Clinical Psychiatry News

The size of the human brain has increased over time, a new finding that may help explain a previously reported decline in incident dementia.

A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.

“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.

The study was published online in JAMA Neurology.
 

Dementia Protection?

An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.

“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.

The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.

Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm² vs 1933 cm²).

Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area. 

“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.

Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.

“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.

While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.

Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference. 
 

Exciting Work 

“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial. 

“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.

“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.

The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.

Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added. 

“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.

Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.

A version of this article appeared on Medscape.com.

The size of the human brain has increased over time, a new finding that may help explain a previously reported decline in incident dementia.

A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.

“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.

The study was published online in JAMA Neurology.
 

Dementia Protection?

An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.

“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.

The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.

Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm² vs 1933 cm²).

Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area. 

“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.

Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.

“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.

While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.

Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference. 
 

Exciting Work 

“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial. 

“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.

“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.

The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.

Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added. 

“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.

Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.

A version of this article appeared on Medscape.com.

The size of the human brain has increased over time, a new finding that may help explain a previously reported decline in incident dementia.

A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.

“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.

The study was published online in JAMA Neurology.
 

Dementia Protection?

An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.

“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.

The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.

Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm² vs 1933 cm²).

Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area. 

“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.

Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.

“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.

While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.

Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference. 
 

Exciting Work 

“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial. 

“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.

“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.

The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.

Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added. 

“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.

Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.

A version of this article appeared on Medscape.com.

The number of women with perinatal mood and anxiety disorder (PMAD) has spiked sharply in the United States. A new study explores trends by state and time period.

Between 2008 and 2020, in a national cohort of 750,004 commercially insured women with a live birth, nearly 1 in 5 (144,037 [19.2%]) were diagnosed with PMAD, according to a paper published in Health Affairs. PMAD diagnoses among privately insured women increased by 93.3% over those years, wrote lead author Kara Zivin, PhD, of the University of Michigan, Veterans Affairs Ann Arbor Healthcare System, and colleagues.

PMAD describes a spectrum of emotional complications with mild to severe symptoms that can affect women while pregnant and through the first year after giving birth.

The total number of perinatal women decreased from a high of 64,842 in 2008 to a low of 52,479 in 2020, a 19.1% decrease, but over the same time, women with diagnosed PMAD increased 56.4% from 9,520 in 2008 to 14,890 in 2020. Prevalence of PMAD doubled from 1,468 per 10,000 deliveries to 2,837 per 10,000 deliveries in 2020, according to the analysis.
 

Differences by State

Increases differed substantially by state. Though average annual changes across all states reached 109 additional PMAD diagnoses per 10,000 deliveries, Iowa had the greatest increase with an additional 163 PMAD diagnoses per 10,000 deliveries annually. New Mexico had the smallest annual growth, at an additional 49 per 10,000 deliveries.

The increases were accompanied by maternal health improvement efforts. The Affordable Care Act (ACA) required insurance companies to cover maternity and preventive services, which likely increased PMAD screening and detection, the researchers noted.

“Diagnosis of PMAD is rising due to increased awareness and in all likelihood, decrease in stigma, but availability of providers is so challenging,” said Lee S. Cohen, MD, who was not part of the study. Dr. Cohen is director of the Ammon-Pinizzotto Center for Women’s Mental Health and Perinatal and Reproductive Psychiatry at Massachusetts General Hospital in Boston. “The navigation to providers by women who are suffering is beyond challenging,” he said.

The authors reported that all states except Vermont saw increasing rates of PMAD diagnoses post-ACA vs. pre-ACA. The researchers also found that relative to the period from 2008 to 2014, psychotherapy rates continued rising from 2015 to 2020 and suicidality (suicidal ideation or self-harm diagnoses) rates declined.
 

States’ Suicidality Rates Vary Widely

“Overall, access to psychotherapy may have stemmed suicidality despite increasing PMAD diagnoses. But although more PMAD diagnoses may have led to increased psychotherapy, therapy access depends on provider availability, which varies by geographic region and insurance coverage network,” the authors wrote.

Suicidality rates differed greatly by state. Louisiana’s annual rate of increase was greatest, at 22 per 10,000 while Maryland had the greatest negative annual rate of change, at −15 per 10,000 deliveries, the authors explained.

“Observed trends in PMAD diagnoses among privately insured people during 2008-2020 and in associated suicidality and psychotherapy use suggest an increasingly rapid worsening of US maternal mental health,” the authors wrote.

The authors noted that this study did not include those on public insurance, a group that may experience disproportionate maternal morbidity and mortality burden, and urged that future studies include them.
 

Strengths of Study

Kimberly McKee, PhD, MPH, assistant professor in the department of family medicine at University of Michigan in Ann Arbor, who was not part of this research, said this paper gives a broader look than prior work because it includes the year before and after birth, rather than delivery and hospitalization.

“It’s really important to look out at least 12 months postpartum,” she noted.

Another strength is that the study was able to look at use of services such as psychotherapy before and post ACA. She noted the increased use of psychotherapy and the decrease in suicidal ideation was an association, but said, “I think it’s reasonable to assume that there was a benefit.”

She noted that these data go through 2020 and the COVID-19 pandemic has even further stressed the healthcare system, which could affect these numbers.

Primary Care’s Role

“The opportunity for primary care to really be the medical home for reproductive-age women is key here,” Dr. McKee said, adding that primary care can provide the continuity if women go off and on insurance around pregnancy and make sure the women get follow-up care and referrals to specialty care.

Models that integrate behavioral health and primary care are particularly promising, she said. Inclusion of social workers at the point of care can also help meet needs regarding social determinants of health.

Telehealth is another avenue for expansion extending the reach for following perinatal women, she said. “Using every tool we have to reach individuals where they are can allow for more frequent check-ins, which is really important here.”

Dr. McKee said the paper highlights an important reality: Mental health is a leading cause and contributor to maternal mortality, which “is 100% preventable.” Yet, current literature continues to show increases.

“This is a fairly common problem that affects not just women, but the fetus, their children, their families,” she noted.

The authors and Dr. Cohen and Dr. McKee reported no relevant financial relationships.

The number of women with perinatal mood and anxiety disorder (PMAD) has spiked sharply in the United States. A new study explores trends by state and time period.

Between 2008 and 2020, in a national cohort of 750,004 commercially insured women with a live birth, nearly 1 in 5 (144,037 [19.2%]) were diagnosed with PMAD, according to a paper published in Health Affairs. PMAD diagnoses among privately insured women increased by 93.3% over those years, wrote lead author Kara Zivin, PhD, of the University of Michigan, Veterans Affairs Ann Arbor Healthcare System, and colleagues.

PMAD describes a spectrum of emotional complications with mild to severe symptoms that can affect women while pregnant and through the first year after giving birth.

The total number of perinatal women decreased from a high of 64,842 in 2008 to a low of 52,479 in 2020, a 19.1% decrease, but over the same time, women with diagnosed PMAD increased 56.4% from 9,520 in 2008 to 14,890 in 2020. Prevalence of PMAD doubled from 1,468 per 10,000 deliveries to 2,837 per 10,000 deliveries in 2020, according to the analysis.
 

Differences by State

Increases differed substantially by state. Though average annual changes across all states reached 109 additional PMAD diagnoses per 10,000 deliveries, Iowa had the greatest increase with an additional 163 PMAD diagnoses per 10,000 deliveries annually. New Mexico had the smallest annual growth, at an additional 49 per 10,000 deliveries.

The increases were accompanied by maternal health improvement efforts. The Affordable Care Act (ACA) required insurance companies to cover maternity and preventive services, which likely increased PMAD screening and detection, the researchers noted.

“Diagnosis of PMAD is rising due to increased awareness and in all likelihood, decrease in stigma, but availability of providers is so challenging,” said Lee S. Cohen, MD, who was not part of the study. Dr. Cohen is director of the Ammon-Pinizzotto Center for Women’s Mental Health and Perinatal and Reproductive Psychiatry at Massachusetts General Hospital in Boston. “The navigation to providers by women who are suffering is beyond challenging,” he said.

The authors reported that all states except Vermont saw increasing rates of PMAD diagnoses post-ACA vs. pre-ACA. The researchers also found that relative to the period from 2008 to 2014, psychotherapy rates continued rising from 2015 to 2020 and suicidality (suicidal ideation or self-harm diagnoses) rates declined.
 

States’ Suicidality Rates Vary Widely

“Overall, access to psychotherapy may have stemmed suicidality despite increasing PMAD diagnoses. But although more PMAD diagnoses may have led to increased psychotherapy, therapy access depends on provider availability, which varies by geographic region and insurance coverage network,” the authors wrote.

Suicidality rates differed greatly by state. Louisiana’s annual rate of increase was greatest, at 22 per 10,000 while Maryland had the greatest negative annual rate of change, at −15 per 10,000 deliveries, the authors explained.

“Observed trends in PMAD diagnoses among privately insured people during 2008-2020 and in associated suicidality and psychotherapy use suggest an increasingly rapid worsening of US maternal mental health,” the authors wrote.

The authors noted that this study did not include those on public insurance, a group that may experience disproportionate maternal morbidity and mortality burden, and urged that future studies include them.
 

Strengths of Study

Kimberly McKee, PhD, MPH, assistant professor in the department of family medicine at University of Michigan in Ann Arbor, who was not part of this research, said this paper gives a broader look than prior work because it includes the year before and after birth, rather than delivery and hospitalization.

“It’s really important to look out at least 12 months postpartum,” she noted.

Another strength is that the study was able to look at use of services such as psychotherapy before and post ACA. She noted the increased use of psychotherapy and the decrease in suicidal ideation was an association, but said, “I think it’s reasonable to assume that there was a benefit.”

She noted that these data go through 2020 and the COVID-19 pandemic has even further stressed the healthcare system, which could affect these numbers.

Primary Care’s Role

“The opportunity for primary care to really be the medical home for reproductive-age women is key here,” Dr. McKee said, adding that primary care can provide the continuity if women go off and on insurance around pregnancy and make sure the women get follow-up care and referrals to specialty care.

Models that integrate behavioral health and primary care are particularly promising, she said. Inclusion of social workers at the point of care can also help meet needs regarding social determinants of health.

Telehealth is another avenue for expansion extending the reach for following perinatal women, she said. “Using every tool we have to reach individuals where they are can allow for more frequent check-ins, which is really important here.”

Dr. McKee said the paper highlights an important reality: Mental health is a leading cause and contributor to maternal mortality, which “is 100% preventable.” Yet, current literature continues to show increases.

“This is a fairly common problem that affects not just women, but the fetus, their children, their families,” she noted.

The authors and Dr. Cohen and Dr. McKee reported no relevant financial relationships.

The number of women with perinatal mood and anxiety disorder (PMAD) has spiked sharply in the United States. A new study explores trends by state and time period.

Between 2008 and 2020, in a national cohort of 750,004 commercially insured women with a live birth, nearly 1 in 5 (144,037 [19.2%]) were diagnosed with PMAD, according to a paper published in Health Affairs. PMAD diagnoses among privately insured women increased by 93.3% over those years, wrote lead author Kara Zivin, PhD, of the University of Michigan, Veterans Affairs Ann Arbor Healthcare System, and colleagues.

PMAD describes a spectrum of emotional complications with mild to severe symptoms that can affect women while pregnant and through the first year after giving birth.

The total number of perinatal women decreased from a high of 64,842 in 2008 to a low of 52,479 in 2020, a 19.1% decrease, but over the same time, women with diagnosed PMAD increased 56.4% from 9,520 in 2008 to 14,890 in 2020. Prevalence of PMAD doubled from 1,468 per 10,000 deliveries to 2,837 per 10,000 deliveries in 2020, according to the analysis.
 

Differences by State

Increases differed substantially by state. Though average annual changes across all states reached 109 additional PMAD diagnoses per 10,000 deliveries, Iowa had the greatest increase with an additional 163 PMAD diagnoses per 10,000 deliveries annually. New Mexico had the smallest annual growth, at an additional 49 per 10,000 deliveries.

The increases were accompanied by maternal health improvement efforts. The Affordable Care Act (ACA) required insurance companies to cover maternity and preventive services, which likely increased PMAD screening and detection, the researchers noted.

“Diagnosis of PMAD is rising due to increased awareness and in all likelihood, decrease in stigma, but availability of providers is so challenging,” said Lee S. Cohen, MD, who was not part of the study. Dr. Cohen is director of the Ammon-Pinizzotto Center for Women’s Mental Health and Perinatal and Reproductive Psychiatry at Massachusetts General Hospital in Boston. “The navigation to providers by women who are suffering is beyond challenging,” he said.

The authors reported that all states except Vermont saw increasing rates of PMAD diagnoses post-ACA vs. pre-ACA. The researchers also found that relative to the period from 2008 to 2014, psychotherapy rates continued rising from 2015 to 2020 and suicidality (suicidal ideation or self-harm diagnoses) rates declined.
 

States’ Suicidality Rates Vary Widely

“Overall, access to psychotherapy may have stemmed suicidality despite increasing PMAD diagnoses. But although more PMAD diagnoses may have led to increased psychotherapy, therapy access depends on provider availability, which varies by geographic region and insurance coverage network,” the authors wrote.

Suicidality rates differed greatly by state. Louisiana’s annual rate of increase was greatest, at 22 per 10,000 while Maryland had the greatest negative annual rate of change, at −15 per 10,000 deliveries, the authors explained.

“Observed trends in PMAD diagnoses among privately insured people during 2008-2020 and in associated suicidality and psychotherapy use suggest an increasingly rapid worsening of US maternal mental health,” the authors wrote.

The authors noted that this study did not include those on public insurance, a group that may experience disproportionate maternal morbidity and mortality burden, and urged that future studies include them.
 

Strengths of Study

Kimberly McKee, PhD, MPH, assistant professor in the department of family medicine at University of Michigan in Ann Arbor, who was not part of this research, said this paper gives a broader look than prior work because it includes the year before and after birth, rather than delivery and hospitalization.

“It’s really important to look out at least 12 months postpartum,” she noted.

Another strength is that the study was able to look at use of services such as psychotherapy before and post ACA. She noted the increased use of psychotherapy and the decrease in suicidal ideation was an association, but said, “I think it’s reasonable to assume that there was a benefit.”

She noted that these data go through 2020 and the COVID-19 pandemic has even further stressed the healthcare system, which could affect these numbers.

Primary Care’s Role

“The opportunity for primary care to really be the medical home for reproductive-age women is key here,” Dr. McKee said, adding that primary care can provide the continuity if women go off and on insurance around pregnancy and make sure the women get follow-up care and referrals to specialty care.

Models that integrate behavioral health and primary care are particularly promising, she said. Inclusion of social workers at the point of care can also help meet needs regarding social determinants of health.

Telehealth is another avenue for expansion extending the reach for following perinatal women, she said. “Using every tool we have to reach individuals where they are can allow for more frequent check-ins, which is really important here.”

Dr. McKee said the paper highlights an important reality: Mental health is a leading cause and contributor to maternal mortality, which “is 100% preventable.” Yet, current literature continues to show increases.

“This is a fairly common problem that affects not just women, but the fetus, their children, their families,” she noted.

The authors and Dr. Cohen and Dr. McKee reported no relevant financial relationships.

Symptoms of sleep apnea, including snorting, gasping, or paused breathing during sleep, are associated with a significantly greater risk for problems with cognitive and memory problems, results from a large study showed.

Data from a representative sample of US adults show that those who reported sleep apnea symptoms were about 50% more likely to also report cognitive issues versus their counterparts without such symptoms.

“For clinicians, these findings suggest a potential benefit of considering sleep apnea as a possible contributing or exacerbating factor in individuals experiencing memory or cognitive problems. This could prompt further evaluation for sleep apnea, particularly in at-risk individuals,” said study investigator Dominique Low, MD, MPH, Department of Neurology, Boston Medical Center.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Need to Raise Awareness

The findings are based on 4257 adults who participated in the 2017-2018 National Health and Nutrition Examination Survey and completed questionnaires covering sleep, memory, cognition, and decision-making abilities.

Those who reported snorting, gasping, or breathing pauses during sleep were categorized as experiencing sleep apnea symptoms. Those who reported memory trouble, periods of confusion, difficulty concentrating, or decision-making problems were classified as having memory or cognitive symptoms.

Overall, 1079 participants reported symptoms of sleep apnea. Compared with people without sleep apnea, those with symptoms were more likely to have cognitive problems (33% vs 20%) and have greater odds of having memory or cognitive symptoms, even after adjusting for age, gender, race, and education (adjusted odds ratio, 2.02; P < .001).

“While the study did not establish a cause-and-effect relationship, the findings suggest the importance of raising awareness about the potential link between sleep and cognitive function. Early identification and treatment may improve overall health and potentially lead to a better quality of life,” Dr. Low said.

Limitations of the study include self-reported data on sleep apnea symptoms and cognitive issues sourced from one survey.
 

Consistent Data

Reached for comment, Matthew Pase, PhD, with the Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia, said the results are similar to earlier work that found a link between obstructive sleep apnea and cognition.

For example, in a recent study, the presence of mild to severe OSA, identified using overnight polysomnography in five community-based cohorts with more than 5900 adults, was associated with poorer cognitive test performance, Dr. Pase said.

“These and other results underscore the importance of healthy sleep for optimal brain health. Future research is needed to test if treating OSA and other sleep disorders can reduce the risk of cognitive impairment,” Dr. Pase said.

Yet, in its latest statement on the topic, the US Preventive Services Task Force concluded there remains insufficient evidence to weigh the balance of benefits and harms of screening for OSA among asymptomatic adults and those with unrecognized symptoms.

The study had no specific funding. Dr. Low and Dr. Pase had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Symptoms of sleep apnea, including snorting, gasping, or paused breathing during sleep, are associated with a significantly greater risk for problems with cognitive and memory problems, results from a large study showed.

Data from a representative sample of US adults show that those who reported sleep apnea symptoms were about 50% more likely to also report cognitive issues versus their counterparts without such symptoms.

“For clinicians, these findings suggest a potential benefit of considering sleep apnea as a possible contributing or exacerbating factor in individuals experiencing memory or cognitive problems. This could prompt further evaluation for sleep apnea, particularly in at-risk individuals,” said study investigator Dominique Low, MD, MPH, Department of Neurology, Boston Medical Center.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Need to Raise Awareness

The findings are based on 4257 adults who participated in the 2017-2018 National Health and Nutrition Examination Survey and completed questionnaires covering sleep, memory, cognition, and decision-making abilities.

Those who reported snorting, gasping, or breathing pauses during sleep were categorized as experiencing sleep apnea symptoms. Those who reported memory trouble, periods of confusion, difficulty concentrating, or decision-making problems were classified as having memory or cognitive symptoms.

Overall, 1079 participants reported symptoms of sleep apnea. Compared with people without sleep apnea, those with symptoms were more likely to have cognitive problems (33% vs 20%) and have greater odds of having memory or cognitive symptoms, even after adjusting for age, gender, race, and education (adjusted odds ratio, 2.02; P < .001).

“While the study did not establish a cause-and-effect relationship, the findings suggest the importance of raising awareness about the potential link between sleep and cognitive function. Early identification and treatment may improve overall health and potentially lead to a better quality of life,” Dr. Low said.

Limitations of the study include self-reported data on sleep apnea symptoms and cognitive issues sourced from one survey.
 

Consistent Data

Reached for comment, Matthew Pase, PhD, with the Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia, said the results are similar to earlier work that found a link between obstructive sleep apnea and cognition.

For example, in a recent study, the presence of mild to severe OSA, identified using overnight polysomnography in five community-based cohorts with more than 5900 adults, was associated with poorer cognitive test performance, Dr. Pase said.

“These and other results underscore the importance of healthy sleep for optimal brain health. Future research is needed to test if treating OSA and other sleep disorders can reduce the risk of cognitive impairment,” Dr. Pase said.

Yet, in its latest statement on the topic, the US Preventive Services Task Force concluded there remains insufficient evidence to weigh the balance of benefits and harms of screening for OSA among asymptomatic adults and those with unrecognized symptoms.

The study had no specific funding. Dr. Low and Dr. Pase had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Symptoms of sleep apnea, including snorting, gasping, or paused breathing during sleep, are associated with a significantly greater risk for problems with cognitive and memory problems, results from a large study showed.

Data from a representative sample of US adults show that those who reported sleep apnea symptoms were about 50% more likely to also report cognitive issues versus their counterparts without such symptoms.

“For clinicians, these findings suggest a potential benefit of considering sleep apnea as a possible contributing or exacerbating factor in individuals experiencing memory or cognitive problems. This could prompt further evaluation for sleep apnea, particularly in at-risk individuals,” said study investigator Dominique Low, MD, MPH, Department of Neurology, Boston Medical Center.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Need to Raise Awareness

The findings are based on 4257 adults who participated in the 2017-2018 National Health and Nutrition Examination Survey and completed questionnaires covering sleep, memory, cognition, and decision-making abilities.

Those who reported snorting, gasping, or breathing pauses during sleep were categorized as experiencing sleep apnea symptoms. Those who reported memory trouble, periods of confusion, difficulty concentrating, or decision-making problems were classified as having memory or cognitive symptoms.

Overall, 1079 participants reported symptoms of sleep apnea. Compared with people without sleep apnea, those with symptoms were more likely to have cognitive problems (33% vs 20%) and have greater odds of having memory or cognitive symptoms, even after adjusting for age, gender, race, and education (adjusted odds ratio, 2.02; P < .001).

“While the study did not establish a cause-and-effect relationship, the findings suggest the importance of raising awareness about the potential link between sleep and cognitive function. Early identification and treatment may improve overall health and potentially lead to a better quality of life,” Dr. Low said.

Limitations of the study include self-reported data on sleep apnea symptoms and cognitive issues sourced from one survey.
 

Consistent Data

Reached for comment, Matthew Pase, PhD, with the Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia, said the results are similar to earlier work that found a link between obstructive sleep apnea and cognition.

For example, in a recent study, the presence of mild to severe OSA, identified using overnight polysomnography in five community-based cohorts with more than 5900 adults, was associated with poorer cognitive test performance, Dr. Pase said.

“These and other results underscore the importance of healthy sleep for optimal brain health. Future research is needed to test if treating OSA and other sleep disorders can reduce the risk of cognitive impairment,” Dr. Pase said.

Yet, in its latest statement on the topic, the US Preventive Services Task Force concluded there remains insufficient evidence to weigh the balance of benefits and harms of screening for OSA among asymptomatic adults and those with unrecognized symptoms.

The study had no specific funding. Dr. Low and Dr. Pase had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Remote cognitive behavioral therapy (CBT) is just as effective as in-person CBT for a range of mental health and somatic disorders, a new review of more than 50 randomized clinical trials (RCTs) showed.

The RCTs included more than 5000 patients receiving CBT for conditions such as mood, anxiety, and body dysmorphic disorders, as well as chronic pain, insomnia, and alcohol use disorder.

“The World Health Organization has designated CBT as essential healthcare, but access remains an important barrier for many people in Canada. Our findings suggest that therapist-guided, remotely delivered CBT can be used to facilitate greater access to evidence-based care,” lead investigator Jason Busse, PhD, McMaster University, Hamilton, Ontario, Canada, said in a press release.

The findings were published online on March 18 in CMAJ.
 

Access Problematic

In Canada, CBT may be provided within existing government-funded healthcare services and by private providers such as registered psychotherapists, social worker, and psychologists who require out-of-pocket expenses.

Access to evidence-based mental healthcare such as CBT can be challenging in a country as geographically large, and as sparsely populated, as Canada. To increase access, some of the provinces have funded Internet-based CBT, but the efficacy of in-person vs remote CBT remains uncertain.

The investigators searched the medical literature for RCTs that enrolled adult patients randomized to receive either therapist-guided remote or in-person CBT.

The study included 52 RCTs with 5463 participants with a mean age of 43 years, and 3354 (61%) were female.

A total of 17 studies focused on the treatment of anxiety and related disorders, 14 on depression and mood disorders, seven on insomnia, six on chronic pain or fatigue syndromes, five on body image or eating disorders, three on tinnitus, and one on alcohol use disorder.

CBT was provided on an individual and group basis. Treatment duration ranged from 5 to 21 sessions, with the median follow-up of 180 days.

Investigators found little to no difference in effectiveness between in-person and therapist-guided remote CBT on primary outcomes (standardized mean difference [SMD], −0.02; 95% CI, −0.11 to 0.07).

Analysis using end scores also showed little to no difference in efficacy between in-person and remote CBT (SMD, −0.01; 95% CI, −0.11 to 0.08).
 

Policy Implications

The authors noted that remote CBT can potentially expand access to care as it is more convenient for patients and potentially more cost-effective.

“Our finding that remote CBT is an effective alternative to in-person delivery has potential policy implications,” they wrote.

The researchers recommended Canadian provinces and territories increase funding to boost access to therapist-guided remote CBT, thereby expanding access to evidence-based care.

Study limitations included the fact that most of the eligible RCTs reviewed in the analysis were conducted in high-income countries with middle-aged patients and followed them for a median 180 days, so generalizability of the findings to older patients living in lower-income patients or for longer follow-up periods was uncertain.

The study was partially funded by the Canadian Institutes of Health Research. Disclosures were noted in the original article.

A version of this article appeared on Medscape.com .

Remote cognitive behavioral therapy (CBT) is just as effective as in-person CBT for a range of mental health and somatic disorders, a new review of more than 50 randomized clinical trials (RCTs) showed.

The RCTs included more than 5000 patients receiving CBT for conditions such as mood, anxiety, and body dysmorphic disorders, as well as chronic pain, insomnia, and alcohol use disorder.

“The World Health Organization has designated CBT as essential healthcare, but access remains an important barrier for many people in Canada. Our findings suggest that therapist-guided, remotely delivered CBT can be used to facilitate greater access to evidence-based care,” lead investigator Jason Busse, PhD, McMaster University, Hamilton, Ontario, Canada, said in a press release.

The findings were published online on March 18 in CMAJ.
 

Access Problematic

In Canada, CBT may be provided within existing government-funded healthcare services and by private providers such as registered psychotherapists, social worker, and psychologists who require out-of-pocket expenses.

Access to evidence-based mental healthcare such as CBT can be challenging in a country as geographically large, and as sparsely populated, as Canada. To increase access, some of the provinces have funded Internet-based CBT, but the efficacy of in-person vs remote CBT remains uncertain.

The investigators searched the medical literature for RCTs that enrolled adult patients randomized to receive either therapist-guided remote or in-person CBT.

The study included 52 RCTs with 5463 participants with a mean age of 43 years, and 3354 (61%) were female.

A total of 17 studies focused on the treatment of anxiety and related disorders, 14 on depression and mood disorders, seven on insomnia, six on chronic pain or fatigue syndromes, five on body image or eating disorders, three on tinnitus, and one on alcohol use disorder.

CBT was provided on an individual and group basis. Treatment duration ranged from 5 to 21 sessions, with the median follow-up of 180 days.

Investigators found little to no difference in effectiveness between in-person and therapist-guided remote CBT on primary outcomes (standardized mean difference [SMD], −0.02; 95% CI, −0.11 to 0.07).

Analysis using end scores also showed little to no difference in efficacy between in-person and remote CBT (SMD, −0.01; 95% CI, −0.11 to 0.08).
 

Policy Implications

The authors noted that remote CBT can potentially expand access to care as it is more convenient for patients and potentially more cost-effective.

“Our finding that remote CBT is an effective alternative to in-person delivery has potential policy implications,” they wrote.

The researchers recommended Canadian provinces and territories increase funding to boost access to therapist-guided remote CBT, thereby expanding access to evidence-based care.

Study limitations included the fact that most of the eligible RCTs reviewed in the analysis were conducted in high-income countries with middle-aged patients and followed them for a median 180 days, so generalizability of the findings to older patients living in lower-income patients or for longer follow-up periods was uncertain.

The study was partially funded by the Canadian Institutes of Health Research. Disclosures were noted in the original article.

A version of this article appeared on Medscape.com .

Remote cognitive behavioral therapy (CBT) is just as effective as in-person CBT for a range of mental health and somatic disorders, a new review of more than 50 randomized clinical trials (RCTs) showed.

The RCTs included more than 5000 patients receiving CBT for conditions such as mood, anxiety, and body dysmorphic disorders, as well as chronic pain, insomnia, and alcohol use disorder.

“The World Health Organization has designated CBT as essential healthcare, but access remains an important barrier for many people in Canada. Our findings suggest that therapist-guided, remotely delivered CBT can be used to facilitate greater access to evidence-based care,” lead investigator Jason Busse, PhD, McMaster University, Hamilton, Ontario, Canada, said in a press release.

The findings were published online on March 18 in CMAJ.
 

Access Problematic

In Canada, CBT may be provided within existing government-funded healthcare services and by private providers such as registered psychotherapists, social worker, and psychologists who require out-of-pocket expenses.

Access to evidence-based mental healthcare such as CBT can be challenging in a country as geographically large, and as sparsely populated, as Canada. To increase access, some of the provinces have funded Internet-based CBT, but the efficacy of in-person vs remote CBT remains uncertain.

The investigators searched the medical literature for RCTs that enrolled adult patients randomized to receive either therapist-guided remote or in-person CBT.

The study included 52 RCTs with 5463 participants with a mean age of 43 years, and 3354 (61%) were female.

A total of 17 studies focused on the treatment of anxiety and related disorders, 14 on depression and mood disorders, seven on insomnia, six on chronic pain or fatigue syndromes, five on body image or eating disorders, three on tinnitus, and one on alcohol use disorder.

CBT was provided on an individual and group basis. Treatment duration ranged from 5 to 21 sessions, with the median follow-up of 180 days.

Investigators found little to no difference in effectiveness between in-person and therapist-guided remote CBT on primary outcomes (standardized mean difference [SMD], −0.02; 95% CI, −0.11 to 0.07).

Analysis using end scores also showed little to no difference in efficacy between in-person and remote CBT (SMD, −0.01; 95% CI, −0.11 to 0.08).
 

Policy Implications

The authors noted that remote CBT can potentially expand access to care as it is more convenient for patients and potentially more cost-effective.

“Our finding that remote CBT is an effective alternative to in-person delivery has potential policy implications,” they wrote.

The researchers recommended Canadian provinces and territories increase funding to boost access to therapist-guided remote CBT, thereby expanding access to evidence-based care.

Study limitations included the fact that most of the eligible RCTs reviewed in the analysis were conducted in high-income countries with middle-aged patients and followed them for a median 180 days, so generalizability of the findings to older patients living in lower-income patients or for longer follow-up periods was uncertain.

The study was partially funded by the Canadian Institutes of Health Research. Disclosures were noted in the original article.

A version of this article appeared on Medscape.com .

Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.

Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.

The findings showed that the association held even after controlling for shared genetic and environmental factors.

The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.

The findings were published online on March 6 in JAMA Psychiatry.
 

Dose-Dependent Effect

Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.

To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.

The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.

The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.

Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.

Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.

More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.

At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
 

Untangling Genes and Environment

To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).

The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.

Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).

“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.

One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.

The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.

Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.

The findings showed that the association held even after controlling for shared genetic and environmental factors.

The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.

The findings were published online on March 6 in JAMA Psychiatry.
 

Dose-Dependent Effect

Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.

To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.

The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.

The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.

Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.

Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.

More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.

At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
 

Untangling Genes and Environment

To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).

The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.

Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).

“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.

One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.

The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.

Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.

The findings showed that the association held even after controlling for shared genetic and environmental factors.

The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.

The findings were published online on March 6 in JAMA Psychiatry.
 

Dose-Dependent Effect

Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.

To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.

The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.

The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.

Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.

Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.

More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.

At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
 

Untangling Genes and Environment

To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).

The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.

Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).

“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.

One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.

The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

Among the potential uses envisioned for artificial intelligence (AI) in healthcare is decreasing provider burden by using the technology to help respond to patients’ questions submitted through portals.

Easing the burden on providers of responding to each question is a target ripe for solutions as during the COVID pandemic, such messages increased 157% from prepandemic levels, say authors of a paper published online in JAMA Network Open. Each additional message added 2.3 minutes to time spent on the electronic health record (EHR) per day.

Researchers at Stanford Health Care, led by Patricia Garcia, MD, with the department of medicine, conducted a 5-week, prospective, single-group quality improvement study from July 10 through August 13, 2023, at Stanford to test an AI response system.
 

Large Language Model Used

All attending physicians, advanced practice providers, clinic nurses, and clinical pharmacists from the divisions of primary care and gastroenterology and hepatology were enrolled in a pilot program that offered the option to answer patients’ questions with drafts that were generated by a Health Insurance Portability and Accountability Act–compliant large language model integrated into EHRs. Drafts were then reviewed by the provider.

The study primarily tested whether providers (162 were included) would use the AI-generated drafts. Secondary outcomes included whether using such a system saved time or improved the clinician experience.

Participants received survey emails before and after the pilot period and answered questions on areas including task load, EHR burden, usability, work exhaustion, burnout, and satisfaction.

Researchers found that the overall average utilization rate per clinician was 20% but there were significant between-group differences. For example, in gastroenterology and hepatology, nurses used the AI tool the most at 29% and physicians/APPs had a 24% usage rate, whereas clinical pharmacists had the highest use rate for primary care at 44% compared with physician use at 15%.
 

Burden Improved, But Didn’t Save Time

AI did not appear to save time but did improve task load scores and work exhaustion scores. The report states that there was no change in reply action time, write time, or read time between the prepilot and pilot periods. However, there were significant reductions in the physician task load score derivative (mean [SD], 61.31 [17.23] pre survey vs 47.26 [17.11] post survey; paired difference, −13.87; 95% CI, −17.38 to −9.50; P < .001) and work exhaustion scores decreased by a third (mean [SD], 1.95 [0.79] pre survey vs 1.62 [0.68] post survey; paired difference, −0.33; 95% CI, −0.50 to −0.17; P < .001)

The authors wrote that improvements in task load and emotional exhaustion scores suggest that generated replies have the potential to lessen cognitive burden and burnout. Though the AI tool didn’t save time, editing responses may be less cognitively taxing than writing responses for providers, the authors suggest.
 

Quality of AI Responses

Comments about AI response message voice and/or tone were the most common and had the highest absolute number of negative comments (10 positive, 2 neutral, and 14 negative). The most negative comments were about length (too long or too short) of the draft message (1 positive, 2 neutral, and 8 negative).

Comments on accuracy of the draft response were fairly even ­— 4 positive and 5 negative — but there were no adverse safety signals, the authors report.

The providers had high expectations about use and quality of the tool that “were either met or exceeded at the end of the pilot,” Dr. Garcia and coauthors write. “Given the evidence that burnout is associated with turnover, reductions in clinical activity, and quality, even a modest improvement may have a substantial impact.”

One coauthor reported grants from Google, Omada Health, and PredictaMed outside the submitted work. Another coauthor reported having a patent for Well-being Index Instruments and Mayo Leadership Impact Index, with royalties paid from Mayo Clinic, and receiving honoraria for presenting grand rounds, keynote lectures, and advising health care organizations on clinician well-being. No other disclosures were reported. 

Among the potential uses envisioned for artificial intelligence (AI) in healthcare is decreasing provider burden by using the technology to help respond to patients’ questions submitted through portals.

Easing the burden on providers of responding to each question is a target ripe for solutions as during the COVID pandemic, such messages increased 157% from prepandemic levels, say authors of a paper published online in JAMA Network Open. Each additional message added 2.3 minutes to time spent on the electronic health record (EHR) per day.

Researchers at Stanford Health Care, led by Patricia Garcia, MD, with the department of medicine, conducted a 5-week, prospective, single-group quality improvement study from July 10 through August 13, 2023, at Stanford to test an AI response system.
 

Large Language Model Used

All attending physicians, advanced practice providers, clinic nurses, and clinical pharmacists from the divisions of primary care and gastroenterology and hepatology were enrolled in a pilot program that offered the option to answer patients’ questions with drafts that were generated by a Health Insurance Portability and Accountability Act–compliant large language model integrated into EHRs. Drafts were then reviewed by the provider.

The study primarily tested whether providers (162 were included) would use the AI-generated drafts. Secondary outcomes included whether using such a system saved time or improved the clinician experience.

Participants received survey emails before and after the pilot period and answered questions on areas including task load, EHR burden, usability, work exhaustion, burnout, and satisfaction.

Researchers found that the overall average utilization rate per clinician was 20% but there were significant between-group differences. For example, in gastroenterology and hepatology, nurses used the AI tool the most at 29% and physicians/APPs had a 24% usage rate, whereas clinical pharmacists had the highest use rate for primary care at 44% compared with physician use at 15%.
 

Burden Improved, But Didn’t Save Time

AI did not appear to save time but did improve task load scores and work exhaustion scores. The report states that there was no change in reply action time, write time, or read time between the prepilot and pilot periods. However, there were significant reductions in the physician task load score derivative (mean [SD], 61.31 [17.23] pre survey vs 47.26 [17.11] post survey; paired difference, −13.87; 95% CI, −17.38 to −9.50; P < .001) and work exhaustion scores decreased by a third (mean [SD], 1.95 [0.79] pre survey vs 1.62 [0.68] post survey; paired difference, −0.33; 95% CI, −0.50 to −0.17; P < .001)

The authors wrote that improvements in task load and emotional exhaustion scores suggest that generated replies have the potential to lessen cognitive burden and burnout. Though the AI tool didn’t save time, editing responses may be less cognitively taxing than writing responses for providers, the authors suggest.
 

Quality of AI Responses

Comments about AI response message voice and/or tone were the most common and had the highest absolute number of negative comments (10 positive, 2 neutral, and 14 negative). The most negative comments were about length (too long or too short) of the draft message (1 positive, 2 neutral, and 8 negative).

Comments on accuracy of the draft response were fairly even ­— 4 positive and 5 negative — but there were no adverse safety signals, the authors report.

The providers had high expectations about use and quality of the tool that “were either met or exceeded at the end of the pilot,” Dr. Garcia and coauthors write. “Given the evidence that burnout is associated with turnover, reductions in clinical activity, and quality, even a modest improvement may have a substantial impact.”

One coauthor reported grants from Google, Omada Health, and PredictaMed outside the submitted work. Another coauthor reported having a patent for Well-being Index Instruments and Mayo Leadership Impact Index, with royalties paid from Mayo Clinic, and receiving honoraria for presenting grand rounds, keynote lectures, and advising health care organizations on clinician well-being. No other disclosures were reported. 

Among the potential uses envisioned for artificial intelligence (AI) in healthcare is decreasing provider burden by using the technology to help respond to patients’ questions submitted through portals.

Easing the burden on providers of responding to each question is a target ripe for solutions as during the COVID pandemic, such messages increased 157% from prepandemic levels, say authors of a paper published online in JAMA Network Open. Each additional message added 2.3 minutes to time spent on the electronic health record (EHR) per day.

Researchers at Stanford Health Care, led by Patricia Garcia, MD, with the department of medicine, conducted a 5-week, prospective, single-group quality improvement study from July 10 through August 13, 2023, at Stanford to test an AI response system.
 

Large Language Model Used

All attending physicians, advanced practice providers, clinic nurses, and clinical pharmacists from the divisions of primary care and gastroenterology and hepatology were enrolled in a pilot program that offered the option to answer patients’ questions with drafts that were generated by a Health Insurance Portability and Accountability Act–compliant large language model integrated into EHRs. Drafts were then reviewed by the provider.

The study primarily tested whether providers (162 were included) would use the AI-generated drafts. Secondary outcomes included whether using such a system saved time or improved the clinician experience.

Participants received survey emails before and after the pilot period and answered questions on areas including task load, EHR burden, usability, work exhaustion, burnout, and satisfaction.

Researchers found that the overall average utilization rate per clinician was 20% but there were significant between-group differences. For example, in gastroenterology and hepatology, nurses used the AI tool the most at 29% and physicians/APPs had a 24% usage rate, whereas clinical pharmacists had the highest use rate for primary care at 44% compared with physician use at 15%.
 

Burden Improved, But Didn’t Save Time

AI did not appear to save time but did improve task load scores and work exhaustion scores. The report states that there was no change in reply action time, write time, or read time between the prepilot and pilot periods. However, there were significant reductions in the physician task load score derivative (mean [SD], 61.31 [17.23] pre survey vs 47.26 [17.11] post survey; paired difference, −13.87; 95% CI, −17.38 to −9.50; P < .001) and work exhaustion scores decreased by a third (mean [SD], 1.95 [0.79] pre survey vs 1.62 [0.68] post survey; paired difference, −0.33; 95% CI, −0.50 to −0.17; P < .001)

The authors wrote that improvements in task load and emotional exhaustion scores suggest that generated replies have the potential to lessen cognitive burden and burnout. Though the AI tool didn’t save time, editing responses may be less cognitively taxing than writing responses for providers, the authors suggest.
 

Quality of AI Responses

Comments about AI response message voice and/or tone were the most common and had the highest absolute number of negative comments (10 positive, 2 neutral, and 14 negative). The most negative comments were about length (too long or too short) of the draft message (1 positive, 2 neutral, and 8 negative).

Comments on accuracy of the draft response were fairly even ­— 4 positive and 5 negative — but there were no adverse safety signals, the authors report.

The providers had high expectations about use and quality of the tool that “were either met or exceeded at the end of the pilot,” Dr. Garcia and coauthors write. “Given the evidence that burnout is associated with turnover, reductions in clinical activity, and quality, even a modest improvement may have a substantial impact.”

One coauthor reported grants from Google, Omada Health, and PredictaMed outside the submitted work. Another coauthor reported having a patent for Well-being Index Instruments and Mayo Leadership Impact Index, with royalties paid from Mayo Clinic, and receiving honoraria for presenting grand rounds, keynote lectures, and advising health care organizations on clinician well-being. No other disclosures were reported. 

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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

This transcript has been edited for clarity.

Rachel S. Rubin, MD: We are here at the Harvard Continuing Medical Education Course in Orlando, Florida. It’s all about testosterone therapy and sexual medicine. I have with me today the wonderful Dr. Marianne Brandon, who is an amazing sex therapist. Could you introduce yourself?

Marianne Brandon, PhD: I am a clinical psychologist and sex therapist. I’ve been in practice for more than 25 years. I’m currently located in Sarasota. I have a Psychology Today blog called The Future of Intimacy, which I have a lot of fun with.

Dr. Rubin: It’s very important, when taking care of patients, that we work in a biopsychosocial model. Yes, we can fix erectile dysfunction. We can help with menopause symptoms and that helps sexual function. But what I find makes my patients able to live their best lives is when they have a team, including a mental health professional — often a sex therapist or a couples’ therapist — where they can learn communication skills. Why is it important for primary care doctors to talk to their patients about sex? My primary care doctor has never asked me about sex.  

Dr. Brandon: For most people, sexual intimacy is critical for their experience of life. It correlates with their relationship satisfaction and life satisfaction. It’s much bigger than what’s happening in the bedroom. People have more struggles than you realize. Sexual dysfunction correlates with emotional issues such as depression and anxiety, with medical problems, and with medication use. Chances are that your patients have some kind of sexual concern, even if that’s not to the degree that it would be classified as a sexual dysfunction.

But sexual concerns wreak havoc. Believing they have a sexual problem, they stop touching, they stop relating to their partner. It becomes a really big deal in their lives. If you can open the door for a conversation about sex with your patients, it could do them a great deal of good. It’s also good for the practitioner, because if your patients think they can talk with you about anything, that’s going to establish your relationship with them. Practitioners avoid these conversations because they don’t have the time or the training to offer help.

Dr. Rubin: You don’t have to know all the answers. You just have to show empathy and compassion and say, “I hear you.” That’s the magic in the doctor-patient relationship. We refer patients to specialists when we don’t know what to do. What happens when I send a patient to a sex therapist? Do they watch them have sex? Of course not, but everyone thinks that is what sex therapists do.

Dr. Brandon: Sex therapy is just like any other type of therapy, but we discuss sexual issues. And because just about anything that’s happening in your patient’s life can trickle down into the bedroom, we end up talking about a lot of stuff that’s not directly related to sex but ultimately impacts the patient’s sex life.

Dr. Rubin: It’s true. Most medical conditions that we treat — from diabetes, hypertension, high cholesterol, and obesity to depression and anxiety — are strongly correlated with sexual health. We treat the underlying condition, but our patients don’t care about their A1c levels. They care about the fact that they cannot get aroused; their genitals don’t feel the same way they used to.

Dr. Brandon: I love that point because people make meaning out of their sexual concerns and dysfunction. Suddenly their body isn’t responding the way it used to. They think something’s wrong with them, or maybe they are with the wrong partner. This meaning becomes very powerful in their mind and perpetuates the sexual problem.

Dr. Rubin: First and foremost, we are educators. We can say, “You have pretty out-of-control diabetes,” or, “You’re a smoker, which can affect the health of your genitals. Have you noticed any issues going on there?” If you don’t ask, patients will not bring up their concerns with their doctors.

So how do people find a sex therapist?

Dr. Brandon: There are a few fabulous organizations that provide on their websites ways to find a therapist: the American Association of Sex Educators, Counselors and Therapists (AASECT) and Sex Therapy and Research (STAR). Giving patients this information is a huge intervention.

Other places to find a therapist include the International Society for Sexual Medicine, and the International Society for the Study of Women’s Sexual Health.

Since COVID, many therapists have gone virtual. Encourage your patients to look within their states to find options for therapists and psychologists. Recent legislation allows psychologists who have signed up for PSYPACT to practice almost throughout the entire United States. We used to think if we didn’t have a therapist in the community, we couldn’t make a referral. That›s not the case anymore.

Dr. Rubin: All doctors are really sexual medicine doctors. We can change the whole world by giving our patients a better quality of life.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, disclosed ties to Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: We are here at the Harvard Continuing Medical Education Course in Orlando, Florida. It’s all about testosterone therapy and sexual medicine. I have with me today the wonderful Dr. Marianne Brandon, who is an amazing sex therapist. Could you introduce yourself?

Marianne Brandon, PhD: I am a clinical psychologist and sex therapist. I’ve been in practice for more than 25 years. I’m currently located in Sarasota. I have a Psychology Today blog called The Future of Intimacy, which I have a lot of fun with.

Dr. Rubin: It’s very important, when taking care of patients, that we work in a biopsychosocial model. Yes, we can fix erectile dysfunction. We can help with menopause symptoms and that helps sexual function. But what I find makes my patients able to live their best lives is when they have a team, including a mental health professional — often a sex therapist or a couples’ therapist — where they can learn communication skills. Why is it important for primary care doctors to talk to their patients about sex? My primary care doctor has never asked me about sex.  

Dr. Brandon: For most people, sexual intimacy is critical for their experience of life. It correlates with their relationship satisfaction and life satisfaction. It’s much bigger than what’s happening in the bedroom. People have more struggles than you realize. Sexual dysfunction correlates with emotional issues such as depression and anxiety, with medical problems, and with medication use. Chances are that your patients have some kind of sexual concern, even if that’s not to the degree that it would be classified as a sexual dysfunction.

But sexual concerns wreak havoc. Believing they have a sexual problem, they stop touching, they stop relating to their partner. It becomes a really big deal in their lives. If you can open the door for a conversation about sex with your patients, it could do them a great deal of good. It’s also good for the practitioner, because if your patients think they can talk with you about anything, that’s going to establish your relationship with them. Practitioners avoid these conversations because they don’t have the time or the training to offer help.

Dr. Rubin: You don’t have to know all the answers. You just have to show empathy and compassion and say, “I hear you.” That’s the magic in the doctor-patient relationship. We refer patients to specialists when we don’t know what to do. What happens when I send a patient to a sex therapist? Do they watch them have sex? Of course not, but everyone thinks that is what sex therapists do.

Dr. Brandon: Sex therapy is just like any other type of therapy, but we discuss sexual issues. And because just about anything that’s happening in your patient’s life can trickle down into the bedroom, we end up talking about a lot of stuff that’s not directly related to sex but ultimately impacts the patient’s sex life.

Dr. Rubin: It’s true. Most medical conditions that we treat — from diabetes, hypertension, high cholesterol, and obesity to depression and anxiety — are strongly correlated with sexual health. We treat the underlying condition, but our patients don’t care about their A1c levels. They care about the fact that they cannot get aroused; their genitals don’t feel the same way they used to.

Dr. Brandon: I love that point because people make meaning out of their sexual concerns and dysfunction. Suddenly their body isn’t responding the way it used to. They think something’s wrong with them, or maybe they are with the wrong partner. This meaning becomes very powerful in their mind and perpetuates the sexual problem.

Dr. Rubin: First and foremost, we are educators. We can say, “You have pretty out-of-control diabetes,” or, “You’re a smoker, which can affect the health of your genitals. Have you noticed any issues going on there?” If you don’t ask, patients will not bring up their concerns with their doctors.

So how do people find a sex therapist?

Dr. Brandon: There are a few fabulous organizations that provide on their websites ways to find a therapist: the American Association of Sex Educators, Counselors and Therapists (AASECT) and Sex Therapy and Research (STAR). Giving patients this information is a huge intervention.

Other places to find a therapist include the International Society for Sexual Medicine, and the International Society for the Study of Women’s Sexual Health.

Since COVID, many therapists have gone virtual. Encourage your patients to look within their states to find options for therapists and psychologists. Recent legislation allows psychologists who have signed up for PSYPACT to practice almost throughout the entire United States. We used to think if we didn’t have a therapist in the community, we couldn’t make a referral. That›s not the case anymore.

Dr. Rubin: All doctors are really sexual medicine doctors. We can change the whole world by giving our patients a better quality of life.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, disclosed ties to Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: We are here at the Harvard Continuing Medical Education Course in Orlando, Florida. It’s all about testosterone therapy and sexual medicine. I have with me today the wonderful Dr. Marianne Brandon, who is an amazing sex therapist. Could you introduce yourself?

Marianne Brandon, PhD: I am a clinical psychologist and sex therapist. I’ve been in practice for more than 25 years. I’m currently located in Sarasota. I have a Psychology Today blog called The Future of Intimacy, which I have a lot of fun with.

Dr. Rubin: It’s very important, when taking care of patients, that we work in a biopsychosocial model. Yes, we can fix erectile dysfunction. We can help with menopause symptoms and that helps sexual function. But what I find makes my patients able to live their best lives is when they have a team, including a mental health professional — often a sex therapist or a couples’ therapist — where they can learn communication skills. Why is it important for primary care doctors to talk to their patients about sex? My primary care doctor has never asked me about sex.  

Dr. Brandon: For most people, sexual intimacy is critical for their experience of life. It correlates with their relationship satisfaction and life satisfaction. It’s much bigger than what’s happening in the bedroom. People have more struggles than you realize. Sexual dysfunction correlates with emotional issues such as depression and anxiety, with medical problems, and with medication use. Chances are that your patients have some kind of sexual concern, even if that’s not to the degree that it would be classified as a sexual dysfunction.

But sexual concerns wreak havoc. Believing they have a sexual problem, they stop touching, they stop relating to their partner. It becomes a really big deal in their lives. If you can open the door for a conversation about sex with your patients, it could do them a great deal of good. It’s also good for the practitioner, because if your patients think they can talk with you about anything, that’s going to establish your relationship with them. Practitioners avoid these conversations because they don’t have the time or the training to offer help.

Dr. Rubin: You don’t have to know all the answers. You just have to show empathy and compassion and say, “I hear you.” That’s the magic in the doctor-patient relationship. We refer patients to specialists when we don’t know what to do. What happens when I send a patient to a sex therapist? Do they watch them have sex? Of course not, but everyone thinks that is what sex therapists do.

Dr. Brandon: Sex therapy is just like any other type of therapy, but we discuss sexual issues. And because just about anything that’s happening in your patient’s life can trickle down into the bedroom, we end up talking about a lot of stuff that’s not directly related to sex but ultimately impacts the patient’s sex life.

Dr. Rubin: It’s true. Most medical conditions that we treat — from diabetes, hypertension, high cholesterol, and obesity to depression and anxiety — are strongly correlated with sexual health. We treat the underlying condition, but our patients don’t care about their A1c levels. They care about the fact that they cannot get aroused; their genitals don’t feel the same way they used to.

Dr. Brandon: I love that point because people make meaning out of their sexual concerns and dysfunction. Suddenly their body isn’t responding the way it used to. They think something’s wrong with them, or maybe they are with the wrong partner. This meaning becomes very powerful in their mind and perpetuates the sexual problem.

Dr. Rubin: First and foremost, we are educators. We can say, “You have pretty out-of-control diabetes,” or, “You’re a smoker, which can affect the health of your genitals. Have you noticed any issues going on there?” If you don’t ask, patients will not bring up their concerns with their doctors.

So how do people find a sex therapist?

Dr. Brandon: There are a few fabulous organizations that provide on their websites ways to find a therapist: the American Association of Sex Educators, Counselors and Therapists (AASECT) and Sex Therapy and Research (STAR). Giving patients this information is a huge intervention.

Other places to find a therapist include the International Society for Sexual Medicine, and the International Society for the Study of Women’s Sexual Health.

Since COVID, many therapists have gone virtual. Encourage your patients to look within their states to find options for therapists and psychologists. Recent legislation allows psychologists who have signed up for PSYPACT to practice almost throughout the entire United States. We used to think if we didn’t have a therapist in the community, we couldn’t make a referral. That›s not the case anymore.

Dr. Rubin: All doctors are really sexual medicine doctors. We can change the whole world by giving our patients a better quality of life.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, disclosed ties to Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) embraced the use of biomarkers and surrogate endpoints in its most recent guidance on developing therapeutics for early Alzheimer’s disease.

The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.

It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.

In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”

The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.

Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
 

A New POV

The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.

In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element. 

In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.

“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted. 

The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).

“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”

However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals. 
 

A Faster Pathway to Approval 

The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”

Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures. 

Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.

The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.

The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added. 

Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.

The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.” 

“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) embraced the use of biomarkers and surrogate endpoints in its most recent guidance on developing therapeutics for early Alzheimer’s disease.

The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.

It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.

In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”

The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.

Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
 

A New POV

The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.

In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element. 

In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.

“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted. 

The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).

“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”

However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals. 
 

A Faster Pathway to Approval 

The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”

Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures. 

Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.

The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.

The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added. 

Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.

The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.” 

“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) embraced the use of biomarkers and surrogate endpoints in its most recent guidance on developing therapeutics for early Alzheimer’s disease.

The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.

It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.

In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”

The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.

Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
 

A New POV

The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.

In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element. 

In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.

“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted. 

The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).

“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”

However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals. 
 

A Faster Pathway to Approval 

The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”

Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures. 

Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.

The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.

The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added. 

Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.

The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.” 

“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.