Neurology

Medicinal and recreational marijuana use has become common across the country, warranting greater awareness among clinicians about any potential adverse effects of marijuana on brain health, a new American Heart Association scientific statement concludes.

The existing evidence base of preclinical and clinical research suggests that marijuana use may have a harmful effect on the brain, although the specific adverse effects have not been well defined, the statement authors said.

Smithore

Fernando D. Testai, MD, PhD, professor of neurology and rehabilitation at the University of Illinois at Chicago, led the writing panel for the statement, published online Feb. 10, 2022, in Stroke.

Numerous research studies challenge the idea that marijuana use is harmless, and instead demonstrate that cannabis, especially tetrahydrocannabinol (THC), has adverse effects on brain health, Dr. Testai and colleagues noted.

“Social media tends to overemphasize the beneficial effects of marijuana. However, its ultimate effect on brain health is still to be established. Physicians should provide periodic and unbiased education to their patients about the known and unknown ramifications of consuming cannabinoids,” Dr. Testai said.

Findings collected from animal studies demonstrate that THC interferes with normal development of signaling pathways and hinders synaptic plasticity. The authors also pointed out that these studies show connections between neurons are affected in the short term, whereas in the long haul, this contributes to changes in how neuronal networks work.

“Personally, the most striking point is the epidemiological data that indicate that the use of marijuana is widespread in the general population, and this starts early in life, particularly during adolescence,” Dr. Testai told this news organization.

Dr. Testai also noted that pregnant women are using cannabis for nausea and vomiting. Other data on prenatal exposure to cannabis show that THC hinders the signaling mechanism of the endocannabinoid system during development and ontogenesis, which ultimately leads to abnormal neurotransmission.

“Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the prefrontal cortex, limbic system, and ventral tegmentum of the midbrain,” the researchers added.

The writing panel also found that marijuana use had effects on human cognition:
 

• Acute marijuana use affects impulsivity, memory, and behavioral disinhibition, they noted, that “can affect performance in real-world activities,” such as driving. The long-term effects of cannabis on cognition are “less well established.”
• Neuroimaging research has highlighted structural changes in the brain, but these data are inconsistent.
• Functional MRI studies show cannabis users may experience functional changes in regions of the brain that play a role in cognition, particularly with prolonged use.

The statement also addresses studies assessing the effects of marijuana use on cerebrovascular risk and disease, which show:

• A relation between cannabis use and increased risk for stroke.
• Frequency and other trends of cannabis use may raise stroke risk.
• Cannabis users often smoke cigarettes, which is an important factor in the association between cannabis use and stroke risk.

Looking ahead, public health initiatives are needed to increase awareness among the public about the negative effects of marijuana use. Other efforts may include setting standards regarding the concentrations of biologically active ingredients and warning notices on available formulations, the group concluded.

The document was prepared on behalf of the AHA Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis, and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease.

The American Academy of Neurology “affirms the value of this statement as an educational tool for neurologists,” the document notes.

Dr. Testai reported no relevant financial relationships.

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

Medicinal and recreational marijuana use has become common across the country, warranting greater awareness among clinicians about any potential adverse effects of marijuana on brain health, a new American Heart Association scientific statement concludes.

The existing evidence base of preclinical and clinical research suggests that marijuana use may have a harmful effect on the brain, although the specific adverse effects have not been well defined, the statement authors said.

Smithore

Fernando D. Testai, MD, PhD, professor of neurology and rehabilitation at the University of Illinois at Chicago, led the writing panel for the statement, published online Feb. 10, 2022, in Stroke.

Numerous research studies challenge the idea that marijuana use is harmless, and instead demonstrate that cannabis, especially tetrahydrocannabinol (THC), has adverse effects on brain health, Dr. Testai and colleagues noted.

“Social media tends to overemphasize the beneficial effects of marijuana. However, its ultimate effect on brain health is still to be established. Physicians should provide periodic and unbiased education to their patients about the known and unknown ramifications of consuming cannabinoids,” Dr. Testai said.

Findings collected from animal studies demonstrate that THC interferes with normal development of signaling pathways and hinders synaptic plasticity. The authors also pointed out that these studies show connections between neurons are affected in the short term, whereas in the long haul, this contributes to changes in how neuronal networks work.

“Personally, the most striking point is the epidemiological data that indicate that the use of marijuana is widespread in the general population, and this starts early in life, particularly during adolescence,” Dr. Testai told this news organization.

Dr. Testai also noted that pregnant women are using cannabis for nausea and vomiting. Other data on prenatal exposure to cannabis show that THC hinders the signaling mechanism of the endocannabinoid system during development and ontogenesis, which ultimately leads to abnormal neurotransmission.

“Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the prefrontal cortex, limbic system, and ventral tegmentum of the midbrain,” the researchers added.

The writing panel also found that marijuana use had effects on human cognition:
 

• Acute marijuana use affects impulsivity, memory, and behavioral disinhibition, they noted, that “can affect performance in real-world activities,” such as driving. The long-term effects of cannabis on cognition are “less well established.”
• Neuroimaging research has highlighted structural changes in the brain, but these data are inconsistent.
• Functional MRI studies show cannabis users may experience functional changes in regions of the brain that play a role in cognition, particularly with prolonged use.

The statement also addresses studies assessing the effects of marijuana use on cerebrovascular risk and disease, which show:

• A relation between cannabis use and increased risk for stroke.
• Frequency and other trends of cannabis use may raise stroke risk.
• Cannabis users often smoke cigarettes, which is an important factor in the association between cannabis use and stroke risk.

Looking ahead, public health initiatives are needed to increase awareness among the public about the negative effects of marijuana use. Other efforts may include setting standards regarding the concentrations of biologically active ingredients and warning notices on available formulations, the group concluded.

The document was prepared on behalf of the AHA Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis, and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease.

The American Academy of Neurology “affirms the value of this statement as an educational tool for neurologists,” the document notes.

Dr. Testai reported no relevant financial relationships.

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

Medicinal and recreational marijuana use has become common across the country, warranting greater awareness among clinicians about any potential adverse effects of marijuana on brain health, a new American Heart Association scientific statement concludes.

The existing evidence base of preclinical and clinical research suggests that marijuana use may have a harmful effect on the brain, although the specific adverse effects have not been well defined, the statement authors said.

Smithore

Fernando D. Testai, MD, PhD, professor of neurology and rehabilitation at the University of Illinois at Chicago, led the writing panel for the statement, published online Feb. 10, 2022, in Stroke.

Numerous research studies challenge the idea that marijuana use is harmless, and instead demonstrate that cannabis, especially tetrahydrocannabinol (THC), has adverse effects on brain health, Dr. Testai and colleagues noted.

“Social media tends to overemphasize the beneficial effects of marijuana. However, its ultimate effect on brain health is still to be established. Physicians should provide periodic and unbiased education to their patients about the known and unknown ramifications of consuming cannabinoids,” Dr. Testai said.

Findings collected from animal studies demonstrate that THC interferes with normal development of signaling pathways and hinders synaptic plasticity. The authors also pointed out that these studies show connections between neurons are affected in the short term, whereas in the long haul, this contributes to changes in how neuronal networks work.

“Personally, the most striking point is the epidemiological data that indicate that the use of marijuana is widespread in the general population, and this starts early in life, particularly during adolescence,” Dr. Testai told this news organization.

Dr. Testai also noted that pregnant women are using cannabis for nausea and vomiting. Other data on prenatal exposure to cannabis show that THC hinders the signaling mechanism of the endocannabinoid system during development and ontogenesis, which ultimately leads to abnormal neurotransmission.

“Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the prefrontal cortex, limbic system, and ventral tegmentum of the midbrain,” the researchers added.

The writing panel also found that marijuana use had effects on human cognition:
 

• Acute marijuana use affects impulsivity, memory, and behavioral disinhibition, they noted, that “can affect performance in real-world activities,” such as driving. The long-term effects of cannabis on cognition are “less well established.”
• Neuroimaging research has highlighted structural changes in the brain, but these data are inconsistent.
• Functional MRI studies show cannabis users may experience functional changes in regions of the brain that play a role in cognition, particularly with prolonged use.

The statement also addresses studies assessing the effects of marijuana use on cerebrovascular risk and disease, which show:

• A relation between cannabis use and increased risk for stroke.
• Frequency and other trends of cannabis use may raise stroke risk.
• Cannabis users often smoke cigarettes, which is an important factor in the association between cannabis use and stroke risk.

Looking ahead, public health initiatives are needed to increase awareness among the public about the negative effects of marijuana use. Other efforts may include setting standards regarding the concentrations of biologically active ingredients and warning notices on available formulations, the group concluded.

The document was prepared on behalf of the AHA Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis, and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease.

The American Academy of Neurology “affirms the value of this statement as an educational tool for neurologists,” the document notes.

Dr. Testai reported no relevant financial relationships.

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

Seizure phobia occurs in nearly one-third of people with epilepsy (PWE), but was mainly associated with variables not related to epilepsy, based on data from 69 adults.

Anxiety and depression are known to affect quality of life in epilepsy patients, and previous studies have shown that anticipatory anxiety of epileptic seizures (AAS) was present in 53% of patients with focal epilepsy, wrote lead author Aviva Weiss of Psychiatric Hostels affiliated with Kidum Rehabilitation Projects, Jerusalem, and colleagues.

“Although recognized by the epilepsy and the psychiatric communities, seizure phobia as a distinct anxiety disorder among PWE is insufficiently described in the medical literature,” they said.

Seizure phobia has been defined as an anxiety disorder in which patients experience fear related to anticipation of seizures in certain situations.

In a study published in Seizure: European Journal of Epilepsy, the researchers recruited 69 PWE who were treated at an outpatient clinic. Data were collected from interviews, questionnaires, and medical records. The average age of the participants was 36.8 years, 41 were women, and 41 were married.

Overall, 19 individuals (27.5%) were diagnosed with seizure phobia. Compared with PWE without seizure phobia, the seizure phobia patients were significantly more likely to be women (84.2% vs. 44.2%; P = .005) and to have comorbid anxiety disorders (84.2% vs. 34.9%; P = .01). Individuals with seizure phobia also were significantly more likely than those without seizure phobia to have a past major depressive episode (63.2% vs. 20.9%; P = .003), and posttraumatic stress disorder (26.3% vs. 7%; P = .05).

Seizure phobia was significantly associated with comorbid psychogenic nonepileptic seizures (PNES) (36.8% vs. 11.6%; P = .034). PNES have been significantly associated with panic attacks, and “all patients with both panic attacks and comorbid PNES were diagnosed with seizure phobia,” the researchers noted. However, no significant association was found with epilepsy-related variables, they said.

A multivariate logistic regression model to predict seizure phobia showed that anxiety and a past MDE were significant predictors; the odds of seizure phobia were 10.45 times higher if a patient reported any anxiety disorder, and 6.85 times higher if the patient had a history of MDE.

The study findings were limited by several factors, including the use of semistructured interviews to diagnose seizure phobia, which are subject to interviewer bias, and by the small study population with a high proportion of comorbid PNES and epilepsy, the researchers noted. However, the results support seizure phobia as a distinct clinical entity worthy of management with education, psychosocial interventions, and potential medication changes, they said.

“Development of appropriate screening tools and implementation of effective treatment interventions is warranted for individual patients, combined with large-scale population-targeted psychoeducation, aimed to mitigate the risk of developing seizure phobia in PWE,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Seizure phobia occurs in nearly one-third of people with epilepsy (PWE), but was mainly associated with variables not related to epilepsy, based on data from 69 adults.

Anxiety and depression are known to affect quality of life in epilepsy patients, and previous studies have shown that anticipatory anxiety of epileptic seizures (AAS) was present in 53% of patients with focal epilepsy, wrote lead author Aviva Weiss of Psychiatric Hostels affiliated with Kidum Rehabilitation Projects, Jerusalem, and colleagues.

“Although recognized by the epilepsy and the psychiatric communities, seizure phobia as a distinct anxiety disorder among PWE is insufficiently described in the medical literature,” they said.

Seizure phobia has been defined as an anxiety disorder in which patients experience fear related to anticipation of seizures in certain situations.

In a study published in Seizure: European Journal of Epilepsy, the researchers recruited 69 PWE who were treated at an outpatient clinic. Data were collected from interviews, questionnaires, and medical records. The average age of the participants was 36.8 years, 41 were women, and 41 were married.

Overall, 19 individuals (27.5%) were diagnosed with seizure phobia. Compared with PWE without seizure phobia, the seizure phobia patients were significantly more likely to be women (84.2% vs. 44.2%; P = .005) and to have comorbid anxiety disorders (84.2% vs. 34.9%; P = .01). Individuals with seizure phobia also were significantly more likely than those without seizure phobia to have a past major depressive episode (63.2% vs. 20.9%; P = .003), and posttraumatic stress disorder (26.3% vs. 7%; P = .05).

Seizure phobia was significantly associated with comorbid psychogenic nonepileptic seizures (PNES) (36.8% vs. 11.6%; P = .034). PNES have been significantly associated with panic attacks, and “all patients with both panic attacks and comorbid PNES were diagnosed with seizure phobia,” the researchers noted. However, no significant association was found with epilepsy-related variables, they said.

A multivariate logistic regression model to predict seizure phobia showed that anxiety and a past MDE were significant predictors; the odds of seizure phobia were 10.45 times higher if a patient reported any anxiety disorder, and 6.85 times higher if the patient had a history of MDE.

The study findings were limited by several factors, including the use of semistructured interviews to diagnose seizure phobia, which are subject to interviewer bias, and by the small study population with a high proportion of comorbid PNES and epilepsy, the researchers noted. However, the results support seizure phobia as a distinct clinical entity worthy of management with education, psychosocial interventions, and potential medication changes, they said.

“Development of appropriate screening tools and implementation of effective treatment interventions is warranted for individual patients, combined with large-scale population-targeted psychoeducation, aimed to mitigate the risk of developing seizure phobia in PWE,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Seizure phobia occurs in nearly one-third of people with epilepsy (PWE), but was mainly associated with variables not related to epilepsy, based on data from 69 adults.

Anxiety and depression are known to affect quality of life in epilepsy patients, and previous studies have shown that anticipatory anxiety of epileptic seizures (AAS) was present in 53% of patients with focal epilepsy, wrote lead author Aviva Weiss of Psychiatric Hostels affiliated with Kidum Rehabilitation Projects, Jerusalem, and colleagues.

“Although recognized by the epilepsy and the psychiatric communities, seizure phobia as a distinct anxiety disorder among PWE is insufficiently described in the medical literature,” they said.

Seizure phobia has been defined as an anxiety disorder in which patients experience fear related to anticipation of seizures in certain situations.

In a study published in Seizure: European Journal of Epilepsy, the researchers recruited 69 PWE who were treated at an outpatient clinic. Data were collected from interviews, questionnaires, and medical records. The average age of the participants was 36.8 years, 41 were women, and 41 were married.

Overall, 19 individuals (27.5%) were diagnosed with seizure phobia. Compared with PWE without seizure phobia, the seizure phobia patients were significantly more likely to be women (84.2% vs. 44.2%; P = .005) and to have comorbid anxiety disorders (84.2% vs. 34.9%; P = .01). Individuals with seizure phobia also were significantly more likely than those without seizure phobia to have a past major depressive episode (63.2% vs. 20.9%; P = .003), and posttraumatic stress disorder (26.3% vs. 7%; P = .05).

Seizure phobia was significantly associated with comorbid psychogenic nonepileptic seizures (PNES) (36.8% vs. 11.6%; P = .034). PNES have been significantly associated with panic attacks, and “all patients with both panic attacks and comorbid PNES were diagnosed with seizure phobia,” the researchers noted. However, no significant association was found with epilepsy-related variables, they said.

A multivariate logistic regression model to predict seizure phobia showed that anxiety and a past MDE were significant predictors; the odds of seizure phobia were 10.45 times higher if a patient reported any anxiety disorder, and 6.85 times higher if the patient had a history of MDE.

The study findings were limited by several factors, including the use of semistructured interviews to diagnose seizure phobia, which are subject to interviewer bias, and by the small study population with a high proportion of comorbid PNES and epilepsy, the researchers noted. However, the results support seizure phobia as a distinct clinical entity worthy of management with education, psychosocial interventions, and potential medication changes, they said.

“Development of appropriate screening tools and implementation of effective treatment interventions is warranted for individual patients, combined with large-scale population-targeted psychoeducation, aimed to mitigate the risk of developing seizure phobia in PWE,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

The International League Against Epilepsy (ILAE) has issued recommendations for treating depression in patients with epilepsy.

The new guidance highlights the high prevalence of depression among patients with epilepsy while offering the first systematic approach to treatment, reported lead author Marco Mula, MD, PhD, of Atkinson Morley Regional Neuroscience Centre at St George’s University Hospital, London, and colleagues.

“Despite evidence that depression represents a frequently encountered comorbidity [among patients with epilepsy], data on the treatment of depression in epilepsy [are] still limited and recommendations rely mostly on individual clinical experience and expertise,” the investigators wrote in Epilepsia.

Recommendations cover first-line treatment of unipolar depression in epilepsy without other psychiatric disorders.

For patients with mild depression, the guidance supports psychological intervention without pharmacologic therapy; however, if the patient wishes to use medication, has had a positive response to medication in the past, or nonpharmacologic treatments have previously failed or are unavailable, then SSRIs should be considered first-choice therapy. For moderate to severe depression, SSRIs are the first choice, according to Dr. Mula and colleagues.

“It has to be acknowledged that there is considerable debate in the psychiatric literature about the treatment of mild depression in adults,” the investigators noted. “A patient-level meta-analysis pointed out that the magnitude of benefit of antidepressant medications compared with placebo increases with severity of depression symptoms and it may be minimal or nonexistent, on average, in patients with mild or moderate symptoms.”

If a patient does not respond to first-line therapy, then venlafaxine should be considered, according to the guidance. When a patient does respond to therapy, treatment should be continued for at least 6 months, and when residual symptoms persist, treatment should be continued until resolution.

“In people with depression it is established that around two-thirds of patients do not achieve full remission with first-line treatment,” Dr. Mula and colleagues wrote. “In people with epilepsy, current data show that up to 50% of patients do not achieve full remission from depression. For this reason, augmentation strategies are often needed. They should be adopted by psychiatrists, neuropsychiatrists, or mental health professionals familiar with such therapeutic strategies.”

Beyond these key recommendations, the guidance covers a range of additional topics, including other pharmacologic options, medication discontinuation strategies, electroconvulsive therapy, light therapy, exercise training, vagus nerve stimulation, and repetitive transcranial magnetic stimulation.
 

Useful advice that counters common misconceptions

According to Jacqueline A. French, MD, a professor at NYU Langone Medical Center, Dr. Mula and colleagues are “top notch,” and their recommendations “hit every nail on the head.”

Dr. French, chief medical officer of The Epilepsy Foundation, emphasized the importance of the publication, which addresses two common misconceptions within the medical community: First, that standard antidepressants are insufficient to treat depression in patients with epilepsy, and second, that antidepressants may trigger seizures.

“The first purpose [of the publication] is to say, yes, these antidepressants do work,” Dr. French said, “and no, they don’t worsen seizures, and you can use them safely, and they are appropriate to use.”

Dr. French explained that managing depression remains a practice gap among epileptologists and neurologists because it is a diagnosis that doesn’t traditionally fall into their purview, yet many patients with epilepsy forgo visiting their primary care providers, who more frequently diagnose and manage depression. Dr. French agreed with the guidance that epilepsy specialists should fill this gap.

“We need to at least be able to take people through their first antidepressant, even though we were not trained to be psychiatrists,” Dr. French said. “That’s part of the best care of our patients.”

Imad Najm, MD, director of the Charles Shor Epilepsy Center, Cleveland Clinic, said the recommendations are a step forward in the field, as they are supported by clinical data, instead of just clinical experience and expertise.

Still, Dr. Najm noted that more work is needed to stratify risk of depression in epilepsy and evaluate a possible causal relationship between epilepsy therapies and depression.

He went on to emphasizes the scale of issue at hand, and the stakes involved.

“Depression, anxiety, and psychosis affect a large number of patients with epilepsy,” Dr. Najm said. “Clinical screening and recognition of these comorbidities leads to the institution of treatment options and significant improvement in quality of life. Mental health professionals should be an integral part of any comprehensive epilepsy center.”

The investigators disclosed relationships with Esai, UCB, Elsevier, and others. Dr. French is indirectly involved with multiple pharmaceutical companies developing epilepsy drugs through her role as director of The Epilepsy Study Consortium, a nonprofit organization. Dr. Najm reported no conflicts of interest.

The International League Against Epilepsy (ILAE) has issued recommendations for treating depression in patients with epilepsy.

The new guidance highlights the high prevalence of depression among patients with epilepsy while offering the first systematic approach to treatment, reported lead author Marco Mula, MD, PhD, of Atkinson Morley Regional Neuroscience Centre at St George’s University Hospital, London, and colleagues.

“Despite evidence that depression represents a frequently encountered comorbidity [among patients with epilepsy], data on the treatment of depression in epilepsy [are] still limited and recommendations rely mostly on individual clinical experience and expertise,” the investigators wrote in Epilepsia.

Recommendations cover first-line treatment of unipolar depression in epilepsy without other psychiatric disorders.

For patients with mild depression, the guidance supports psychological intervention without pharmacologic therapy; however, if the patient wishes to use medication, has had a positive response to medication in the past, or nonpharmacologic treatments have previously failed or are unavailable, then SSRIs should be considered first-choice therapy. For moderate to severe depression, SSRIs are the first choice, according to Dr. Mula and colleagues.

“It has to be acknowledged that there is considerable debate in the psychiatric literature about the treatment of mild depression in adults,” the investigators noted. “A patient-level meta-analysis pointed out that the magnitude of benefit of antidepressant medications compared with placebo increases with severity of depression symptoms and it may be minimal or nonexistent, on average, in patients with mild or moderate symptoms.”

If a patient does not respond to first-line therapy, then venlafaxine should be considered, according to the guidance. When a patient does respond to therapy, treatment should be continued for at least 6 months, and when residual symptoms persist, treatment should be continued until resolution.

“In people with depression it is established that around two-thirds of patients do not achieve full remission with first-line treatment,” Dr. Mula and colleagues wrote. “In people with epilepsy, current data show that up to 50% of patients do not achieve full remission from depression. For this reason, augmentation strategies are often needed. They should be adopted by psychiatrists, neuropsychiatrists, or mental health professionals familiar with such therapeutic strategies.”

Beyond these key recommendations, the guidance covers a range of additional topics, including other pharmacologic options, medication discontinuation strategies, electroconvulsive therapy, light therapy, exercise training, vagus nerve stimulation, and repetitive transcranial magnetic stimulation.
 

Useful advice that counters common misconceptions

According to Jacqueline A. French, MD, a professor at NYU Langone Medical Center, Dr. Mula and colleagues are “top notch,” and their recommendations “hit every nail on the head.”

Dr. French, chief medical officer of The Epilepsy Foundation, emphasized the importance of the publication, which addresses two common misconceptions within the medical community: First, that standard antidepressants are insufficient to treat depression in patients with epilepsy, and second, that antidepressants may trigger seizures.

“The first purpose [of the publication] is to say, yes, these antidepressants do work,” Dr. French said, “and no, they don’t worsen seizures, and you can use them safely, and they are appropriate to use.”

Dr. French explained that managing depression remains a practice gap among epileptologists and neurologists because it is a diagnosis that doesn’t traditionally fall into their purview, yet many patients with epilepsy forgo visiting their primary care providers, who more frequently diagnose and manage depression. Dr. French agreed with the guidance that epilepsy specialists should fill this gap.

“We need to at least be able to take people through their first antidepressant, even though we were not trained to be psychiatrists,” Dr. French said. “That’s part of the best care of our patients.”

Imad Najm, MD, director of the Charles Shor Epilepsy Center, Cleveland Clinic, said the recommendations are a step forward in the field, as they are supported by clinical data, instead of just clinical experience and expertise.

Still, Dr. Najm noted that more work is needed to stratify risk of depression in epilepsy and evaluate a possible causal relationship between epilepsy therapies and depression.

He went on to emphasizes the scale of issue at hand, and the stakes involved.

“Depression, anxiety, and psychosis affect a large number of patients with epilepsy,” Dr. Najm said. “Clinical screening and recognition of these comorbidities leads to the institution of treatment options and significant improvement in quality of life. Mental health professionals should be an integral part of any comprehensive epilepsy center.”

The investigators disclosed relationships with Esai, UCB, Elsevier, and others. Dr. French is indirectly involved with multiple pharmaceutical companies developing epilepsy drugs through her role as director of The Epilepsy Study Consortium, a nonprofit organization. Dr. Najm reported no conflicts of interest.

The International League Against Epilepsy (ILAE) has issued recommendations for treating depression in patients with epilepsy.

The new guidance highlights the high prevalence of depression among patients with epilepsy while offering the first systematic approach to treatment, reported lead author Marco Mula, MD, PhD, of Atkinson Morley Regional Neuroscience Centre at St George’s University Hospital, London, and colleagues.

“Despite evidence that depression represents a frequently encountered comorbidity [among patients with epilepsy], data on the treatment of depression in epilepsy [are] still limited and recommendations rely mostly on individual clinical experience and expertise,” the investigators wrote in Epilepsia.

Recommendations cover first-line treatment of unipolar depression in epilepsy without other psychiatric disorders.

For patients with mild depression, the guidance supports psychological intervention without pharmacologic therapy; however, if the patient wishes to use medication, has had a positive response to medication in the past, or nonpharmacologic treatments have previously failed or are unavailable, then SSRIs should be considered first-choice therapy. For moderate to severe depression, SSRIs are the first choice, according to Dr. Mula and colleagues.

“It has to be acknowledged that there is considerable debate in the psychiatric literature about the treatment of mild depression in adults,” the investigators noted. “A patient-level meta-analysis pointed out that the magnitude of benefit of antidepressant medications compared with placebo increases with severity of depression symptoms and it may be minimal or nonexistent, on average, in patients with mild or moderate symptoms.”

If a patient does not respond to first-line therapy, then venlafaxine should be considered, according to the guidance. When a patient does respond to therapy, treatment should be continued for at least 6 months, and when residual symptoms persist, treatment should be continued until resolution.

“In people with depression it is established that around two-thirds of patients do not achieve full remission with first-line treatment,” Dr. Mula and colleagues wrote. “In people with epilepsy, current data show that up to 50% of patients do not achieve full remission from depression. For this reason, augmentation strategies are often needed. They should be adopted by psychiatrists, neuropsychiatrists, or mental health professionals familiar with such therapeutic strategies.”

Beyond these key recommendations, the guidance covers a range of additional topics, including other pharmacologic options, medication discontinuation strategies, electroconvulsive therapy, light therapy, exercise training, vagus nerve stimulation, and repetitive transcranial magnetic stimulation.
 

Useful advice that counters common misconceptions

According to Jacqueline A. French, MD, a professor at NYU Langone Medical Center, Dr. Mula and colleagues are “top notch,” and their recommendations “hit every nail on the head.”

Dr. French, chief medical officer of The Epilepsy Foundation, emphasized the importance of the publication, which addresses two common misconceptions within the medical community: First, that standard antidepressants are insufficient to treat depression in patients with epilepsy, and second, that antidepressants may trigger seizures.

“The first purpose [of the publication] is to say, yes, these antidepressants do work,” Dr. French said, “and no, they don’t worsen seizures, and you can use them safely, and they are appropriate to use.”

Dr. French explained that managing depression remains a practice gap among epileptologists and neurologists because it is a diagnosis that doesn’t traditionally fall into their purview, yet many patients with epilepsy forgo visiting their primary care providers, who more frequently diagnose and manage depression. Dr. French agreed with the guidance that epilepsy specialists should fill this gap.

“We need to at least be able to take people through their first antidepressant, even though we were not trained to be psychiatrists,” Dr. French said. “That’s part of the best care of our patients.”

Imad Najm, MD, director of the Charles Shor Epilepsy Center, Cleveland Clinic, said the recommendations are a step forward in the field, as they are supported by clinical data, instead of just clinical experience and expertise.

Still, Dr. Najm noted that more work is needed to stratify risk of depression in epilepsy and evaluate a possible causal relationship between epilepsy therapies and depression.

He went on to emphasizes the scale of issue at hand, and the stakes involved.

“Depression, anxiety, and psychosis affect a large number of patients with epilepsy,” Dr. Najm said. “Clinical screening and recognition of these comorbidities leads to the institution of treatment options and significant improvement in quality of life. Mental health professionals should be an integral part of any comprehensive epilepsy center.”

The investigators disclosed relationships with Esai, UCB, Elsevier, and others. Dr. French is indirectly involved with multiple pharmaceutical companies developing epilepsy drugs through her role as director of The Epilepsy Study Consortium, a nonprofit organization. Dr. Najm reported no conflicts of interest.

The Centers for Disease Control and Prevention and the American Academy of Pediatrics recently issued revised milestone guidelines for their developmental surveillance campaign, Learn the Signs, Act Early (LTSAE).

The new guidelines, published in Pediatrics, were drafted in “easy-to-understand” language and identify the behaviors that 75% or more of children should exhibit at certain ages based on developmental resources, existing data, and clinician experience. The previous milestone checklists, developed in 2004, used 50th percentile or average-age milestones.

The CDC, in collaboration with the AAP, convened a group of eight subject matter experts in various fields of child development, including a developmental pediatrician and researcher from Kennedy Krieger Institute, to develop new and clearer guidelines.

“The goals of the group were to identify evidence-informed milestones to include in CDC checklists, clarify when most children can be expected to reach a milestone (to discourage a wait-and-see approach), and support clinical judgment regarding screening between recommended ages,” wrote lead author Jennifer M. Zubler, MD, of the National Center on Birth Defects and Developmental Disabilities in Atlanta, and colleagues.
 

Key changes

The experts established 11 criteria for CDC surveillance milestones and tools, including milestones most children (75% or more) would be expected to reach by defined health supervision visit ages and those that are easily recognized in natural settings.

Criteria for developmental milestones and surveillance tools:

• Milestones are included at the age most (≥75%) children would be expected to demonstrate the milestone.
• Eliminate “warning signs.”
• Are easy for families of different social, cultural, and ethnic backgrounds to observe and use.
• Are able to be answered with yes, not yet, or not sure.
• Use plain language, avoiding vague terms like may, can, and begins.
• Are organized in developmental domains.
• Show progression of skills with age, when possible.
• Milestones are not repeated across checklists.
• Include open-ended questions.
• Include information for developmental promotion.
• Include information on how to act early if there are concerns.

The previous guidelines were critiqued by some clinicians as being “not helpful to individual families who had concerns about their child’s development,” and in some cases, led to delays in diagnoses as decision-makers opted for a “wait-and-see approach.”

“The earlier a child is identified with a developmental delay the better, as treatment as well as learning interventions can begin,” Paul Lipkin, MD, an associate professor of pediatrics at the Johns Hopkins University, Baltimore, said in an accompanying press release. “Revising the guidelines with expertise and data from clinicians in the field accomplishes these goals.”

Additional changes included new checklists for children between the ages of 15 and 30 months, additional social and emotional milestones, as well as the removal of complex language and duplicate milestones. The experts also developed new, open-ended questions to aid discussions with families.

“Review of a child’s development with these milestones opens up a continuous dialogue between a parent and the health care provider about their child’s present and future development,” said Dr. Lipkin.

Originally pioneered in 2005, the LTSAE awareness campaign provides free resources to clinicians and families to support early detection of children with developmental delays and disabilities. After the new guidelines were drafted, they were presented to parents of various racial groups, income levels, and educational backgrounds to confirm ease of use and understandability.

“These criteria and revised checklists can be used to support developmental surveillance, clinical judgment regarding additional developmental screening, and research in developmental surveillance processes,” wrote Dr. Zubler.
 

Expert perspective

“These new guidelines will allow us to catch more children with developmental delays as they raise the threshold to 75% of children achieving those milestones at that particular age,” Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview.

Dr. Kinsella added that the new guidelines simplify the milestones and reduce redundancy across different developmental domains. “Most importantly, it gave me the opportunity to see just how great the CDC milestone tracker app is – I think parents would really like it.”

This project was supported by the CDC and Prevention of the Department of Health & Human Services. One author is a developer of the Ages & Stages Questionnaires and receives royalties from Brookes Publishing, the company that publishes this tool; the other authors have indicated they have no relevant conflicts of interest to disclose.

The Centers for Disease Control and Prevention and the American Academy of Pediatrics recently issued revised milestone guidelines for their developmental surveillance campaign, Learn the Signs, Act Early (LTSAE).

The new guidelines, published in Pediatrics, were drafted in “easy-to-understand” language and identify the behaviors that 75% or more of children should exhibit at certain ages based on developmental resources, existing data, and clinician experience. The previous milestone checklists, developed in 2004, used 50th percentile or average-age milestones.

The CDC, in collaboration with the AAP, convened a group of eight subject matter experts in various fields of child development, including a developmental pediatrician and researcher from Kennedy Krieger Institute, to develop new and clearer guidelines.

“The goals of the group were to identify evidence-informed milestones to include in CDC checklists, clarify when most children can be expected to reach a milestone (to discourage a wait-and-see approach), and support clinical judgment regarding screening between recommended ages,” wrote lead author Jennifer M. Zubler, MD, of the National Center on Birth Defects and Developmental Disabilities in Atlanta, and colleagues.
 

Key changes

The experts established 11 criteria for CDC surveillance milestones and tools, including milestones most children (75% or more) would be expected to reach by defined health supervision visit ages and those that are easily recognized in natural settings.

Criteria for developmental milestones and surveillance tools:

• Milestones are included at the age most (≥75%) children would be expected to demonstrate the milestone.
• Eliminate “warning signs.”
• Are easy for families of different social, cultural, and ethnic backgrounds to observe and use.
• Are able to be answered with yes, not yet, or not sure.
• Use plain language, avoiding vague terms like may, can, and begins.
• Are organized in developmental domains.
• Show progression of skills with age, when possible.
• Milestones are not repeated across checklists.
• Include open-ended questions.
• Include information for developmental promotion.
• Include information on how to act early if there are concerns.

The previous guidelines were critiqued by some clinicians as being “not helpful to individual families who had concerns about their child’s development,” and in some cases, led to delays in diagnoses as decision-makers opted for a “wait-and-see approach.”

“The earlier a child is identified with a developmental delay the better, as treatment as well as learning interventions can begin,” Paul Lipkin, MD, an associate professor of pediatrics at the Johns Hopkins University, Baltimore, said in an accompanying press release. “Revising the guidelines with expertise and data from clinicians in the field accomplishes these goals.”

Additional changes included new checklists for children between the ages of 15 and 30 months, additional social and emotional milestones, as well as the removal of complex language and duplicate milestones. The experts also developed new, open-ended questions to aid discussions with families.

“Review of a child’s development with these milestones opens up a continuous dialogue between a parent and the health care provider about their child’s present and future development,” said Dr. Lipkin.

Originally pioneered in 2005, the LTSAE awareness campaign provides free resources to clinicians and families to support early detection of children with developmental delays and disabilities. After the new guidelines were drafted, they were presented to parents of various racial groups, income levels, and educational backgrounds to confirm ease of use and understandability.

“These criteria and revised checklists can be used to support developmental surveillance, clinical judgment regarding additional developmental screening, and research in developmental surveillance processes,” wrote Dr. Zubler.
 

Expert perspective

“These new guidelines will allow us to catch more children with developmental delays as they raise the threshold to 75% of children achieving those milestones at that particular age,” Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview.

Dr. Kinsella added that the new guidelines simplify the milestones and reduce redundancy across different developmental domains. “Most importantly, it gave me the opportunity to see just how great the CDC milestone tracker app is – I think parents would really like it.”

This project was supported by the CDC and Prevention of the Department of Health & Human Services. One author is a developer of the Ages & Stages Questionnaires and receives royalties from Brookes Publishing, the company that publishes this tool; the other authors have indicated they have no relevant conflicts of interest to disclose.

The Centers for Disease Control and Prevention and the American Academy of Pediatrics recently issued revised milestone guidelines for their developmental surveillance campaign, Learn the Signs, Act Early (LTSAE).

The new guidelines, published in Pediatrics, were drafted in “easy-to-understand” language and identify the behaviors that 75% or more of children should exhibit at certain ages based on developmental resources, existing data, and clinician experience. The previous milestone checklists, developed in 2004, used 50th percentile or average-age milestones.

The CDC, in collaboration with the AAP, convened a group of eight subject matter experts in various fields of child development, including a developmental pediatrician and researcher from Kennedy Krieger Institute, to develop new and clearer guidelines.

“The goals of the group were to identify evidence-informed milestones to include in CDC checklists, clarify when most children can be expected to reach a milestone (to discourage a wait-and-see approach), and support clinical judgment regarding screening between recommended ages,” wrote lead author Jennifer M. Zubler, MD, of the National Center on Birth Defects and Developmental Disabilities in Atlanta, and colleagues.
 

Key changes

The experts established 11 criteria for CDC surveillance milestones and tools, including milestones most children (75% or more) would be expected to reach by defined health supervision visit ages and those that are easily recognized in natural settings.

Criteria for developmental milestones and surveillance tools:

• Milestones are included at the age most (≥75%) children would be expected to demonstrate the milestone.
• Eliminate “warning signs.”
• Are easy for families of different social, cultural, and ethnic backgrounds to observe and use.
• Are able to be answered with yes, not yet, or not sure.
• Use plain language, avoiding vague terms like may, can, and begins.
• Are organized in developmental domains.
• Show progression of skills with age, when possible.
• Milestones are not repeated across checklists.
• Include open-ended questions.
• Include information for developmental promotion.
• Include information on how to act early if there are concerns.

The previous guidelines were critiqued by some clinicians as being “not helpful to individual families who had concerns about their child’s development,” and in some cases, led to delays in diagnoses as decision-makers opted for a “wait-and-see approach.”

“The earlier a child is identified with a developmental delay the better, as treatment as well as learning interventions can begin,” Paul Lipkin, MD, an associate professor of pediatrics at the Johns Hopkins University, Baltimore, said in an accompanying press release. “Revising the guidelines with expertise and data from clinicians in the field accomplishes these goals.”

Additional changes included new checklists for children between the ages of 15 and 30 months, additional social and emotional milestones, as well as the removal of complex language and duplicate milestones. The experts also developed new, open-ended questions to aid discussions with families.

“Review of a child’s development with these milestones opens up a continuous dialogue between a parent and the health care provider about their child’s present and future development,” said Dr. Lipkin.

Originally pioneered in 2005, the LTSAE awareness campaign provides free resources to clinicians and families to support early detection of children with developmental delays and disabilities. After the new guidelines were drafted, they were presented to parents of various racial groups, income levels, and educational backgrounds to confirm ease of use and understandability.

“These criteria and revised checklists can be used to support developmental surveillance, clinical judgment regarding additional developmental screening, and research in developmental surveillance processes,” wrote Dr. Zubler.
 

Expert perspective

“These new guidelines will allow us to catch more children with developmental delays as they raise the threshold to 75% of children achieving those milestones at that particular age,” Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview.

Dr. Kinsella added that the new guidelines simplify the milestones and reduce redundancy across different developmental domains. “Most importantly, it gave me the opportunity to see just how great the CDC milestone tracker app is – I think parents would really like it.”

This project was supported by the CDC and Prevention of the Department of Health & Human Services. One author is a developer of the Ages & Stages Questionnaires and receives royalties from Brookes Publishing, the company that publishes this tool; the other authors have indicated they have no relevant conflicts of interest to disclose.

All-cause mortality is significantly higher for individuals with autism spectrum disorder or attention-deficit/hyperactivity disorder than for the general population, based on data from more than 600,000 individuals.

Studies of individuals with mental disorders have suggested an increased mortality risk, compared with the general population, but similar studies of individuals with autism spectrum disorder (ASD) or ADHD have yielded inconsistent results, Ferrán Catalá-López, PhD, of the Institute of Health Carlos III, Madrid, and colleagues wrote.

In a systematic review and meta-analysis published in JAMA Pediatrics, the researchers examined 27 studies including 642,260 individuals; 154,238 with ASD and 396,488 with ADHD. The studies were published up to April 1, 2021, and included deaths from natural causes (such as respiratory illness or cancer) and unnatural (external) causes, such as accident, injury, or poisoning. The proportion of females in the studies ranged from 14% to 100%; the follow-up ranged from 3 to 33 years; and three studies included first-degree relatives.

Overall, all-cause mortality was significantly higher among individuals with ASD (rate ratio, 2.37) and ADHD (RR, 2.13), compared with the general population. Among individuals with ASD, deaths from natural causes and unnatural causes were significantly increased, compared with the general population (RR, 3.80 and RR, 2.50, respectively). Among individuals with ADHD, deaths from natural causes were not significantly increased (RR, 1.62), but deaths from unnatural causes were significantly increased, compared with the general population (RR, 2.81).

Potential mechanisms to explain the excess mortality among individuals with ASD and ADHD include health determinants and biological pathways, but the complex nature of the associations make the establishment of causality a challenge, the researchers wrote in their discussion of the findings. In general, “severe mental and behavioral disorders appear to be associated with reduced life expectancy, both in terms of mortality from external causes and mortality from other medical conditions or diseases.” With regard to ASD/ADHD in particular, these individuals often experience emotional and social problems as they enter adulthood. “Behaviors such as impulsivity and/or inattention can be contributing factors for injuries and unintentional incidents in children with ASD/ADHD,” they added.

The study findings were limited by several factors including the possible omission of studies and the use of study-level data rather than individual participant data, as well as the limitation of electronic health records, the researchers noted. Also, the studies were mostly conducted in Western countries and the results may not be generalizable to other countries.

Although ASD and ADHD were associated with a significant increased risk of all-cause mortality, “the results should be interpreted with caution because there was evidence of heterogeneity between study estimates of the mortality risks,” the researchers said. However, the results were strengthened by the large study sample, and offer a comprehensive look at the evidence supporting increased mortality risk among individuals with ASD or ADHD, and highlight the need to identify modifiable risk factors.

“Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups of children and young people as an approach to improve public health,” they said.
 

Recent research support associations

The study was important because ASD and ADHD may persist into adulthood, but data from previous epidemiological studies on the impact of these disorders on mortality are inconsistent, lead author Dr. Catalá-López said in an interview.

“We conducted a systematic review and meta-analysis to evaluate all available studies of mortality associations in people with these disorders, which provide the most updated and evidence-based approach,” he explained. “Our study has only become possible in the past few years because several large population-based epidemiological studies have been available reporting similar mortality-related outcomes.”

Dr. Catalá-López said that the study findings have value in clinical practice. “We found that people with autism or attention-deficit/hyperactivity disorders would have an increased risk of mortality when compared to the general population. In our opinion, understanding the causes and mechanisms of these associations can lead to specific strategies to prevent avoidable deaths.

“Autism and attention-hyperactivity/deficit disorder are problems that can be managed with adequate and concrete programs at an early age, and most premature deaths, at least deaths from unnatural causes, can be prevented,” Dr. Catalá-López said.

“Furthermore, we believe that these results may shed some light for future research. For example, more prospective studies would be needed, particularly to examine cause-specific mortality, in larger populations of children and youth with autism/attention-deficit/hyperactivity disorder, including some of the more common comorbidities,” Dr. Catalá-López added.
 

Findings support need for screening and prevention strategies

The clear message that individuals with ASD or ADHD often die of preventable or unnatural causes demands attention and “demands widespread recognition and the implementation of systematic screening and preventive approaches,” Russell A. Barkley, PhD, of Virginia Commonwealth University, Richmond, and Geraldine Dawson, PhD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

The studies included in the review also demonstrate that ADHD is associated with more than a twofold risk of early mortality in children and a more than a fourfold risk in mortality by age 45 years, they said.

The editorialists noted that the increased mortality risk may explain the ongoing conundrum among clinicians as to why the prevalence of ADHD seems to decline with age, “such that 5%-8% of children may meet diagnostic criteria for ADHD while that figure falls to 4%-5% of adults and 2%-3% of older adults,” despite evidence that a majority of childhood cases will be rediagnosed in adulthood. However, the current study offers an alternative. “This systematic review and meta-analysis and the studies included within it make plain that another explanation is the greater loss of individuals with these conditions from the population over time owing to heightened mortality, compared with typical peers,” they said.

“In addition to ADHD diagnosis, ASD diagnosis is also associated with other psychiatric comorbidities that are correlated with increased risk for mortality, including anxiety and affective disorders,” the editorialists noted. Other considerations for increased mortality among individuals with ASD include different protective and risk factors associated with suicide risk, compared with the general population, as well as poorer social and daily living skills compared to the general population.

The study findings “argue for individuals with ADHD and individuals with ASD being viewed through a public health lens with screening and prevention strategies offered beginning in early childhood. These findings should also give impetus to efforts to try to reduce the first order risk factors that are predisposing to reduced life expectancy, such as obesity, substance use, poor diet, poor sleep, and limited exercise among children and adults with ASD and ADHD,” they said.

“A preventive strategy would necessitate primary care physicians becoming more aware of the linkage between both ASD diagnosis and ADHD diagnosis and early mortality as well as their link to reduced [estimated life expectancy],” and such an approach could potentially reduce the higher mortality risk identified in the current review, they concluded.

Dr. Barkley reported speaking and other fees from Takeda, Medice Pharmaceutical, and AstraZeneca; book royalties from Guilford Publications and the American Psychological Association; and course royalties from ContiningEdCourses.net and Premier Educational Seminars. Dr. Dawson reported grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health during the submitted work and personal fees from Apple. Dr. Dawson also disclosed a patent for license to Apple, and Dr. Dawson and Duke University have benefited financially from technology and data that have been licensed to Apple. The study was supported by the Institute of Health Carlos III and Generalitat Valenciana. Researchers including lead author Dr. Catalá-López received funding from sources including the Centro de Investigación Biomédica en Red de Salud Mental; one coauthor received support from an Australian Research Council Discovery Early Career Researcher Award, a new investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network, the Spanish Health Services Research on Chronic Patients Network, and Institute of Health Carlos III. The researchers had no financial conflicts to disclose.

All-cause mortality is significantly higher for individuals with autism spectrum disorder or attention-deficit/hyperactivity disorder than for the general population, based on data from more than 600,000 individuals.

Studies of individuals with mental disorders have suggested an increased mortality risk, compared with the general population, but similar studies of individuals with autism spectrum disorder (ASD) or ADHD have yielded inconsistent results, Ferrán Catalá-López, PhD, of the Institute of Health Carlos III, Madrid, and colleagues wrote.

In a systematic review and meta-analysis published in JAMA Pediatrics, the researchers examined 27 studies including 642,260 individuals; 154,238 with ASD and 396,488 with ADHD. The studies were published up to April 1, 2021, and included deaths from natural causes (such as respiratory illness or cancer) and unnatural (external) causes, such as accident, injury, or poisoning. The proportion of females in the studies ranged from 14% to 100%; the follow-up ranged from 3 to 33 years; and three studies included first-degree relatives.

Overall, all-cause mortality was significantly higher among individuals with ASD (rate ratio, 2.37) and ADHD (RR, 2.13), compared with the general population. Among individuals with ASD, deaths from natural causes and unnatural causes were significantly increased, compared with the general population (RR, 3.80 and RR, 2.50, respectively). Among individuals with ADHD, deaths from natural causes were not significantly increased (RR, 1.62), but deaths from unnatural causes were significantly increased, compared with the general population (RR, 2.81).

Potential mechanisms to explain the excess mortality among individuals with ASD and ADHD include health determinants and biological pathways, but the complex nature of the associations make the establishment of causality a challenge, the researchers wrote in their discussion of the findings. In general, “severe mental and behavioral disorders appear to be associated with reduced life expectancy, both in terms of mortality from external causes and mortality from other medical conditions or diseases.” With regard to ASD/ADHD in particular, these individuals often experience emotional and social problems as they enter adulthood. “Behaviors such as impulsivity and/or inattention can be contributing factors for injuries and unintentional incidents in children with ASD/ADHD,” they added.

The study findings were limited by several factors including the possible omission of studies and the use of study-level data rather than individual participant data, as well as the limitation of electronic health records, the researchers noted. Also, the studies were mostly conducted in Western countries and the results may not be generalizable to other countries.

Although ASD and ADHD were associated with a significant increased risk of all-cause mortality, “the results should be interpreted with caution because there was evidence of heterogeneity between study estimates of the mortality risks,” the researchers said. However, the results were strengthened by the large study sample, and offer a comprehensive look at the evidence supporting increased mortality risk among individuals with ASD or ADHD, and highlight the need to identify modifiable risk factors.

“Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups of children and young people as an approach to improve public health,” they said.
 

Recent research support associations

The study was important because ASD and ADHD may persist into adulthood, but data from previous epidemiological studies on the impact of these disorders on mortality are inconsistent, lead author Dr. Catalá-López said in an interview.

“We conducted a systematic review and meta-analysis to evaluate all available studies of mortality associations in people with these disorders, which provide the most updated and evidence-based approach,” he explained. “Our study has only become possible in the past few years because several large population-based epidemiological studies have been available reporting similar mortality-related outcomes.”

Dr. Catalá-López said that the study findings have value in clinical practice. “We found that people with autism or attention-deficit/hyperactivity disorders would have an increased risk of mortality when compared to the general population. In our opinion, understanding the causes and mechanisms of these associations can lead to specific strategies to prevent avoidable deaths.

“Autism and attention-hyperactivity/deficit disorder are problems that can be managed with adequate and concrete programs at an early age, and most premature deaths, at least deaths from unnatural causes, can be prevented,” Dr. Catalá-López said.

“Furthermore, we believe that these results may shed some light for future research. For example, more prospective studies would be needed, particularly to examine cause-specific mortality, in larger populations of children and youth with autism/attention-deficit/hyperactivity disorder, including some of the more common comorbidities,” Dr. Catalá-López added.
 

Findings support need for screening and prevention strategies

The clear message that individuals with ASD or ADHD often die of preventable or unnatural causes demands attention and “demands widespread recognition and the implementation of systematic screening and preventive approaches,” Russell A. Barkley, PhD, of Virginia Commonwealth University, Richmond, and Geraldine Dawson, PhD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

The studies included in the review also demonstrate that ADHD is associated with more than a twofold risk of early mortality in children and a more than a fourfold risk in mortality by age 45 years, they said.

The editorialists noted that the increased mortality risk may explain the ongoing conundrum among clinicians as to why the prevalence of ADHD seems to decline with age, “such that 5%-8% of children may meet diagnostic criteria for ADHD while that figure falls to 4%-5% of adults and 2%-3% of older adults,” despite evidence that a majority of childhood cases will be rediagnosed in adulthood. However, the current study offers an alternative. “This systematic review and meta-analysis and the studies included within it make plain that another explanation is the greater loss of individuals with these conditions from the population over time owing to heightened mortality, compared with typical peers,” they said.

“In addition to ADHD diagnosis, ASD diagnosis is also associated with other psychiatric comorbidities that are correlated with increased risk for mortality, including anxiety and affective disorders,” the editorialists noted. Other considerations for increased mortality among individuals with ASD include different protective and risk factors associated with suicide risk, compared with the general population, as well as poorer social and daily living skills compared to the general population.

The study findings “argue for individuals with ADHD and individuals with ASD being viewed through a public health lens with screening and prevention strategies offered beginning in early childhood. These findings should also give impetus to efforts to try to reduce the first order risk factors that are predisposing to reduced life expectancy, such as obesity, substance use, poor diet, poor sleep, and limited exercise among children and adults with ASD and ADHD,” they said.

“A preventive strategy would necessitate primary care physicians becoming more aware of the linkage between both ASD diagnosis and ADHD diagnosis and early mortality as well as their link to reduced [estimated life expectancy],” and such an approach could potentially reduce the higher mortality risk identified in the current review, they concluded.

Dr. Barkley reported speaking and other fees from Takeda, Medice Pharmaceutical, and AstraZeneca; book royalties from Guilford Publications and the American Psychological Association; and course royalties from ContiningEdCourses.net and Premier Educational Seminars. Dr. Dawson reported grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health during the submitted work and personal fees from Apple. Dr. Dawson also disclosed a patent for license to Apple, and Dr. Dawson and Duke University have benefited financially from technology and data that have been licensed to Apple. The study was supported by the Institute of Health Carlos III and Generalitat Valenciana. Researchers including lead author Dr. Catalá-López received funding from sources including the Centro de Investigación Biomédica en Red de Salud Mental; one coauthor received support from an Australian Research Council Discovery Early Career Researcher Award, a new investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network, the Spanish Health Services Research on Chronic Patients Network, and Institute of Health Carlos III. The researchers had no financial conflicts to disclose.

All-cause mortality is significantly higher for individuals with autism spectrum disorder or attention-deficit/hyperactivity disorder than for the general population, based on data from more than 600,000 individuals.

Studies of individuals with mental disorders have suggested an increased mortality risk, compared with the general population, but similar studies of individuals with autism spectrum disorder (ASD) or ADHD have yielded inconsistent results, Ferrán Catalá-López, PhD, of the Institute of Health Carlos III, Madrid, and colleagues wrote.

In a systematic review and meta-analysis published in JAMA Pediatrics, the researchers examined 27 studies including 642,260 individuals; 154,238 with ASD and 396,488 with ADHD. The studies were published up to April 1, 2021, and included deaths from natural causes (such as respiratory illness or cancer) and unnatural (external) causes, such as accident, injury, or poisoning. The proportion of females in the studies ranged from 14% to 100%; the follow-up ranged from 3 to 33 years; and three studies included first-degree relatives.

Overall, all-cause mortality was significantly higher among individuals with ASD (rate ratio, 2.37) and ADHD (RR, 2.13), compared with the general population. Among individuals with ASD, deaths from natural causes and unnatural causes were significantly increased, compared with the general population (RR, 3.80 and RR, 2.50, respectively). Among individuals with ADHD, deaths from natural causes were not significantly increased (RR, 1.62), but deaths from unnatural causes were significantly increased, compared with the general population (RR, 2.81).

Potential mechanisms to explain the excess mortality among individuals with ASD and ADHD include health determinants and biological pathways, but the complex nature of the associations make the establishment of causality a challenge, the researchers wrote in their discussion of the findings. In general, “severe mental and behavioral disorders appear to be associated with reduced life expectancy, both in terms of mortality from external causes and mortality from other medical conditions or diseases.” With regard to ASD/ADHD in particular, these individuals often experience emotional and social problems as they enter adulthood. “Behaviors such as impulsivity and/or inattention can be contributing factors for injuries and unintentional incidents in children with ASD/ADHD,” they added.

The study findings were limited by several factors including the possible omission of studies and the use of study-level data rather than individual participant data, as well as the limitation of electronic health records, the researchers noted. Also, the studies were mostly conducted in Western countries and the results may not be generalizable to other countries.

Although ASD and ADHD were associated with a significant increased risk of all-cause mortality, “the results should be interpreted with caution because there was evidence of heterogeneity between study estimates of the mortality risks,” the researchers said. However, the results were strengthened by the large study sample, and offer a comprehensive look at the evidence supporting increased mortality risk among individuals with ASD or ADHD, and highlight the need to identify modifiable risk factors.

“Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups of children and young people as an approach to improve public health,” they said.
 

Recent research support associations

The study was important because ASD and ADHD may persist into adulthood, but data from previous epidemiological studies on the impact of these disorders on mortality are inconsistent, lead author Dr. Catalá-López said in an interview.

“We conducted a systematic review and meta-analysis to evaluate all available studies of mortality associations in people with these disorders, which provide the most updated and evidence-based approach,” he explained. “Our study has only become possible in the past few years because several large population-based epidemiological studies have been available reporting similar mortality-related outcomes.”

Dr. Catalá-López said that the study findings have value in clinical practice. “We found that people with autism or attention-deficit/hyperactivity disorders would have an increased risk of mortality when compared to the general population. In our opinion, understanding the causes and mechanisms of these associations can lead to specific strategies to prevent avoidable deaths.

“Autism and attention-hyperactivity/deficit disorder are problems that can be managed with adequate and concrete programs at an early age, and most premature deaths, at least deaths from unnatural causes, can be prevented,” Dr. Catalá-López said.

“Furthermore, we believe that these results may shed some light for future research. For example, more prospective studies would be needed, particularly to examine cause-specific mortality, in larger populations of children and youth with autism/attention-deficit/hyperactivity disorder, including some of the more common comorbidities,” Dr. Catalá-López added.
 

Findings support need for screening and prevention strategies

The clear message that individuals with ASD or ADHD often die of preventable or unnatural causes demands attention and “demands widespread recognition and the implementation of systematic screening and preventive approaches,” Russell A. Barkley, PhD, of Virginia Commonwealth University, Richmond, and Geraldine Dawson, PhD, of Duke University, Durham, N.C., wrote in an accompanying editorial.

The studies included in the review also demonstrate that ADHD is associated with more than a twofold risk of early mortality in children and a more than a fourfold risk in mortality by age 45 years, they said.

The editorialists noted that the increased mortality risk may explain the ongoing conundrum among clinicians as to why the prevalence of ADHD seems to decline with age, “such that 5%-8% of children may meet diagnostic criteria for ADHD while that figure falls to 4%-5% of adults and 2%-3% of older adults,” despite evidence that a majority of childhood cases will be rediagnosed in adulthood. However, the current study offers an alternative. “This systematic review and meta-analysis and the studies included within it make plain that another explanation is the greater loss of individuals with these conditions from the population over time owing to heightened mortality, compared with typical peers,” they said.

“In addition to ADHD diagnosis, ASD diagnosis is also associated with other psychiatric comorbidities that are correlated with increased risk for mortality, including anxiety and affective disorders,” the editorialists noted. Other considerations for increased mortality among individuals with ASD include different protective and risk factors associated with suicide risk, compared with the general population, as well as poorer social and daily living skills compared to the general population.

The study findings “argue for individuals with ADHD and individuals with ASD being viewed through a public health lens with screening and prevention strategies offered beginning in early childhood. These findings should also give impetus to efforts to try to reduce the first order risk factors that are predisposing to reduced life expectancy, such as obesity, substance use, poor diet, poor sleep, and limited exercise among children and adults with ASD and ADHD,” they said.

“A preventive strategy would necessitate primary care physicians becoming more aware of the linkage between both ASD diagnosis and ADHD diagnosis and early mortality as well as their link to reduced [estimated life expectancy],” and such an approach could potentially reduce the higher mortality risk identified in the current review, they concluded.

Dr. Barkley reported speaking and other fees from Takeda, Medice Pharmaceutical, and AstraZeneca; book royalties from Guilford Publications and the American Psychological Association; and course royalties from ContiningEdCourses.net and Premier Educational Seminars. Dr. Dawson reported grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health during the submitted work and personal fees from Apple. Dr. Dawson also disclosed a patent for license to Apple, and Dr. Dawson and Duke University have benefited financially from technology and data that have been licensed to Apple. The study was supported by the Institute of Health Carlos III and Generalitat Valenciana. Researchers including lead author Dr. Catalá-López received funding from sources including the Centro de Investigación Biomédica en Red de Salud Mental; one coauthor received support from an Australian Research Council Discovery Early Career Researcher Award, a new investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network, the Spanish Health Services Research on Chronic Patients Network, and Institute of Health Carlos III. The researchers had no financial conflicts to disclose.

Sepsis is an alarmingly common cause behind ICU admissions in patients with multiple sclerosis (MS), a retrospective, population-based cohort study indicates.

Furthermore, it contributes to a disproportionately high percentage of the short-term mortality risk among patients with MS admitted to the ICU, findings also show. Short-term mortality risk was defined in the study as a combination of in-hospital death or discharge to hospice.

“We found that the risk of short-term mortality in critically ill patients with MS is four times higher among those with sepsis ... so sepsis appears to be comparatively more lethal among patients with MS than in the general population,” Lavi Oud, MD, professor of medicine, Texas Tech University HSC at the Permian Basin, Odessa, said in an email.

“[Although] the specific mechanisms underlying the markedly higher risk of sepsis among patients with MS compared to the general population remain to be fully elucidated ... it’s thought that the risk may stem from the dysfunction of the immune system in these patients related to MS itself and to the potentially adverse effect of the immunomodulating therapy we use in these patients,” he added.

The study was published online Jan. 11 in the Journal of Critical Care.
 

Sepsis rates

The Texas Inpatient Public Use Data File was used to identify adults with a diagnosis of MS admitted to the hospital between 2010 and 2017. Among the 19,837 patients with MS admitted to the ICU during the study interval, almost one-third (31.5%) had sepsis, investigators report. “The rate of sepsis among ICU admissions increased with age, ranging from 20.8% among those aged 18-44 to 39.4% among those aged 65 years or older,” investigators note.

The most common site of infection among MS patients admitted to the ICU were urinary in nature (65.2%), followed by respiratory (36.1%). A smaller proportion of infections (7.6%) involved the skin and soft tissues, researchers note. A full one-quarter of patients developed septic shock in response to their infection while the length of stay among patients with sepsis (mean of 10.9 days) was substantially longer than it was for those without sepsis (mean of 5.6 days), they observe.

At a mean total hospital cost of $121,797 for each ICU patient with sepsis, the cost of caring for each patient was nearly twofold higher than the mean total cost of taking care of ICU patients without sepsis (mean total cost, $65,179). On adjusted analysis, sepsis was associated with a 42.7% (95% confidence interval, 38.9-46.5; P < .0001) longer length of hospital stay and a 26.2% (95% CI, 23.1-29.1; P < .0001) higher total hospital cost compared with patients without sepsis, the authors point out.

Indeed, ICU admissions with sepsis accounted for 47.3% of all hospital days and for 46.1% of the aggregate hospital charges among all MS patients admitted to the ICU.

“The adjusted probability of short-term mortality was 13.4% (95% CI, 13.0-13.7) among ICU admissions with sepsis and 3.3% (95% CI, 3.2-3.4) among ICU admissions without sepsis,” the authors report.

This translated into a 44% higher risk of short-term mortality at an adjusted odds ratio of 1.44 (95% CI, 1.23-1.69; P < .0001) for those with sepsis, compared with those without, they add. Among all ICU admissions, sepsis was reported in over two-thirds of documented short-term mortality events. The risk of short-term mortality was also almost threefold higher among patients with sepsis who were age 65 years and older compared with patients aged 18-44. 

As Dr. Oud noted, there is no specific test for sepsis, and it can initially present in an atypical manner, especially in older, frailer, chronically ill patients as well as in patients with immune dysfunction. “Thus, considering sepsis as a possible cause of new deterioration in a patient’s condition is essential, along with the timely start of sepsis-related care,” Dr. Oud observed.

A limitation of the study was that the dataset did not include information on the type of MS a patient had, the duration of their illness, the treatment received, the level of disease activity, or the level of disability.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Sepsis is an alarmingly common cause behind ICU admissions in patients with multiple sclerosis (MS), a retrospective, population-based cohort study indicates.

Furthermore, it contributes to a disproportionately high percentage of the short-term mortality risk among patients with MS admitted to the ICU, findings also show. Short-term mortality risk was defined in the study as a combination of in-hospital death or discharge to hospice.

“We found that the risk of short-term mortality in critically ill patients with MS is four times higher among those with sepsis ... so sepsis appears to be comparatively more lethal among patients with MS than in the general population,” Lavi Oud, MD, professor of medicine, Texas Tech University HSC at the Permian Basin, Odessa, said in an email.

“[Although] the specific mechanisms underlying the markedly higher risk of sepsis among patients with MS compared to the general population remain to be fully elucidated ... it’s thought that the risk may stem from the dysfunction of the immune system in these patients related to MS itself and to the potentially adverse effect of the immunomodulating therapy we use in these patients,” he added.

The study was published online Jan. 11 in the Journal of Critical Care.
 

Sepsis rates

The Texas Inpatient Public Use Data File was used to identify adults with a diagnosis of MS admitted to the hospital between 2010 and 2017. Among the 19,837 patients with MS admitted to the ICU during the study interval, almost one-third (31.5%) had sepsis, investigators report. “The rate of sepsis among ICU admissions increased with age, ranging from 20.8% among those aged 18-44 to 39.4% among those aged 65 years or older,” investigators note.

The most common site of infection among MS patients admitted to the ICU were urinary in nature (65.2%), followed by respiratory (36.1%). A smaller proportion of infections (7.6%) involved the skin and soft tissues, researchers note. A full one-quarter of patients developed septic shock in response to their infection while the length of stay among patients with sepsis (mean of 10.9 days) was substantially longer than it was for those without sepsis (mean of 5.6 days), they observe.

At a mean total hospital cost of $121,797 for each ICU patient with sepsis, the cost of caring for each patient was nearly twofold higher than the mean total cost of taking care of ICU patients without sepsis (mean total cost, $65,179). On adjusted analysis, sepsis was associated with a 42.7% (95% confidence interval, 38.9-46.5; P < .0001) longer length of hospital stay and a 26.2% (95% CI, 23.1-29.1; P < .0001) higher total hospital cost compared with patients without sepsis, the authors point out.

Indeed, ICU admissions with sepsis accounted for 47.3% of all hospital days and for 46.1% of the aggregate hospital charges among all MS patients admitted to the ICU.

“The adjusted probability of short-term mortality was 13.4% (95% CI, 13.0-13.7) among ICU admissions with sepsis and 3.3% (95% CI, 3.2-3.4) among ICU admissions without sepsis,” the authors report.

This translated into a 44% higher risk of short-term mortality at an adjusted odds ratio of 1.44 (95% CI, 1.23-1.69; P < .0001) for those with sepsis, compared with those without, they add. Among all ICU admissions, sepsis was reported in over two-thirds of documented short-term mortality events. The risk of short-term mortality was also almost threefold higher among patients with sepsis who were age 65 years and older compared with patients aged 18-44. 

As Dr. Oud noted, there is no specific test for sepsis, and it can initially present in an atypical manner, especially in older, frailer, chronically ill patients as well as in patients with immune dysfunction. “Thus, considering sepsis as a possible cause of new deterioration in a patient’s condition is essential, along with the timely start of sepsis-related care,” Dr. Oud observed.

A limitation of the study was that the dataset did not include information on the type of MS a patient had, the duration of their illness, the treatment received, the level of disease activity, or the level of disability.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Sepsis is an alarmingly common cause behind ICU admissions in patients with multiple sclerosis (MS), a retrospective, population-based cohort study indicates.

Furthermore, it contributes to a disproportionately high percentage of the short-term mortality risk among patients with MS admitted to the ICU, findings also show. Short-term mortality risk was defined in the study as a combination of in-hospital death or discharge to hospice.

“We found that the risk of short-term mortality in critically ill patients with MS is four times higher among those with sepsis ... so sepsis appears to be comparatively more lethal among patients with MS than in the general population,” Lavi Oud, MD, professor of medicine, Texas Tech University HSC at the Permian Basin, Odessa, said in an email.

“[Although] the specific mechanisms underlying the markedly higher risk of sepsis among patients with MS compared to the general population remain to be fully elucidated ... it’s thought that the risk may stem from the dysfunction of the immune system in these patients related to MS itself and to the potentially adverse effect of the immunomodulating therapy we use in these patients,” he added.

The study was published online Jan. 11 in the Journal of Critical Care.
 

Sepsis rates

The Texas Inpatient Public Use Data File was used to identify adults with a diagnosis of MS admitted to the hospital between 2010 and 2017. Among the 19,837 patients with MS admitted to the ICU during the study interval, almost one-third (31.5%) had sepsis, investigators report. “The rate of sepsis among ICU admissions increased with age, ranging from 20.8% among those aged 18-44 to 39.4% among those aged 65 years or older,” investigators note.

The most common site of infection among MS patients admitted to the ICU were urinary in nature (65.2%), followed by respiratory (36.1%). A smaller proportion of infections (7.6%) involved the skin and soft tissues, researchers note. A full one-quarter of patients developed septic shock in response to their infection while the length of stay among patients with sepsis (mean of 10.9 days) was substantially longer than it was for those without sepsis (mean of 5.6 days), they observe.

At a mean total hospital cost of $121,797 for each ICU patient with sepsis, the cost of caring for each patient was nearly twofold higher than the mean total cost of taking care of ICU patients without sepsis (mean total cost, $65,179). On adjusted analysis, sepsis was associated with a 42.7% (95% confidence interval, 38.9-46.5; P < .0001) longer length of hospital stay and a 26.2% (95% CI, 23.1-29.1; P < .0001) higher total hospital cost compared with patients without sepsis, the authors point out.

Indeed, ICU admissions with sepsis accounted for 47.3% of all hospital days and for 46.1% of the aggregate hospital charges among all MS patients admitted to the ICU.

“The adjusted probability of short-term mortality was 13.4% (95% CI, 13.0-13.7) among ICU admissions with sepsis and 3.3% (95% CI, 3.2-3.4) among ICU admissions without sepsis,” the authors report.

This translated into a 44% higher risk of short-term mortality at an adjusted odds ratio of 1.44 (95% CI, 1.23-1.69; P < .0001) for those with sepsis, compared with those without, they add. Among all ICU admissions, sepsis was reported in over two-thirds of documented short-term mortality events. The risk of short-term mortality was also almost threefold higher among patients with sepsis who were age 65 years and older compared with patients aged 18-44. 

As Dr. Oud noted, there is no specific test for sepsis, and it can initially present in an atypical manner, especially in older, frailer, chronically ill patients as well as in patients with immune dysfunction. “Thus, considering sepsis as a possible cause of new deterioration in a patient’s condition is essential, along with the timely start of sepsis-related care,” Dr. Oud observed.

A limitation of the study was that the dataset did not include information on the type of MS a patient had, the duration of their illness, the treatment received, the level of disease activity, or the level of disability.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.

The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.

Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.

The study was published online Feb. 2 in Neurology.
 

Ongoing controversy

Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.

There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.

This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.

The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.

The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.

Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”

Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.

The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
 

More common in boys

Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.

The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.

They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.

At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.

During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.

Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.

However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).

This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.

Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
 

Other pathogens?

Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.

“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”

Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.

It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.

Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.

“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”

The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”

The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.

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

Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.

The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.

Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.

The study was published online Feb. 2 in Neurology.
 

Ongoing controversy

Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.

There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.

This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.

The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.

The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.

Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”

Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.

The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
 

More common in boys

Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.

The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.

They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.

At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.

During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.

Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.

However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).

This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.

Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
 

Other pathogens?

Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.

“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”

Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.

It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.

Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.

“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”

The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”

The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.

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

Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.

The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.

Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.

The study was published online Feb. 2 in Neurology.
 

Ongoing controversy

Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.

There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.

This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.

The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.

The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.

Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”

Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.

The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
 

More common in boys

Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.

The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.

They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.

At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.

During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.

Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.

However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).

This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.

Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
 

Other pathogens?

Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.

“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”

Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.

It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.

Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.

“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”

The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”

The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.

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

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.