Conference Coverage

Older adults with schizophrenia are not a homogeneous patient population, with various subgroups that differ significantly in terms of comorbid illness and mortality rates and causes, new research shows.

For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.

American Psychiatric Association

“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.

“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added. 

The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
 

Widening mortality gap

The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.

Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”

The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.

Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.

The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).

The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.

The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
 

Disease prevalence rates

Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.

The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.

Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.

On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.

“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.

The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.

More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
 

High rates of accidental death

The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.

The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.

Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”

The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.

One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.

Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.

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

Older adults with schizophrenia are not a homogeneous patient population, with various subgroups that differ significantly in terms of comorbid illness and mortality rates and causes, new research shows.

For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.

American Psychiatric Association

“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.

“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added. 

The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
 

Widening mortality gap

The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.

Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”

The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.

Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.

The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).

The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.

The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
 

Disease prevalence rates

Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.

The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.

Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.

On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.

“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.

The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.

More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
 

High rates of accidental death

The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.

The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.

Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”

The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.

One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.

Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.

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

Older adults with schizophrenia are not a homogeneous patient population, with various subgroups that differ significantly in terms of comorbid illness and mortality rates and causes, new research shows.

For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.

American Psychiatric Association

“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.

“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added. 

The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
 

Widening mortality gap

The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.

Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”

The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.

Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.

The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).

The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.

The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
 

Disease prevalence rates

Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.

The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.

Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.

On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.

“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.

The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.

More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
 

High rates of accidental death

The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.

The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.

Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”

The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.

One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.

Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.

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

CHICAGO – Patients undergoing primary reverse shoulder arthroplasty (RSA) for their glenohumeral osteoarthritis had more complications of care and higher hospital costs when they also had a diagnosis of depression, new data show.

The abstract was presented at the annual meeting of the American Academy of Orthopedic Surgeons.

Researchers, led by Keith Diamond, MD, an orthopedic surgeon at Maimonides Medical Center in New York, queried a private payer database looking for patients who had primary RSA for treatment of glenohumeral OA and also had a diagnosis of depressive disorder (DD) from 2010 to 2019. Patients without DD served as the controls.

After the randomized matching with controls at a 1:5 ratio, the study consisted of 28,410 patients: 4,084 in the DD group and 24,326 in the control group.

Researchers found that patients with depression had longer hospital stays (3 vs. 2 days, P = .0007). They also had higher frequency and odds of developing side effects within the period of care (47.4% vs. 14.7%; odds ratio, 2.27; 95% CI, 2.10-2.45,  P < .0001).

Patients with depression also had significantly higher rates of medical complications surrounding the surgery and costs were higher ($19,363 vs. $17,927, P < .0001).

Pneumonia rates were much higher in patients with DD (10% vs. 1.8%; OR, 2.88; P < .0001).

Patients with depression had higher odds of cerebrovascular accident (3.1% vs. 0.7%; OR, 2.69, P < .0001); myocardial infarctions (2% vs. 0.4%; OR, 2.54; P < .0001); acute kidney injuries (11.1% vs. 2.3%; OR, 2.11, P < .0001); surgical site infections (4.4% vs. 2.4%; OR, 1.52, P < .0001); and other complications, the authors wrote.

Dr. Diamond said in an interview that there may be a few potential reasons for the associations.

In regard to the strong association with pneumonia, Dr. Diamond hypothesized, “patients with depression can be shown to have lower respiratory drive. If a patient isn’t motivated to get out of bed, that can lead to decreased inflation of the lungs.”

Acute kidney injury could be linked with depression-related lack of self-care in properly hydrating, he said. Surgical site infections could come from suboptimal hygiene related to managing the cast after surgery, which may be more difficult when patients also struggle with depression.

Asked to comment on Dr. Diamond’s study, Grant Garrigues, MD, an associate professor at Rush University Medical Center, Chicago, and director of upper extremity research, told this news organization the study helps confirm known associations between depression and arthritis.

“We know that people with depression and anxiety feel pain differently,” he said. “It might have to do with your outlook – are you catastrophizing or thinking it’s a minor inconvenience? It’s not that it’s just in your head – you physically feel it differently. That is something we’re certainly attuned to. We want to make sure the mental health part of the picture is optimized as much as possible.”

He added that there is increasing evidence of links between depression and the development of arthritis.

“I’m not saying that everyone with arthritis has depression, but with arthritis being multifactorial, there’s a relatively high incidence of symptomatic arthritis in patients with depression,” Dr. Garrigues said.

“We think it may have something to do with the fight-or-flight hormones in your body that may be revved up if you are living in a stressful environment or are living with a mental health problem. Those will actually change – on a cellular and biochemical basis – some of the things that affect arthritis.”
 

Stronger emphasis on mental health

Dr. Diamond said the field needs more emphasis on perioperative state of mind.  

“As orthopedic surgeons, we are preoccupied with the mechanical, the structural aspects of health care as we try to fix bones, ligaments, and tendons. But I think we need to recognize and explore the connection between the psychiatric and psychological health with our musculoskeletal health.”

He noted that, in the preoperative setting, providers look for hypertension, diabetes, smoking status, and other conditions that could complicate surgical outcomes and said mental health should be a factor in whether a surgery proceeds.

“If someone’s diabetes isn’t controlled you can delay an elective case until their [hemoglobin] A1c is under the recommended limit and you get clearance from their primary care doctor. I think that’s something that should be applied to patients with depressive disorders,” Dr. Diamond said.

This study did not distinguish between patients who were being treated for depression at the time of surgery and those not on treatment. More study related to whether treatment affects depression’s association with RSA outcomes is needed, Dr. Diamond added.

Dr. Garrigues said he talks candidly with patients considering surgery about how they are managing their mental health struggles.

“If they say they haven’t seen their psychiatrist or are off their medications, that’s a nonstarter,” he said.

“Anything outside of the surgery you can optimize, whether it’s mental health, medical, social situations – you want to have all your ducks in a row before you dive into surgery,” Dr. Garrigues said.

He added that patients’ mental health status may even affect the venue for the patient – whether outpatient or inpatient, where they can get more supervision and help in making transitions after surgery.

Dr. Diamond and coauthors and Dr. Garrigues disclosed no relevant financial relationships.

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

CHICAGO – Patients undergoing primary reverse shoulder arthroplasty (RSA) for their glenohumeral osteoarthritis had more complications of care and higher hospital costs when they also had a diagnosis of depression, new data show.

The abstract was presented at the annual meeting of the American Academy of Orthopedic Surgeons.

Researchers, led by Keith Diamond, MD, an orthopedic surgeon at Maimonides Medical Center in New York, queried a private payer database looking for patients who had primary RSA for treatment of glenohumeral OA and also had a diagnosis of depressive disorder (DD) from 2010 to 2019. Patients without DD served as the controls.

After the randomized matching with controls at a 1:5 ratio, the study consisted of 28,410 patients: 4,084 in the DD group and 24,326 in the control group.

Researchers found that patients with depression had longer hospital stays (3 vs. 2 days, P = .0007). They also had higher frequency and odds of developing side effects within the period of care (47.4% vs. 14.7%; odds ratio, 2.27; 95% CI, 2.10-2.45,  P < .0001).

Patients with depression also had significantly higher rates of medical complications surrounding the surgery and costs were higher ($19,363 vs. $17,927, P < .0001).

Pneumonia rates were much higher in patients with DD (10% vs. 1.8%; OR, 2.88; P < .0001).

Patients with depression had higher odds of cerebrovascular accident (3.1% vs. 0.7%; OR, 2.69, P < .0001); myocardial infarctions (2% vs. 0.4%; OR, 2.54; P < .0001); acute kidney injuries (11.1% vs. 2.3%; OR, 2.11, P < .0001); surgical site infections (4.4% vs. 2.4%; OR, 1.52, P < .0001); and other complications, the authors wrote.

Dr. Diamond said in an interview that there may be a few potential reasons for the associations.

In regard to the strong association with pneumonia, Dr. Diamond hypothesized, “patients with depression can be shown to have lower respiratory drive. If a patient isn’t motivated to get out of bed, that can lead to decreased inflation of the lungs.”

Acute kidney injury could be linked with depression-related lack of self-care in properly hydrating, he said. Surgical site infections could come from suboptimal hygiene related to managing the cast after surgery, which may be more difficult when patients also struggle with depression.

Asked to comment on Dr. Diamond’s study, Grant Garrigues, MD, an associate professor at Rush University Medical Center, Chicago, and director of upper extremity research, told this news organization the study helps confirm known associations between depression and arthritis.

“We know that people with depression and anxiety feel pain differently,” he said. “It might have to do with your outlook – are you catastrophizing or thinking it’s a minor inconvenience? It’s not that it’s just in your head – you physically feel it differently. That is something we’re certainly attuned to. We want to make sure the mental health part of the picture is optimized as much as possible.”

He added that there is increasing evidence of links between depression and the development of arthritis.

“I’m not saying that everyone with arthritis has depression, but with arthritis being multifactorial, there’s a relatively high incidence of symptomatic arthritis in patients with depression,” Dr. Garrigues said.

“We think it may have something to do with the fight-or-flight hormones in your body that may be revved up if you are living in a stressful environment or are living with a mental health problem. Those will actually change – on a cellular and biochemical basis – some of the things that affect arthritis.”
 

Stronger emphasis on mental health

Dr. Diamond said the field needs more emphasis on perioperative state of mind.  

“As orthopedic surgeons, we are preoccupied with the mechanical, the structural aspects of health care as we try to fix bones, ligaments, and tendons. But I think we need to recognize and explore the connection between the psychiatric and psychological health with our musculoskeletal health.”

He noted that, in the preoperative setting, providers look for hypertension, diabetes, smoking status, and other conditions that could complicate surgical outcomes and said mental health should be a factor in whether a surgery proceeds.

“If someone’s diabetes isn’t controlled you can delay an elective case until their [hemoglobin] A1c is under the recommended limit and you get clearance from their primary care doctor. I think that’s something that should be applied to patients with depressive disorders,” Dr. Diamond said.

This study did not distinguish between patients who were being treated for depression at the time of surgery and those not on treatment. More study related to whether treatment affects depression’s association with RSA outcomes is needed, Dr. Diamond added.

Dr. Garrigues said he talks candidly with patients considering surgery about how they are managing their mental health struggles.

“If they say they haven’t seen their psychiatrist or are off their medications, that’s a nonstarter,” he said.

“Anything outside of the surgery you can optimize, whether it’s mental health, medical, social situations – you want to have all your ducks in a row before you dive into surgery,” Dr. Garrigues said.

He added that patients’ mental health status may even affect the venue for the patient – whether outpatient or inpatient, where they can get more supervision and help in making transitions after surgery.

Dr. Diamond and coauthors and Dr. Garrigues disclosed no relevant financial relationships.

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

CHICAGO – Patients undergoing primary reverse shoulder arthroplasty (RSA) for their glenohumeral osteoarthritis had more complications of care and higher hospital costs when they also had a diagnosis of depression, new data show.

The abstract was presented at the annual meeting of the American Academy of Orthopedic Surgeons.

Researchers, led by Keith Diamond, MD, an orthopedic surgeon at Maimonides Medical Center in New York, queried a private payer database looking for patients who had primary RSA for treatment of glenohumeral OA and also had a diagnosis of depressive disorder (DD) from 2010 to 2019. Patients without DD served as the controls.

After the randomized matching with controls at a 1:5 ratio, the study consisted of 28,410 patients: 4,084 in the DD group and 24,326 in the control group.

Researchers found that patients with depression had longer hospital stays (3 vs. 2 days, P = .0007). They also had higher frequency and odds of developing side effects within the period of care (47.4% vs. 14.7%; odds ratio, 2.27; 95% CI, 2.10-2.45,  P < .0001).

Patients with depression also had significantly higher rates of medical complications surrounding the surgery and costs were higher ($19,363 vs. $17,927, P < .0001).

Pneumonia rates were much higher in patients with DD (10% vs. 1.8%; OR, 2.88; P < .0001).

Patients with depression had higher odds of cerebrovascular accident (3.1% vs. 0.7%; OR, 2.69, P < .0001); myocardial infarctions (2% vs. 0.4%; OR, 2.54; P < .0001); acute kidney injuries (11.1% vs. 2.3%; OR, 2.11, P < .0001); surgical site infections (4.4% vs. 2.4%; OR, 1.52, P < .0001); and other complications, the authors wrote.

Dr. Diamond said in an interview that there may be a few potential reasons for the associations.

In regard to the strong association with pneumonia, Dr. Diamond hypothesized, “patients with depression can be shown to have lower respiratory drive. If a patient isn’t motivated to get out of bed, that can lead to decreased inflation of the lungs.”

Acute kidney injury could be linked with depression-related lack of self-care in properly hydrating, he said. Surgical site infections could come from suboptimal hygiene related to managing the cast after surgery, which may be more difficult when patients also struggle with depression.

Asked to comment on Dr. Diamond’s study, Grant Garrigues, MD, an associate professor at Rush University Medical Center, Chicago, and director of upper extremity research, told this news organization the study helps confirm known associations between depression and arthritis.

“We know that people with depression and anxiety feel pain differently,” he said. “It might have to do with your outlook – are you catastrophizing or thinking it’s a minor inconvenience? It’s not that it’s just in your head – you physically feel it differently. That is something we’re certainly attuned to. We want to make sure the mental health part of the picture is optimized as much as possible.”

He added that there is increasing evidence of links between depression and the development of arthritis.

“I’m not saying that everyone with arthritis has depression, but with arthritis being multifactorial, there’s a relatively high incidence of symptomatic arthritis in patients with depression,” Dr. Garrigues said.

“We think it may have something to do with the fight-or-flight hormones in your body that may be revved up if you are living in a stressful environment or are living with a mental health problem. Those will actually change – on a cellular and biochemical basis – some of the things that affect arthritis.”
 

Stronger emphasis on mental health

Dr. Diamond said the field needs more emphasis on perioperative state of mind.  

“As orthopedic surgeons, we are preoccupied with the mechanical, the structural aspects of health care as we try to fix bones, ligaments, and tendons. But I think we need to recognize and explore the connection between the psychiatric and psychological health with our musculoskeletal health.”

He noted that, in the preoperative setting, providers look for hypertension, diabetes, smoking status, and other conditions that could complicate surgical outcomes and said mental health should be a factor in whether a surgery proceeds.

“If someone’s diabetes isn’t controlled you can delay an elective case until their [hemoglobin] A1c is under the recommended limit and you get clearance from their primary care doctor. I think that’s something that should be applied to patients with depressive disorders,” Dr. Diamond said.

This study did not distinguish between patients who were being treated for depression at the time of surgery and those not on treatment. More study related to whether treatment affects depression’s association with RSA outcomes is needed, Dr. Diamond added.

Dr. Garrigues said he talks candidly with patients considering surgery about how they are managing their mental health struggles.

“If they say they haven’t seen their psychiatrist or are off their medications, that’s a nonstarter,” he said.

“Anything outside of the surgery you can optimize, whether it’s mental health, medical, social situations – you want to have all your ducks in a row before you dive into surgery,” Dr. Garrigues said.

He added that patients’ mental health status may even affect the venue for the patient – whether outpatient or inpatient, where they can get more supervision and help in making transitions after surgery.

Dr. Diamond and coauthors and Dr. Garrigues disclosed no relevant financial relationships.

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

CHICAGO - Posterior-stabilized (PS) bearings used in total knee arthroplasty (TKA) may increase the risk of revision compared with bearings of other design, new data suggest.

That possibility has previously been reported in studies outside the United States, and now an analysis of more than 300,000 cases in the American Joint Replacement Registry (AJRR) suggests it’s the case in the United States as well.

Principal investigator Ryland Kagan, MD, of the department of orthopedic surgery at Oregon Health & Science University in Portland, told this news organization, “What’s unique about our experience in the U.S. is our overall high use of PS implants.”

More than half of TKAs in the United States use the PS bearings; in comparison, in Australia and European countries, PS use is closer to 20%, he said. Because of this disparity, previous studies have not been seen as generalizable to the United States, he said.

Researchers used AJRR data from 2012 to 2019 and identified all primary TKA procedures performed during that period. Cases were linked to supplemental Centers for Medicare & Medicaid Services data to find revision procedures that may not have been included in the AJRR database.

Jamil Kendall, MD, an orthopedic resident at OHSU, was first author on the study. The team evaluated patient demographics, polyethylene characteristics, procedure dates, and cause for revision in the 305,279 cases.

Of those cases in which implant characteristics were reported, 161,486 (52.9%) patients received PS bearings, and 143,793 (47.1%) received minimally stabilized bearings.

The researchers compared three minimally stabilized implants (cruciate retaining [CR], anterior stabilized [AS], or pivot bearing designs) with each other for risk and then compared minimally stabilized options as a group with the PS bearings.

They found no significant differences among the three minimally stabilized options.

But revision risk was higher when they compared the minimally stabilized implants with the PS bearing implants. Use of PS bearings had a hazard ratio of 1.25 (95% confidence interval, 1.2-1.3; P < .0001) for all-cause revision and an HR of 1.18 (95% CI, 1.0-1.4; P = .02) for infection.

Among the patients with minimally stabilized bearings, 1,693 (1.2%) underwent revision for any cause, and 334 (0.2%) underwent revision for infection. For patients with PS bearings, 2,406 (1.5%) underwent revision for any cause, and 446 (0.3%) underwent revision for infection.

Even a small difference significant

Dr. Kagan said, “The difference isn’t dramatic, but when you think of the total number of total knee arthroplasties done, you’re talking about millions of procedures. Even with a small increased risk, you’re going to see a large influence for a population.”

Richard Lynn Illgen, MD, director of the University of Wisconsin-Madison joint replacement program, told this news organization this work identifies a trend, but he pointed out that registry-based studies have important limitations.

“They cannot establish causality,” he said. “There are many potential confounding variables and potential selection biases that could affect the study. Specifically, the study did not control for degree of deformity or medical comorbidities. Although some surgeons routinely use PS designs for all primary TKAs, others use PS designs for patients with more severe deformities. It is possible that PS designs were used more frequently in patients with a greater degree of deformity, and this could introduce a selection bias.”

He added that no data were included to enable stratification of groups according to medical comorbidities.

“It is possible that selection bias exists comparing the relative degree of medical comorbidities between patients in the PS TKA and minimally constrained TKA groups,” Dr. Illgen said.

He said further prospective, randomized studies are needed to eliminate selection bias and to better determine whether the observed pattern of increased risk of revision holds up, compared with the minimally supported versions.

The authors acknowledged those limitations, but Dr. Kagan said the high percentage of PS procedures in the United States helps mitigate potential bias.

Dr. Illgen serves as a consultant and developer for Stryker, is chair of the AAOS AJRR Research Projects Subcommittee, and is a member of the AJRR Steering Committee. Dr. Kagan receives research support from KCI, Ortho Development, and Smith & Nephew, where he is also a paid consultant. Dr. Kendall reports no relevant financial relationships. Another coauthor of the study is a paid consultant for 3M, Heraeus, Immunis, Smith & Nephew, Zimmer Biomet, and Total Joint Orthopedics and has stock or stock options in Joint Development.

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

CHICAGO - Posterior-stabilized (PS) bearings used in total knee arthroplasty (TKA) may increase the risk of revision compared with bearings of other design, new data suggest.

That possibility has previously been reported in studies outside the United States, and now an analysis of more than 300,000 cases in the American Joint Replacement Registry (AJRR) suggests it’s the case in the United States as well.

Principal investigator Ryland Kagan, MD, of the department of orthopedic surgery at Oregon Health & Science University in Portland, told this news organization, “What’s unique about our experience in the U.S. is our overall high use of PS implants.”

More than half of TKAs in the United States use the PS bearings; in comparison, in Australia and European countries, PS use is closer to 20%, he said. Because of this disparity, previous studies have not been seen as generalizable to the United States, he said.

Researchers used AJRR data from 2012 to 2019 and identified all primary TKA procedures performed during that period. Cases were linked to supplemental Centers for Medicare & Medicaid Services data to find revision procedures that may not have been included in the AJRR database.

Jamil Kendall, MD, an orthopedic resident at OHSU, was first author on the study. The team evaluated patient demographics, polyethylene characteristics, procedure dates, and cause for revision in the 305,279 cases.

Of those cases in which implant characteristics were reported, 161,486 (52.9%) patients received PS bearings, and 143,793 (47.1%) received minimally stabilized bearings.

The researchers compared three minimally stabilized implants (cruciate retaining [CR], anterior stabilized [AS], or pivot bearing designs) with each other for risk and then compared minimally stabilized options as a group with the PS bearings.

They found no significant differences among the three minimally stabilized options.

But revision risk was higher when they compared the minimally stabilized implants with the PS bearing implants. Use of PS bearings had a hazard ratio of 1.25 (95% confidence interval, 1.2-1.3; P < .0001) for all-cause revision and an HR of 1.18 (95% CI, 1.0-1.4; P = .02) for infection.

Among the patients with minimally stabilized bearings, 1,693 (1.2%) underwent revision for any cause, and 334 (0.2%) underwent revision for infection. For patients with PS bearings, 2,406 (1.5%) underwent revision for any cause, and 446 (0.3%) underwent revision for infection.

Even a small difference significant

Dr. Kagan said, “The difference isn’t dramatic, but when you think of the total number of total knee arthroplasties done, you’re talking about millions of procedures. Even with a small increased risk, you’re going to see a large influence for a population.”

Richard Lynn Illgen, MD, director of the University of Wisconsin-Madison joint replacement program, told this news organization this work identifies a trend, but he pointed out that registry-based studies have important limitations.

“They cannot establish causality,” he said. “There are many potential confounding variables and potential selection biases that could affect the study. Specifically, the study did not control for degree of deformity or medical comorbidities. Although some surgeons routinely use PS designs for all primary TKAs, others use PS designs for patients with more severe deformities. It is possible that PS designs were used more frequently in patients with a greater degree of deformity, and this could introduce a selection bias.”

He added that no data were included to enable stratification of groups according to medical comorbidities.

“It is possible that selection bias exists comparing the relative degree of medical comorbidities between patients in the PS TKA and minimally constrained TKA groups,” Dr. Illgen said.

He said further prospective, randomized studies are needed to eliminate selection bias and to better determine whether the observed pattern of increased risk of revision holds up, compared with the minimally supported versions.

The authors acknowledged those limitations, but Dr. Kagan said the high percentage of PS procedures in the United States helps mitigate potential bias.

Dr. Illgen serves as a consultant and developer for Stryker, is chair of the AAOS AJRR Research Projects Subcommittee, and is a member of the AJRR Steering Committee. Dr. Kagan receives research support from KCI, Ortho Development, and Smith & Nephew, where he is also a paid consultant. Dr. Kendall reports no relevant financial relationships. Another coauthor of the study is a paid consultant for 3M, Heraeus, Immunis, Smith & Nephew, Zimmer Biomet, and Total Joint Orthopedics and has stock or stock options in Joint Development.

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

CHICAGO - Posterior-stabilized (PS) bearings used in total knee arthroplasty (TKA) may increase the risk of revision compared with bearings of other design, new data suggest.

That possibility has previously been reported in studies outside the United States, and now an analysis of more than 300,000 cases in the American Joint Replacement Registry (AJRR) suggests it’s the case in the United States as well.

Principal investigator Ryland Kagan, MD, of the department of orthopedic surgery at Oregon Health & Science University in Portland, told this news organization, “What’s unique about our experience in the U.S. is our overall high use of PS implants.”

More than half of TKAs in the United States use the PS bearings; in comparison, in Australia and European countries, PS use is closer to 20%, he said. Because of this disparity, previous studies have not been seen as generalizable to the United States, he said.

Researchers used AJRR data from 2012 to 2019 and identified all primary TKA procedures performed during that period. Cases were linked to supplemental Centers for Medicare & Medicaid Services data to find revision procedures that may not have been included in the AJRR database.

Jamil Kendall, MD, an orthopedic resident at OHSU, was first author on the study. The team evaluated patient demographics, polyethylene characteristics, procedure dates, and cause for revision in the 305,279 cases.

Of those cases in which implant characteristics were reported, 161,486 (52.9%) patients received PS bearings, and 143,793 (47.1%) received minimally stabilized bearings.

The researchers compared three minimally stabilized implants (cruciate retaining [CR], anterior stabilized [AS], or pivot bearing designs) with each other for risk and then compared minimally stabilized options as a group with the PS bearings.

They found no significant differences among the three minimally stabilized options.

But revision risk was higher when they compared the minimally stabilized implants with the PS bearing implants. Use of PS bearings had a hazard ratio of 1.25 (95% confidence interval, 1.2-1.3; P < .0001) for all-cause revision and an HR of 1.18 (95% CI, 1.0-1.4; P = .02) for infection.

Among the patients with minimally stabilized bearings, 1,693 (1.2%) underwent revision for any cause, and 334 (0.2%) underwent revision for infection. For patients with PS bearings, 2,406 (1.5%) underwent revision for any cause, and 446 (0.3%) underwent revision for infection.

Even a small difference significant

Dr. Kagan said, “The difference isn’t dramatic, but when you think of the total number of total knee arthroplasties done, you’re talking about millions of procedures. Even with a small increased risk, you’re going to see a large influence for a population.”

Richard Lynn Illgen, MD, director of the University of Wisconsin-Madison joint replacement program, told this news organization this work identifies a trend, but he pointed out that registry-based studies have important limitations.

“They cannot establish causality,” he said. “There are many potential confounding variables and potential selection biases that could affect the study. Specifically, the study did not control for degree of deformity or medical comorbidities. Although some surgeons routinely use PS designs for all primary TKAs, others use PS designs for patients with more severe deformities. It is possible that PS designs were used more frequently in patients with a greater degree of deformity, and this could introduce a selection bias.”

He added that no data were included to enable stratification of groups according to medical comorbidities.

“It is possible that selection bias exists comparing the relative degree of medical comorbidities between patients in the PS TKA and minimally constrained TKA groups,” Dr. Illgen said.

He said further prospective, randomized studies are needed to eliminate selection bias and to better determine whether the observed pattern of increased risk of revision holds up, compared with the minimally supported versions.

The authors acknowledged those limitations, but Dr. Kagan said the high percentage of PS procedures in the United States helps mitigate potential bias.

Dr. Illgen serves as a consultant and developer for Stryker, is chair of the AAOS AJRR Research Projects Subcommittee, and is a member of the AJRR Steering Committee. Dr. Kagan receives research support from KCI, Ortho Development, and Smith & Nephew, where he is also a paid consultant. Dr. Kendall reports no relevant financial relationships. Another coauthor of the study is a paid consultant for 3M, Heraeus, Immunis, Smith & Nephew, Zimmer Biomet, and Total Joint Orthopedics and has stock or stock options in Joint Development.

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

CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.

Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.

Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.

Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.

Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).   

Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.

Reassuring older patients

However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).

“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”

These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.

The number of total knee replacements is expected to rise dramatically in the United States.

In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”

Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”

He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.

In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).

Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.

The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.

A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.

“It’s a small and manageable risk if you pick the right patients,” he said.

Demand for TKAs rises as population ages

As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.

“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.

This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.

“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”

Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.

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

CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.

Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.

Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.

Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.

Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).   

Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.

Reassuring older patients

However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).

“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”

These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.

The number of total knee replacements is expected to rise dramatically in the United States.

In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”

Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”

He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.

In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).

Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.

The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.

A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.

“It’s a small and manageable risk if you pick the right patients,” he said.

Demand for TKAs rises as population ages

As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.

“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.

This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.

“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”

Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.

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

CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.

Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.

Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.

Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.

Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).   

Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.

Reassuring older patients

However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).

“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”

These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.

The number of total knee replacements is expected to rise dramatically in the United States.

In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”

Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”

He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.

In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).

Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.

The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.

A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.

“It’s a small and manageable risk if you pick the right patients,” he said.

Demand for TKAs rises as population ages

As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.

“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.

This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.

“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”

Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.

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

WASHINGTON – Probiotics are generally used in relatively nontargeted, nonspecific ways. But with the gut microbiome being an integral component of a budding precision medicine model of care, and with “multi-omics” research picking up, this is bound to change, gastroenterologist Purna C. Kashyap, MBBS, said in an interview after the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

“There are so many missing pieces of information because, at the very basic level, we don’t know exactly how gut bacteria drive diseases,” he told GI & Hepatology News.

“The idea is to go toward a more precise, accurate approach where the newer generation of probiotics are designed to target a specific process, like block a microbial pathway that contributes to disease pathogenesis, or produce a metabolite that improves host function,” he said. “It’s this shift that is going on in the field. It’s already started, and it has momentum.” Dr. Kashyap is a professor of medicine and physiology at the Mayo Clinic College of Medicine in Rochester, Minn., and codirector of the institution’s microbiome program.

In a keynote lecture at the meeting, Dr. Kashyap said that the current approach to precision medicine, which aims to tailor treatments to defined subgroups of patients, needs to take into account “much more than the human genome.”

To the extent possible, it needs to consider the host (lifestyle, gene variants, etc.), the microbiome, and the exposome (environmental exposures such as diet, medications, and air and water quality).

The microbiome’s relative contribution to any one disease, in turn, likely varies from one individual or subgroup to another, he said.

Researchers are increasingly working with different layers of data and using machine learning methods and artificial intelligence approaches to integrate clinical data and “omics” measurements (e.g., from genome, proteome, metabolome).

Such approaches can help pinpoint the microbiome’s relative contributions, identify microbial-host behaviors and microbial-driven disease mechanisms, and ultimately personalize treatment approaches, Dr. Kashyap said.

For instance, Dr. Kashyap’s team has taken a multi-omics approach to studying patients with irritable bowel syndrome (IBS). Thus far, their research has identified subtype-specific variation in microbial composition and function, and by integrating omics from the host and microbiome, it has confirmed the role of several microbial pathways in subtypes of IBS.

His team has also identified a new pathway – the host and gut microbiota’s modulation of purine metabolism – as a potential driver of symptoms in patients with IBS (Cell 2020;182[6]:1460-73), he said.

Such findings provide opportunities to develop new microbial therapeutics – by engineering bacteria to produce metabolites that target a specific pathway, for instance, he said.
 

Predicting probiotic engraftment

Understanding the extent to which microbes actually engraft in the gut – and the forces governing engraftment – is part of a rational approach to designing future probiotic cocktails and to moving toward personalized, precision medicine, Eric Alm, PhD, said during a plenary session on the future of probiotics, moderated by Dr. Kashyap. Dr. Alm is a professor of biological, civil, and environmental engineering who directs the Center for Microbiome Informatics and Therapeutics at the Massachusetts Institute of Technology in Cambridge.

“One of the best datasets we have when thinking about designing therapeutic microbes is FMT (fecal microbiota transplant) data” in patients with Clostridioides difficile infection (CDI), said Dr. Alm.

“We wondered, can you predict what a patient will look like post FMT given what they looked like before and given what the donor looks like?” he said. “We found that engraftment can be predicted surprisingly well.”

Using computational algorithms and metagenomics sequencing data from donors and recipients, the researchers found that engraftment can be predicted largely from the abundance and strains of bacteria in the donor and the pre-FMT patient microbiome (Cell Host Microbe 2018;23[2]:229-40.e5).

They also observed two behaviors: Previously undetected strains (not transplanted) frequently show up in patients who received FMT, and all donor strains within a species engrafted in an all-or-nothing fashion.

“Seeding a patient with a new species allows them to collect more strains of that species from the environment – this is fairly common,” said Dr. Alm. “But if I give five different strains of Faecalibacterium prausnitzii to a patient who doesn’t have any, they’ll get either zero, or they’ll get all five ... this is an observation we don’t fully understand yet.”

These types of observations “guide our thinking in how to produce rationally designed cocktails,” he said.
 

Other approaches to probiotics

In another type of research, Philippe Langella, PhD, who leads a laboratory of Commensal and Probiotics-Host Interactions at the Micalis Institute in France, has been investigating the use of genetically modified lactic acid bacteria to deliver anti-proteases and other types of molecules to patients with disease, such as the antiprotease elafin to patients with inflammatory bowel disease (IBD).

There is “a lack of elafin in Crohn’s disease and ulcerative colitis patients,” Dr. Langella said during the plenary session. “The idea is to use the genetically modified lactic acid bacteria to counterbalance the protease-antiprotease imbalance in IBD.”

In animal and in vitro models, elafin-expressing lactic acid bacteria decreased elastolytic activity and inflammation in the gut and restored intestinal permeability. The goal now, he said, is to construct biologically contained strains of the engineered bacteria to test in clinical trials.

While today’s probiotics are generally considered to be safe and to have beneficial effects, the next generation will be more targeted – more “rational,“ Dr. Kashyap said in his interview. Each of these researchers,” he said, “is working on different pieces of the puzzle and, eventually, this will allow us to accelerate the development of novel therapies.”

Dr. Kashyap said he has no disclosures relevant to his keynote address or moderation of the plenary session. In his presentation, Dr. Alm disclosed his involvement with Finch Therapeutics, OpenBiome, and Biobot Analytics.

Dr. Langella disclosed in his presentation that he is co-founder of Exeliom Biosciences and has research grants with various pharmaceutical companies, food supplement companies, and agro-food companies.

The 2022 Gut Microbiota for Health World Summit was supported by sponsorships from Danone, Ferring Pharmaceuticals, Aimmune Therapeutics and Seres Therapeutics, Sanofi, and Intrinsic Medicine Inc. with additional support from educational grants provided by Ferring Pharmaceuticals and Salix Pharmaceuticals.

This article was updated 4/5/22.

WASHINGTON – Probiotics are generally used in relatively nontargeted, nonspecific ways. But with the gut microbiome being an integral component of a budding precision medicine model of care, and with “multi-omics” research picking up, this is bound to change, gastroenterologist Purna C. Kashyap, MBBS, said in an interview after the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

“There are so many missing pieces of information because, at the very basic level, we don’t know exactly how gut bacteria drive diseases,” he told GI & Hepatology News.

“The idea is to go toward a more precise, accurate approach where the newer generation of probiotics are designed to target a specific process, like block a microbial pathway that contributes to disease pathogenesis, or produce a metabolite that improves host function,” he said. “It’s this shift that is going on in the field. It’s already started, and it has momentum.” Dr. Kashyap is a professor of medicine and physiology at the Mayo Clinic College of Medicine in Rochester, Minn., and codirector of the institution’s microbiome program.

In a keynote lecture at the meeting, Dr. Kashyap said that the current approach to precision medicine, which aims to tailor treatments to defined subgroups of patients, needs to take into account “much more than the human genome.”

To the extent possible, it needs to consider the host (lifestyle, gene variants, etc.), the microbiome, and the exposome (environmental exposures such as diet, medications, and air and water quality).

The microbiome’s relative contribution to any one disease, in turn, likely varies from one individual or subgroup to another, he said.

Researchers are increasingly working with different layers of data and using machine learning methods and artificial intelligence approaches to integrate clinical data and “omics” measurements (e.g., from genome, proteome, metabolome).

Such approaches can help pinpoint the microbiome’s relative contributions, identify microbial-host behaviors and microbial-driven disease mechanisms, and ultimately personalize treatment approaches, Dr. Kashyap said.

For instance, Dr. Kashyap’s team has taken a multi-omics approach to studying patients with irritable bowel syndrome (IBS). Thus far, their research has identified subtype-specific variation in microbial composition and function, and by integrating omics from the host and microbiome, it has confirmed the role of several microbial pathways in subtypes of IBS.

His team has also identified a new pathway – the host and gut microbiota’s modulation of purine metabolism – as a potential driver of symptoms in patients with IBS (Cell 2020;182[6]:1460-73), he said.

Such findings provide opportunities to develop new microbial therapeutics – by engineering bacteria to produce metabolites that target a specific pathway, for instance, he said.
 

Predicting probiotic engraftment

Understanding the extent to which microbes actually engraft in the gut – and the forces governing engraftment – is part of a rational approach to designing future probiotic cocktails and to moving toward personalized, precision medicine, Eric Alm, PhD, said during a plenary session on the future of probiotics, moderated by Dr. Kashyap. Dr. Alm is a professor of biological, civil, and environmental engineering who directs the Center for Microbiome Informatics and Therapeutics at the Massachusetts Institute of Technology in Cambridge.

“One of the best datasets we have when thinking about designing therapeutic microbes is FMT (fecal microbiota transplant) data” in patients with Clostridioides difficile infection (CDI), said Dr. Alm.

“We wondered, can you predict what a patient will look like post FMT given what they looked like before and given what the donor looks like?” he said. “We found that engraftment can be predicted surprisingly well.”

Using computational algorithms and metagenomics sequencing data from donors and recipients, the researchers found that engraftment can be predicted largely from the abundance and strains of bacteria in the donor and the pre-FMT patient microbiome (Cell Host Microbe 2018;23[2]:229-40.e5).

They also observed two behaviors: Previously undetected strains (not transplanted) frequently show up in patients who received FMT, and all donor strains within a species engrafted in an all-or-nothing fashion.

“Seeding a patient with a new species allows them to collect more strains of that species from the environment – this is fairly common,” said Dr. Alm. “But if I give five different strains of Faecalibacterium prausnitzii to a patient who doesn’t have any, they’ll get either zero, or they’ll get all five ... this is an observation we don’t fully understand yet.”

These types of observations “guide our thinking in how to produce rationally designed cocktails,” he said.
 

Other approaches to probiotics

In another type of research, Philippe Langella, PhD, who leads a laboratory of Commensal and Probiotics-Host Interactions at the Micalis Institute in France, has been investigating the use of genetically modified lactic acid bacteria to deliver anti-proteases and other types of molecules to patients with disease, such as the antiprotease elafin to patients with inflammatory bowel disease (IBD).

There is “a lack of elafin in Crohn’s disease and ulcerative colitis patients,” Dr. Langella said during the plenary session. “The idea is to use the genetically modified lactic acid bacteria to counterbalance the protease-antiprotease imbalance in IBD.”

In animal and in vitro models, elafin-expressing lactic acid bacteria decreased elastolytic activity and inflammation in the gut and restored intestinal permeability. The goal now, he said, is to construct biologically contained strains of the engineered bacteria to test in clinical trials.

While today’s probiotics are generally considered to be safe and to have beneficial effects, the next generation will be more targeted – more “rational,“ Dr. Kashyap said in his interview. Each of these researchers,” he said, “is working on different pieces of the puzzle and, eventually, this will allow us to accelerate the development of novel therapies.”

Dr. Kashyap said he has no disclosures relevant to his keynote address or moderation of the plenary session. In his presentation, Dr. Alm disclosed his involvement with Finch Therapeutics, OpenBiome, and Biobot Analytics.

Dr. Langella disclosed in his presentation that he is co-founder of Exeliom Biosciences and has research grants with various pharmaceutical companies, food supplement companies, and agro-food companies.

The 2022 Gut Microbiota for Health World Summit was supported by sponsorships from Danone, Ferring Pharmaceuticals, Aimmune Therapeutics and Seres Therapeutics, Sanofi, and Intrinsic Medicine Inc. with additional support from educational grants provided by Ferring Pharmaceuticals and Salix Pharmaceuticals.

This article was updated 4/5/22.

WASHINGTON – Probiotics are generally used in relatively nontargeted, nonspecific ways. But with the gut microbiome being an integral component of a budding precision medicine model of care, and with “multi-omics” research picking up, this is bound to change, gastroenterologist Purna C. Kashyap, MBBS, said in an interview after the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

“There are so many missing pieces of information because, at the very basic level, we don’t know exactly how gut bacteria drive diseases,” he told GI & Hepatology News.

“The idea is to go toward a more precise, accurate approach where the newer generation of probiotics are designed to target a specific process, like block a microbial pathway that contributes to disease pathogenesis, or produce a metabolite that improves host function,” he said. “It’s this shift that is going on in the field. It’s already started, and it has momentum.” Dr. Kashyap is a professor of medicine and physiology at the Mayo Clinic College of Medicine in Rochester, Minn., and codirector of the institution’s microbiome program.

In a keynote lecture at the meeting, Dr. Kashyap said that the current approach to precision medicine, which aims to tailor treatments to defined subgroups of patients, needs to take into account “much more than the human genome.”

To the extent possible, it needs to consider the host (lifestyle, gene variants, etc.), the microbiome, and the exposome (environmental exposures such as diet, medications, and air and water quality).

The microbiome’s relative contribution to any one disease, in turn, likely varies from one individual or subgroup to another, he said.

Researchers are increasingly working with different layers of data and using machine learning methods and artificial intelligence approaches to integrate clinical data and “omics” measurements (e.g., from genome, proteome, metabolome).

Such approaches can help pinpoint the microbiome’s relative contributions, identify microbial-host behaviors and microbial-driven disease mechanisms, and ultimately personalize treatment approaches, Dr. Kashyap said.

For instance, Dr. Kashyap’s team has taken a multi-omics approach to studying patients with irritable bowel syndrome (IBS). Thus far, their research has identified subtype-specific variation in microbial composition and function, and by integrating omics from the host and microbiome, it has confirmed the role of several microbial pathways in subtypes of IBS.

His team has also identified a new pathway – the host and gut microbiota’s modulation of purine metabolism – as a potential driver of symptoms in patients with IBS (Cell 2020;182[6]:1460-73), he said.

Such findings provide opportunities to develop new microbial therapeutics – by engineering bacteria to produce metabolites that target a specific pathway, for instance, he said.
 

Predicting probiotic engraftment

Understanding the extent to which microbes actually engraft in the gut – and the forces governing engraftment – is part of a rational approach to designing future probiotic cocktails and to moving toward personalized, precision medicine, Eric Alm, PhD, said during a plenary session on the future of probiotics, moderated by Dr. Kashyap. Dr. Alm is a professor of biological, civil, and environmental engineering who directs the Center for Microbiome Informatics and Therapeutics at the Massachusetts Institute of Technology in Cambridge.

“One of the best datasets we have when thinking about designing therapeutic microbes is FMT (fecal microbiota transplant) data” in patients with Clostridioides difficile infection (CDI), said Dr. Alm.

“We wondered, can you predict what a patient will look like post FMT given what they looked like before and given what the donor looks like?” he said. “We found that engraftment can be predicted surprisingly well.”

Using computational algorithms and metagenomics sequencing data from donors and recipients, the researchers found that engraftment can be predicted largely from the abundance and strains of bacteria in the donor and the pre-FMT patient microbiome (Cell Host Microbe 2018;23[2]:229-40.e5).

They also observed two behaviors: Previously undetected strains (not transplanted) frequently show up in patients who received FMT, and all donor strains within a species engrafted in an all-or-nothing fashion.

“Seeding a patient with a new species allows them to collect more strains of that species from the environment – this is fairly common,” said Dr. Alm. “But if I give five different strains of Faecalibacterium prausnitzii to a patient who doesn’t have any, they’ll get either zero, or they’ll get all five ... this is an observation we don’t fully understand yet.”

These types of observations “guide our thinking in how to produce rationally designed cocktails,” he said.
 

Other approaches to probiotics

In another type of research, Philippe Langella, PhD, who leads a laboratory of Commensal and Probiotics-Host Interactions at the Micalis Institute in France, has been investigating the use of genetically modified lactic acid bacteria to deliver anti-proteases and other types of molecules to patients with disease, such as the antiprotease elafin to patients with inflammatory bowel disease (IBD).

There is “a lack of elafin in Crohn’s disease and ulcerative colitis patients,” Dr. Langella said during the plenary session. “The idea is to use the genetically modified lactic acid bacteria to counterbalance the protease-antiprotease imbalance in IBD.”

In animal and in vitro models, elafin-expressing lactic acid bacteria decreased elastolytic activity and inflammation in the gut and restored intestinal permeability. The goal now, he said, is to construct biologically contained strains of the engineered bacteria to test in clinical trials.

While today’s probiotics are generally considered to be safe and to have beneficial effects, the next generation will be more targeted – more “rational,“ Dr. Kashyap said in his interview. Each of these researchers,” he said, “is working on different pieces of the puzzle and, eventually, this will allow us to accelerate the development of novel therapies.”

Dr. Kashyap said he has no disclosures relevant to his keynote address or moderation of the plenary session. In his presentation, Dr. Alm disclosed his involvement with Finch Therapeutics, OpenBiome, and Biobot Analytics.

Dr. Langella disclosed in his presentation that he is co-founder of Exeliom Biosciences and has research grants with various pharmaceutical companies, food supplement companies, and agro-food companies.

The 2022 Gut Microbiota for Health World Summit was supported by sponsorships from Danone, Ferring Pharmaceuticals, Aimmune Therapeutics and Seres Therapeutics, Sanofi, and Intrinsic Medicine Inc. with additional support from educational grants provided by Ferring Pharmaceuticals and Salix Pharmaceuticals.

This article was updated 4/5/22.

WASHINGTON – Research on standardized microbiome-based therapies designed to prevent the recurrence of Clostridioides difficile infection (CDI) is moving “with a lot of momentum,” according to one expert, and modulation of the gut microbiome may even enhance responses to immunotherapy and/or abrogate toxicity, according to another.

Several products for prevention of CDI recurrence are poised for either phase 3 trials or upcoming Food and Drug Administration approval, Sahil Khanna, MBBS, MS, professor of medicine, gastroenterology, and hepatology at the Mayo Clinic in Rochester, Minn., reported at the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center, Houston, described her investigations of microbiome modulation’s role in cancer treatment. “I used to say yes [we can do this] somewhat enthusiastically without data, but now we have data to support this,” she said at the meeting. “The answer now is totally yes.”

New approaches for CDI

“Based on how the field is moving, we might be able to [offer our patients] earlier microbiome restoration” than is currently afforded with fecal microbiota transplantation (FMT), Dr. Khanna said. “Right now the [Food and Drug Administration] and our clinical guidelines say we should do FMT after three or more episodes [of CDI] – that’s heartbreaking for patients.”

Several of the microbiome-based therapies under investigation – including two that have completed phase 3 trials – have shown efficacy after a second episode of CDI, and one of these two has also had positive results after one episode of CDI in patients 65 at older, a group at particularly high risk of recurrence, said Dr. Khanna.

The value of standardized, mostly pill-form microbiome therapies has been heightened during the pandemic. “We’ve been doing conventional FMT for recurrent C. difficile for over a decade now, and it’s probably the most effective treatment we have,” said Colleen R. Kelly, MD, associate professor of medicine at Brown University, Providence, R.I., and moderator of the session on microbiota-based therapies.

Prepandemic “it got really hard, with issues of identifying donors, and quality control and safety ... And then when COVID hit the stool banks shut down,” she said in an interview after the meeting. With stool testing for SARS-CoV-2 now in place, some stool is again available, “but it made me realize how fragile our current system is,” Dr. Kelly said. “The fact that companies are putting these products through the FDA pipeline and investigating them in rigorous, scientific randomized controlled trials is really good for the field.”

The products vary in composition; some are live multi-strain biotherapeutics derived from donor stool, for instance, while others are defined live bacterial consortia not from stool. Most are oral formulations, given one or multiple times, that do not require any bowel preparation.

One of the products most advanced in the pipeline, RBX2660 (Rebiotix, Ferring Pharmaceuticals) is stool derived and rectally administered. In phase 3 research, 70.5% of patients who received one active enema after having had two or more CDI recurrences and standard-of-care antibiotic treatment had no additional recurrence at 8 weeks compared to 58.1% in the placebo group, Dr. Khanna said.

The other product with positive phase 3 results, SER-109 (Seres Therapeutics), is a donor stool-derived oral formulation of purified Firmicutes spores that is administered after bowel prep. In results published earlier this year, the percentage of patients with recurrence of CDI up to 8 weeks after standard antibiotic treatment was 12% in the SER-109 group and 40% in the placebo group.

Patients in this trial were required to have had three episodes of CDI, and interestingly, Dr. Khanna said, the diagnosis of CDI was made only by toxin enzyme immunoassay (EIA). Earlier phase 2 research, which allowed either toxin EIA or polymerase chain reaction testing for the diagnosis of CDI (as other trials have done), produced negative results, leading investigators to surmise that some of the included patients had been colonized with C. difficile rather than being actively infected, Dr. Khanna said.

Researchers of these trials are documenting not only resolution of CDI but what they believe are positive shifts in the gut microbiota after microbiome-based therapy, he said. For instance, a phase 1 trial he led of the product RBX7455 (Rebiotix, Ferring Pharmaceuticals) – an oral capsule of lyophilized stool-based bacteria that can be kept for several days at room temperature – showed increases in Bacteroides and Clostridia.

And other trials’ analyses of microbiome engraftment have demonstrated that “you can restore [species] even when these bacteria aren’t [included in the therapy],” he noted. “As the milieu of the gut improves, species that were not detected start coming back up.”

Asked about rates of efficacy in the trials’ placebo arms, Dr. Khanna said that “we’ve become smarter with our antibiotic regimens ... the placebo response rate is the response to newer guideline-based therapies.”

In addition to CDI, microbiome-based therapies are being studied, mostly in phase 1 research, for indications such as Crohn’s disease, ulcerative colitis, autism spectrum disorder, hepatitis B, and hepatic encephalopathy, Dr. Khanna noted.

Dr. Kelly, whose own research has focused on FMT for CDI, said she anticipates an expansion of research into other indications once products to prevent CDI recurrence are on the market. “There have been a couple of promising ulcerative colitis trials that haven’t gone anywhere clinically yet,” she said in the interview. “But will we now identify patients with [ulcerative colitis] who may be more sensitive to microbial manipulation, for whom we can use these microbial therapies along with a biologic?”

Some of her patients with IBD and CDI who are treated with FMT have not only had their CDI eradicated but have subsequently seen improvements in their IBD, she noted.

The role of traditional FMT and of stool banks will likely change in the future with new standardized oral microbiome-based therapies that can be approved and regulated by the FDA, she said. However, “we think the stool banks will still have some value,” she said, certainly for clinical research and probably for some treatment purposes as well. Regarding new therapies, “I just really hope they’re affordable,” she said.

Help your patients understand their C. difficile diagnosis by sending them this resource from the AGA GI Patient Center.

Gut microbiome manipulation for cancer

Dr. Wargo’s research at MD Anderson has focused on metastatic breast cancer and immunotherapeutic checkpoint blockade. By sequencing microbiota samples and performing immune profiling in hundreds of patients, her team found that responders to PD-1 blockage have a greater diversity of gut bacteria and that “favorable signatures in the gut microbiome” are associated with enhanced immune responses in the tumor microenvironment.

Studies published last year in Science from investigators in Israel (2021 Feb 5;371[6529]:602-9) and Pittsburgh (2021 Feb 5;371[6529]:595-602), demonstrated that FMT promotes response in immunotherapy-refractory melanoma patients. In one study, FMT provided clinical benefit in 6 of 15 patients whose cancer had progressed on prior anti-PD-1 therapy, “which is pretty remarkable,” Dr. Wargo said.

Both research groups, she noted, saw favorable changes in the gut microbiome and immune cell infiltrates both at the level of the colon and the tumor.

Current research on FMT and other microbiome modulation strategies for cancer is guided in part by knowledge that tumors have microbial signatures – these signatures are now being identified across all tumor types – and by findings of “cross talk” between the gut and tumor microbiomes, she explained.

“Researchers are working hard to identify optimal consortia to enhance immune responses in the cancer setting, with promising work in preclinical models,” she said, and clinical trials are in progress. The role of diet in modulating the microbiome and enhancing anti-tumor immunity, with a focus on high dietary fiber intake, is also being investigated, she said.

Get the latest information on the gut microbiome on the AGA website.

Dr. Wargo reported that she serves on the advisory boards and is a paid speaker of numerous pharmaceutical and biotechnology companies, and is the coinventor of a patent submitted by the Texas MD Anderson Cancer Center on modulating the microbiome to enhance response to checkpoint blockade, and another related patent. Dr. Khanna reported that he is involved in research with Ferring/Rebiotix, Finch, Seres, Pfizer and Vedanta, and does consulting for Immuron and several other companies. Dr. Kelly said she serves as an unpaid adviser for OpenBiome, a nonprofit stool bank, and that her site has enrolled patients in two of the trials testing products for CDI.

WASHINGTON – Research on standardized microbiome-based therapies designed to prevent the recurrence of Clostridioides difficile infection (CDI) is moving “with a lot of momentum,” according to one expert, and modulation of the gut microbiome may even enhance responses to immunotherapy and/or abrogate toxicity, according to another.

Several products for prevention of CDI recurrence are poised for either phase 3 trials or upcoming Food and Drug Administration approval, Sahil Khanna, MBBS, MS, professor of medicine, gastroenterology, and hepatology at the Mayo Clinic in Rochester, Minn., reported at the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center, Houston, described her investigations of microbiome modulation’s role in cancer treatment. “I used to say yes [we can do this] somewhat enthusiastically without data, but now we have data to support this,” she said at the meeting. “The answer now is totally yes.”

New approaches for CDI

“Based on how the field is moving, we might be able to [offer our patients] earlier microbiome restoration” than is currently afforded with fecal microbiota transplantation (FMT), Dr. Khanna said. “Right now the [Food and Drug Administration] and our clinical guidelines say we should do FMT after three or more episodes [of CDI] – that’s heartbreaking for patients.”

Several of the microbiome-based therapies under investigation – including two that have completed phase 3 trials – have shown efficacy after a second episode of CDI, and one of these two has also had positive results after one episode of CDI in patients 65 at older, a group at particularly high risk of recurrence, said Dr. Khanna.

The value of standardized, mostly pill-form microbiome therapies has been heightened during the pandemic. “We’ve been doing conventional FMT for recurrent C. difficile for over a decade now, and it’s probably the most effective treatment we have,” said Colleen R. Kelly, MD, associate professor of medicine at Brown University, Providence, R.I., and moderator of the session on microbiota-based therapies.

Prepandemic “it got really hard, with issues of identifying donors, and quality control and safety ... And then when COVID hit the stool banks shut down,” she said in an interview after the meeting. With stool testing for SARS-CoV-2 now in place, some stool is again available, “but it made me realize how fragile our current system is,” Dr. Kelly said. “The fact that companies are putting these products through the FDA pipeline and investigating them in rigorous, scientific randomized controlled trials is really good for the field.”

The products vary in composition; some are live multi-strain biotherapeutics derived from donor stool, for instance, while others are defined live bacterial consortia not from stool. Most are oral formulations, given one or multiple times, that do not require any bowel preparation.

One of the products most advanced in the pipeline, RBX2660 (Rebiotix, Ferring Pharmaceuticals) is stool derived and rectally administered. In phase 3 research, 70.5% of patients who received one active enema after having had two or more CDI recurrences and standard-of-care antibiotic treatment had no additional recurrence at 8 weeks compared to 58.1% in the placebo group, Dr. Khanna said.

The other product with positive phase 3 results, SER-109 (Seres Therapeutics), is a donor stool-derived oral formulation of purified Firmicutes spores that is administered after bowel prep. In results published earlier this year, the percentage of patients with recurrence of CDI up to 8 weeks after standard antibiotic treatment was 12% in the SER-109 group and 40% in the placebo group.

Patients in this trial were required to have had three episodes of CDI, and interestingly, Dr. Khanna said, the diagnosis of CDI was made only by toxin enzyme immunoassay (EIA). Earlier phase 2 research, which allowed either toxin EIA or polymerase chain reaction testing for the diagnosis of CDI (as other trials have done), produced negative results, leading investigators to surmise that some of the included patients had been colonized with C. difficile rather than being actively infected, Dr. Khanna said.

Researchers of these trials are documenting not only resolution of CDI but what they believe are positive shifts in the gut microbiota after microbiome-based therapy, he said. For instance, a phase 1 trial he led of the product RBX7455 (Rebiotix, Ferring Pharmaceuticals) – an oral capsule of lyophilized stool-based bacteria that can be kept for several days at room temperature – showed increases in Bacteroides and Clostridia.

And other trials’ analyses of microbiome engraftment have demonstrated that “you can restore [species] even when these bacteria aren’t [included in the therapy],” he noted. “As the milieu of the gut improves, species that were not detected start coming back up.”

Asked about rates of efficacy in the trials’ placebo arms, Dr. Khanna said that “we’ve become smarter with our antibiotic regimens ... the placebo response rate is the response to newer guideline-based therapies.”

In addition to CDI, microbiome-based therapies are being studied, mostly in phase 1 research, for indications such as Crohn’s disease, ulcerative colitis, autism spectrum disorder, hepatitis B, and hepatic encephalopathy, Dr. Khanna noted.

Dr. Kelly, whose own research has focused on FMT for CDI, said she anticipates an expansion of research into other indications once products to prevent CDI recurrence are on the market. “There have been a couple of promising ulcerative colitis trials that haven’t gone anywhere clinically yet,” she said in the interview. “But will we now identify patients with [ulcerative colitis] who may be more sensitive to microbial manipulation, for whom we can use these microbial therapies along with a biologic?”

Some of her patients with IBD and CDI who are treated with FMT have not only had their CDI eradicated but have subsequently seen improvements in their IBD, she noted.

The role of traditional FMT and of stool banks will likely change in the future with new standardized oral microbiome-based therapies that can be approved and regulated by the FDA, she said. However, “we think the stool banks will still have some value,” she said, certainly for clinical research and probably for some treatment purposes as well. Regarding new therapies, “I just really hope they’re affordable,” she said.

Help your patients understand their C. difficile diagnosis by sending them this resource from the AGA GI Patient Center.

Gut microbiome manipulation for cancer

Dr. Wargo’s research at MD Anderson has focused on metastatic breast cancer and immunotherapeutic checkpoint blockade. By sequencing microbiota samples and performing immune profiling in hundreds of patients, her team found that responders to PD-1 blockage have a greater diversity of gut bacteria and that “favorable signatures in the gut microbiome” are associated with enhanced immune responses in the tumor microenvironment.

Studies published last year in Science from investigators in Israel (2021 Feb 5;371[6529]:602-9) and Pittsburgh (2021 Feb 5;371[6529]:595-602), demonstrated that FMT promotes response in immunotherapy-refractory melanoma patients. In one study, FMT provided clinical benefit in 6 of 15 patients whose cancer had progressed on prior anti-PD-1 therapy, “which is pretty remarkable,” Dr. Wargo said.

Both research groups, she noted, saw favorable changes in the gut microbiome and immune cell infiltrates both at the level of the colon and the tumor.

Current research on FMT and other microbiome modulation strategies for cancer is guided in part by knowledge that tumors have microbial signatures – these signatures are now being identified across all tumor types – and by findings of “cross talk” between the gut and tumor microbiomes, she explained.

“Researchers are working hard to identify optimal consortia to enhance immune responses in the cancer setting, with promising work in preclinical models,” she said, and clinical trials are in progress. The role of diet in modulating the microbiome and enhancing anti-tumor immunity, with a focus on high dietary fiber intake, is also being investigated, she said.

Get the latest information on the gut microbiome on the AGA website.

Dr. Wargo reported that she serves on the advisory boards and is a paid speaker of numerous pharmaceutical and biotechnology companies, and is the coinventor of a patent submitted by the Texas MD Anderson Cancer Center on modulating the microbiome to enhance response to checkpoint blockade, and another related patent. Dr. Khanna reported that he is involved in research with Ferring/Rebiotix, Finch, Seres, Pfizer and Vedanta, and does consulting for Immuron and several other companies. Dr. Kelly said she serves as an unpaid adviser for OpenBiome, a nonprofit stool bank, and that her site has enrolled patients in two of the trials testing products for CDI.

WASHINGTON – Research on standardized microbiome-based therapies designed to prevent the recurrence of Clostridioides difficile infection (CDI) is moving “with a lot of momentum,” according to one expert, and modulation of the gut microbiome may even enhance responses to immunotherapy and/or abrogate toxicity, according to another.

Several products for prevention of CDI recurrence are poised for either phase 3 trials or upcoming Food and Drug Administration approval, Sahil Khanna, MBBS, MS, professor of medicine, gastroenterology, and hepatology at the Mayo Clinic in Rochester, Minn., reported at the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center, Houston, described her investigations of microbiome modulation’s role in cancer treatment. “I used to say yes [we can do this] somewhat enthusiastically without data, but now we have data to support this,” she said at the meeting. “The answer now is totally yes.”

New approaches for CDI

“Based on how the field is moving, we might be able to [offer our patients] earlier microbiome restoration” than is currently afforded with fecal microbiota transplantation (FMT), Dr. Khanna said. “Right now the [Food and Drug Administration] and our clinical guidelines say we should do FMT after three or more episodes [of CDI] – that’s heartbreaking for patients.”

Several of the microbiome-based therapies under investigation – including two that have completed phase 3 trials – have shown efficacy after a second episode of CDI, and one of these two has also had positive results after one episode of CDI in patients 65 at older, a group at particularly high risk of recurrence, said Dr. Khanna.

The value of standardized, mostly pill-form microbiome therapies has been heightened during the pandemic. “We’ve been doing conventional FMT for recurrent C. difficile for over a decade now, and it’s probably the most effective treatment we have,” said Colleen R. Kelly, MD, associate professor of medicine at Brown University, Providence, R.I., and moderator of the session on microbiota-based therapies.

Prepandemic “it got really hard, with issues of identifying donors, and quality control and safety ... And then when COVID hit the stool banks shut down,” she said in an interview after the meeting. With stool testing for SARS-CoV-2 now in place, some stool is again available, “but it made me realize how fragile our current system is,” Dr. Kelly said. “The fact that companies are putting these products through the FDA pipeline and investigating them in rigorous, scientific randomized controlled trials is really good for the field.”

The products vary in composition; some are live multi-strain biotherapeutics derived from donor stool, for instance, while others are defined live bacterial consortia not from stool. Most are oral formulations, given one or multiple times, that do not require any bowel preparation.

One of the products most advanced in the pipeline, RBX2660 (Rebiotix, Ferring Pharmaceuticals) is stool derived and rectally administered. In phase 3 research, 70.5% of patients who received one active enema after having had two or more CDI recurrences and standard-of-care antibiotic treatment had no additional recurrence at 8 weeks compared to 58.1% in the placebo group, Dr. Khanna said.

The other product with positive phase 3 results, SER-109 (Seres Therapeutics), is a donor stool-derived oral formulation of purified Firmicutes spores that is administered after bowel prep. In results published earlier this year, the percentage of patients with recurrence of CDI up to 8 weeks after standard antibiotic treatment was 12% in the SER-109 group and 40% in the placebo group.

Patients in this trial were required to have had three episodes of CDI, and interestingly, Dr. Khanna said, the diagnosis of CDI was made only by toxin enzyme immunoassay (EIA). Earlier phase 2 research, which allowed either toxin EIA or polymerase chain reaction testing for the diagnosis of CDI (as other trials have done), produced negative results, leading investigators to surmise that some of the included patients had been colonized with C. difficile rather than being actively infected, Dr. Khanna said.

Researchers of these trials are documenting not only resolution of CDI but what they believe are positive shifts in the gut microbiota after microbiome-based therapy, he said. For instance, a phase 1 trial he led of the product RBX7455 (Rebiotix, Ferring Pharmaceuticals) – an oral capsule of lyophilized stool-based bacteria that can be kept for several days at room temperature – showed increases in Bacteroides and Clostridia.

And other trials’ analyses of microbiome engraftment have demonstrated that “you can restore [species] even when these bacteria aren’t [included in the therapy],” he noted. “As the milieu of the gut improves, species that were not detected start coming back up.”

Asked about rates of efficacy in the trials’ placebo arms, Dr. Khanna said that “we’ve become smarter with our antibiotic regimens ... the placebo response rate is the response to newer guideline-based therapies.”

In addition to CDI, microbiome-based therapies are being studied, mostly in phase 1 research, for indications such as Crohn’s disease, ulcerative colitis, autism spectrum disorder, hepatitis B, and hepatic encephalopathy, Dr. Khanna noted.

Dr. Kelly, whose own research has focused on FMT for CDI, said she anticipates an expansion of research into other indications once products to prevent CDI recurrence are on the market. “There have been a couple of promising ulcerative colitis trials that haven’t gone anywhere clinically yet,” she said in the interview. “But will we now identify patients with [ulcerative colitis] who may be more sensitive to microbial manipulation, for whom we can use these microbial therapies along with a biologic?”

Some of her patients with IBD and CDI who are treated with FMT have not only had their CDI eradicated but have subsequently seen improvements in their IBD, she noted.

The role of traditional FMT and of stool banks will likely change in the future with new standardized oral microbiome-based therapies that can be approved and regulated by the FDA, she said. However, “we think the stool banks will still have some value,” she said, certainly for clinical research and probably for some treatment purposes as well. Regarding new therapies, “I just really hope they’re affordable,” she said.

Help your patients understand their C. difficile diagnosis by sending them this resource from the AGA GI Patient Center.

Gut microbiome manipulation for cancer

Dr. Wargo’s research at MD Anderson has focused on metastatic breast cancer and immunotherapeutic checkpoint blockade. By sequencing microbiota samples and performing immune profiling in hundreds of patients, her team found that responders to PD-1 blockage have a greater diversity of gut bacteria and that “favorable signatures in the gut microbiome” are associated with enhanced immune responses in the tumor microenvironment.

Studies published last year in Science from investigators in Israel (2021 Feb 5;371[6529]:602-9) and Pittsburgh (2021 Feb 5;371[6529]:595-602), demonstrated that FMT promotes response in immunotherapy-refractory melanoma patients. In one study, FMT provided clinical benefit in 6 of 15 patients whose cancer had progressed on prior anti-PD-1 therapy, “which is pretty remarkable,” Dr. Wargo said.

Both research groups, she noted, saw favorable changes in the gut microbiome and immune cell infiltrates both at the level of the colon and the tumor.

Current research on FMT and other microbiome modulation strategies for cancer is guided in part by knowledge that tumors have microbial signatures – these signatures are now being identified across all tumor types – and by findings of “cross talk” between the gut and tumor microbiomes, she explained.

“Researchers are working hard to identify optimal consortia to enhance immune responses in the cancer setting, with promising work in preclinical models,” she said, and clinical trials are in progress. The role of diet in modulating the microbiome and enhancing anti-tumor immunity, with a focus on high dietary fiber intake, is also being investigated, she said.

Get the latest information on the gut microbiome on the AGA website.

Dr. Wargo reported that she serves on the advisory boards and is a paid speaker of numerous pharmaceutical and biotechnology companies, and is the coinventor of a patent submitted by the Texas MD Anderson Cancer Center on modulating the microbiome to enhance response to checkpoint blockade, and another related patent. Dr. Khanna reported that he is involved in research with Ferring/Rebiotix, Finch, Seres, Pfizer and Vedanta, and does consulting for Immuron and several other companies. Dr. Kelly said she serves as an unpaid adviser for OpenBiome, a nonprofit stool bank, and that her site has enrolled patients in two of the trials testing products for CDI.

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.

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

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.

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

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.

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

Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.

It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.

The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.

Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”

Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.

The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
 

COVID-19 brought the issue to a head

Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.

The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”

The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.

The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.

Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.

Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.

Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.

Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.

There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.

Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.

It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.

The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.

Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”

Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.

The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
 

COVID-19 brought the issue to a head

Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.

The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”

The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.

The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.

Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.

Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.

Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.

Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.

There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.

Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.

It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.

The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.

Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”

Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.

The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
 

COVID-19 brought the issue to a head

Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.

The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”

The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.

The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.

Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.

Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.

Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.

Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.

There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.

Complete gross resection is much less likely for advanced ovarian cancer in women with mesenchymal tumors and complex preoperative CT findings, according to a report at the Society of Gynecologic Oncology annual meeting.

Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.

The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.

He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”

For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.

Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.

What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.

The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.

The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.

Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.

Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”

Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).

Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.

“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.

No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.

Complete gross resection is much less likely for advanced ovarian cancer in women with mesenchymal tumors and complex preoperative CT findings, according to a report at the Society of Gynecologic Oncology annual meeting.

Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.

The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.

He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”

For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.

Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.

What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.

The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.

The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.

Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.

Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”

Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).

Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.

“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.

No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.

Complete gross resection is much less likely for advanced ovarian cancer in women with mesenchymal tumors and complex preoperative CT findings, according to a report at the Society of Gynecologic Oncology annual meeting.

Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.

The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.

He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”

For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.

Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.

What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.

The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.

The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.

Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.

Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”

Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).

Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.

“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.

No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.

DENVER – Deficits in executive function (EF) are linked to with development of posttraumatic stress disorder (PTSD) symptoms and exacerbation of such symptoms over time, new research suggests.

“To our knowledge, this study is the first to show that executive-function deficits maintain PTSD symptoms following trauma exposure,” investigators noted in research presented at the Anxiety and Depression Association of America (ADAA) Anxiety & Depression conference.

Courtesy Auburn University

The results are important in “developing precision medicine–based approaches for alleviating [posttraumatic stress] symptoms, and improving well-established PTSD treatments for those with relative deficits in executive function,” study investigator Joseph R. Bardeen, PhD, associate professor at Auburn (Ala.) University, told meeting attendees.

The findings were published in the Journal of Anxiety Disorders.
 

Cognitive impairment

In earlier research, deficits in EF were associated with an increased vulnerability for PTSD symptoms. However, less is known about the role of these deficits, which can impair higher-level cognitive ability, in sustaining PTSD symptoms.

To investigate, the authors conducted a longitudinal study that included 98 participants aged 18-65 years who had been identified via phone screening as experiencing clinically significant PTSD symptoms.

Participants completed self-report measures for PTSD symptoms, as well as measures for EF deficits at baseline and 6-month (n = 92) and 12-month (n = 91) follow-up sessions.

A path analysis showed a significant relationship between baseline PTSD symptoms and EF deficits at 6 months (P < .001). Baseline PTSD symptoms were associated with 12-month PTSD symptoms (P < .04).

EF deficits at 6 months were also associated with 12-month PTSD symptoms (P = .02).

Importantly, no associations were observed between baseline or 6-month PTSD symptoms and EF deficits at 12 months. However, EF deficits at 6 months drove the relationship between PTSD symptoms at baseline and at 1 year (indirect effect = .061).

“What this suggests is that executive-function deficits are a mechanism that maintains patients’ symptoms over the course of 1 year,” Dr. Bardeen said.

“And you don’t see the reverse,” he added. “You don’t see that PTSD symptoms at [6 months] mediate the relationship between [baseline] and 6 month executive-function deficits.”
 

Surprising finding

The findings suggest deficits in executive functioning have a stronger role in maintaining PTSD symptoms than these symptoms have in maintaining EF deficits, Dr. Bardeen told this news organization.

“I had originally hypothesized a bidirectional relationship in which PTSD symptoms influenced future executive-function deficits and executive-function deficits influenced future PTSD symptoms,” he said.

“So, it was a surprise that, when accounting for both variables in the same model, executive-function deficits predicted future PTSD symptoms, but PTSD symptoms did not significantly predict future EF deficits,” he added.

Dr. Bardeen noted this suggests that EF deficits “may be a particularly important maintenance factor.”  

In addition, he recommended the use of neuropsychological assessments prior to treatment to identify individuals with EF deficits and distinguish those deficits from PTSD symptoms.

“There is certainly overlap between executive-function deficits and PTSD symptoms,” Dr. Bardeen said. “For example, several of the symptoms of PTSD, such as concentration difficulties, may be indicators of executive-function deficits.”

He noted assessments such as the Delis Kaplan Executive Function System, and Clinician Administered PTSD Scale for DSM-5, when used as part of a larger assessment battery, can help differentiate between the EF deficits and PTSD.

“This would take several hours to administer, but in cases in which serious cognitive impairment is suspected, a comprehensive assessment is the way to go,” Dr. Bardeen said.

The standard approaches of prolonged exposure therapy and cognitive processing therapy can be effective in patients without EF deficits, while some modifications may benefit those with these deficits, he added.

“For example, it’s important to provide a more directive and structured environment in which the practitioner repeats key points frequently, uses concrete language, simplifies worksheets, and provides written summaries and reminder cards,” he said.
 

Further findings

In additional research presented at the meeting, Elsa Mattson, a PhD student from Case Western Reserve University, Cleveland, and colleagues reported findings further distinguishing the role of EF in PTSD.

In that study of 149 patients with chronic PTSD, those with low performing working memory, but not high working memory, had higher pre- as well as posttreatment PTSD symptom severity and depressive symptoms.

“Clinicians should consider that impairments in executive function may play a role in reduced treatment response, potentially impairing a client’s ability to learn new information in treatment,” the investigators wrote.

“Understanding how executive function processes change over the course of treatment, particularly in relation to processing the trauma memories, is an important next step,” they added.

The first study was supported by a grant from the National Institute of Mental Health. The investigators have disclosed no relevant financial relationships.

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

DENVER – Deficits in executive function (EF) are linked to with development of posttraumatic stress disorder (PTSD) symptoms and exacerbation of such symptoms over time, new research suggests.

“To our knowledge, this study is the first to show that executive-function deficits maintain PTSD symptoms following trauma exposure,” investigators noted in research presented at the Anxiety and Depression Association of America (ADAA) Anxiety & Depression conference.

Courtesy Auburn University

The results are important in “developing precision medicine–based approaches for alleviating [posttraumatic stress] symptoms, and improving well-established PTSD treatments for those with relative deficits in executive function,” study investigator Joseph R. Bardeen, PhD, associate professor at Auburn (Ala.) University, told meeting attendees.

The findings were published in the Journal of Anxiety Disorders.
 

Cognitive impairment

In earlier research, deficits in EF were associated with an increased vulnerability for PTSD symptoms. However, less is known about the role of these deficits, which can impair higher-level cognitive ability, in sustaining PTSD symptoms.

To investigate, the authors conducted a longitudinal study that included 98 participants aged 18-65 years who had been identified via phone screening as experiencing clinically significant PTSD symptoms.

Participants completed self-report measures for PTSD symptoms, as well as measures for EF deficits at baseline and 6-month (n = 92) and 12-month (n = 91) follow-up sessions.

A path analysis showed a significant relationship between baseline PTSD symptoms and EF deficits at 6 months (P < .001). Baseline PTSD symptoms were associated with 12-month PTSD symptoms (P < .04).

EF deficits at 6 months were also associated with 12-month PTSD symptoms (P = .02).

Importantly, no associations were observed between baseline or 6-month PTSD symptoms and EF deficits at 12 months. However, EF deficits at 6 months drove the relationship between PTSD symptoms at baseline and at 1 year (indirect effect = .061).

“What this suggests is that executive-function deficits are a mechanism that maintains patients’ symptoms over the course of 1 year,” Dr. Bardeen said.

“And you don’t see the reverse,” he added. “You don’t see that PTSD symptoms at [6 months] mediate the relationship between [baseline] and 6 month executive-function deficits.”
 

Surprising finding

The findings suggest deficits in executive functioning have a stronger role in maintaining PTSD symptoms than these symptoms have in maintaining EF deficits, Dr. Bardeen told this news organization.

“I had originally hypothesized a bidirectional relationship in which PTSD symptoms influenced future executive-function deficits and executive-function deficits influenced future PTSD symptoms,” he said.

“So, it was a surprise that, when accounting for both variables in the same model, executive-function deficits predicted future PTSD symptoms, but PTSD symptoms did not significantly predict future EF deficits,” he added.

Dr. Bardeen noted this suggests that EF deficits “may be a particularly important maintenance factor.”  

In addition, he recommended the use of neuropsychological assessments prior to treatment to identify individuals with EF deficits and distinguish those deficits from PTSD symptoms.

“There is certainly overlap between executive-function deficits and PTSD symptoms,” Dr. Bardeen said. “For example, several of the symptoms of PTSD, such as concentration difficulties, may be indicators of executive-function deficits.”

He noted assessments such as the Delis Kaplan Executive Function System, and Clinician Administered PTSD Scale for DSM-5, when used as part of a larger assessment battery, can help differentiate between the EF deficits and PTSD.

“This would take several hours to administer, but in cases in which serious cognitive impairment is suspected, a comprehensive assessment is the way to go,” Dr. Bardeen said.

The standard approaches of prolonged exposure therapy and cognitive processing therapy can be effective in patients without EF deficits, while some modifications may benefit those with these deficits, he added.

“For example, it’s important to provide a more directive and structured environment in which the practitioner repeats key points frequently, uses concrete language, simplifies worksheets, and provides written summaries and reminder cards,” he said.
 

Further findings

In additional research presented at the meeting, Elsa Mattson, a PhD student from Case Western Reserve University, Cleveland, and colleagues reported findings further distinguishing the role of EF in PTSD.

In that study of 149 patients with chronic PTSD, those with low performing working memory, but not high working memory, had higher pre- as well as posttreatment PTSD symptom severity and depressive symptoms.

“Clinicians should consider that impairments in executive function may play a role in reduced treatment response, potentially impairing a client’s ability to learn new information in treatment,” the investigators wrote.

“Understanding how executive function processes change over the course of treatment, particularly in relation to processing the trauma memories, is an important next step,” they added.

The first study was supported by a grant from the National Institute of Mental Health. The investigators have disclosed no relevant financial relationships.

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

DENVER – Deficits in executive function (EF) are linked to with development of posttraumatic stress disorder (PTSD) symptoms and exacerbation of such symptoms over time, new research suggests.

“To our knowledge, this study is the first to show that executive-function deficits maintain PTSD symptoms following trauma exposure,” investigators noted in research presented at the Anxiety and Depression Association of America (ADAA) Anxiety & Depression conference.

Courtesy Auburn University

The results are important in “developing precision medicine–based approaches for alleviating [posttraumatic stress] symptoms, and improving well-established PTSD treatments for those with relative deficits in executive function,” study investigator Joseph R. Bardeen, PhD, associate professor at Auburn (Ala.) University, told meeting attendees.

The findings were published in the Journal of Anxiety Disorders.
 

Cognitive impairment

In earlier research, deficits in EF were associated with an increased vulnerability for PTSD symptoms. However, less is known about the role of these deficits, which can impair higher-level cognitive ability, in sustaining PTSD symptoms.

To investigate, the authors conducted a longitudinal study that included 98 participants aged 18-65 years who had been identified via phone screening as experiencing clinically significant PTSD symptoms.

Participants completed self-report measures for PTSD symptoms, as well as measures for EF deficits at baseline and 6-month (n = 92) and 12-month (n = 91) follow-up sessions.

A path analysis showed a significant relationship between baseline PTSD symptoms and EF deficits at 6 months (P < .001). Baseline PTSD symptoms were associated with 12-month PTSD symptoms (P < .04).

EF deficits at 6 months were also associated with 12-month PTSD symptoms (P = .02).

Importantly, no associations were observed between baseline or 6-month PTSD symptoms and EF deficits at 12 months. However, EF deficits at 6 months drove the relationship between PTSD symptoms at baseline and at 1 year (indirect effect = .061).

“What this suggests is that executive-function deficits are a mechanism that maintains patients’ symptoms over the course of 1 year,” Dr. Bardeen said.

“And you don’t see the reverse,” he added. “You don’t see that PTSD symptoms at [6 months] mediate the relationship between [baseline] and 6 month executive-function deficits.”
 

Surprising finding

The findings suggest deficits in executive functioning have a stronger role in maintaining PTSD symptoms than these symptoms have in maintaining EF deficits, Dr. Bardeen told this news organization.

“I had originally hypothesized a bidirectional relationship in which PTSD symptoms influenced future executive-function deficits and executive-function deficits influenced future PTSD symptoms,” he said.

“So, it was a surprise that, when accounting for both variables in the same model, executive-function deficits predicted future PTSD symptoms, but PTSD symptoms did not significantly predict future EF deficits,” he added.

Dr. Bardeen noted this suggests that EF deficits “may be a particularly important maintenance factor.”  

In addition, he recommended the use of neuropsychological assessments prior to treatment to identify individuals with EF deficits and distinguish those deficits from PTSD symptoms.

“There is certainly overlap between executive-function deficits and PTSD symptoms,” Dr. Bardeen said. “For example, several of the symptoms of PTSD, such as concentration difficulties, may be indicators of executive-function deficits.”

He noted assessments such as the Delis Kaplan Executive Function System, and Clinician Administered PTSD Scale for DSM-5, when used as part of a larger assessment battery, can help differentiate between the EF deficits and PTSD.

“This would take several hours to administer, but in cases in which serious cognitive impairment is suspected, a comprehensive assessment is the way to go,” Dr. Bardeen said.

The standard approaches of prolonged exposure therapy and cognitive processing therapy can be effective in patients without EF deficits, while some modifications may benefit those with these deficits, he added.

“For example, it’s important to provide a more directive and structured environment in which the practitioner repeats key points frequently, uses concrete language, simplifies worksheets, and provides written summaries and reminder cards,” he said.
 

Further findings

In additional research presented at the meeting, Elsa Mattson, a PhD student from Case Western Reserve University, Cleveland, and colleagues reported findings further distinguishing the role of EF in PTSD.

In that study of 149 patients with chronic PTSD, those with low performing working memory, but not high working memory, had higher pre- as well as posttreatment PTSD symptom severity and depressive symptoms.

“Clinicians should consider that impairments in executive function may play a role in reduced treatment response, potentially impairing a client’s ability to learn new information in treatment,” the investigators wrote.

“Understanding how executive function processes change over the course of treatment, particularly in relation to processing the trauma memories, is an important next step,” they added.

The first study was supported by a grant from the National Institute of Mental Health. The investigators have disclosed no relevant financial relationships.

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