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Two Canadian provinces lift licensing barriers for U.S. doctors
They’ll no longer have to start with a limited license and take additional exams or be supervised for up to a year to become fully licensed.
Canada is experiencing an acute shortage of licensed physicians that’s expected to intensify over the next decade. The shortfall is estimated to be about 44,000 physicians by 2028, with family doctors accounting for 72% of the deficit.
“Reducing licensing barriers should make Canada a more attractive option for U.S. doctors who may be considering a move north,” said Tom Florence, president of AMN Healthcare’s Physician Solutions division, which recruits American physicians to work in Canada.
“Canada also has a truly expedited work visa process for qualifying physicians who have a job offer and wish to practice there,” said Mr. Florence. It usually takes about 6 months compared with at least 18 months for Canadian physicians who want to work in the United States, he said.
Few U.S.-trained physicians work in Canada, which has a population of nearly 39 million. Just 812 of them practiced in Canada in 2019, the last year data was collected, according to the Canadian Medical Association.
But Canada may attract American physicians who find U.S. medicine to be fraught with ethical dilemmas and restrictions from insurance companies and elected officials, said Theresa Rohr-Kirchgraber, MD, an internist and immediate past president of the American Medical Women’s Association.
“Rather than give up practicing medicine, a move to Canada may be a welcome respite for some U.S. physicians,” she said.
Physician recruiters in Ontario and Nova Scotia welcomed the news. About 13% of the population is without a family doctor, according to news reports.
A number of U.S. physicians have started practices in Nova Scotia in recent years, said Katrina Philopoulos, Nova Scotia Health’s director of physician recruitment. “I think this momentum will help us,” she said.
Other Canadian provinces with physician shortages are also considering making similar changes. Alberta recently announced a 5-year pilot project to waive some licensing requirements for family doctors and general practitioners trained in Australia, Ireland, United Kingdom, and the United States.
What are the pros and cons of working in Canada?
“Some U.S. physicians may be attracted by a single-payer system in which all patients have access to coverage, but there are a range of drawbacks and benefits to consider in both systems,” said Mr. Florence.
U.S. physicians generally earn more than their Canadian counterparts, so income is not likely to be a draw, he said.
That appears to be the case for both family medicine physicians and specialists when comparing average net annual salaries. (To obtain Canadian salaries, 2021 gross income data from the Canadian Institute for Health Information were used; 20% was deducted for operation costs; and Canadian dollars were converted into U.S. dollars based on the current exchange rate.)
A family medicine doctor in Canada will earn an annual average salary of $195,853 USD compared with $236,000 in the United States. A cardiologist in Canada will earn $314,051 USD annually compared with $459,000 in the United States. A dermatologist in Canada will earn $270,018 annually compared with $394,000 in the United States.
Everett Fuller, MD, an emergency medicine physician who moved from Texas to Nova Scotia in 2015 for his Canadian wife, recently wrote about the pros and cons of working there compared with the United States. For him, it was a worthwhile move.
“It’s getting back to making medicine and patient care the priority instead of the business of medicine,” Dr. Fuller wrote.
“I have the comfort of knowing that a patient and their family will not go bankrupt trying to pay medical bills if I make a catastrophic diagnosis. There’s no out-of-pocket cost, other than prescriptions (depending on their drug plan).”
Dr. Fuller also doesn’t have to fight insurers for reimbursement or preapprovals, and he pays much less for medical malpractice premiums in a less litigious environment, he said.
But he mentioned a few negatives. Some treatment is rationed, which can lead to long wait times for patients to get appointments. Also, “hospitals aren’t in it for the profit, so you’re not going to get a CT, MRI, and cath lab in every hospital,” he noted.
Mr. Florence doesn’t think either system “offers a panacea for many of the challenges physicians face today. Even with reduced barriers to licensure, we do not anticipate an exodus to U.S. physicians to the north.”
A version of this article first appeared on Medscape.com.
They’ll no longer have to start with a limited license and take additional exams or be supervised for up to a year to become fully licensed.
Canada is experiencing an acute shortage of licensed physicians that’s expected to intensify over the next decade. The shortfall is estimated to be about 44,000 physicians by 2028, with family doctors accounting for 72% of the deficit.
“Reducing licensing barriers should make Canada a more attractive option for U.S. doctors who may be considering a move north,” said Tom Florence, president of AMN Healthcare’s Physician Solutions division, which recruits American physicians to work in Canada.
“Canada also has a truly expedited work visa process for qualifying physicians who have a job offer and wish to practice there,” said Mr. Florence. It usually takes about 6 months compared with at least 18 months for Canadian physicians who want to work in the United States, he said.
Few U.S.-trained physicians work in Canada, which has a population of nearly 39 million. Just 812 of them practiced in Canada in 2019, the last year data was collected, according to the Canadian Medical Association.
But Canada may attract American physicians who find U.S. medicine to be fraught with ethical dilemmas and restrictions from insurance companies and elected officials, said Theresa Rohr-Kirchgraber, MD, an internist and immediate past president of the American Medical Women’s Association.
“Rather than give up practicing medicine, a move to Canada may be a welcome respite for some U.S. physicians,” she said.
Physician recruiters in Ontario and Nova Scotia welcomed the news. About 13% of the population is without a family doctor, according to news reports.
A number of U.S. physicians have started practices in Nova Scotia in recent years, said Katrina Philopoulos, Nova Scotia Health’s director of physician recruitment. “I think this momentum will help us,” she said.
Other Canadian provinces with physician shortages are also considering making similar changes. Alberta recently announced a 5-year pilot project to waive some licensing requirements for family doctors and general practitioners trained in Australia, Ireland, United Kingdom, and the United States.
What are the pros and cons of working in Canada?
“Some U.S. physicians may be attracted by a single-payer system in which all patients have access to coverage, but there are a range of drawbacks and benefits to consider in both systems,” said Mr. Florence.
U.S. physicians generally earn more than their Canadian counterparts, so income is not likely to be a draw, he said.
That appears to be the case for both family medicine physicians and specialists when comparing average net annual salaries. (To obtain Canadian salaries, 2021 gross income data from the Canadian Institute for Health Information were used; 20% was deducted for operation costs; and Canadian dollars were converted into U.S. dollars based on the current exchange rate.)
A family medicine doctor in Canada will earn an annual average salary of $195,853 USD compared with $236,000 in the United States. A cardiologist in Canada will earn $314,051 USD annually compared with $459,000 in the United States. A dermatologist in Canada will earn $270,018 annually compared with $394,000 in the United States.
Everett Fuller, MD, an emergency medicine physician who moved from Texas to Nova Scotia in 2015 for his Canadian wife, recently wrote about the pros and cons of working there compared with the United States. For him, it was a worthwhile move.
“It’s getting back to making medicine and patient care the priority instead of the business of medicine,” Dr. Fuller wrote.
“I have the comfort of knowing that a patient and their family will not go bankrupt trying to pay medical bills if I make a catastrophic diagnosis. There’s no out-of-pocket cost, other than prescriptions (depending on their drug plan).”
Dr. Fuller also doesn’t have to fight insurers for reimbursement or preapprovals, and he pays much less for medical malpractice premiums in a less litigious environment, he said.
But he mentioned a few negatives. Some treatment is rationed, which can lead to long wait times for patients to get appointments. Also, “hospitals aren’t in it for the profit, so you’re not going to get a CT, MRI, and cath lab in every hospital,” he noted.
Mr. Florence doesn’t think either system “offers a panacea for many of the challenges physicians face today. Even with reduced barriers to licensure, we do not anticipate an exodus to U.S. physicians to the north.”
A version of this article first appeared on Medscape.com.
They’ll no longer have to start with a limited license and take additional exams or be supervised for up to a year to become fully licensed.
Canada is experiencing an acute shortage of licensed physicians that’s expected to intensify over the next decade. The shortfall is estimated to be about 44,000 physicians by 2028, with family doctors accounting for 72% of the deficit.
“Reducing licensing barriers should make Canada a more attractive option for U.S. doctors who may be considering a move north,” said Tom Florence, president of AMN Healthcare’s Physician Solutions division, which recruits American physicians to work in Canada.
“Canada also has a truly expedited work visa process for qualifying physicians who have a job offer and wish to practice there,” said Mr. Florence. It usually takes about 6 months compared with at least 18 months for Canadian physicians who want to work in the United States, he said.
Few U.S.-trained physicians work in Canada, which has a population of nearly 39 million. Just 812 of them practiced in Canada in 2019, the last year data was collected, according to the Canadian Medical Association.
But Canada may attract American physicians who find U.S. medicine to be fraught with ethical dilemmas and restrictions from insurance companies and elected officials, said Theresa Rohr-Kirchgraber, MD, an internist and immediate past president of the American Medical Women’s Association.
“Rather than give up practicing medicine, a move to Canada may be a welcome respite for some U.S. physicians,” she said.
Physician recruiters in Ontario and Nova Scotia welcomed the news. About 13% of the population is without a family doctor, according to news reports.
A number of U.S. physicians have started practices in Nova Scotia in recent years, said Katrina Philopoulos, Nova Scotia Health’s director of physician recruitment. “I think this momentum will help us,” she said.
Other Canadian provinces with physician shortages are also considering making similar changes. Alberta recently announced a 5-year pilot project to waive some licensing requirements for family doctors and general practitioners trained in Australia, Ireland, United Kingdom, and the United States.
What are the pros and cons of working in Canada?
“Some U.S. physicians may be attracted by a single-payer system in which all patients have access to coverage, but there are a range of drawbacks and benefits to consider in both systems,” said Mr. Florence.
U.S. physicians generally earn more than their Canadian counterparts, so income is not likely to be a draw, he said.
That appears to be the case for both family medicine physicians and specialists when comparing average net annual salaries. (To obtain Canadian salaries, 2021 gross income data from the Canadian Institute for Health Information were used; 20% was deducted for operation costs; and Canadian dollars were converted into U.S. dollars based on the current exchange rate.)
A family medicine doctor in Canada will earn an annual average salary of $195,853 USD compared with $236,000 in the United States. A cardiologist in Canada will earn $314,051 USD annually compared with $459,000 in the United States. A dermatologist in Canada will earn $270,018 annually compared with $394,000 in the United States.
Everett Fuller, MD, an emergency medicine physician who moved from Texas to Nova Scotia in 2015 for his Canadian wife, recently wrote about the pros and cons of working there compared with the United States. For him, it was a worthwhile move.
“It’s getting back to making medicine and patient care the priority instead of the business of medicine,” Dr. Fuller wrote.
“I have the comfort of knowing that a patient and their family will not go bankrupt trying to pay medical bills if I make a catastrophic diagnosis. There’s no out-of-pocket cost, other than prescriptions (depending on their drug plan).”
Dr. Fuller also doesn’t have to fight insurers for reimbursement or preapprovals, and he pays much less for medical malpractice premiums in a less litigious environment, he said.
But he mentioned a few negatives. Some treatment is rationed, which can lead to long wait times for patients to get appointments. Also, “hospitals aren’t in it for the profit, so you’re not going to get a CT, MRI, and cath lab in every hospital,” he noted.
Mr. Florence doesn’t think either system “offers a panacea for many of the challenges physicians face today. Even with reduced barriers to licensure, we do not anticipate an exodus to U.S. physicians to the north.”
A version of this article first appeared on Medscape.com.
Four profiles help identify kids at risk for suicide
The profiles were developed from their study of children and adolescents aged 5-18 years who had been admitted with a neuropsychiatric event to two children’s hospitals.
The researchers used Bayesian regression to identify the profiles developed from 32 covariates: age, sex, and 30 mental health diagnostic groups from April 2016 to March 2020. The profiles include low-, moderate-, high- and very-high-risk categories.
The study, led by Mert Sekmen with the division of hospital medicine at Monroe Carell Jr. Children’s Hospital, and a student at Vanderbilt University Medical Center in Nashville, Tenn., included 1,098 children, average age 14. Of those, 406 (37%) were diagnosed with a self-harm event.
Traditionally, single diagnoses have been linked with risk of self-harm, independent of other comorbidities, but this study gauges risk for a set of diagnoses.
Findings were published online in Pediatrics.
The risk groups were described as follows:
- Low risk. (45% of the study population; median risk of 0.04 (interquartile range, 0.03-0.04; odds ratio, 0.08). The group included children aged 5-9 years with a non–mental health diagnosis, and without mood, behavioral, psychotic, developmental, trauma, or substance-related disorders.
- Moderate risk. (8% of the study group). This group had the same risk as the baseline risk for the entire cohort (37%) and served as the reference group, with a median risk of 0.30 (IQR, 0.27-0.33). This profile was characterized by several mood disorders and behavioral disorders but without depressive disorders.
- High risk. (36%) This group had an average risk of 0.69 (IQR, 0.67-0.71; OR, 5.09). This profile included female adolescents ages 14-17 with depression and anxiety in conjunction with substance- and trauma-related disorders. Personality and eating disorders were significant in this group. Importantly, the authors wrote, the high-risk group did not include behavioral and developmental disorders.
- Very high risk. (11%) The very-high-risk profile had the highest average risk of 0.79 (IQR, 0.73-0.79; OR, 7.21) and included male children aged 10-13. This profile, like the high-risk profile, included anxiety and depressive disorders. The very-high-risk profile differed from the high-risk with its inclusion of bipolar disorder; attention-deficit/hyperactivity disorder; and trauma-related and developmental disorders such as autism spectrum disorder or intellectual disability, along with conduct disorders. Neither the high- nor the very-high-risk profiles included a concurrent non–mental health diagnosis.
Differences by sex
The authors explained some of the differences by sex. They noted that in a study of children aged 5-11, deaths by suicide were more prevalent among boys. A mental health diagnosis was identified in 31%, the most common being ADHD, depression, and other unspecified co-occurring disorders.
“The very-high-risk group also reflects a concerning rise in death by suicide among (males) aged 10-13, who have seen rates nearly triple from 2007 to 2017,” the authors wrote.
The authors pointed out that, although incidence of anxiety and depressive disorders between male and female children is much the same before adolescence, “female adolescents are twice as likely to be diagnosed with either disorder during adolescence. Girls also have higher rates of suicidal ideation and attempts after puberty.”
Eating disorders were also included in the high-risk profile. A study showed that emergency department visits for adolescent girls attempting suicide were 51% higher from February to March 2021, compared with the same period in the pre-COVID-19 year 2019.
Jason Lewis, PhD, psychologist and section director of mood, anxiety and trauma disorders in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia, who was not part of the research team, said the “constellations of risk factors put into acuity levels” helps to better project risk than knowing the risk associated with a particular diagnosis.
Gap closing between young children, adolescents
Dr. Lewis said he was surprised by the young age of 10-13 among the boys in the highest-risk category. That speaks to the differences from standard thinking this paper points out, he said. “Generally, we think about adolescents as being at the highest risk of suicide death and suicidal behavior,” he said.
Dr. Lewis said it’s important to note that the authors acknowledge these profiles are not static. He gave an example that the rate of suicide deaths among females is rising.
“As things like that change, some of these risk profiles will change as well.”
Dr. Lewis said the profiles may be especially helpful to medical providers in emergency departments or those making discharge decisions who don’t have an ongoing relationship with a patient.
The information could also help educators and lay people, “think about suicide in the youth population in ways we don’t normally think about it,” Dr. Lewis said.
Covariates considered for profiles were determined through expert consensus between pediatric psychiatrists, general pediatricians, pediatric hospitalists, pediatric complex care physicians, and pediatric pharmacoepidemiologists.
Age was broken into three groups: 5-9 years, 10-13 years, and 14-17 years based on Centers for Disease Control and Prevention reporting and previous studies that showed significant increases in suicide rates in these age-based subgroups.
Results are preliminary
The authors note that the profiles were developed using data from 1,000 children with neuropsychiatric complaints at two academic children’s hospitals and are thus preliminary.
“Future studies should focus on validating these risk profiles in a larger, more heterogeneous population of children and adolescents,” the authors write.
They also acknowledge that they were not able to include factors such as medication use, previous suicidal behavior, and family and social support, which also factor into risk.
The study authors and Dr. Lewis report no relevant financial relationships.
The profiles were developed from their study of children and adolescents aged 5-18 years who had been admitted with a neuropsychiatric event to two children’s hospitals.
The researchers used Bayesian regression to identify the profiles developed from 32 covariates: age, sex, and 30 mental health diagnostic groups from April 2016 to March 2020. The profiles include low-, moderate-, high- and very-high-risk categories.
The study, led by Mert Sekmen with the division of hospital medicine at Monroe Carell Jr. Children’s Hospital, and a student at Vanderbilt University Medical Center in Nashville, Tenn., included 1,098 children, average age 14. Of those, 406 (37%) were diagnosed with a self-harm event.
Traditionally, single diagnoses have been linked with risk of self-harm, independent of other comorbidities, but this study gauges risk for a set of diagnoses.
Findings were published online in Pediatrics.
The risk groups were described as follows:
- Low risk. (45% of the study population; median risk of 0.04 (interquartile range, 0.03-0.04; odds ratio, 0.08). The group included children aged 5-9 years with a non–mental health diagnosis, and without mood, behavioral, psychotic, developmental, trauma, or substance-related disorders.
- Moderate risk. (8% of the study group). This group had the same risk as the baseline risk for the entire cohort (37%) and served as the reference group, with a median risk of 0.30 (IQR, 0.27-0.33). This profile was characterized by several mood disorders and behavioral disorders but without depressive disorders.
- High risk. (36%) This group had an average risk of 0.69 (IQR, 0.67-0.71; OR, 5.09). This profile included female adolescents ages 14-17 with depression and anxiety in conjunction with substance- and trauma-related disorders. Personality and eating disorders were significant in this group. Importantly, the authors wrote, the high-risk group did not include behavioral and developmental disorders.
- Very high risk. (11%) The very-high-risk profile had the highest average risk of 0.79 (IQR, 0.73-0.79; OR, 7.21) and included male children aged 10-13. This profile, like the high-risk profile, included anxiety and depressive disorders. The very-high-risk profile differed from the high-risk with its inclusion of bipolar disorder; attention-deficit/hyperactivity disorder; and trauma-related and developmental disorders such as autism spectrum disorder or intellectual disability, along with conduct disorders. Neither the high- nor the very-high-risk profiles included a concurrent non–mental health diagnosis.
Differences by sex
The authors explained some of the differences by sex. They noted that in a study of children aged 5-11, deaths by suicide were more prevalent among boys. A mental health diagnosis was identified in 31%, the most common being ADHD, depression, and other unspecified co-occurring disorders.
“The very-high-risk group also reflects a concerning rise in death by suicide among (males) aged 10-13, who have seen rates nearly triple from 2007 to 2017,” the authors wrote.
The authors pointed out that, although incidence of anxiety and depressive disorders between male and female children is much the same before adolescence, “female adolescents are twice as likely to be diagnosed with either disorder during adolescence. Girls also have higher rates of suicidal ideation and attempts after puberty.”
Eating disorders were also included in the high-risk profile. A study showed that emergency department visits for adolescent girls attempting suicide were 51% higher from February to March 2021, compared with the same period in the pre-COVID-19 year 2019.
Jason Lewis, PhD, psychologist and section director of mood, anxiety and trauma disorders in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia, who was not part of the research team, said the “constellations of risk factors put into acuity levels” helps to better project risk than knowing the risk associated with a particular diagnosis.
Gap closing between young children, adolescents
Dr. Lewis said he was surprised by the young age of 10-13 among the boys in the highest-risk category. That speaks to the differences from standard thinking this paper points out, he said. “Generally, we think about adolescents as being at the highest risk of suicide death and suicidal behavior,” he said.
Dr. Lewis said it’s important to note that the authors acknowledge these profiles are not static. He gave an example that the rate of suicide deaths among females is rising.
“As things like that change, some of these risk profiles will change as well.”
Dr. Lewis said the profiles may be especially helpful to medical providers in emergency departments or those making discharge decisions who don’t have an ongoing relationship with a patient.
The information could also help educators and lay people, “think about suicide in the youth population in ways we don’t normally think about it,” Dr. Lewis said.
Covariates considered for profiles were determined through expert consensus between pediatric psychiatrists, general pediatricians, pediatric hospitalists, pediatric complex care physicians, and pediatric pharmacoepidemiologists.
Age was broken into three groups: 5-9 years, 10-13 years, and 14-17 years based on Centers for Disease Control and Prevention reporting and previous studies that showed significant increases in suicide rates in these age-based subgroups.
Results are preliminary
The authors note that the profiles were developed using data from 1,000 children with neuropsychiatric complaints at two academic children’s hospitals and are thus preliminary.
“Future studies should focus on validating these risk profiles in a larger, more heterogeneous population of children and adolescents,” the authors write.
They also acknowledge that they were not able to include factors such as medication use, previous suicidal behavior, and family and social support, which also factor into risk.
The study authors and Dr. Lewis report no relevant financial relationships.
The profiles were developed from their study of children and adolescents aged 5-18 years who had been admitted with a neuropsychiatric event to two children’s hospitals.
The researchers used Bayesian regression to identify the profiles developed from 32 covariates: age, sex, and 30 mental health diagnostic groups from April 2016 to March 2020. The profiles include low-, moderate-, high- and very-high-risk categories.
The study, led by Mert Sekmen with the division of hospital medicine at Monroe Carell Jr. Children’s Hospital, and a student at Vanderbilt University Medical Center in Nashville, Tenn., included 1,098 children, average age 14. Of those, 406 (37%) were diagnosed with a self-harm event.
Traditionally, single diagnoses have been linked with risk of self-harm, independent of other comorbidities, but this study gauges risk for a set of diagnoses.
Findings were published online in Pediatrics.
The risk groups were described as follows:
- Low risk. (45% of the study population; median risk of 0.04 (interquartile range, 0.03-0.04; odds ratio, 0.08). The group included children aged 5-9 years with a non–mental health diagnosis, and without mood, behavioral, psychotic, developmental, trauma, or substance-related disorders.
- Moderate risk. (8% of the study group). This group had the same risk as the baseline risk for the entire cohort (37%) and served as the reference group, with a median risk of 0.30 (IQR, 0.27-0.33). This profile was characterized by several mood disorders and behavioral disorders but without depressive disorders.
- High risk. (36%) This group had an average risk of 0.69 (IQR, 0.67-0.71; OR, 5.09). This profile included female adolescents ages 14-17 with depression and anxiety in conjunction with substance- and trauma-related disorders. Personality and eating disorders were significant in this group. Importantly, the authors wrote, the high-risk group did not include behavioral and developmental disorders.
- Very high risk. (11%) The very-high-risk profile had the highest average risk of 0.79 (IQR, 0.73-0.79; OR, 7.21) and included male children aged 10-13. This profile, like the high-risk profile, included anxiety and depressive disorders. The very-high-risk profile differed from the high-risk with its inclusion of bipolar disorder; attention-deficit/hyperactivity disorder; and trauma-related and developmental disorders such as autism spectrum disorder or intellectual disability, along with conduct disorders. Neither the high- nor the very-high-risk profiles included a concurrent non–mental health diagnosis.
Differences by sex
The authors explained some of the differences by sex. They noted that in a study of children aged 5-11, deaths by suicide were more prevalent among boys. A mental health diagnosis was identified in 31%, the most common being ADHD, depression, and other unspecified co-occurring disorders.
“The very-high-risk group also reflects a concerning rise in death by suicide among (males) aged 10-13, who have seen rates nearly triple from 2007 to 2017,” the authors wrote.
The authors pointed out that, although incidence of anxiety and depressive disorders between male and female children is much the same before adolescence, “female adolescents are twice as likely to be diagnosed with either disorder during adolescence. Girls also have higher rates of suicidal ideation and attempts after puberty.”
Eating disorders were also included in the high-risk profile. A study showed that emergency department visits for adolescent girls attempting suicide were 51% higher from February to March 2021, compared with the same period in the pre-COVID-19 year 2019.
Jason Lewis, PhD, psychologist and section director of mood, anxiety and trauma disorders in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia, who was not part of the research team, said the “constellations of risk factors put into acuity levels” helps to better project risk than knowing the risk associated with a particular diagnosis.
Gap closing between young children, adolescents
Dr. Lewis said he was surprised by the young age of 10-13 among the boys in the highest-risk category. That speaks to the differences from standard thinking this paper points out, he said. “Generally, we think about adolescents as being at the highest risk of suicide death and suicidal behavior,” he said.
Dr. Lewis said it’s important to note that the authors acknowledge these profiles are not static. He gave an example that the rate of suicide deaths among females is rising.
“As things like that change, some of these risk profiles will change as well.”
Dr. Lewis said the profiles may be especially helpful to medical providers in emergency departments or those making discharge decisions who don’t have an ongoing relationship with a patient.
The information could also help educators and lay people, “think about suicide in the youth population in ways we don’t normally think about it,” Dr. Lewis said.
Covariates considered for profiles were determined through expert consensus between pediatric psychiatrists, general pediatricians, pediatric hospitalists, pediatric complex care physicians, and pediatric pharmacoepidemiologists.
Age was broken into three groups: 5-9 years, 10-13 years, and 14-17 years based on Centers for Disease Control and Prevention reporting and previous studies that showed significant increases in suicide rates in these age-based subgroups.
Results are preliminary
The authors note that the profiles were developed using data from 1,000 children with neuropsychiatric complaints at two academic children’s hospitals and are thus preliminary.
“Future studies should focus on validating these risk profiles in a larger, more heterogeneous population of children and adolescents,” the authors write.
They also acknowledge that they were not able to include factors such as medication use, previous suicidal behavior, and family and social support, which also factor into risk.
The study authors and Dr. Lewis report no relevant financial relationships.
FROM PEDIATRICS
Researchers seek to understand post-COVID autoimmune disease risk
Since the COVID-19 pandemic started more than 3 years ago, the longer-lasting effects of SARS-CoV-2 infection have continued to reveal themselves. Approximately 28% of Americans report having ever experienced post-COVID conditions, such as brain fog, postexertional malaise, and joint pain, and 11% say they are still experiencing these long-term effects. Now, new research is showing that people who have had COVID are more likely to newly develop an autoimmune disease. Exactly why this is happening is less clear, experts say.
Two preprint studies and one study published in a peer-reviewed journal provide strong evidence that patients who have been infected with SARS-CoV-2 are at elevated risk of developing an autoimmune disease. The studies retrospectively reviewed medical records from three countries and compared the incidence of new-onset autoimmune disease among patients who had polymerase chain reaction–confirmed COVID-19 and those who had never been diagnosed with the virus.
A study analyzing the health records of 3.8 million U.S. patients – more than 888,460 with confirmed COVID-19 – found that the COVID-19 group was two to three times as likely to develop various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. A U.K. preprint study that included more than 458,000 people with confirmed COVID found that those who had previously been infected with SARS-CoV-2 were 22% more likely to develop an autoimmune disease compared with the control group. In this cohort, the diseases most strongly associated with COVID-19 were type 1 diabetes, inflammatory bowel disease, and psoriasis. A preprint study from German researchers found that COVID-19 patients were almost 43% more likely to develop an autoimmune disease, compared with those who had never been infected. COVID-19 was most strongly linked to vasculitis.
These large studies are telling us, “Yes, this link is there, so we have to accept it,” Sonia Sharma, PhD, of the Center for Autoimmunity and Inflammation at the La Jolla (Calif.) Institute for Immunology, told this news organization. But this is not the first time that autoimmune diseases have been linked to previous infections.
Researchers have known for decades that Epstein-Barr virus infection is linked to several autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. More recent research suggests the virus may activate certain genes associated with these immune disorders. Hepatitis C virus can induce cryoglobulinemia, and infection with cytomegalovirus has been implicated in several autoimmune diseases. Bacterial infections have also been linked to autoimmunity, such as group A streptococcus and rheumatic fever, as well as salmonella and reactive arthritis, to name only a few.
“In a way, this isn’t necessarily a new concept to physicians, particularly rheumatologists,” said Jeffrey A. Sparks, MD, a rheumatologist at Brigham and Women’s Hospital in Boston. “There’s a fine line between appropriately clearing an infection and the body overreacting and setting off a cascade where the immune system is chronically overactive that can manifest as an autoimmune disease,” he told this news organization.
A dysregulated response to infection
It takes the immune system a week or two to develop antigen-specific antibodies to a new pathogen. But for patients with serious infections – in this instance, COVID-19 – that’s time they don’t have. Therefore, the immune system has an alternative pathway, called extrafollicular activation, that creates fast-acting antibodies, explained Matthew Woodruff, PhD, an instructor of immunology and rheumatology at Emory University, Atlanta.
The trade-off is that these antibodies are not as specific and can target the body’s own tissues. This dysregulation of antibody selection is generally short lived and fades when more targeted antibodies are produced and take over, but in some cases, this process can lead to high levels of self-targeting antibodies that can harm the body’s organs and tissues. Research also suggests that for patients who experience long COVID, the same autoantibodies that drive the initial immune response are detectable in the body months after infection, though it is not known whether these lingering immune cells cause these longer-lasting symptoms.
“If you have a virus that causes hyperinflammation plus organ damage, that is a recipe for disaster,” Dr. Sharma said. “It’s a recipe for autoantibodies and autoreactive T cells that down the road can attack the body’s own tissues, especially in people whose immune system is trained in such a way to cause self-reactivity,” she added.
This hyperinflammation can result in rare but serious complications, such as multisystem inflammatory syndrome in children and adults, which can occur 2-6 weeks after SARS-CoV-2 infection. But even in these patients with severe illness, organ-specific complications tend to resolve in 6 months with “no significant sequelae 1 year after diagnosis,” according to the Centers for Disease Control and Prevention. And while long COVID can last for a year or longer, data suggest that symptoms do eventually resolve for most people. What is not clear is why acute autoimmunity triggered by COVID-19 can become a chronic condition in certain patients.
Predisposition to autoimmunity
P. J. Utz, MD, PhD, professor of immunology and rheumatology at Stanford (Calif.) University, said that people who develop autoimmune disease after SARS-CoV-2 infection may have already been predisposed toward autoimmunity. Especially for autoimmune diseases such as type 1 diabetes and lupus, autoantibodies can appear and circulate in the body for more than a decade in some people before they present with any clinical symptoms. “Their immune system is primed such that if they get infected with something – or they have some other environmental trigger that maybe we don’t know about yet – that is enough to then push them over the edge so that they get full-blown autoimmunity,” he said. What is not known is whether these patients’ conditions would have advanced to true clinical disease had they not been infected, he said.
He also noted that the presence of autoantibodies does not necessarily mean someone has autoimmune disease; healthy people can also have autoantibodies, and everyone develops them with age. “My advice would be, ‘Don’t lose sleep over this,’ “ he said.
Dr. Sparks agreed that while these retrospective studies did show an elevated risk of autoimmune disease after COVID-19, that risk appears to be relatively small. “As a practicing rheumatologist, we aren’t seeing a stampede of patients with new-onset rheumatic diseases,” he said. “It’s not like we’re overwhelmed with autoimmune patients, even though almost everyone’s had COVID. So, if there is a risk, it’s very modest.”
Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Utz receives research funding from Pfizer. Dr. Sharma and Dr. Woodruff have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Since the COVID-19 pandemic started more than 3 years ago, the longer-lasting effects of SARS-CoV-2 infection have continued to reveal themselves. Approximately 28% of Americans report having ever experienced post-COVID conditions, such as brain fog, postexertional malaise, and joint pain, and 11% say they are still experiencing these long-term effects. Now, new research is showing that people who have had COVID are more likely to newly develop an autoimmune disease. Exactly why this is happening is less clear, experts say.
Two preprint studies and one study published in a peer-reviewed journal provide strong evidence that patients who have been infected with SARS-CoV-2 are at elevated risk of developing an autoimmune disease. The studies retrospectively reviewed medical records from three countries and compared the incidence of new-onset autoimmune disease among patients who had polymerase chain reaction–confirmed COVID-19 and those who had never been diagnosed with the virus.
A study analyzing the health records of 3.8 million U.S. patients – more than 888,460 with confirmed COVID-19 – found that the COVID-19 group was two to three times as likely to develop various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. A U.K. preprint study that included more than 458,000 people with confirmed COVID found that those who had previously been infected with SARS-CoV-2 were 22% more likely to develop an autoimmune disease compared with the control group. In this cohort, the diseases most strongly associated with COVID-19 were type 1 diabetes, inflammatory bowel disease, and psoriasis. A preprint study from German researchers found that COVID-19 patients were almost 43% more likely to develop an autoimmune disease, compared with those who had never been infected. COVID-19 was most strongly linked to vasculitis.
These large studies are telling us, “Yes, this link is there, so we have to accept it,” Sonia Sharma, PhD, of the Center for Autoimmunity and Inflammation at the La Jolla (Calif.) Institute for Immunology, told this news organization. But this is not the first time that autoimmune diseases have been linked to previous infections.
Researchers have known for decades that Epstein-Barr virus infection is linked to several autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. More recent research suggests the virus may activate certain genes associated with these immune disorders. Hepatitis C virus can induce cryoglobulinemia, and infection with cytomegalovirus has been implicated in several autoimmune diseases. Bacterial infections have also been linked to autoimmunity, such as group A streptococcus and rheumatic fever, as well as salmonella and reactive arthritis, to name only a few.
“In a way, this isn’t necessarily a new concept to physicians, particularly rheumatologists,” said Jeffrey A. Sparks, MD, a rheumatologist at Brigham and Women’s Hospital in Boston. “There’s a fine line between appropriately clearing an infection and the body overreacting and setting off a cascade where the immune system is chronically overactive that can manifest as an autoimmune disease,” he told this news organization.
A dysregulated response to infection
It takes the immune system a week or two to develop antigen-specific antibodies to a new pathogen. But for patients with serious infections – in this instance, COVID-19 – that’s time they don’t have. Therefore, the immune system has an alternative pathway, called extrafollicular activation, that creates fast-acting antibodies, explained Matthew Woodruff, PhD, an instructor of immunology and rheumatology at Emory University, Atlanta.
The trade-off is that these antibodies are not as specific and can target the body’s own tissues. This dysregulation of antibody selection is generally short lived and fades when more targeted antibodies are produced and take over, but in some cases, this process can lead to high levels of self-targeting antibodies that can harm the body’s organs and tissues. Research also suggests that for patients who experience long COVID, the same autoantibodies that drive the initial immune response are detectable in the body months after infection, though it is not known whether these lingering immune cells cause these longer-lasting symptoms.
“If you have a virus that causes hyperinflammation plus organ damage, that is a recipe for disaster,” Dr. Sharma said. “It’s a recipe for autoantibodies and autoreactive T cells that down the road can attack the body’s own tissues, especially in people whose immune system is trained in such a way to cause self-reactivity,” she added.
This hyperinflammation can result in rare but serious complications, such as multisystem inflammatory syndrome in children and adults, which can occur 2-6 weeks after SARS-CoV-2 infection. But even in these patients with severe illness, organ-specific complications tend to resolve in 6 months with “no significant sequelae 1 year after diagnosis,” according to the Centers for Disease Control and Prevention. And while long COVID can last for a year or longer, data suggest that symptoms do eventually resolve for most people. What is not clear is why acute autoimmunity triggered by COVID-19 can become a chronic condition in certain patients.
Predisposition to autoimmunity
P. J. Utz, MD, PhD, professor of immunology and rheumatology at Stanford (Calif.) University, said that people who develop autoimmune disease after SARS-CoV-2 infection may have already been predisposed toward autoimmunity. Especially for autoimmune diseases such as type 1 diabetes and lupus, autoantibodies can appear and circulate in the body for more than a decade in some people before they present with any clinical symptoms. “Their immune system is primed such that if they get infected with something – or they have some other environmental trigger that maybe we don’t know about yet – that is enough to then push them over the edge so that they get full-blown autoimmunity,” he said. What is not known is whether these patients’ conditions would have advanced to true clinical disease had they not been infected, he said.
He also noted that the presence of autoantibodies does not necessarily mean someone has autoimmune disease; healthy people can also have autoantibodies, and everyone develops them with age. “My advice would be, ‘Don’t lose sleep over this,’ “ he said.
Dr. Sparks agreed that while these retrospective studies did show an elevated risk of autoimmune disease after COVID-19, that risk appears to be relatively small. “As a practicing rheumatologist, we aren’t seeing a stampede of patients with new-onset rheumatic diseases,” he said. “It’s not like we’re overwhelmed with autoimmune patients, even though almost everyone’s had COVID. So, if there is a risk, it’s very modest.”
Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Utz receives research funding from Pfizer. Dr. Sharma and Dr. Woodruff have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Since the COVID-19 pandemic started more than 3 years ago, the longer-lasting effects of SARS-CoV-2 infection have continued to reveal themselves. Approximately 28% of Americans report having ever experienced post-COVID conditions, such as brain fog, postexertional malaise, and joint pain, and 11% say they are still experiencing these long-term effects. Now, new research is showing that people who have had COVID are more likely to newly develop an autoimmune disease. Exactly why this is happening is less clear, experts say.
Two preprint studies and one study published in a peer-reviewed journal provide strong evidence that patients who have been infected with SARS-CoV-2 are at elevated risk of developing an autoimmune disease. The studies retrospectively reviewed medical records from three countries and compared the incidence of new-onset autoimmune disease among patients who had polymerase chain reaction–confirmed COVID-19 and those who had never been diagnosed with the virus.
A study analyzing the health records of 3.8 million U.S. patients – more than 888,460 with confirmed COVID-19 – found that the COVID-19 group was two to three times as likely to develop various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. A U.K. preprint study that included more than 458,000 people with confirmed COVID found that those who had previously been infected with SARS-CoV-2 were 22% more likely to develop an autoimmune disease compared with the control group. In this cohort, the diseases most strongly associated with COVID-19 were type 1 diabetes, inflammatory bowel disease, and psoriasis. A preprint study from German researchers found that COVID-19 patients were almost 43% more likely to develop an autoimmune disease, compared with those who had never been infected. COVID-19 was most strongly linked to vasculitis.
These large studies are telling us, “Yes, this link is there, so we have to accept it,” Sonia Sharma, PhD, of the Center for Autoimmunity and Inflammation at the La Jolla (Calif.) Institute for Immunology, told this news organization. But this is not the first time that autoimmune diseases have been linked to previous infections.
Researchers have known for decades that Epstein-Barr virus infection is linked to several autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. More recent research suggests the virus may activate certain genes associated with these immune disorders. Hepatitis C virus can induce cryoglobulinemia, and infection with cytomegalovirus has been implicated in several autoimmune diseases. Bacterial infections have also been linked to autoimmunity, such as group A streptococcus and rheumatic fever, as well as salmonella and reactive arthritis, to name only a few.
“In a way, this isn’t necessarily a new concept to physicians, particularly rheumatologists,” said Jeffrey A. Sparks, MD, a rheumatologist at Brigham and Women’s Hospital in Boston. “There’s a fine line between appropriately clearing an infection and the body overreacting and setting off a cascade where the immune system is chronically overactive that can manifest as an autoimmune disease,” he told this news organization.
A dysregulated response to infection
It takes the immune system a week or two to develop antigen-specific antibodies to a new pathogen. But for patients with serious infections – in this instance, COVID-19 – that’s time they don’t have. Therefore, the immune system has an alternative pathway, called extrafollicular activation, that creates fast-acting antibodies, explained Matthew Woodruff, PhD, an instructor of immunology and rheumatology at Emory University, Atlanta.
The trade-off is that these antibodies are not as specific and can target the body’s own tissues. This dysregulation of antibody selection is generally short lived and fades when more targeted antibodies are produced and take over, but in some cases, this process can lead to high levels of self-targeting antibodies that can harm the body’s organs and tissues. Research also suggests that for patients who experience long COVID, the same autoantibodies that drive the initial immune response are detectable in the body months after infection, though it is not known whether these lingering immune cells cause these longer-lasting symptoms.
“If you have a virus that causes hyperinflammation plus organ damage, that is a recipe for disaster,” Dr. Sharma said. “It’s a recipe for autoantibodies and autoreactive T cells that down the road can attack the body’s own tissues, especially in people whose immune system is trained in such a way to cause self-reactivity,” she added.
This hyperinflammation can result in rare but serious complications, such as multisystem inflammatory syndrome in children and adults, which can occur 2-6 weeks after SARS-CoV-2 infection. But even in these patients with severe illness, organ-specific complications tend to resolve in 6 months with “no significant sequelae 1 year after diagnosis,” according to the Centers for Disease Control and Prevention. And while long COVID can last for a year or longer, data suggest that symptoms do eventually resolve for most people. What is not clear is why acute autoimmunity triggered by COVID-19 can become a chronic condition in certain patients.
Predisposition to autoimmunity
P. J. Utz, MD, PhD, professor of immunology and rheumatology at Stanford (Calif.) University, said that people who develop autoimmune disease after SARS-CoV-2 infection may have already been predisposed toward autoimmunity. Especially for autoimmune diseases such as type 1 diabetes and lupus, autoantibodies can appear and circulate in the body for more than a decade in some people before they present with any clinical symptoms. “Their immune system is primed such that if they get infected with something – or they have some other environmental trigger that maybe we don’t know about yet – that is enough to then push them over the edge so that they get full-blown autoimmunity,” he said. What is not known is whether these patients’ conditions would have advanced to true clinical disease had they not been infected, he said.
He also noted that the presence of autoantibodies does not necessarily mean someone has autoimmune disease; healthy people can also have autoantibodies, and everyone develops them with age. “My advice would be, ‘Don’t lose sleep over this,’ “ he said.
Dr. Sparks agreed that while these retrospective studies did show an elevated risk of autoimmune disease after COVID-19, that risk appears to be relatively small. “As a practicing rheumatologist, we aren’t seeing a stampede of patients with new-onset rheumatic diseases,” he said. “It’s not like we’re overwhelmed with autoimmune patients, even though almost everyone’s had COVID. So, if there is a risk, it’s very modest.”
Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Utz receives research funding from Pfizer. Dr. Sharma and Dr. Woodruff have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Can you spot hypermobility spectrum disorder?
Joint hypermobility syndrome, popularly known as being double-jointed, may be a common but underrecognized disorder in adults that is difficult to diagnose and often mistaken for fibromyalgia or other conditions.
So said Matthew B. Carroll, MD, a board-certified rheumatologist with Singing River Health System, Ocean Springs, Miss., during a presentation about hypermobility at the annual meeting of the American College of Physicians.
According to Dr. Carroll, the concept of a hypermobility spectrum disorder (HSD) associated with double-jointedness is relatively new and not part of the conventional nomenclature.
“One of the frustrations about HSD is that there really aren’t any good theories,” as to why some with hypermobility suffer from the syndrome while others do not, Dr. Carroll said.
Hypermobility is defined as having joints that are looser than normal. Examples of this include hyperextending the forearm at the elbow or pressing the thumb against the surface of the forearm.
Approximately 20% of the adult population has hypermobility, which affects women more than men and is more common in younger people. In children ages 3-19 years, 32% of girls and 18% of boys are hypermobile.
But the condition is not a diagnosis, “it’s a descriptor of a finding that you notice on a physical exam,” Dr. Carroll said.
When flexibility is a problem
Although hypermobility often is benign and rarely progresses to more serious health issues, HSD can cause symptoms such as recurrent dislocations, joint pain, and other degenerative changes. Recent evidence suggests that abnormal bleeding may also accompany hypermobility.
A 2013 survey in the United Kingdom found that about 3% of respondents reported pain as a consequence of their hypermobility. Dr. Carroll hypothesized that up to a quarter of those diagnosed with hypermobility have some associated pain.
“We kind of think of hypermobility as either being benign, or you kind of have it as a kid and grow out of it,” Dr. Carroll said. “But the reality is a lot of our patients keep that into adulthood and can have problems as a consequence.”
Because some of the symptoms of HSD, such as abdominal pain and fatigue, mimic other whole-body pain conditions, specifically fibromyalgia, Dr. Carroll said it likely is widely undiagnosed.
“I think a lot of these patients were diagnosed with fibromyalgia,” Dr. Carroll said. “It’s incumbent upon us to be able to start teasing some of those nuances out, or at least have rheumatology help you and other specialists figure out where you can go with these patients and their health.”
Causes of HSD
HSD can be both genetic and environmental in nature; sports injuries, spontaneous dislocations, and a fear of injury leading to a sedentary lifestyle should also be considered. The condition can overlap with Ehlers-Danlos syndromes, a rare group of inherited conditions that affect connectivity tissue.
Treating patients with HSD requires a multidisciplinary approach, including primary care, rheumatologists, geneticists, and orthopedists. If primary care physicians suspect their patient has hypermobility, they should explore this possibility before moving on to another diagnosis. Whether an adult has or had joint mobility can be determined through a series of simple questions:
- Can you bend your thumb to touch your forearm?
- As a child, did you amuse your friends by contorting your body into strange shapes?
- Do you consider yourself double-jointed?
“It gets really kind of muddy and really difficult to tease out, but I think it’s something that takes time in an iterative process to figure out,” Dr. Carroll said.
Treatment options for HSD are limited. No disease-directed pharmacologic agents exist, and interventions in general lack rigorous studies to support their use. Dr. Carroll recommends anti-inflammatory drugs and physical therapy as first-line approaches. He also stressed that lifestyle interventions – particularly exercise and weight loss – are essential. The role of surgery at this time is unclear and only used in highly selected cases. An appointment with a geneticist could also be necessary to explore family history and look for Ehlers‐Danlos syndromes.
“You’re going to need several different specialists to try to really help our patients get back up and running,” he said.
Dr. Carroll reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Joint hypermobility syndrome, popularly known as being double-jointed, may be a common but underrecognized disorder in adults that is difficult to diagnose and often mistaken for fibromyalgia or other conditions.
So said Matthew B. Carroll, MD, a board-certified rheumatologist with Singing River Health System, Ocean Springs, Miss., during a presentation about hypermobility at the annual meeting of the American College of Physicians.
According to Dr. Carroll, the concept of a hypermobility spectrum disorder (HSD) associated with double-jointedness is relatively new and not part of the conventional nomenclature.
“One of the frustrations about HSD is that there really aren’t any good theories,” as to why some with hypermobility suffer from the syndrome while others do not, Dr. Carroll said.
Hypermobility is defined as having joints that are looser than normal. Examples of this include hyperextending the forearm at the elbow or pressing the thumb against the surface of the forearm.
Approximately 20% of the adult population has hypermobility, which affects women more than men and is more common in younger people. In children ages 3-19 years, 32% of girls and 18% of boys are hypermobile.
But the condition is not a diagnosis, “it’s a descriptor of a finding that you notice on a physical exam,” Dr. Carroll said.
When flexibility is a problem
Although hypermobility often is benign and rarely progresses to more serious health issues, HSD can cause symptoms such as recurrent dislocations, joint pain, and other degenerative changes. Recent evidence suggests that abnormal bleeding may also accompany hypermobility.
A 2013 survey in the United Kingdom found that about 3% of respondents reported pain as a consequence of their hypermobility. Dr. Carroll hypothesized that up to a quarter of those diagnosed with hypermobility have some associated pain.
“We kind of think of hypermobility as either being benign, or you kind of have it as a kid and grow out of it,” Dr. Carroll said. “But the reality is a lot of our patients keep that into adulthood and can have problems as a consequence.”
Because some of the symptoms of HSD, such as abdominal pain and fatigue, mimic other whole-body pain conditions, specifically fibromyalgia, Dr. Carroll said it likely is widely undiagnosed.
“I think a lot of these patients were diagnosed with fibromyalgia,” Dr. Carroll said. “It’s incumbent upon us to be able to start teasing some of those nuances out, or at least have rheumatology help you and other specialists figure out where you can go with these patients and their health.”
Causes of HSD
HSD can be both genetic and environmental in nature; sports injuries, spontaneous dislocations, and a fear of injury leading to a sedentary lifestyle should also be considered. The condition can overlap with Ehlers-Danlos syndromes, a rare group of inherited conditions that affect connectivity tissue.
Treating patients with HSD requires a multidisciplinary approach, including primary care, rheumatologists, geneticists, and orthopedists. If primary care physicians suspect their patient has hypermobility, they should explore this possibility before moving on to another diagnosis. Whether an adult has or had joint mobility can be determined through a series of simple questions:
- Can you bend your thumb to touch your forearm?
- As a child, did you amuse your friends by contorting your body into strange shapes?
- Do you consider yourself double-jointed?
“It gets really kind of muddy and really difficult to tease out, but I think it’s something that takes time in an iterative process to figure out,” Dr. Carroll said.
Treatment options for HSD are limited. No disease-directed pharmacologic agents exist, and interventions in general lack rigorous studies to support their use. Dr. Carroll recommends anti-inflammatory drugs and physical therapy as first-line approaches. He also stressed that lifestyle interventions – particularly exercise and weight loss – are essential. The role of surgery at this time is unclear and only used in highly selected cases. An appointment with a geneticist could also be necessary to explore family history and look for Ehlers‐Danlos syndromes.
“You’re going to need several different specialists to try to really help our patients get back up and running,” he said.
Dr. Carroll reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Joint hypermobility syndrome, popularly known as being double-jointed, may be a common but underrecognized disorder in adults that is difficult to diagnose and often mistaken for fibromyalgia or other conditions.
So said Matthew B. Carroll, MD, a board-certified rheumatologist with Singing River Health System, Ocean Springs, Miss., during a presentation about hypermobility at the annual meeting of the American College of Physicians.
According to Dr. Carroll, the concept of a hypermobility spectrum disorder (HSD) associated with double-jointedness is relatively new and not part of the conventional nomenclature.
“One of the frustrations about HSD is that there really aren’t any good theories,” as to why some with hypermobility suffer from the syndrome while others do not, Dr. Carroll said.
Hypermobility is defined as having joints that are looser than normal. Examples of this include hyperextending the forearm at the elbow or pressing the thumb against the surface of the forearm.
Approximately 20% of the adult population has hypermobility, which affects women more than men and is more common in younger people. In children ages 3-19 years, 32% of girls and 18% of boys are hypermobile.
But the condition is not a diagnosis, “it’s a descriptor of a finding that you notice on a physical exam,” Dr. Carroll said.
When flexibility is a problem
Although hypermobility often is benign and rarely progresses to more serious health issues, HSD can cause symptoms such as recurrent dislocations, joint pain, and other degenerative changes. Recent evidence suggests that abnormal bleeding may also accompany hypermobility.
A 2013 survey in the United Kingdom found that about 3% of respondents reported pain as a consequence of their hypermobility. Dr. Carroll hypothesized that up to a quarter of those diagnosed with hypermobility have some associated pain.
“We kind of think of hypermobility as either being benign, or you kind of have it as a kid and grow out of it,” Dr. Carroll said. “But the reality is a lot of our patients keep that into adulthood and can have problems as a consequence.”
Because some of the symptoms of HSD, such as abdominal pain and fatigue, mimic other whole-body pain conditions, specifically fibromyalgia, Dr. Carroll said it likely is widely undiagnosed.
“I think a lot of these patients were diagnosed with fibromyalgia,” Dr. Carroll said. “It’s incumbent upon us to be able to start teasing some of those nuances out, or at least have rheumatology help you and other specialists figure out where you can go with these patients and their health.”
Causes of HSD
HSD can be both genetic and environmental in nature; sports injuries, spontaneous dislocations, and a fear of injury leading to a sedentary lifestyle should also be considered. The condition can overlap with Ehlers-Danlos syndromes, a rare group of inherited conditions that affect connectivity tissue.
Treating patients with HSD requires a multidisciplinary approach, including primary care, rheumatologists, geneticists, and orthopedists. If primary care physicians suspect their patient has hypermobility, they should explore this possibility before moving on to another diagnosis. Whether an adult has or had joint mobility can be determined through a series of simple questions:
- Can you bend your thumb to touch your forearm?
- As a child, did you amuse your friends by contorting your body into strange shapes?
- Do you consider yourself double-jointed?
“It gets really kind of muddy and really difficult to tease out, but I think it’s something that takes time in an iterative process to figure out,” Dr. Carroll said.
Treatment options for HSD are limited. No disease-directed pharmacologic agents exist, and interventions in general lack rigorous studies to support their use. Dr. Carroll recommends anti-inflammatory drugs and physical therapy as first-line approaches. He also stressed that lifestyle interventions – particularly exercise and weight loss – are essential. The role of surgery at this time is unclear and only used in highly selected cases. An appointment with a geneticist could also be necessary to explore family history and look for Ehlers‐Danlos syndromes.
“You’re going to need several different specialists to try to really help our patients get back up and running,” he said.
Dr. Carroll reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM INTERNAL MEDICINE 2023
Donanemab bests aducanumab in head-to-head Alzheimer’s trial
BOSTON –
Nearly 40% of patients treated with donanemab had amyloid clearance at 6 months compared with less than 2% of those who received aducanumab, which was approved in 2021 amid a great deal of controversy.
Titration for donanemab progressed more quickly, with participants receiving a maximum dose twice as early as those on aducanumab, without any increase in rates of amyloid-related imaging abnormalities (ARIA) – the most common side effect of amyloid drugs.
Early results from the randomized phase 3 TRAILBLAZER-ALZ 4 trial of donanemab come just 3 months after the Food and Drug Administration denied manufacturer Eli Lilly’s request for accelerated approval for the drug.
“This study shows that the drug with the quicker titration scheme, donanemab, produced more amyloid lowering and did it without having more ARIA,” said lead investigator Stephen P. Salloway, MD, director of the Memory and Aging Program at Butler Hospital in Providence, R.I., and a professor of neurology at Brown University.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
Multicenter, head-to-head trial
Donanemab received breakthrough therapy designation in 2021. The drug works similarly to aducanumab and lecanemab, which was approved earlier this year. All three bind to different parts of the amyloid molecule and stimulate an immune response to help clear amyloid plaques, although they each have a distinctive binding component.
TRAILBLAZER-ALZ 4 was conducted at 31 sites across the United States, enrolling 140 patients aged 50-85 years with early and symptomatic Alzheimer’s disease. Study participants received donanemab or aducanumab at escalating doses for 18 months.
Donanemab was titrated more quickly, with participants receiving 700 mg via IV infusion once a month for 3 months before reaching the maximum dose of 1,400 mg in the fourth month of the study.
Aducanumab titration was slower, beginning at 1 mg/kg via IV monthly for 2 months, then 3 mg/kg for another 2 months, and 6 mg/kg for 2 more months before reaching the maximum dose of 10 mg/kg in the seventh month.
After 6 months of treatment, PET scan analysis revealed that 37.9% of donanemab-treated patients achieved amyloid clearance compared with just 1.6% of those who received aducanumab (P < .001).
Among patients with intermediate tau levels (n = 27 for donanemab and n = 28 for aducanumab), 38.5% of those who received donanemab achieved amyloid clearance compared with 3.8% of patients in the aducanumab group (P = .008).
Amyloid levels were 65.2% lower in donanemab patients, while levels in those receiving aducanumab were reduced by 17.0% (P < .001). Among those with intermediate tau, amyloid levels decreased with donanemab by 63.9% and 25.4% with aducanumab (P ≤ .001).
Investigators also noted a greater reduction in plasma ptau217 with donanemab.
Adverse events were similar between groups, with 62.0% of the donanemab group and 66.7% of aducanumab-treated participants reporting an adverse event.
There were no serious adverse events due to ARIA with donanemab, but one participant in the aducanumab group had a serious adverse event linked to ARIA.
“Even though the amyloid lowering was greater with donanemab, the rate of ARIA was similar, which suggests that the speed and depth of amyloid removal is not driving ARIA,” Dr. Salloway said.
There are three other Trailblazer trials of donanemab. Unlike in similar trials, participants in all three of these studies who received the trial drug could discontinue treatment once criteria for amyloid clearance were met.
That’s precisely what happened with Trailblazer 2, the study on which Lilly based its request for accelerated approval. Ironically, that trial design also contributed to the FDA’s decision to reject that request.
The FDA required data from at least 100 patients who had received donanemab for a minimum of 1 year. While the trial included more than 100 patients, many patients discontinued treatment early after achieving the targeted amount of amyloid clearance.
“They had success, and they got punished for it, in my opinion,” Dr. Salloway said.
Final data from Trailblazer 2 is due in the next month, and if results are positive, Lilly is expected to file for full approval.
Questions remain
“This is an interesting study that suggests donanemab may remove amyloid faster in more people than aducanumab,” said Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings.
Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, also commented on the findings. He noted that faster amyloid clearance “means less time for requiring sometimes burdensome and expensive infusions.”
Both Dr. Snyder and Dr. Fillit noted that longer-term results are needed, along with studies of whether amyloid clearance offers a protective benefit against Alzheimer’s dementia. More results from Trailblazer 4 will be reported after 12 months and again at 18 months.
“There are obviously still a lot of questions about these drugs and whether reducing amyloid plaque will actually preserve cognitive function or at least slow decline,” Dr. Fillit said.
It will also be important to understand the timing of treatment, including when anti-amyloid therapies should be administered and for how long.
“It will be important to understand how these results translate to patient care and treatment plans, should this drug receive FDA approval,” Dr. Snyder said. “Patients should have the opportunity to make a decision, alongside their physician, on a treatment path that is right for them.”
The study was funded by Eli Lilly. Dr. Salloway has been a consultant for Biogen, EISAI, Lilly, Genentech, Novo Nordisk, Prothena, and others. Dr. Snyder and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON –
Nearly 40% of patients treated with donanemab had amyloid clearance at 6 months compared with less than 2% of those who received aducanumab, which was approved in 2021 amid a great deal of controversy.
Titration for donanemab progressed more quickly, with participants receiving a maximum dose twice as early as those on aducanumab, without any increase in rates of amyloid-related imaging abnormalities (ARIA) – the most common side effect of amyloid drugs.
Early results from the randomized phase 3 TRAILBLAZER-ALZ 4 trial of donanemab come just 3 months after the Food and Drug Administration denied manufacturer Eli Lilly’s request for accelerated approval for the drug.
“This study shows that the drug with the quicker titration scheme, donanemab, produced more amyloid lowering and did it without having more ARIA,” said lead investigator Stephen P. Salloway, MD, director of the Memory and Aging Program at Butler Hospital in Providence, R.I., and a professor of neurology at Brown University.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
Multicenter, head-to-head trial
Donanemab received breakthrough therapy designation in 2021. The drug works similarly to aducanumab and lecanemab, which was approved earlier this year. All three bind to different parts of the amyloid molecule and stimulate an immune response to help clear amyloid plaques, although they each have a distinctive binding component.
TRAILBLAZER-ALZ 4 was conducted at 31 sites across the United States, enrolling 140 patients aged 50-85 years with early and symptomatic Alzheimer’s disease. Study participants received donanemab or aducanumab at escalating doses for 18 months.
Donanemab was titrated more quickly, with participants receiving 700 mg via IV infusion once a month for 3 months before reaching the maximum dose of 1,400 mg in the fourth month of the study.
Aducanumab titration was slower, beginning at 1 mg/kg via IV monthly for 2 months, then 3 mg/kg for another 2 months, and 6 mg/kg for 2 more months before reaching the maximum dose of 10 mg/kg in the seventh month.
After 6 months of treatment, PET scan analysis revealed that 37.9% of donanemab-treated patients achieved amyloid clearance compared with just 1.6% of those who received aducanumab (P < .001).
Among patients with intermediate tau levels (n = 27 for donanemab and n = 28 for aducanumab), 38.5% of those who received donanemab achieved amyloid clearance compared with 3.8% of patients in the aducanumab group (P = .008).
Amyloid levels were 65.2% lower in donanemab patients, while levels in those receiving aducanumab were reduced by 17.0% (P < .001). Among those with intermediate tau, amyloid levels decreased with donanemab by 63.9% and 25.4% with aducanumab (P ≤ .001).
Investigators also noted a greater reduction in plasma ptau217 with donanemab.
Adverse events were similar between groups, with 62.0% of the donanemab group and 66.7% of aducanumab-treated participants reporting an adverse event.
There were no serious adverse events due to ARIA with donanemab, but one participant in the aducanumab group had a serious adverse event linked to ARIA.
“Even though the amyloid lowering was greater with donanemab, the rate of ARIA was similar, which suggests that the speed and depth of amyloid removal is not driving ARIA,” Dr. Salloway said.
There are three other Trailblazer trials of donanemab. Unlike in similar trials, participants in all three of these studies who received the trial drug could discontinue treatment once criteria for amyloid clearance were met.
That’s precisely what happened with Trailblazer 2, the study on which Lilly based its request for accelerated approval. Ironically, that trial design also contributed to the FDA’s decision to reject that request.
The FDA required data from at least 100 patients who had received donanemab for a minimum of 1 year. While the trial included more than 100 patients, many patients discontinued treatment early after achieving the targeted amount of amyloid clearance.
“They had success, and they got punished for it, in my opinion,” Dr. Salloway said.
Final data from Trailblazer 2 is due in the next month, and if results are positive, Lilly is expected to file for full approval.
Questions remain
“This is an interesting study that suggests donanemab may remove amyloid faster in more people than aducanumab,” said Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings.
Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, also commented on the findings. He noted that faster amyloid clearance “means less time for requiring sometimes burdensome and expensive infusions.”
Both Dr. Snyder and Dr. Fillit noted that longer-term results are needed, along with studies of whether amyloid clearance offers a protective benefit against Alzheimer’s dementia. More results from Trailblazer 4 will be reported after 12 months and again at 18 months.
“There are obviously still a lot of questions about these drugs and whether reducing amyloid plaque will actually preserve cognitive function or at least slow decline,” Dr. Fillit said.
It will also be important to understand the timing of treatment, including when anti-amyloid therapies should be administered and for how long.
“It will be important to understand how these results translate to patient care and treatment plans, should this drug receive FDA approval,” Dr. Snyder said. “Patients should have the opportunity to make a decision, alongside their physician, on a treatment path that is right for them.”
The study was funded by Eli Lilly. Dr. Salloway has been a consultant for Biogen, EISAI, Lilly, Genentech, Novo Nordisk, Prothena, and others. Dr. Snyder and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON –
Nearly 40% of patients treated with donanemab had amyloid clearance at 6 months compared with less than 2% of those who received aducanumab, which was approved in 2021 amid a great deal of controversy.
Titration for donanemab progressed more quickly, with participants receiving a maximum dose twice as early as those on aducanumab, without any increase in rates of amyloid-related imaging abnormalities (ARIA) – the most common side effect of amyloid drugs.
Early results from the randomized phase 3 TRAILBLAZER-ALZ 4 trial of donanemab come just 3 months after the Food and Drug Administration denied manufacturer Eli Lilly’s request for accelerated approval for the drug.
“This study shows that the drug with the quicker titration scheme, donanemab, produced more amyloid lowering and did it without having more ARIA,” said lead investigator Stephen P. Salloway, MD, director of the Memory and Aging Program at Butler Hospital in Providence, R.I., and a professor of neurology at Brown University.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
Multicenter, head-to-head trial
Donanemab received breakthrough therapy designation in 2021. The drug works similarly to aducanumab and lecanemab, which was approved earlier this year. All three bind to different parts of the amyloid molecule and stimulate an immune response to help clear amyloid plaques, although they each have a distinctive binding component.
TRAILBLAZER-ALZ 4 was conducted at 31 sites across the United States, enrolling 140 patients aged 50-85 years with early and symptomatic Alzheimer’s disease. Study participants received donanemab or aducanumab at escalating doses for 18 months.
Donanemab was titrated more quickly, with participants receiving 700 mg via IV infusion once a month for 3 months before reaching the maximum dose of 1,400 mg in the fourth month of the study.
Aducanumab titration was slower, beginning at 1 mg/kg via IV monthly for 2 months, then 3 mg/kg for another 2 months, and 6 mg/kg for 2 more months before reaching the maximum dose of 10 mg/kg in the seventh month.
After 6 months of treatment, PET scan analysis revealed that 37.9% of donanemab-treated patients achieved amyloid clearance compared with just 1.6% of those who received aducanumab (P < .001).
Among patients with intermediate tau levels (n = 27 for donanemab and n = 28 for aducanumab), 38.5% of those who received donanemab achieved amyloid clearance compared with 3.8% of patients in the aducanumab group (P = .008).
Amyloid levels were 65.2% lower in donanemab patients, while levels in those receiving aducanumab were reduced by 17.0% (P < .001). Among those with intermediate tau, amyloid levels decreased with donanemab by 63.9% and 25.4% with aducanumab (P ≤ .001).
Investigators also noted a greater reduction in plasma ptau217 with donanemab.
Adverse events were similar between groups, with 62.0% of the donanemab group and 66.7% of aducanumab-treated participants reporting an adverse event.
There were no serious adverse events due to ARIA with donanemab, but one participant in the aducanumab group had a serious adverse event linked to ARIA.
“Even though the amyloid lowering was greater with donanemab, the rate of ARIA was similar, which suggests that the speed and depth of amyloid removal is not driving ARIA,” Dr. Salloway said.
There are three other Trailblazer trials of donanemab. Unlike in similar trials, participants in all three of these studies who received the trial drug could discontinue treatment once criteria for amyloid clearance were met.
That’s precisely what happened with Trailblazer 2, the study on which Lilly based its request for accelerated approval. Ironically, that trial design also contributed to the FDA’s decision to reject that request.
The FDA required data from at least 100 patients who had received donanemab for a minimum of 1 year. While the trial included more than 100 patients, many patients discontinued treatment early after achieving the targeted amount of amyloid clearance.
“They had success, and they got punished for it, in my opinion,” Dr. Salloway said.
Final data from Trailblazer 2 is due in the next month, and if results are positive, Lilly is expected to file for full approval.
Questions remain
“This is an interesting study that suggests donanemab may remove amyloid faster in more people than aducanumab,” said Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings.
Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, also commented on the findings. He noted that faster amyloid clearance “means less time for requiring sometimes burdensome and expensive infusions.”
Both Dr. Snyder and Dr. Fillit noted that longer-term results are needed, along with studies of whether amyloid clearance offers a protective benefit against Alzheimer’s dementia. More results from Trailblazer 4 will be reported after 12 months and again at 18 months.
“There are obviously still a lot of questions about these drugs and whether reducing amyloid plaque will actually preserve cognitive function or at least slow decline,” Dr. Fillit said.
It will also be important to understand the timing of treatment, including when anti-amyloid therapies should be administered and for how long.
“It will be important to understand how these results translate to patient care and treatment plans, should this drug receive FDA approval,” Dr. Snyder said. “Patients should have the opportunity to make a decision, alongside their physician, on a treatment path that is right for them.”
The study was funded by Eli Lilly. Dr. Salloway has been a consultant for Biogen, EISAI, Lilly, Genentech, Novo Nordisk, Prothena, and others. Dr. Snyder and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAN 2023
New hope for adult children with ‘failure to launch’ syndrome
WASHINGTON – , a new pilot study shows.
Known as failure to launch (FTL) syndrome, the criteria for this condition include the absence of a neurodevelopmental, mental, or intellectual condition, difficulty adapting to the challenges of adulthood, and living with or at the expense of parents.
Results suggest that the program benefits families dealing with FTL, said study investigator Uri Berger, PhD, postdoctoral associate, Yale Child Study Center Anxiety and Mood Disorders Program, New Haven, Conn.
“If you encounter parents who are say 50-60 years old who have a child with FTL, you can tell them there’s something they can do; there’s work they can do even if their child is refusing to go to therapy,” he said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Anxious, isolated
Estimates suggest that there are 3.3 million physically able adults with FTL and that the disorder may be on the rise. These individuals often present with mental health symptoms including anxiety, depression, and suicidality, and tend to be socially isolated.
The investigators noted that intervening is often challenging because individuals with the syndrome are frequently noncompliant with therapy, and currently there is no standard of care.
“The longer you’re isolated, the harder it is getting out of your cocoon, and when these adult children get to the point where they seek help, they’re less likely to comply,” he said. However, he noted, this is not because they are lazy; it’s that they’re “very, very anxious.”
Parents and other family members are also negatively affected. Dr. Berger noted that 15% of parents of a child with FTL equate their caregiver burden with having a family member with a chronic physical illness. “It’s huge; parents go through hell and it’s very hard on them. Many believe it is their fault and they feel a lot of shame.”
Supportive Parenting for Anxious Childhood Emotions (SPACE) is a manualized, parent-based program for childhood anxiety and obsessive-compulsive disorder. It has been tested in clinical trials and found to be noninferior to cognitive behavioral therapy for childhood anxiety.
The research adapted it to treat FTL. SPACE-FTL focuses on reducing parents’ family accommodation (FA), a descriptor for a child’s excessive dependence on their parents to help them avoid anxiety-provoking situations.
The study examined the feasibility, acceptability, and treatment satisfaction and its effect on adult child psychopathology symptoms, parents’ FA, and the paternal burden of caring for adult children.
The study included parents (mean age, 59.46 years; 85% female) of 40 adult children with FTL (mean age, 23.51 years; 20% female) from across the United States.
Parents were randomized to a 13-week wait-list or the SPACE-FTL program, which involves 13-20 therapy sessions, depending on the need. The average number of sessions in the study was 15. The program has five key components:
- Providing information emphasizing FTL as not a character flaw but a problem with anxiety.
- Helping parents identify how they accommodate their child’s behavior, and facilitating an environment that encourages independence.
- Getting parents to show acceptance and confidence in their child who’s trying to overcome anxiety when, for example, they seek employment, instead of being overprotective and demanding.
- Focusing on change nonconfrontationally.
- Involving other family, community members, and professionals who can support the parent, child, or both.
The recruitment, treatment sessions, and assessments were all done online. Most participants rated the intervention as highly satisfactory on the Client Satisfaction Questionnaire (CSQ-8; mean score, 27.7 out of a maximum of 32). About 60% of the offspring no longer met full criteria for FTL (P < .001; Cohen’s D = 1.76).
All children of the wait-listed parents still met criteria for FTL.
FTL symptoms decreased significantly in the offspring of the intervention group, as seen in both in the Adult Entitled Dependence Scale (AED; P < .05; Cohen’s D = 0.84); and the Adaptive Behaviors Scale (ABS; P < .05; Cohen’s D = 0.70).
There was no change in anxiety as assessed by the Adult Behavior Checklist (ABCL). But Dr. Berger noted that child anxiety is difficult to assess through parental report.
“This population is self-isolating and parents sometimes don’t know what’s going on,” and ABCL measures may not be “as sensitive as we would have liked them to be,” Dr. Berger said.
Parental burden was significantly decreased as measured by the Zarit Burden Interview (ZBI; P < .05; Cohen’s D = 0.70). In addition, family accommodation decreased significantly as determined by the Family Accommodation Scale–Anxiety (FASA; P < .05; Cohen’s D = 0.70).
Innovative work
In a comment, Jonathan E. Alpert, MD, PhD, chair, department of psychiatry and behavioral sciences, and professor of psychiatry, neuroscience, and pediatrics, Albert Einstein College of Medicine, New York, described the program as “innovative.”
He noted that the SPACE-FTL approach provides parents with education and skills to reduce behaviors that reinforce their child’s avoidance of independent activities. Such behaviors “may inadvertently contribute to the adult child remaining stuck,” he said.
“Through its involvement of parents and use of a structured approach, SPACE-FTL is a very interesting step toward more evidence-based therapies.”
However, he noted that the number of study participants is still “very low” and further work is needed to better characterize this condition and develop effective therapies.
He noted that parents of adult children with FTL should not be judged or blamed. “They have been living with a worrisome problem for years and are simply doing their best to cope as any of us would do.”
In addition, he noted that some adult children aren’t capable of launching because of a serious mental illness or substance use disorder that needs treatment.
It’s unclear just how many adult children have FTL, as the condition lacks formal, agreed-upon clinical and research criteria and a reliable evidence base for treatment, Dr. Alpert said.
“Whatever the actual numbers of FTL, my anecdotal clinical experience suggests that it is a very common problem which is understudied.”
He added that the definitions of FTL should include cultural context. In some groups, it’s quite normal for adults in their 20s, 30s, or even older to live with their parents, Dr. Alpert said.
Dr. Berger and Dr. Albert report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – , a new pilot study shows.
Known as failure to launch (FTL) syndrome, the criteria for this condition include the absence of a neurodevelopmental, mental, or intellectual condition, difficulty adapting to the challenges of adulthood, and living with or at the expense of parents.
Results suggest that the program benefits families dealing with FTL, said study investigator Uri Berger, PhD, postdoctoral associate, Yale Child Study Center Anxiety and Mood Disorders Program, New Haven, Conn.
“If you encounter parents who are say 50-60 years old who have a child with FTL, you can tell them there’s something they can do; there’s work they can do even if their child is refusing to go to therapy,” he said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Anxious, isolated
Estimates suggest that there are 3.3 million physically able adults with FTL and that the disorder may be on the rise. These individuals often present with mental health symptoms including anxiety, depression, and suicidality, and tend to be socially isolated.
The investigators noted that intervening is often challenging because individuals with the syndrome are frequently noncompliant with therapy, and currently there is no standard of care.
“The longer you’re isolated, the harder it is getting out of your cocoon, and when these adult children get to the point where they seek help, they’re less likely to comply,” he said. However, he noted, this is not because they are lazy; it’s that they’re “very, very anxious.”
Parents and other family members are also negatively affected. Dr. Berger noted that 15% of parents of a child with FTL equate their caregiver burden with having a family member with a chronic physical illness. “It’s huge; parents go through hell and it’s very hard on them. Many believe it is their fault and they feel a lot of shame.”
Supportive Parenting for Anxious Childhood Emotions (SPACE) is a manualized, parent-based program for childhood anxiety and obsessive-compulsive disorder. It has been tested in clinical trials and found to be noninferior to cognitive behavioral therapy for childhood anxiety.
The research adapted it to treat FTL. SPACE-FTL focuses on reducing parents’ family accommodation (FA), a descriptor for a child’s excessive dependence on their parents to help them avoid anxiety-provoking situations.
The study examined the feasibility, acceptability, and treatment satisfaction and its effect on adult child psychopathology symptoms, parents’ FA, and the paternal burden of caring for adult children.
The study included parents (mean age, 59.46 years; 85% female) of 40 adult children with FTL (mean age, 23.51 years; 20% female) from across the United States.
Parents were randomized to a 13-week wait-list or the SPACE-FTL program, which involves 13-20 therapy sessions, depending on the need. The average number of sessions in the study was 15. The program has five key components:
- Providing information emphasizing FTL as not a character flaw but a problem with anxiety.
- Helping parents identify how they accommodate their child’s behavior, and facilitating an environment that encourages independence.
- Getting parents to show acceptance and confidence in their child who’s trying to overcome anxiety when, for example, they seek employment, instead of being overprotective and demanding.
- Focusing on change nonconfrontationally.
- Involving other family, community members, and professionals who can support the parent, child, or both.
The recruitment, treatment sessions, and assessments were all done online. Most participants rated the intervention as highly satisfactory on the Client Satisfaction Questionnaire (CSQ-8; mean score, 27.7 out of a maximum of 32). About 60% of the offspring no longer met full criteria for FTL (P < .001; Cohen’s D = 1.76).
All children of the wait-listed parents still met criteria for FTL.
FTL symptoms decreased significantly in the offspring of the intervention group, as seen in both in the Adult Entitled Dependence Scale (AED; P < .05; Cohen’s D = 0.84); and the Adaptive Behaviors Scale (ABS; P < .05; Cohen’s D = 0.70).
There was no change in anxiety as assessed by the Adult Behavior Checklist (ABCL). But Dr. Berger noted that child anxiety is difficult to assess through parental report.
“This population is self-isolating and parents sometimes don’t know what’s going on,” and ABCL measures may not be “as sensitive as we would have liked them to be,” Dr. Berger said.
Parental burden was significantly decreased as measured by the Zarit Burden Interview (ZBI; P < .05; Cohen’s D = 0.70). In addition, family accommodation decreased significantly as determined by the Family Accommodation Scale–Anxiety (FASA; P < .05; Cohen’s D = 0.70).
Innovative work
In a comment, Jonathan E. Alpert, MD, PhD, chair, department of psychiatry and behavioral sciences, and professor of psychiatry, neuroscience, and pediatrics, Albert Einstein College of Medicine, New York, described the program as “innovative.”
He noted that the SPACE-FTL approach provides parents with education and skills to reduce behaviors that reinforce their child’s avoidance of independent activities. Such behaviors “may inadvertently contribute to the adult child remaining stuck,” he said.
“Through its involvement of parents and use of a structured approach, SPACE-FTL is a very interesting step toward more evidence-based therapies.”
However, he noted that the number of study participants is still “very low” and further work is needed to better characterize this condition and develop effective therapies.
He noted that parents of adult children with FTL should not be judged or blamed. “They have been living with a worrisome problem for years and are simply doing their best to cope as any of us would do.”
In addition, he noted that some adult children aren’t capable of launching because of a serious mental illness or substance use disorder that needs treatment.
It’s unclear just how many adult children have FTL, as the condition lacks formal, agreed-upon clinical and research criteria and a reliable evidence base for treatment, Dr. Alpert said.
“Whatever the actual numbers of FTL, my anecdotal clinical experience suggests that it is a very common problem which is understudied.”
He added that the definitions of FTL should include cultural context. In some groups, it’s quite normal for adults in their 20s, 30s, or even older to live with their parents, Dr. Alpert said.
Dr. Berger and Dr. Albert report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – , a new pilot study shows.
Known as failure to launch (FTL) syndrome, the criteria for this condition include the absence of a neurodevelopmental, mental, or intellectual condition, difficulty adapting to the challenges of adulthood, and living with or at the expense of parents.
Results suggest that the program benefits families dealing with FTL, said study investigator Uri Berger, PhD, postdoctoral associate, Yale Child Study Center Anxiety and Mood Disorders Program, New Haven, Conn.
“If you encounter parents who are say 50-60 years old who have a child with FTL, you can tell them there’s something they can do; there’s work they can do even if their child is refusing to go to therapy,” he said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Anxious, isolated
Estimates suggest that there are 3.3 million physically able adults with FTL and that the disorder may be on the rise. These individuals often present with mental health symptoms including anxiety, depression, and suicidality, and tend to be socially isolated.
The investigators noted that intervening is often challenging because individuals with the syndrome are frequently noncompliant with therapy, and currently there is no standard of care.
“The longer you’re isolated, the harder it is getting out of your cocoon, and when these adult children get to the point where they seek help, they’re less likely to comply,” he said. However, he noted, this is not because they are lazy; it’s that they’re “very, very anxious.”
Parents and other family members are also negatively affected. Dr. Berger noted that 15% of parents of a child with FTL equate their caregiver burden with having a family member with a chronic physical illness. “It’s huge; parents go through hell and it’s very hard on them. Many believe it is their fault and they feel a lot of shame.”
Supportive Parenting for Anxious Childhood Emotions (SPACE) is a manualized, parent-based program for childhood anxiety and obsessive-compulsive disorder. It has been tested in clinical trials and found to be noninferior to cognitive behavioral therapy for childhood anxiety.
The research adapted it to treat FTL. SPACE-FTL focuses on reducing parents’ family accommodation (FA), a descriptor for a child’s excessive dependence on their parents to help them avoid anxiety-provoking situations.
The study examined the feasibility, acceptability, and treatment satisfaction and its effect on adult child psychopathology symptoms, parents’ FA, and the paternal burden of caring for adult children.
The study included parents (mean age, 59.46 years; 85% female) of 40 adult children with FTL (mean age, 23.51 years; 20% female) from across the United States.
Parents were randomized to a 13-week wait-list or the SPACE-FTL program, which involves 13-20 therapy sessions, depending on the need. The average number of sessions in the study was 15. The program has five key components:
- Providing information emphasizing FTL as not a character flaw but a problem with anxiety.
- Helping parents identify how they accommodate their child’s behavior, and facilitating an environment that encourages independence.
- Getting parents to show acceptance and confidence in their child who’s trying to overcome anxiety when, for example, they seek employment, instead of being overprotective and demanding.
- Focusing on change nonconfrontationally.
- Involving other family, community members, and professionals who can support the parent, child, or both.
The recruitment, treatment sessions, and assessments were all done online. Most participants rated the intervention as highly satisfactory on the Client Satisfaction Questionnaire (CSQ-8; mean score, 27.7 out of a maximum of 32). About 60% of the offspring no longer met full criteria for FTL (P < .001; Cohen’s D = 1.76).
All children of the wait-listed parents still met criteria for FTL.
FTL symptoms decreased significantly in the offspring of the intervention group, as seen in both in the Adult Entitled Dependence Scale (AED; P < .05; Cohen’s D = 0.84); and the Adaptive Behaviors Scale (ABS; P < .05; Cohen’s D = 0.70).
There was no change in anxiety as assessed by the Adult Behavior Checklist (ABCL). But Dr. Berger noted that child anxiety is difficult to assess through parental report.
“This population is self-isolating and parents sometimes don’t know what’s going on,” and ABCL measures may not be “as sensitive as we would have liked them to be,” Dr. Berger said.
Parental burden was significantly decreased as measured by the Zarit Burden Interview (ZBI; P < .05; Cohen’s D = 0.70). In addition, family accommodation decreased significantly as determined by the Family Accommodation Scale–Anxiety (FASA; P < .05; Cohen’s D = 0.70).
Innovative work
In a comment, Jonathan E. Alpert, MD, PhD, chair, department of psychiatry and behavioral sciences, and professor of psychiatry, neuroscience, and pediatrics, Albert Einstein College of Medicine, New York, described the program as “innovative.”
He noted that the SPACE-FTL approach provides parents with education and skills to reduce behaviors that reinforce their child’s avoidance of independent activities. Such behaviors “may inadvertently contribute to the adult child remaining stuck,” he said.
“Through its involvement of parents and use of a structured approach, SPACE-FTL is a very interesting step toward more evidence-based therapies.”
However, he noted that the number of study participants is still “very low” and further work is needed to better characterize this condition and develop effective therapies.
He noted that parents of adult children with FTL should not be judged or blamed. “They have been living with a worrisome problem for years and are simply doing their best to cope as any of us would do.”
In addition, he noted that some adult children aren’t capable of launching because of a serious mental illness or substance use disorder that needs treatment.
It’s unclear just how many adult children have FTL, as the condition lacks formal, agreed-upon clinical and research criteria and a reliable evidence base for treatment, Dr. Alpert said.
“Whatever the actual numbers of FTL, my anecdotal clinical experience suggests that it is a very common problem which is understudied.”
He added that the definitions of FTL should include cultural context. In some groups, it’s quite normal for adults in their 20s, 30s, or even older to live with their parents, Dr. Alpert said.
Dr. Berger and Dr. Albert report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADAA 2023
Cautious optimism for new Alzheimer’s disease biomarkers and treatments, expert says
SAN DIEGO – said a presenter at the annual meeting of the American College of Physicians.
Dementia prevalence is increasing as the proportion of the U.S. population older than 65 rises, said Zaldy Tan, MD, professor of neurology at Cedars-Sinai Medical Center, Los Angeles. AD deaths more than doubled between 2000 and 2018, he noted, while deaths from HIV infection, stroke, and heart disease decreased.
Most people in the United States who have AD are White, but studies suggest that, compared with Whites, the risk of AD is two times higher in Blacks and 1.5 times higher in Hispanics . “These data suggest that both genes and social determinants of health are at play,” Dr. Tan said.
Diagnosis of Alzheimer’s disease
The different types of dementia make it challenging for primary care physicians to identify the cause of cognitive impairment. “Even though AD is the most common type, clinicians should keep in mind that another type of dementia may be the cause of cognitive impairment,” Dr. Tan cautioned. Other dementia diagnoses include vascular, Lewy body, and frontotemporal.
Diagnostic criteria for AD include evidence of significant cognitive decline in at least one cognitive domain that interferes with independence in everyday activities, as well as the absence of another mental disorder or delirium that would explain the cognitive deficits.
“We see many patients with depressive symptoms and mild cognitive impairment, and it is not always easy to tell which of them have dementia because of the overlap in the symptoms of depression and AD,” said internist Roderick Kim, MD, of Grand Rapids, Mich., who attended the session.
It can be challenging to convince patients to undergo the appropriate diagnostic workup, Dr. Kim said. “This can delay treatment, so it is important to explain to patients that cognitive decline can progress quickly and that there are treatment options to slow it down.”
Why do we need biomarkers for Alzheimer’s disease?
AD is characterized by a long preclinical phase with no specific symptoms other than the typical signs and symptoms of aging, Dr. Tan said. That means cognitive impairment progresses rapidly after diagnosis in most patients with AD.
“In most cases, an accurate history, physical and neurologic examinations, basic labs, and neuroimaging are sufficient for memory loss evaluation. However, as more disease-modifying therapies come to market, biomarkers will rise in importance in primary care,” he said.
This long asymptomatic phase of AD creates the need for diagnostic biomarkers for an earlier diagnosis, he said. Amyloid-beta and tau deposits in PET images and the levels of amyloid-beta seeds, phosphorylated tau, and neurofilament light chain in the cerebrospinal fluid can be used as diagnostic biomarkers in patients with suspected AD. Emerging blood biomarkers for earlier detection include the levels of amyloid-beta1–42, phosphorylated tau, and neurofilament light chain.
With biomarkers and other new tools for the diagnosis of dementia in primary care, Dr. Tan said: “The greatest challenge is cost, as blood-based biomarkers are not currently covered by insurance and still rather costly. In addition, blood-based biomarkers will need to receive [Food and Drug Administration] approval in order to have more widespread availability.”
New and emerging therapies for Alzheimer’s disease
There are two classes of FDA-approved medications to manage cognitive symptoms of dementia: acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The selections may be trial and error for each patient, Dr. Tan said.
“The approved medications can exert subtle benefits that are clinically observable. Thus, barring any contraindications or intolerance, most patients with AD would benefit from a trial of one or both of these medication classes,” said Dr. Tan. He added that it is equally important to wean off and discontinue these medications if there is intolerance or lack of a subjective or objective beneficial response.
Other medications are available for some of the most common behavioral problems associated with dementia, such as agitation, depression, and disorientation. Dr. Tan advised not to prescribe behavioral medications until nonpharmacologic interventions prove to be ineffective or impractical. Behavioral medications have many side effects, some of which are potentially serious, he said, so the risk-benefit ratio should be considered.
In his own practice, when nonpharmacologic strategies do not improve the behavioral symptoms of dementia, Dr. Tan said that, “in cases where a person is at risk of harm to themselves or others, a discussion with the patient and their caregivers about the pros and cons of medications to treat the behavior need to be had. Careful monitoring of the response and dose escalation or deprescribing when appropriate is important to keep in mind.”
Disease-modifying agents have recently provided new hope for AD treatment. Aducanumab and lecanemab, both monoclonal antibodies that target amyloids, are the first two drugs that received accelerated FDA approval for AD.
Although these monoclonal antibodies can help clear deposited amyloid plaques and show some benefit in slowing cognitive impairment in clinical trials, the real-world benefits were unclear enough for Medicare to limit coverage to people enrolled in approved studies to gather more data. Additionally, these agents can cause potentially amyloid-related imaging abnormalities, which may indicate edema, effusion, or microhemorrhage. Therefore, clinicians need to have a clear conversation of risks and benefits with patients and caregivers about these treatments.
Looking ahead
When asked about the most promising emerging technologies or techniques related to dementia diagnosis and management, Dr. Tan noted that multiple technology companies and start-ups are looking for new ways to detect dementia earlier or keep persons with dementia safe at home. Some devices deliver brain waves, computerized brain games or tests, automated pill dispensers, and fall monitors.
“Some of these are potentially helpful, but not every person with dementia will benefit. In addition, most of these technologies are out-of-pocket expenses for the patients and their families. It is important to know what is out there but also be cautious about outrageous claims,” he added.
Dr. Tan reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing health care products used by or on patients.
SAN DIEGO – said a presenter at the annual meeting of the American College of Physicians.
Dementia prevalence is increasing as the proportion of the U.S. population older than 65 rises, said Zaldy Tan, MD, professor of neurology at Cedars-Sinai Medical Center, Los Angeles. AD deaths more than doubled between 2000 and 2018, he noted, while deaths from HIV infection, stroke, and heart disease decreased.
Most people in the United States who have AD are White, but studies suggest that, compared with Whites, the risk of AD is two times higher in Blacks and 1.5 times higher in Hispanics . “These data suggest that both genes and social determinants of health are at play,” Dr. Tan said.
Diagnosis of Alzheimer’s disease
The different types of dementia make it challenging for primary care physicians to identify the cause of cognitive impairment. “Even though AD is the most common type, clinicians should keep in mind that another type of dementia may be the cause of cognitive impairment,” Dr. Tan cautioned. Other dementia diagnoses include vascular, Lewy body, and frontotemporal.
Diagnostic criteria for AD include evidence of significant cognitive decline in at least one cognitive domain that interferes with independence in everyday activities, as well as the absence of another mental disorder or delirium that would explain the cognitive deficits.
“We see many patients with depressive symptoms and mild cognitive impairment, and it is not always easy to tell which of them have dementia because of the overlap in the symptoms of depression and AD,” said internist Roderick Kim, MD, of Grand Rapids, Mich., who attended the session.
It can be challenging to convince patients to undergo the appropriate diagnostic workup, Dr. Kim said. “This can delay treatment, so it is important to explain to patients that cognitive decline can progress quickly and that there are treatment options to slow it down.”
Why do we need biomarkers for Alzheimer’s disease?
AD is characterized by a long preclinical phase with no specific symptoms other than the typical signs and symptoms of aging, Dr. Tan said. That means cognitive impairment progresses rapidly after diagnosis in most patients with AD.
“In most cases, an accurate history, physical and neurologic examinations, basic labs, and neuroimaging are sufficient for memory loss evaluation. However, as more disease-modifying therapies come to market, biomarkers will rise in importance in primary care,” he said.
This long asymptomatic phase of AD creates the need for diagnostic biomarkers for an earlier diagnosis, he said. Amyloid-beta and tau deposits in PET images and the levels of amyloid-beta seeds, phosphorylated tau, and neurofilament light chain in the cerebrospinal fluid can be used as diagnostic biomarkers in patients with suspected AD. Emerging blood biomarkers for earlier detection include the levels of amyloid-beta1–42, phosphorylated tau, and neurofilament light chain.
With biomarkers and other new tools for the diagnosis of dementia in primary care, Dr. Tan said: “The greatest challenge is cost, as blood-based biomarkers are not currently covered by insurance and still rather costly. In addition, blood-based biomarkers will need to receive [Food and Drug Administration] approval in order to have more widespread availability.”
New and emerging therapies for Alzheimer’s disease
There are two classes of FDA-approved medications to manage cognitive symptoms of dementia: acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The selections may be trial and error for each patient, Dr. Tan said.
“The approved medications can exert subtle benefits that are clinically observable. Thus, barring any contraindications or intolerance, most patients with AD would benefit from a trial of one or both of these medication classes,” said Dr. Tan. He added that it is equally important to wean off and discontinue these medications if there is intolerance or lack of a subjective or objective beneficial response.
Other medications are available for some of the most common behavioral problems associated with dementia, such as agitation, depression, and disorientation. Dr. Tan advised not to prescribe behavioral medications until nonpharmacologic interventions prove to be ineffective or impractical. Behavioral medications have many side effects, some of which are potentially serious, he said, so the risk-benefit ratio should be considered.
In his own practice, when nonpharmacologic strategies do not improve the behavioral symptoms of dementia, Dr. Tan said that, “in cases where a person is at risk of harm to themselves or others, a discussion with the patient and their caregivers about the pros and cons of medications to treat the behavior need to be had. Careful monitoring of the response and dose escalation or deprescribing when appropriate is important to keep in mind.”
Disease-modifying agents have recently provided new hope for AD treatment. Aducanumab and lecanemab, both monoclonal antibodies that target amyloids, are the first two drugs that received accelerated FDA approval for AD.
Although these monoclonal antibodies can help clear deposited amyloid plaques and show some benefit in slowing cognitive impairment in clinical trials, the real-world benefits were unclear enough for Medicare to limit coverage to people enrolled in approved studies to gather more data. Additionally, these agents can cause potentially amyloid-related imaging abnormalities, which may indicate edema, effusion, or microhemorrhage. Therefore, clinicians need to have a clear conversation of risks and benefits with patients and caregivers about these treatments.
Looking ahead
When asked about the most promising emerging technologies or techniques related to dementia diagnosis and management, Dr. Tan noted that multiple technology companies and start-ups are looking for new ways to detect dementia earlier or keep persons with dementia safe at home. Some devices deliver brain waves, computerized brain games or tests, automated pill dispensers, and fall monitors.
“Some of these are potentially helpful, but not every person with dementia will benefit. In addition, most of these technologies are out-of-pocket expenses for the patients and their families. It is important to know what is out there but also be cautious about outrageous claims,” he added.
Dr. Tan reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing health care products used by or on patients.
SAN DIEGO – said a presenter at the annual meeting of the American College of Physicians.
Dementia prevalence is increasing as the proportion of the U.S. population older than 65 rises, said Zaldy Tan, MD, professor of neurology at Cedars-Sinai Medical Center, Los Angeles. AD deaths more than doubled between 2000 and 2018, he noted, while deaths from HIV infection, stroke, and heart disease decreased.
Most people in the United States who have AD are White, but studies suggest that, compared with Whites, the risk of AD is two times higher in Blacks and 1.5 times higher in Hispanics . “These data suggest that both genes and social determinants of health are at play,” Dr. Tan said.
Diagnosis of Alzheimer’s disease
The different types of dementia make it challenging for primary care physicians to identify the cause of cognitive impairment. “Even though AD is the most common type, clinicians should keep in mind that another type of dementia may be the cause of cognitive impairment,” Dr. Tan cautioned. Other dementia diagnoses include vascular, Lewy body, and frontotemporal.
Diagnostic criteria for AD include evidence of significant cognitive decline in at least one cognitive domain that interferes with independence in everyday activities, as well as the absence of another mental disorder or delirium that would explain the cognitive deficits.
“We see many patients with depressive symptoms and mild cognitive impairment, and it is not always easy to tell which of them have dementia because of the overlap in the symptoms of depression and AD,” said internist Roderick Kim, MD, of Grand Rapids, Mich., who attended the session.
It can be challenging to convince patients to undergo the appropriate diagnostic workup, Dr. Kim said. “This can delay treatment, so it is important to explain to patients that cognitive decline can progress quickly and that there are treatment options to slow it down.”
Why do we need biomarkers for Alzheimer’s disease?
AD is characterized by a long preclinical phase with no specific symptoms other than the typical signs and symptoms of aging, Dr. Tan said. That means cognitive impairment progresses rapidly after diagnosis in most patients with AD.
“In most cases, an accurate history, physical and neurologic examinations, basic labs, and neuroimaging are sufficient for memory loss evaluation. However, as more disease-modifying therapies come to market, biomarkers will rise in importance in primary care,” he said.
This long asymptomatic phase of AD creates the need for diagnostic biomarkers for an earlier diagnosis, he said. Amyloid-beta and tau deposits in PET images and the levels of amyloid-beta seeds, phosphorylated tau, and neurofilament light chain in the cerebrospinal fluid can be used as diagnostic biomarkers in patients with suspected AD. Emerging blood biomarkers for earlier detection include the levels of amyloid-beta1–42, phosphorylated tau, and neurofilament light chain.
With biomarkers and other new tools for the diagnosis of dementia in primary care, Dr. Tan said: “The greatest challenge is cost, as blood-based biomarkers are not currently covered by insurance and still rather costly. In addition, blood-based biomarkers will need to receive [Food and Drug Administration] approval in order to have more widespread availability.”
New and emerging therapies for Alzheimer’s disease
There are two classes of FDA-approved medications to manage cognitive symptoms of dementia: acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The selections may be trial and error for each patient, Dr. Tan said.
“The approved medications can exert subtle benefits that are clinically observable. Thus, barring any contraindications or intolerance, most patients with AD would benefit from a trial of one or both of these medication classes,” said Dr. Tan. He added that it is equally important to wean off and discontinue these medications if there is intolerance or lack of a subjective or objective beneficial response.
Other medications are available for some of the most common behavioral problems associated with dementia, such as agitation, depression, and disorientation. Dr. Tan advised not to prescribe behavioral medications until nonpharmacologic interventions prove to be ineffective or impractical. Behavioral medications have many side effects, some of which are potentially serious, he said, so the risk-benefit ratio should be considered.
In his own practice, when nonpharmacologic strategies do not improve the behavioral symptoms of dementia, Dr. Tan said that, “in cases where a person is at risk of harm to themselves or others, a discussion with the patient and their caregivers about the pros and cons of medications to treat the behavior need to be had. Careful monitoring of the response and dose escalation or deprescribing when appropriate is important to keep in mind.”
Disease-modifying agents have recently provided new hope for AD treatment. Aducanumab and lecanemab, both monoclonal antibodies that target amyloids, are the first two drugs that received accelerated FDA approval for AD.
Although these monoclonal antibodies can help clear deposited amyloid plaques and show some benefit in slowing cognitive impairment in clinical trials, the real-world benefits were unclear enough for Medicare to limit coverage to people enrolled in approved studies to gather more data. Additionally, these agents can cause potentially amyloid-related imaging abnormalities, which may indicate edema, effusion, or microhemorrhage. Therefore, clinicians need to have a clear conversation of risks and benefits with patients and caregivers about these treatments.
Looking ahead
When asked about the most promising emerging technologies or techniques related to dementia diagnosis and management, Dr. Tan noted that multiple technology companies and start-ups are looking for new ways to detect dementia earlier or keep persons with dementia safe at home. Some devices deliver brain waves, computerized brain games or tests, automated pill dispensers, and fall monitors.
“Some of these are potentially helpful, but not every person with dementia will benefit. In addition, most of these technologies are out-of-pocket expenses for the patients and their families. It is important to know what is out there but also be cautious about outrageous claims,” he added.
Dr. Tan reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing health care products used by or on patients.
AT INTERNAL MEDICINE 2023
Liquid biopsy assay can predict CRC recurrence early
A (CRC).
Patients who were ctDNA methylation positive 1 month after surgery were 17.5 times more likely to relapse, compared with ctDNA-negative patients. And following adjuvant chemotherapy, ctDNA-positive patients had a significantly shorter recurrence-free survival than their ctDNA-negative peers.
Overall, “we found that ctDNA methylation was the most significant prognostic factor for recurrence-free survival among all clinicopathologic risk factors on multivariable analysis,” the authors, led by Shaobo Mo, MD, Fudan University Shanghai (China) Cancer Center, reported in research published in JAMA Oncology.
Van Morris, MD, an oncologist with University of Texas MD Anderson Cancer Center, Houston, who was not involved in the research, noted that other commercially available ctDNA assays have achieved similar findings, but this assay involves the least number of biomarkers.
More notably, the broader message emerging from this research is that “ctDNA is a powerful tool in oncology that is here to stay,” said Dr. Morris.
Dr. Morris added a note of caution, however: Despite the study providing further support for this technology in CRC, “we do not have definitive predictive utility for routinely guiding adjuvant chemotherapy decisions with the use of this [or other] ctDNA assays.”
Recurrence common, predictors important
CRC has a relatively high recurrence rate even after curative-intent therapies, with a 5-year survival rate as low as 60%. Adjuvant chemotherapy in patients with stage III CRC generally lowers the risk of recurrence by about 10%-20%; however, the benefits of adjuvant chemotherapy among patients with stage II CRC remain unclear.
Strategies to identify patients most likely to relapse after adjuvant therapy largely focus on CRC stage and clinical risk factors, though postoperative ctDNA testing has emerged as a tool to help identify patients at risk for recurrence. Often, however, this approach involves ultradeep next-generation sequencing, which limits the strategy’s ease of implementation and cost effectiveness.
As an alternative, the authors used a plasma ctDNA methylation test, ColonAiQ, which identifies the presence of six genomic biomarkers hypermethylated in CRC. This test avoids the complex process of primary tumor profiling among individual patients.
In the multicenter, prospective longitudinal cohort study, conducted from December 2019 to February 2022, Dr. Mo and colleagues evaluated 1,228 blood samples from 299 patients with stage I-III CRC. Samples were collected before and after surgery, during and after adjuvant chemotherapy, and every 3 months for up to 2 years.
Of 296 patients with preoperative samples available, as many as 232 (78.4%) tested positive for at least one of the 6 ctDNA methylation markers. The detection rates were 65.1% for stage I CRC, 82.7% for stage II disease, and 81.5% for stage III disease.
At postoperative month 1, ctDNA methylation–positive patients were 17.5 times more likely to relapse, compared with ctDNA-negative patients (hazard ratio, 17.5; P < .001).
When integrating carcinoembryonic antigen testing alongside ctDNA testing, patients with positive test results had significantly worse prognoses, compared with those who had negative results (HR, 19.0; P < .001).
The association of ctDNA methylation positivity at postoperative month 1 and CRC recurrence was consistent across varying durations and intensities of adjuvant chemotherapy. The researchers found that ctDNA methylation analysis detected CRC recurrence a median of 3.3 months earlier than radiologically confirmed recurrence.
Patients who were ctDNA positive also had significantly shorter periods of recurrence-free survival following adjuvant chemotherapy, compared with ctDNA-negative patients (HR, 13.8; P < .001). That effect was enhanced when positive ctDNA status was maintained longitudinally, compared with those who were persistently ctDNA negative (HR, 68.8; P < .001).
More specifically, 140 patients exhibited sustained ctDNA-positive status over time; 6 of 7 ctDNA-positive patients experienced recurrence within 12 months, whereas 129 of 133 ctDNA-negative patients (97%) remained relapse free. And being ctDNA negative before surgery indicated patients’ relapse risk, with 95.3% of patients who were ctDNA negative presurgery remaining relapse free.
Dr. Mo and colleagues concluded that the simplicity of the assay work flow and convenience of taking blood samples make this approach practical and cost effective in the clinical setting.
In an editorial published alongside the study, Juan Ruiz-Bañobre, MD, PhD, and Ajay Goel, PhD, noted that the field is evolving rapidly but “there is substantial value in prospectively validating the clinical importance of ColonAiQ in randomized clinical trials.”
“If successful, this liquid biopsy assay could represent a simple and cost-effective means for a more accessible and facile decentralized implementation in routine clinical practice,” said Dr. Ruiz-Bañobre, of the University of Santiago de Compostela, A Coruña, Spain, and Dr. Goel, from City of Hope Comprehensive Cancer Center in Duarte, Calif.
Several of the study coauthors are employees of Singlera Genomics, which makes the ColonAiQ test. Dr. Ruiz-Bañobre reported grants from the Spanish Cooperative Group for the Treatment of Digestive Tumors and support from Institute of Health Carlos III. Dr. Morris is the principal investigator on the NRG GI005 trial of the Guardant Reveal liquid biopsy, sponsored by Guardant Health in collaboration with funding support from the National Cancer Institute.
A version of this article first appeared on Medscape.com.
A (CRC).
Patients who were ctDNA methylation positive 1 month after surgery were 17.5 times more likely to relapse, compared with ctDNA-negative patients. And following adjuvant chemotherapy, ctDNA-positive patients had a significantly shorter recurrence-free survival than their ctDNA-negative peers.
Overall, “we found that ctDNA methylation was the most significant prognostic factor for recurrence-free survival among all clinicopathologic risk factors on multivariable analysis,” the authors, led by Shaobo Mo, MD, Fudan University Shanghai (China) Cancer Center, reported in research published in JAMA Oncology.
Van Morris, MD, an oncologist with University of Texas MD Anderson Cancer Center, Houston, who was not involved in the research, noted that other commercially available ctDNA assays have achieved similar findings, but this assay involves the least number of biomarkers.
More notably, the broader message emerging from this research is that “ctDNA is a powerful tool in oncology that is here to stay,” said Dr. Morris.
Dr. Morris added a note of caution, however: Despite the study providing further support for this technology in CRC, “we do not have definitive predictive utility for routinely guiding adjuvant chemotherapy decisions with the use of this [or other] ctDNA assays.”
Recurrence common, predictors important
CRC has a relatively high recurrence rate even after curative-intent therapies, with a 5-year survival rate as low as 60%. Adjuvant chemotherapy in patients with stage III CRC generally lowers the risk of recurrence by about 10%-20%; however, the benefits of adjuvant chemotherapy among patients with stage II CRC remain unclear.
Strategies to identify patients most likely to relapse after adjuvant therapy largely focus on CRC stage and clinical risk factors, though postoperative ctDNA testing has emerged as a tool to help identify patients at risk for recurrence. Often, however, this approach involves ultradeep next-generation sequencing, which limits the strategy’s ease of implementation and cost effectiveness.
As an alternative, the authors used a plasma ctDNA methylation test, ColonAiQ, which identifies the presence of six genomic biomarkers hypermethylated in CRC. This test avoids the complex process of primary tumor profiling among individual patients.
In the multicenter, prospective longitudinal cohort study, conducted from December 2019 to February 2022, Dr. Mo and colleagues evaluated 1,228 blood samples from 299 patients with stage I-III CRC. Samples were collected before and after surgery, during and after adjuvant chemotherapy, and every 3 months for up to 2 years.
Of 296 patients with preoperative samples available, as many as 232 (78.4%) tested positive for at least one of the 6 ctDNA methylation markers. The detection rates were 65.1% for stage I CRC, 82.7% for stage II disease, and 81.5% for stage III disease.
At postoperative month 1, ctDNA methylation–positive patients were 17.5 times more likely to relapse, compared with ctDNA-negative patients (hazard ratio, 17.5; P < .001).
When integrating carcinoembryonic antigen testing alongside ctDNA testing, patients with positive test results had significantly worse prognoses, compared with those who had negative results (HR, 19.0; P < .001).
The association of ctDNA methylation positivity at postoperative month 1 and CRC recurrence was consistent across varying durations and intensities of adjuvant chemotherapy. The researchers found that ctDNA methylation analysis detected CRC recurrence a median of 3.3 months earlier than radiologically confirmed recurrence.
Patients who were ctDNA positive also had significantly shorter periods of recurrence-free survival following adjuvant chemotherapy, compared with ctDNA-negative patients (HR, 13.8; P < .001). That effect was enhanced when positive ctDNA status was maintained longitudinally, compared with those who were persistently ctDNA negative (HR, 68.8; P < .001).
More specifically, 140 patients exhibited sustained ctDNA-positive status over time; 6 of 7 ctDNA-positive patients experienced recurrence within 12 months, whereas 129 of 133 ctDNA-negative patients (97%) remained relapse free. And being ctDNA negative before surgery indicated patients’ relapse risk, with 95.3% of patients who were ctDNA negative presurgery remaining relapse free.
Dr. Mo and colleagues concluded that the simplicity of the assay work flow and convenience of taking blood samples make this approach practical and cost effective in the clinical setting.
In an editorial published alongside the study, Juan Ruiz-Bañobre, MD, PhD, and Ajay Goel, PhD, noted that the field is evolving rapidly but “there is substantial value in prospectively validating the clinical importance of ColonAiQ in randomized clinical trials.”
“If successful, this liquid biopsy assay could represent a simple and cost-effective means for a more accessible and facile decentralized implementation in routine clinical practice,” said Dr. Ruiz-Bañobre, of the University of Santiago de Compostela, A Coruña, Spain, and Dr. Goel, from City of Hope Comprehensive Cancer Center in Duarte, Calif.
Several of the study coauthors are employees of Singlera Genomics, which makes the ColonAiQ test. Dr. Ruiz-Bañobre reported grants from the Spanish Cooperative Group for the Treatment of Digestive Tumors and support from Institute of Health Carlos III. Dr. Morris is the principal investigator on the NRG GI005 trial of the Guardant Reveal liquid biopsy, sponsored by Guardant Health in collaboration with funding support from the National Cancer Institute.
A version of this article first appeared on Medscape.com.
A (CRC).
Patients who were ctDNA methylation positive 1 month after surgery were 17.5 times more likely to relapse, compared with ctDNA-negative patients. And following adjuvant chemotherapy, ctDNA-positive patients had a significantly shorter recurrence-free survival than their ctDNA-negative peers.
Overall, “we found that ctDNA methylation was the most significant prognostic factor for recurrence-free survival among all clinicopathologic risk factors on multivariable analysis,” the authors, led by Shaobo Mo, MD, Fudan University Shanghai (China) Cancer Center, reported in research published in JAMA Oncology.
Van Morris, MD, an oncologist with University of Texas MD Anderson Cancer Center, Houston, who was not involved in the research, noted that other commercially available ctDNA assays have achieved similar findings, but this assay involves the least number of biomarkers.
More notably, the broader message emerging from this research is that “ctDNA is a powerful tool in oncology that is here to stay,” said Dr. Morris.
Dr. Morris added a note of caution, however: Despite the study providing further support for this technology in CRC, “we do not have definitive predictive utility for routinely guiding adjuvant chemotherapy decisions with the use of this [or other] ctDNA assays.”
Recurrence common, predictors important
CRC has a relatively high recurrence rate even after curative-intent therapies, with a 5-year survival rate as low as 60%. Adjuvant chemotherapy in patients with stage III CRC generally lowers the risk of recurrence by about 10%-20%; however, the benefits of adjuvant chemotherapy among patients with stage II CRC remain unclear.
Strategies to identify patients most likely to relapse after adjuvant therapy largely focus on CRC stage and clinical risk factors, though postoperative ctDNA testing has emerged as a tool to help identify patients at risk for recurrence. Often, however, this approach involves ultradeep next-generation sequencing, which limits the strategy’s ease of implementation and cost effectiveness.
As an alternative, the authors used a plasma ctDNA methylation test, ColonAiQ, which identifies the presence of six genomic biomarkers hypermethylated in CRC. This test avoids the complex process of primary tumor profiling among individual patients.
In the multicenter, prospective longitudinal cohort study, conducted from December 2019 to February 2022, Dr. Mo and colleagues evaluated 1,228 blood samples from 299 patients with stage I-III CRC. Samples were collected before and after surgery, during and after adjuvant chemotherapy, and every 3 months for up to 2 years.
Of 296 patients with preoperative samples available, as many as 232 (78.4%) tested positive for at least one of the 6 ctDNA methylation markers. The detection rates were 65.1% for stage I CRC, 82.7% for stage II disease, and 81.5% for stage III disease.
At postoperative month 1, ctDNA methylation–positive patients were 17.5 times more likely to relapse, compared with ctDNA-negative patients (hazard ratio, 17.5; P < .001).
When integrating carcinoembryonic antigen testing alongside ctDNA testing, patients with positive test results had significantly worse prognoses, compared with those who had negative results (HR, 19.0; P < .001).
The association of ctDNA methylation positivity at postoperative month 1 and CRC recurrence was consistent across varying durations and intensities of adjuvant chemotherapy. The researchers found that ctDNA methylation analysis detected CRC recurrence a median of 3.3 months earlier than radiologically confirmed recurrence.
Patients who were ctDNA positive also had significantly shorter periods of recurrence-free survival following adjuvant chemotherapy, compared with ctDNA-negative patients (HR, 13.8; P < .001). That effect was enhanced when positive ctDNA status was maintained longitudinally, compared with those who were persistently ctDNA negative (HR, 68.8; P < .001).
More specifically, 140 patients exhibited sustained ctDNA-positive status over time; 6 of 7 ctDNA-positive patients experienced recurrence within 12 months, whereas 129 of 133 ctDNA-negative patients (97%) remained relapse free. And being ctDNA negative before surgery indicated patients’ relapse risk, with 95.3% of patients who were ctDNA negative presurgery remaining relapse free.
Dr. Mo and colleagues concluded that the simplicity of the assay work flow and convenience of taking blood samples make this approach practical and cost effective in the clinical setting.
In an editorial published alongside the study, Juan Ruiz-Bañobre, MD, PhD, and Ajay Goel, PhD, noted that the field is evolving rapidly but “there is substantial value in prospectively validating the clinical importance of ColonAiQ in randomized clinical trials.”
“If successful, this liquid biopsy assay could represent a simple and cost-effective means for a more accessible and facile decentralized implementation in routine clinical practice,” said Dr. Ruiz-Bañobre, of the University of Santiago de Compostela, A Coruña, Spain, and Dr. Goel, from City of Hope Comprehensive Cancer Center in Duarte, Calif.
Several of the study coauthors are employees of Singlera Genomics, which makes the ColonAiQ test. Dr. Ruiz-Bañobre reported grants from the Spanish Cooperative Group for the Treatment of Digestive Tumors and support from Institute of Health Carlos III. Dr. Morris is the principal investigator on the NRG GI005 trial of the Guardant Reveal liquid biopsy, sponsored by Guardant Health in collaboration with funding support from the National Cancer Institute.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
Experts outline comprehensive preeclampsia prevention strategy
Preeclampsia is a leading cause of maternal mortality and premature births. The report, published in the American Journal of Obstetrics and Gynecology, developed by a working group of clinicians, researchers, patients, advocates, and payers, recommends daily low-dose aspirin, surveillance, behavioral strategies, patient and provider education, long-term follow-up, and addressing social determinants of health.
Titled “Care plan for individuals at risk for preeclampsia: Shared approach to education, strategies for prevention, surveillance and follow up,” the report includes recommendations for providers and for patients at moderate to high risk of preeclampsia.
Top recommendations for providers include performing a risk assessment, including social determinants of health, medication recommendations (including daily aspirin and antihypertensive therapy), and behavioral recommendations (including specific information about diet, exercise, and sleep.)
The recommendations for patients include asking providers about aspirin use, checking blood pressure at home, and reporting any readings greater than 140/90. For those with BPs measuring 140/90 mm Hg or higher, the plan recommends antihypertensive therapy. The recommendations include making changes to diet, exercise, and sleep in consultation with providers.
Home blood pressure checks controversial
James Roberts, MD, a maternal-fetal medicine researcher at the Magee-Women’s Research Institute at University of Pittsburgh Medical Center and lead author on the paper, told this publication the home blood pressure checks may be the most controversial item in the report as not all insurers cover the at-home equipment.
In this report, the authors write that the working group “strongly advocates that payers of health care services cover the modest expense of home blood pressure determination including equipment and training.”
Dr. Roberts is the founding principal investigator of the Global Pregnancy Collaboration (CoLab), a consortium of 40 centers and one of the groups leading the creation of this report.
He said that while most of the recommendations are already recommended in guidelines, the report puts the preeclampsia plan into easy-to-read steps and downloadable checklists and compiles the evidence all in one place.
Dr. Roberts said the working group hopes this report will be adapted into guidelines developed by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, and made part of electronic health records.
So far, the authors say, a comprehensive, integrated preeclampsia care plan has not been widely adopted.
Fewer than half of patients at risk receive aspirin
The coauthors note that “today, most pregnant individuals at increased risk do not receive even one of the interventions to prevent preeclampsia. For example, less than half of high-risk patients receive low-dose aspirin.”
A big part of this plan, Dr. Roberts said, calls for further educating both providers and patients.
Vesna Garovic, MD, PhD, a preeclampsia specialist at the Mayo Clinic in Rochester, Minn., who was not part of the working group, said, “This is the first comprehensive plan that provides a safe, cost-effective approach to reduce the risk of preeclampsia in individuals at moderate to high risk for this condition who qualify to receive aspirin for prevention.”
Dr. Garovic said the plan is novel in several ways, including the multispecialty input that also includes patients and advocates. Also, she says, it can be easily included in electronic health records and routine care of patients.
“The recommendations that were made, other than self-monitoring of blood pressure, are already standard of care. It will be important to understand as to which extent this comprehensive program, compared to the standard approach, would reduce further the risk of preeclampsia,” Dr. Garovic said. “A prospective, adequately powered comparative study would not only address this question, but will investigate compliance of providers and pregnant women with this shared approach, as well as patient satisfaction.”
The authors note the approach presented is for care in developed countries and that low- and middle-income countries would need to tailor the plan. The Care Plan is also meant only for prevention and is not meant to guide care for women who have developed preeclampsia.
Funding was provided to The Precia Group and the Global Pregnancy Collaboration to assemble this care plan by Mirvie, which is developing a biochemical predictor for preeclampsia. Precia and CoLab used a portion of these funds to support the time of some of the authors. Mirvie had no part in selecting authors or in the content of the manuscript.
Several authors received an honorarium for participation in the Working Group that developed the Care Plan. Two coauthors are site principal investigators overseeing sample collection on a Mirvie project. The remaining authors and Dr. Garovic report no conflicts of interest.
Preeclampsia is a leading cause of maternal mortality and premature births. The report, published in the American Journal of Obstetrics and Gynecology, developed by a working group of clinicians, researchers, patients, advocates, and payers, recommends daily low-dose aspirin, surveillance, behavioral strategies, patient and provider education, long-term follow-up, and addressing social determinants of health.
Titled “Care plan for individuals at risk for preeclampsia: Shared approach to education, strategies for prevention, surveillance and follow up,” the report includes recommendations for providers and for patients at moderate to high risk of preeclampsia.
Top recommendations for providers include performing a risk assessment, including social determinants of health, medication recommendations (including daily aspirin and antihypertensive therapy), and behavioral recommendations (including specific information about diet, exercise, and sleep.)
The recommendations for patients include asking providers about aspirin use, checking blood pressure at home, and reporting any readings greater than 140/90. For those with BPs measuring 140/90 mm Hg or higher, the plan recommends antihypertensive therapy. The recommendations include making changes to diet, exercise, and sleep in consultation with providers.
Home blood pressure checks controversial
James Roberts, MD, a maternal-fetal medicine researcher at the Magee-Women’s Research Institute at University of Pittsburgh Medical Center and lead author on the paper, told this publication the home blood pressure checks may be the most controversial item in the report as not all insurers cover the at-home equipment.
In this report, the authors write that the working group “strongly advocates that payers of health care services cover the modest expense of home blood pressure determination including equipment and training.”
Dr. Roberts is the founding principal investigator of the Global Pregnancy Collaboration (CoLab), a consortium of 40 centers and one of the groups leading the creation of this report.
He said that while most of the recommendations are already recommended in guidelines, the report puts the preeclampsia plan into easy-to-read steps and downloadable checklists and compiles the evidence all in one place.
Dr. Roberts said the working group hopes this report will be adapted into guidelines developed by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, and made part of electronic health records.
So far, the authors say, a comprehensive, integrated preeclampsia care plan has not been widely adopted.
Fewer than half of patients at risk receive aspirin
The coauthors note that “today, most pregnant individuals at increased risk do not receive even one of the interventions to prevent preeclampsia. For example, less than half of high-risk patients receive low-dose aspirin.”
A big part of this plan, Dr. Roberts said, calls for further educating both providers and patients.
Vesna Garovic, MD, PhD, a preeclampsia specialist at the Mayo Clinic in Rochester, Minn., who was not part of the working group, said, “This is the first comprehensive plan that provides a safe, cost-effective approach to reduce the risk of preeclampsia in individuals at moderate to high risk for this condition who qualify to receive aspirin for prevention.”
Dr. Garovic said the plan is novel in several ways, including the multispecialty input that also includes patients and advocates. Also, she says, it can be easily included in electronic health records and routine care of patients.
“The recommendations that were made, other than self-monitoring of blood pressure, are already standard of care. It will be important to understand as to which extent this comprehensive program, compared to the standard approach, would reduce further the risk of preeclampsia,” Dr. Garovic said. “A prospective, adequately powered comparative study would not only address this question, but will investigate compliance of providers and pregnant women with this shared approach, as well as patient satisfaction.”
The authors note the approach presented is for care in developed countries and that low- and middle-income countries would need to tailor the plan. The Care Plan is also meant only for prevention and is not meant to guide care for women who have developed preeclampsia.
Funding was provided to The Precia Group and the Global Pregnancy Collaboration to assemble this care plan by Mirvie, which is developing a biochemical predictor for preeclampsia. Precia and CoLab used a portion of these funds to support the time of some of the authors. Mirvie had no part in selecting authors or in the content of the manuscript.
Several authors received an honorarium for participation in the Working Group that developed the Care Plan. Two coauthors are site principal investigators overseeing sample collection on a Mirvie project. The remaining authors and Dr. Garovic report no conflicts of interest.
Preeclampsia is a leading cause of maternal mortality and premature births. The report, published in the American Journal of Obstetrics and Gynecology, developed by a working group of clinicians, researchers, patients, advocates, and payers, recommends daily low-dose aspirin, surveillance, behavioral strategies, patient and provider education, long-term follow-up, and addressing social determinants of health.
Titled “Care plan for individuals at risk for preeclampsia: Shared approach to education, strategies for prevention, surveillance and follow up,” the report includes recommendations for providers and for patients at moderate to high risk of preeclampsia.
Top recommendations for providers include performing a risk assessment, including social determinants of health, medication recommendations (including daily aspirin and antihypertensive therapy), and behavioral recommendations (including specific information about diet, exercise, and sleep.)
The recommendations for patients include asking providers about aspirin use, checking blood pressure at home, and reporting any readings greater than 140/90. For those with BPs measuring 140/90 mm Hg or higher, the plan recommends antihypertensive therapy. The recommendations include making changes to diet, exercise, and sleep in consultation with providers.
Home blood pressure checks controversial
James Roberts, MD, a maternal-fetal medicine researcher at the Magee-Women’s Research Institute at University of Pittsburgh Medical Center and lead author on the paper, told this publication the home blood pressure checks may be the most controversial item in the report as not all insurers cover the at-home equipment.
In this report, the authors write that the working group “strongly advocates that payers of health care services cover the modest expense of home blood pressure determination including equipment and training.”
Dr. Roberts is the founding principal investigator of the Global Pregnancy Collaboration (CoLab), a consortium of 40 centers and one of the groups leading the creation of this report.
He said that while most of the recommendations are already recommended in guidelines, the report puts the preeclampsia plan into easy-to-read steps and downloadable checklists and compiles the evidence all in one place.
Dr. Roberts said the working group hopes this report will be adapted into guidelines developed by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, and made part of electronic health records.
So far, the authors say, a comprehensive, integrated preeclampsia care plan has not been widely adopted.
Fewer than half of patients at risk receive aspirin
The coauthors note that “today, most pregnant individuals at increased risk do not receive even one of the interventions to prevent preeclampsia. For example, less than half of high-risk patients receive low-dose aspirin.”
A big part of this plan, Dr. Roberts said, calls for further educating both providers and patients.
Vesna Garovic, MD, PhD, a preeclampsia specialist at the Mayo Clinic in Rochester, Minn., who was not part of the working group, said, “This is the first comprehensive plan that provides a safe, cost-effective approach to reduce the risk of preeclampsia in individuals at moderate to high risk for this condition who qualify to receive aspirin for prevention.”
Dr. Garovic said the plan is novel in several ways, including the multispecialty input that also includes patients and advocates. Also, she says, it can be easily included in electronic health records and routine care of patients.
“The recommendations that were made, other than self-monitoring of blood pressure, are already standard of care. It will be important to understand as to which extent this comprehensive program, compared to the standard approach, would reduce further the risk of preeclampsia,” Dr. Garovic said. “A prospective, adequately powered comparative study would not only address this question, but will investigate compliance of providers and pregnant women with this shared approach, as well as patient satisfaction.”
The authors note the approach presented is for care in developed countries and that low- and middle-income countries would need to tailor the plan. The Care Plan is also meant only for prevention and is not meant to guide care for women who have developed preeclampsia.
Funding was provided to The Precia Group and the Global Pregnancy Collaboration to assemble this care plan by Mirvie, which is developing a biochemical predictor for preeclampsia. Precia and CoLab used a portion of these funds to support the time of some of the authors. Mirvie had no part in selecting authors or in the content of the manuscript.
Several authors received an honorarium for participation in the Working Group that developed the Care Plan. Two coauthors are site principal investigators overseeing sample collection on a Mirvie project. The remaining authors and Dr. Garovic report no conflicts of interest.
FROM AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
High-dose vitamin D and MS relapse: New phase 3 data
, results from a randomized control trial show. However, at least one expert believes the study’s exclusion criteria may have been too broad.
The investigation of vitamin D to prevent relapse of MS is based on older observational studies of people who already had higher blood levels of vitamin D and were less likely to develop MS, said study investigator Ellen Mowry, MD, Richard T. and Frances W. Johnson professor of neurology, Johns Hopkins University, Baltimore.
Later research where participants were given vitamin D as a therapeutic option for MS “were disappointing as the vitamin D had minimal effect,” she said.
“While we were excited by early data suggesting that vitamin D may have an important impact on MS, it’s essential to follow those linkage studies with the gold standard clinical evidence, which we have here,” Dr. Mowry added.
The findings were published online in eClinicalMedicine.
No difference in relapse risk
The multisite, phase 3 Vitamin D to Ameliorate MS (VIDAMS) clinical trial included 172 participants aged 18-50 years with RRMS from 16 neurology clinics between 2012 and 2019.
Inclusion criteria were having one or more clinical episodes of MS in the past year and at least one brain lesion on MRI in the past year or having two or more clinical episodes in the past year. Eligible participants also had to have a score of 4 or less on the Kurtzke Expanded Disability Status Scale.
A total of 83 participants were randomly assigned to receive low-dose vitamin D3 (600 IU/day) and 89 to receive high-dose vitamin D3 (5,000 IU/day). Each participant took the vitamin tablet with glatiramer acetate, a synthetic protein that simulates myelin.
Participants were assessed every 12 weeks to measure serum 25(OH)D levels and every 24 weeks for a number of movement and coordination tests, as well as two 3T clinical brain MRIs to check for lesions.
By the trial’s end at 96 weeks, the researchers found no differences in relapse risk between the high- and low-dose groups (P = .57). In addition, there were no differences in MRI outcomes between the two groups.
Dr. Mowry said that more than a few people have asked her if she is disappointed by the results of the VIDAMS trial. “I tell them that no, I’m not – that we are scientists and clinicians, and it is our job to understand what they can do to fight their disease. And if the answer is not vitamin D, that’s OK – we have many other ideas.”
These include helping patients minimize cardiometabolic comorbidities, such as heart disease and blood pressure, she said.
Exclusion criteria too broad?
Commenting on the findings, Alberto Ascherio, MD, professor of epidemiology and nutrition at Harvard School of Public Health, Boston, said a key principle of recommending vitamin supplements is that they are, generally speaking, only beneficial for individuals with vitamin deficiencies.
He noted that “patients with vitamin D deficiency (25(OH)D < 15 ng/mL, which corresponds to 37.5 nmol/L) were excluded from this study. Most importantly, the baseline mean 25(OH)D levels were about 30 ng/mL (75 nmol/L), which is considered a sufficient level (the IOM considers 20 ng/mL = 50 nmol/L as an adequate level),” with the level further increasing during the trial due to the supplementation.
“It would be a serious mistake to conclude from this trial (or any of the previous trials) that vitamin D supplementation is not important in MS patients,” Dr. Ascherio said.
He added that many individuals with MS have serum vitamin D levels below 20 ng/mL (50 nmol/L) and that this was the median serum value in studies among individuals with MS in Europe.
“These patients would almost certainly benefit from moderate doses of vitamin D supplements or judicious UV light exposure. Most likely even patients with sufficient but suboptimal 25(OH)D levels (between 20 and 30 ng/mL, or 50 and 75 nmol/L) would benefit from an increase,” he said.
The study was funded by the National Multiple Sclerosis Society, Teva Neuroscience, and the National Institute of Health. Dr. Mowry reported grant support from the National MS Society, Biogen, Genentech, and Teva Neuroscience; honoraria from UpToDate; and consulting fees from BeCare Link.
A version of this article first appeared on Medscape.com.
, results from a randomized control trial show. However, at least one expert believes the study’s exclusion criteria may have been too broad.
The investigation of vitamin D to prevent relapse of MS is based on older observational studies of people who already had higher blood levels of vitamin D and were less likely to develop MS, said study investigator Ellen Mowry, MD, Richard T. and Frances W. Johnson professor of neurology, Johns Hopkins University, Baltimore.
Later research where participants were given vitamin D as a therapeutic option for MS “were disappointing as the vitamin D had minimal effect,” she said.
“While we were excited by early data suggesting that vitamin D may have an important impact on MS, it’s essential to follow those linkage studies with the gold standard clinical evidence, which we have here,” Dr. Mowry added.
The findings were published online in eClinicalMedicine.
No difference in relapse risk
The multisite, phase 3 Vitamin D to Ameliorate MS (VIDAMS) clinical trial included 172 participants aged 18-50 years with RRMS from 16 neurology clinics between 2012 and 2019.
Inclusion criteria were having one or more clinical episodes of MS in the past year and at least one brain lesion on MRI in the past year or having two or more clinical episodes in the past year. Eligible participants also had to have a score of 4 or less on the Kurtzke Expanded Disability Status Scale.
A total of 83 participants were randomly assigned to receive low-dose vitamin D3 (600 IU/day) and 89 to receive high-dose vitamin D3 (5,000 IU/day). Each participant took the vitamin tablet with glatiramer acetate, a synthetic protein that simulates myelin.
Participants were assessed every 12 weeks to measure serum 25(OH)D levels and every 24 weeks for a number of movement and coordination tests, as well as two 3T clinical brain MRIs to check for lesions.
By the trial’s end at 96 weeks, the researchers found no differences in relapse risk between the high- and low-dose groups (P = .57). In addition, there were no differences in MRI outcomes between the two groups.
Dr. Mowry said that more than a few people have asked her if she is disappointed by the results of the VIDAMS trial. “I tell them that no, I’m not – that we are scientists and clinicians, and it is our job to understand what they can do to fight their disease. And if the answer is not vitamin D, that’s OK – we have many other ideas.”
These include helping patients minimize cardiometabolic comorbidities, such as heart disease and blood pressure, she said.
Exclusion criteria too broad?
Commenting on the findings, Alberto Ascherio, MD, professor of epidemiology and nutrition at Harvard School of Public Health, Boston, said a key principle of recommending vitamin supplements is that they are, generally speaking, only beneficial for individuals with vitamin deficiencies.
He noted that “patients with vitamin D deficiency (25(OH)D < 15 ng/mL, which corresponds to 37.5 nmol/L) were excluded from this study. Most importantly, the baseline mean 25(OH)D levels were about 30 ng/mL (75 nmol/L), which is considered a sufficient level (the IOM considers 20 ng/mL = 50 nmol/L as an adequate level),” with the level further increasing during the trial due to the supplementation.
“It would be a serious mistake to conclude from this trial (or any of the previous trials) that vitamin D supplementation is not important in MS patients,” Dr. Ascherio said.
He added that many individuals with MS have serum vitamin D levels below 20 ng/mL (50 nmol/L) and that this was the median serum value in studies among individuals with MS in Europe.
“These patients would almost certainly benefit from moderate doses of vitamin D supplements or judicious UV light exposure. Most likely even patients with sufficient but suboptimal 25(OH)D levels (between 20 and 30 ng/mL, or 50 and 75 nmol/L) would benefit from an increase,” he said.
The study was funded by the National Multiple Sclerosis Society, Teva Neuroscience, and the National Institute of Health. Dr. Mowry reported grant support from the National MS Society, Biogen, Genentech, and Teva Neuroscience; honoraria from UpToDate; and consulting fees from BeCare Link.
A version of this article first appeared on Medscape.com.
, results from a randomized control trial show. However, at least one expert believes the study’s exclusion criteria may have been too broad.
The investigation of vitamin D to prevent relapse of MS is based on older observational studies of people who already had higher blood levels of vitamin D and were less likely to develop MS, said study investigator Ellen Mowry, MD, Richard T. and Frances W. Johnson professor of neurology, Johns Hopkins University, Baltimore.
Later research where participants were given vitamin D as a therapeutic option for MS “were disappointing as the vitamin D had minimal effect,” she said.
“While we were excited by early data suggesting that vitamin D may have an important impact on MS, it’s essential to follow those linkage studies with the gold standard clinical evidence, which we have here,” Dr. Mowry added.
The findings were published online in eClinicalMedicine.
No difference in relapse risk
The multisite, phase 3 Vitamin D to Ameliorate MS (VIDAMS) clinical trial included 172 participants aged 18-50 years with RRMS from 16 neurology clinics between 2012 and 2019.
Inclusion criteria were having one or more clinical episodes of MS in the past year and at least one brain lesion on MRI in the past year or having two or more clinical episodes in the past year. Eligible participants also had to have a score of 4 or less on the Kurtzke Expanded Disability Status Scale.
A total of 83 participants were randomly assigned to receive low-dose vitamin D3 (600 IU/day) and 89 to receive high-dose vitamin D3 (5,000 IU/day). Each participant took the vitamin tablet with glatiramer acetate, a synthetic protein that simulates myelin.
Participants were assessed every 12 weeks to measure serum 25(OH)D levels and every 24 weeks for a number of movement and coordination tests, as well as two 3T clinical brain MRIs to check for lesions.
By the trial’s end at 96 weeks, the researchers found no differences in relapse risk between the high- and low-dose groups (P = .57). In addition, there were no differences in MRI outcomes between the two groups.
Dr. Mowry said that more than a few people have asked her if she is disappointed by the results of the VIDAMS trial. “I tell them that no, I’m not – that we are scientists and clinicians, and it is our job to understand what they can do to fight their disease. And if the answer is not vitamin D, that’s OK – we have many other ideas.”
These include helping patients minimize cardiometabolic comorbidities, such as heart disease and blood pressure, she said.
Exclusion criteria too broad?
Commenting on the findings, Alberto Ascherio, MD, professor of epidemiology and nutrition at Harvard School of Public Health, Boston, said a key principle of recommending vitamin supplements is that they are, generally speaking, only beneficial for individuals with vitamin deficiencies.
He noted that “patients with vitamin D deficiency (25(OH)D < 15 ng/mL, which corresponds to 37.5 nmol/L) were excluded from this study. Most importantly, the baseline mean 25(OH)D levels were about 30 ng/mL (75 nmol/L), which is considered a sufficient level (the IOM considers 20 ng/mL = 50 nmol/L as an adequate level),” with the level further increasing during the trial due to the supplementation.
“It would be a serious mistake to conclude from this trial (or any of the previous trials) that vitamin D supplementation is not important in MS patients,” Dr. Ascherio said.
He added that many individuals with MS have serum vitamin D levels below 20 ng/mL (50 nmol/L) and that this was the median serum value in studies among individuals with MS in Europe.
“These patients would almost certainly benefit from moderate doses of vitamin D supplements or judicious UV light exposure. Most likely even patients with sufficient but suboptimal 25(OH)D levels (between 20 and 30 ng/mL, or 50 and 75 nmol/L) would benefit from an increase,” he said.
The study was funded by the National Multiple Sclerosis Society, Teva Neuroscience, and the National Institute of Health. Dr. Mowry reported grant support from the National MS Society, Biogen, Genentech, and Teva Neuroscience; honoraria from UpToDate; and consulting fees from BeCare Link.
A version of this article first appeared on Medscape.com.
FROM ECLINICALMEDICINE