2 g/d to induce remission. However, because this patient lost response to this treatment, the next step in the guidelines are appropriate oral systemic corticosteroids.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships

Women diagnosed with early breast cancer facing surgery often have a choice of having all of their breast or only a part of the breast removed.

A new study shows that a patient’s satisfaction with their breasts at 10 years after surgery is similar for both groups of women.

However, superior psychosocial and sexual well-being at 10 years after surgery was reported by women who underwent breast-conserving surgery and adjuvant radiation therapy (RT), compared with those who underwent mastectomy and reconstruction.

“These findings may inform preference-sensitive decision-making for women with early-stage breast cancer,” write the authors, led by Benjamin D. Smith, MD, department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.

The study was published online in JAMA Surgery.

These findings have important implications for patient decision-making, given that more women eligible for breast-conserving surgery are opting for a mastectomy, say Sudheer Vemuru, MD, from the University of Colorado at Denver, Aurora, and colleagues, writing in an accompanying editorial.

“Overall, the preponderance of evidence suggests superior short-term and long-term patient-reported outcomes in patients with early-stage breast cancer undergoing breast conserving surgery compared with mastectomy,” they comment.
 

Study details

For their study, Dr. Smith and colleagues conducted a comparative effectiveness research study using data from the Texas Cancer Registry and identified women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008.

A total of 647 patients were included in their analysis (40%; 356 had undergone breast-conserving surgery; 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236).

The median age of the cohort was 53 years and the median time from diagnosis to survey was 10.3 years. Mastectomy and reconstruction were more common among women who were White, younger, node positive, had larger tumors, had bilateral breast cancer, received chemotherapy, and had higher income.

The primary outcome was patient satisfaction with their breasts, as measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included physical well-being, psychosocial well-being, and sexual well-being. The EuroQol Health-Related Quality of Life 5-Dimension, 3-Level gaged health utility, and local therapy decisional regret was measured via the Decisional Regret Scale.

Using breast-conserving surgery plus RT as the referent, the authors did not find any significant differences in breast satisfaction, physical well-being, health utility, or decisional regret among the study cohorts: breast satisfaction: effect size, 2.71 (P = .30); physical well-being: effect size, –1.80 (P = .36); health utility: effect size, –0.003 (P = .83); and decisional regret: effect size, 1.32 (P = .61).

However, psychosocial well-being (effect size, –8.61; P < .001) and sexual well-being (effect size, –10.68; P < .001) were significantly worse among women who had undergone mastectomy and reconstruction without RT.

They noted that interactions of race and ethnicity and age by treatment group were not significant for reported satisfaction with breast outcomes. But the findings “indicated that the burden of poor long-term QOL outcomes was greater among younger individuals, those with lower educational attainment and income, and certain racial and ethnic minority populations,” they write. “These findings suggest that opportunities exist to enhance equity in the long-term QOL of individuals with breast cancer.”

The editorialists note that previous studies have also found diminished quality of life following mastectomy compared with breast-conserving surgery. However, most of these prior studies included patients undergoing breast-conserving surgery without RT, patients undergoing mastectomy without reconstruction, and patients undergoing mastectomy with RT.

In contrast, this latest study “directly compared breast-conserving surgery with RT vs. mastectomy and reconstruction without RT to avoid those potential confounders,” they point out.

The study was supported by grants from the National Cancer Institute and other bodies. Several of the study authors disclosed relationships with industry and/or with nonprofit organizations. The full list can be found with the original article. Editorialist Clara Lee, MD, reported receiving grants from the Agency for Healthcare Research and Quality during the conduct of the study.

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

Women diagnosed with early breast cancer facing surgery often have a choice of having all of their breast or only a part of the breast removed.

A new study shows that a patient’s satisfaction with their breasts at 10 years after surgery is similar for both groups of women.

However, superior psychosocial and sexual well-being at 10 years after surgery was reported by women who underwent breast-conserving surgery and adjuvant radiation therapy (RT), compared with those who underwent mastectomy and reconstruction.

“These findings may inform preference-sensitive decision-making for women with early-stage breast cancer,” write the authors, led by Benjamin D. Smith, MD, department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.

The study was published online in JAMA Surgery.

These findings have important implications for patient decision-making, given that more women eligible for breast-conserving surgery are opting for a mastectomy, say Sudheer Vemuru, MD, from the University of Colorado at Denver, Aurora, and colleagues, writing in an accompanying editorial.

“Overall, the preponderance of evidence suggests superior short-term and long-term patient-reported outcomes in patients with early-stage breast cancer undergoing breast conserving surgery compared with mastectomy,” they comment.
 

Study details

For their study, Dr. Smith and colleagues conducted a comparative effectiveness research study using data from the Texas Cancer Registry and identified women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008.

A total of 647 patients were included in their analysis (40%; 356 had undergone breast-conserving surgery; 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236).

The median age of the cohort was 53 years and the median time from diagnosis to survey was 10.3 years. Mastectomy and reconstruction were more common among women who were White, younger, node positive, had larger tumors, had bilateral breast cancer, received chemotherapy, and had higher income.

The primary outcome was patient satisfaction with their breasts, as measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included physical well-being, psychosocial well-being, and sexual well-being. The EuroQol Health-Related Quality of Life 5-Dimension, 3-Level gaged health utility, and local therapy decisional regret was measured via the Decisional Regret Scale.

Using breast-conserving surgery plus RT as the referent, the authors did not find any significant differences in breast satisfaction, physical well-being, health utility, or decisional regret among the study cohorts: breast satisfaction: effect size, 2.71 (P = .30); physical well-being: effect size, –1.80 (P = .36); health utility: effect size, –0.003 (P = .83); and decisional regret: effect size, 1.32 (P = .61).

However, psychosocial well-being (effect size, –8.61; P < .001) and sexual well-being (effect size, –10.68; P < .001) were significantly worse among women who had undergone mastectomy and reconstruction without RT.

They noted that interactions of race and ethnicity and age by treatment group were not significant for reported satisfaction with breast outcomes. But the findings “indicated that the burden of poor long-term QOL outcomes was greater among younger individuals, those with lower educational attainment and income, and certain racial and ethnic minority populations,” they write. “These findings suggest that opportunities exist to enhance equity in the long-term QOL of individuals with breast cancer.”

The editorialists note that previous studies have also found diminished quality of life following mastectomy compared with breast-conserving surgery. However, most of these prior studies included patients undergoing breast-conserving surgery without RT, patients undergoing mastectomy without reconstruction, and patients undergoing mastectomy with RT.

In contrast, this latest study “directly compared breast-conserving surgery with RT vs. mastectomy and reconstruction without RT to avoid those potential confounders,” they point out.

The study was supported by grants from the National Cancer Institute and other bodies. Several of the study authors disclosed relationships with industry and/or with nonprofit organizations. The full list can be found with the original article. Editorialist Clara Lee, MD, reported receiving grants from the Agency for Healthcare Research and Quality during the conduct of the study.

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

Women diagnosed with early breast cancer facing surgery often have a choice of having all of their breast or only a part of the breast removed.

A new study shows that a patient’s satisfaction with their breasts at 10 years after surgery is similar for both groups of women.

However, superior psychosocial and sexual well-being at 10 years after surgery was reported by women who underwent breast-conserving surgery and adjuvant radiation therapy (RT), compared with those who underwent mastectomy and reconstruction.

“These findings may inform preference-sensitive decision-making for women with early-stage breast cancer,” write the authors, led by Benjamin D. Smith, MD, department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.

The study was published online in JAMA Surgery.

These findings have important implications for patient decision-making, given that more women eligible for breast-conserving surgery are opting for a mastectomy, say Sudheer Vemuru, MD, from the University of Colorado at Denver, Aurora, and colleagues, writing in an accompanying editorial.

“Overall, the preponderance of evidence suggests superior short-term and long-term patient-reported outcomes in patients with early-stage breast cancer undergoing breast conserving surgery compared with mastectomy,” they comment.
 

Study details

For their study, Dr. Smith and colleagues conducted a comparative effectiveness research study using data from the Texas Cancer Registry and identified women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008.

A total of 647 patients were included in their analysis (40%; 356 had undergone breast-conserving surgery; 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236).

The median age of the cohort was 53 years and the median time from diagnosis to survey was 10.3 years. Mastectomy and reconstruction were more common among women who were White, younger, node positive, had larger tumors, had bilateral breast cancer, received chemotherapy, and had higher income.

The primary outcome was patient satisfaction with their breasts, as measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included physical well-being, psychosocial well-being, and sexual well-being. The EuroQol Health-Related Quality of Life 5-Dimension, 3-Level gaged health utility, and local therapy decisional regret was measured via the Decisional Regret Scale.

Using breast-conserving surgery plus RT as the referent, the authors did not find any significant differences in breast satisfaction, physical well-being, health utility, or decisional regret among the study cohorts: breast satisfaction: effect size, 2.71 (P = .30); physical well-being: effect size, –1.80 (P = .36); health utility: effect size, –0.003 (P = .83); and decisional regret: effect size, 1.32 (P = .61).

However, psychosocial well-being (effect size, –8.61; P < .001) and sexual well-being (effect size, –10.68; P < .001) were significantly worse among women who had undergone mastectomy and reconstruction without RT.

They noted that interactions of race and ethnicity and age by treatment group were not significant for reported satisfaction with breast outcomes. But the findings “indicated that the burden of poor long-term QOL outcomes was greater among younger individuals, those with lower educational attainment and income, and certain racial and ethnic minority populations,” they write. “These findings suggest that opportunities exist to enhance equity in the long-term QOL of individuals with breast cancer.”

The editorialists note that previous studies have also found diminished quality of life following mastectomy compared with breast-conserving surgery. However, most of these prior studies included patients undergoing breast-conserving surgery without RT, patients undergoing mastectomy without reconstruction, and patients undergoing mastectomy with RT.

In contrast, this latest study “directly compared breast-conserving surgery with RT vs. mastectomy and reconstruction without RT to avoid those potential confounders,” they point out.

The study was supported by grants from the National Cancer Institute and other bodies. Several of the study authors disclosed relationships with industry and/or with nonprofit organizations. The full list can be found with the original article. Editorialist Clara Lee, MD, reported receiving grants from the Agency for Healthcare Research and Quality during the conduct of the study.

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

PCOS is most often defined according to the Rotterdam criteria, which stipulate that at least two of the following be present: irregular ovulation, biochemical/clinical hyperandrogenism, and polycystic ovaries (seen in the MRI scan above). Insulin resistance is part of the pathogenesis of PCOS, and insulin resistance is associated with T2D in PCOS. 

In fact, PCOS is an independent risk factor for T2D, even after adjustment for BMI and obesity. Even normal-weight women with PCOS have an increased risk for T2D. More than half of women with PCOS develop T2D by age 40. 

Even though family history and obesity are major contributors in the development of diabetes in patients with PCOS, diabetes can still occur in lean patients with PCOS who have no family history, mainly secondary to insulin resistance.

The Endocrine Society recommends that all individuals with PCOS undergo an oral glucose tolerance test every 3-5 years, with more frequent screening for those who develop symptoms of T2D, significant weight gain, or central adiposity. In guidelines published in 2015 by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the Androgen Excess and PCOS Society, an annual oral glucose tolerance test is recommended for patients with PCOS and impaired glucose tolerance, whereas those with a family history of T2D or a BMI above 30 should be screened every 1-2 years.

Management of T2D with PCOS is similar to that of T2D without PCOS. Accordingly, metformin and lifestyle changes are the treatments of choice; any antidiabetic agent may be added in patients who do not achieve glycemic targets despite treatment with metformin.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships

PCOS is most often defined according to the Rotterdam criteria, which stipulate that at least two of the following be present: irregular ovulation, biochemical/clinical hyperandrogenism, and polycystic ovaries (seen in the MRI scan above). Insulin resistance is part of the pathogenesis of PCOS, and insulin resistance is associated with T2D in PCOS. 

In fact, PCOS is an independent risk factor for T2D, even after adjustment for BMI and obesity. Even normal-weight women with PCOS have an increased risk for T2D. More than half of women with PCOS develop T2D by age 40. 

Even though family history and obesity are major contributors in the development of diabetes in patients with PCOS, diabetes can still occur in lean patients with PCOS who have no family history, mainly secondary to insulin resistance.

The Endocrine Society recommends that all individuals with PCOS undergo an oral glucose tolerance test every 3-5 years, with more frequent screening for those who develop symptoms of T2D, significant weight gain, or central adiposity. In guidelines published in 2015 by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the Androgen Excess and PCOS Society, an annual oral glucose tolerance test is recommended for patients with PCOS and impaired glucose tolerance, whereas those with a family history of T2D or a BMI above 30 should be screened every 1-2 years.

Management of T2D with PCOS is similar to that of T2D without PCOS. Accordingly, metformin and lifestyle changes are the treatments of choice; any antidiabetic agent may be added in patients who do not achieve glycemic targets despite treatment with metformin.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships

PCOS is most often defined according to the Rotterdam criteria, which stipulate that at least two of the following be present: irregular ovulation, biochemical/clinical hyperandrogenism, and polycystic ovaries (seen in the MRI scan above). Insulin resistance is part of the pathogenesis of PCOS, and insulin resistance is associated with T2D in PCOS. 

In fact, PCOS is an independent risk factor for T2D, even after adjustment for BMI and obesity. Even normal-weight women with PCOS have an increased risk for T2D. More than half of women with PCOS develop T2D by age 40. 

Even though family history and obesity are major contributors in the development of diabetes in patients with PCOS, diabetes can still occur in lean patients with PCOS who have no family history, mainly secondary to insulin resistance.

The Endocrine Society recommends that all individuals with PCOS undergo an oral glucose tolerance test every 3-5 years, with more frequent screening for those who develop symptoms of T2D, significant weight gain, or central adiposity. In guidelines published in 2015 by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the Androgen Excess and PCOS Society, an annual oral glucose tolerance test is recommended for patients with PCOS and impaired glucose tolerance, whereas those with a family history of T2D or a BMI above 30 should be screened every 1-2 years.

Management of T2D with PCOS is similar to that of T2D without PCOS. Accordingly, metformin and lifestyle changes are the treatments of choice; any antidiabetic agent may be added in patients who do not achieve glycemic targets despite treatment with metformin.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships

Psychiatric disorders are tied to an increased risk of COVID-19 breakthrough infection, particularly among older adults, new research shows.

“Psychiatric disorders remained significantly associated with incident breakthrough infections above and beyond sociodemographic and medical factors, suggesting that mental health is important to consider in conjunction with other risk factors,” wrote the investigators, led by Aoife O’Donovan, PhD, University of California, San Francisco.

Individuals with psychiatric disorders “should be prioritized for booster vaccinations and other critical preventive efforts, including increased SARS-CoV-2 screening, public health campaigns, or COVID-19 discussions during clinical care,” they added.

The study was published online in JAMA Network Open.
 

Elderly most vulnerable

The researchers reviewed the records of 263,697 veterans who were fully vaccinated against COVID-19.

Just over a half (51.4%) had one or more psychiatric diagnoses within the last 5 years and 14.8% developed breakthrough COVID-19 infections, confirmed by a positive SARS-CoV-2 test.

Psychiatric diagnoses among the veterans included depression, posttraumatic stress, anxiety, adjustment disorder, substance use disorder, bipolar disorder, psychosis, ADHD, dissociation, and eating disorders.

In the overall sample, a history of any psychiatric disorder was associated with a 7% higher incidence of breakthrough COVID-19 infection in models adjusted for potential confounders (adjusted relative risk, 1.07; 95% confidence interval, 1.05-1.09) and a 3% higher incidence in models additionally adjusted for underlying medical comorbidities and smoking (aRR, 1.03; 95% CI, 1.01-1.05).

Most psychiatric disorders were associated with a higher incidence of breakthrough infection, with the highest relative risk observed for substance use disorders (aRR, 1.16; 95% CI, 1.12 -1.21) and adjustment disorder (aRR, 1.13; 95% CI, 1.10-1.16) in fully adjusted models.

Older vaccinated veterans with psychiatric illnesses appear to be most vulnerable to COVID-19 reinfection.

In veterans aged 65 and older, all psychiatric disorders were associated with an increased incidence of breakthrough infection, with increases in the incidence rate ranging from 3% to 24% in fully adjusted models.

In the younger veterans, in contrast, only anxiety, adjustment, and substance use disorders were associated with an increased incidence of breakthrough infection in fully adjusted models.

Psychotic disorders were associated with a 10% lower incidence of breakthrough infection among younger veterans, perhaps because of greater social isolation, the researchers said.
 

Risky behavior or impaired immunity?

“Although some of the larger observed effect sizes are compelling at an individual level, even the relatively modest effect sizes may have a large effect at the population level when considering the high prevalence of psychiatric disorders and the global reach and scale of the pandemic,” Dr. O’Donovan and colleagues wrote.

They noted that psychiatric disorders, including depression, schizophrenia, and bipolar disorders, have been associated with impaired cellular immunity and blunted response to vaccines. Therefore, it’s possible that those with psychiatric disorders have poorer responses to COVID-19 vaccination.

It’s also possible that immunity following vaccination wanes more quickly or more strongly in people with psychiatric disorders and they could have less protection against new variants, they added.

Patients with psychiatric disorders could be more apt to engage in risky behaviors for contracting COVID-19, which could also increase the risk for breakthrough infection, they said.

The study was supported by a UCSF Department of Psychiatry Rapid Award and UCSF Faculty Resource Fund Award. Dr. O’Donovan reported no relevant disclosures.

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

Psychiatric disorders are tied to an increased risk of COVID-19 breakthrough infection, particularly among older adults, new research shows.

“Psychiatric disorders remained significantly associated with incident breakthrough infections above and beyond sociodemographic and medical factors, suggesting that mental health is important to consider in conjunction with other risk factors,” wrote the investigators, led by Aoife O’Donovan, PhD, University of California, San Francisco.

Individuals with psychiatric disorders “should be prioritized for booster vaccinations and other critical preventive efforts, including increased SARS-CoV-2 screening, public health campaigns, or COVID-19 discussions during clinical care,” they added.

The study was published online in JAMA Network Open.
 

Elderly most vulnerable

The researchers reviewed the records of 263,697 veterans who were fully vaccinated against COVID-19.

Just over a half (51.4%) had one or more psychiatric diagnoses within the last 5 years and 14.8% developed breakthrough COVID-19 infections, confirmed by a positive SARS-CoV-2 test.

Psychiatric diagnoses among the veterans included depression, posttraumatic stress, anxiety, adjustment disorder, substance use disorder, bipolar disorder, psychosis, ADHD, dissociation, and eating disorders.

In the overall sample, a history of any psychiatric disorder was associated with a 7% higher incidence of breakthrough COVID-19 infection in models adjusted for potential confounders (adjusted relative risk, 1.07; 95% confidence interval, 1.05-1.09) and a 3% higher incidence in models additionally adjusted for underlying medical comorbidities and smoking (aRR, 1.03; 95% CI, 1.01-1.05).

Most psychiatric disorders were associated with a higher incidence of breakthrough infection, with the highest relative risk observed for substance use disorders (aRR, 1.16; 95% CI, 1.12 -1.21) and adjustment disorder (aRR, 1.13; 95% CI, 1.10-1.16) in fully adjusted models.

Older vaccinated veterans with psychiatric illnesses appear to be most vulnerable to COVID-19 reinfection.

In veterans aged 65 and older, all psychiatric disorders were associated with an increased incidence of breakthrough infection, with increases in the incidence rate ranging from 3% to 24% in fully adjusted models.

In the younger veterans, in contrast, only anxiety, adjustment, and substance use disorders were associated with an increased incidence of breakthrough infection in fully adjusted models.

Psychotic disorders were associated with a 10% lower incidence of breakthrough infection among younger veterans, perhaps because of greater social isolation, the researchers said.
 

Risky behavior or impaired immunity?

“Although some of the larger observed effect sizes are compelling at an individual level, even the relatively modest effect sizes may have a large effect at the population level when considering the high prevalence of psychiatric disorders and the global reach and scale of the pandemic,” Dr. O’Donovan and colleagues wrote.

They noted that psychiatric disorders, including depression, schizophrenia, and bipolar disorders, have been associated with impaired cellular immunity and blunted response to vaccines. Therefore, it’s possible that those with psychiatric disorders have poorer responses to COVID-19 vaccination.

It’s also possible that immunity following vaccination wanes more quickly or more strongly in people with psychiatric disorders and they could have less protection against new variants, they added.

Patients with psychiatric disorders could be more apt to engage in risky behaviors for contracting COVID-19, which could also increase the risk for breakthrough infection, they said.

The study was supported by a UCSF Department of Psychiatry Rapid Award and UCSF Faculty Resource Fund Award. Dr. O’Donovan reported no relevant disclosures.

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

Psychiatric disorders are tied to an increased risk of COVID-19 breakthrough infection, particularly among older adults, new research shows.

“Psychiatric disorders remained significantly associated with incident breakthrough infections above and beyond sociodemographic and medical factors, suggesting that mental health is important to consider in conjunction with other risk factors,” wrote the investigators, led by Aoife O’Donovan, PhD, University of California, San Francisco.

Individuals with psychiatric disorders “should be prioritized for booster vaccinations and other critical preventive efforts, including increased SARS-CoV-2 screening, public health campaigns, or COVID-19 discussions during clinical care,” they added.

The study was published online in JAMA Network Open.
 

Elderly most vulnerable

The researchers reviewed the records of 263,697 veterans who were fully vaccinated against COVID-19.

Just over a half (51.4%) had one or more psychiatric diagnoses within the last 5 years and 14.8% developed breakthrough COVID-19 infections, confirmed by a positive SARS-CoV-2 test.

Psychiatric diagnoses among the veterans included depression, posttraumatic stress, anxiety, adjustment disorder, substance use disorder, bipolar disorder, psychosis, ADHD, dissociation, and eating disorders.

In the overall sample, a history of any psychiatric disorder was associated with a 7% higher incidence of breakthrough COVID-19 infection in models adjusted for potential confounders (adjusted relative risk, 1.07; 95% confidence interval, 1.05-1.09) and a 3% higher incidence in models additionally adjusted for underlying medical comorbidities and smoking (aRR, 1.03; 95% CI, 1.01-1.05).

Most psychiatric disorders were associated with a higher incidence of breakthrough infection, with the highest relative risk observed for substance use disorders (aRR, 1.16; 95% CI, 1.12 -1.21) and adjustment disorder (aRR, 1.13; 95% CI, 1.10-1.16) in fully adjusted models.

Older vaccinated veterans with psychiatric illnesses appear to be most vulnerable to COVID-19 reinfection.

In veterans aged 65 and older, all psychiatric disorders were associated with an increased incidence of breakthrough infection, with increases in the incidence rate ranging from 3% to 24% in fully adjusted models.

In the younger veterans, in contrast, only anxiety, adjustment, and substance use disorders were associated with an increased incidence of breakthrough infection in fully adjusted models.

Psychotic disorders were associated with a 10% lower incidence of breakthrough infection among younger veterans, perhaps because of greater social isolation, the researchers said.
 

Risky behavior or impaired immunity?

“Although some of the larger observed effect sizes are compelling at an individual level, even the relatively modest effect sizes may have a large effect at the population level when considering the high prevalence of psychiatric disorders and the global reach and scale of the pandemic,” Dr. O’Donovan and colleagues wrote.

They noted that psychiatric disorders, including depression, schizophrenia, and bipolar disorders, have been associated with impaired cellular immunity and blunted response to vaccines. Therefore, it’s possible that those with psychiatric disorders have poorer responses to COVID-19 vaccination.

It’s also possible that immunity following vaccination wanes more quickly or more strongly in people with psychiatric disorders and they could have less protection against new variants, they added.

Patients with psychiatric disorders could be more apt to engage in risky behaviors for contracting COVID-19, which could also increase the risk for breakthrough infection, they said.

The study was supported by a UCSF Department of Psychiatry Rapid Award and UCSF Faculty Resource Fund Award. Dr. O’Donovan reported no relevant disclosures.

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