There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

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

There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

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

There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

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

Researchers have identified four distinct clinical profiles for young people at risk for serious self-harm. 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.

Researchers have identified four distinct clinical profiles for young people at risk for serious self-harm. 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.

Researchers have identified four distinct clinical profiles for young people at risk for serious self-harm. 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.

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.

La Jolla Institute for Immunology

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.

Emory University School of Medicine

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.

Steve Fisch

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.

La Jolla Institute for Immunology

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.

Emory University School of Medicine

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.

Steve Fisch

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.

La Jolla Institute for Immunology

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.

Emory University School of Medicine

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.

Steve Fisch

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.

Up to half of patients with type 2 diabetes report poor adherence to their non-insulin medications. In this ReCAP, Dr Anne Peters, director of the University of Southern California Clinical Diabetes Programs in Los Angeles, California, offers clinicians suggestions on how to get their patients to "buy in" to these treatments, many of which do not make them feel any better. Research shows that quality of life, short- and long-term clinical outcomes, and side effects are important factors in treatment adherence. Dr Peters explains that adherence may be improved if patients understand why they need to take a medication, how it might make them feel, what to do about it, and how taking it will fit into their daily pattern. She also points out that access and affordability of the medication regimen are additional factors for which patients may need support to increase treatment adherence.

--

Anne L. Peters, MD, Professor, Department of Clinical Medicine, Clinical Scholar, Keck School of Medicine of the University of Southern California; Director, USC Clinical Diabetes Programs, University of Southern California Westside Center for Diabetes, Los Angeles, California

Anne L. Peters, MD, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or a trustee for: Blue Circle Health; Vertex; Abbott Diabetes Care Received research grant from: Abbott Diabetes Care; Insulet Stock options from: Teladoc; Omada Health

Up to half of patients with type 2 diabetes report poor adherence to their non-insulin medications. In this ReCAP, Dr Anne Peters, director of the University of Southern California Clinical Diabetes Programs in Los Angeles, California, offers clinicians suggestions on how to get their patients to "buy in" to these treatments, many of which do not make them feel any better. Research shows that quality of life, short- and long-term clinical outcomes, and side effects are important factors in treatment adherence. Dr Peters explains that adherence may be improved if patients understand why they need to take a medication, how it might make them feel, what to do about it, and how taking it will fit into their daily pattern. She also points out that access and affordability of the medication regimen are additional factors for which patients may need support to increase treatment adherence.

--

Anne L. Peters, MD, Professor, Department of Clinical Medicine, Clinical Scholar, Keck School of Medicine of the University of Southern California; Director, USC Clinical Diabetes Programs, University of Southern California Westside Center for Diabetes, Los Angeles, California

Anne L. Peters, MD, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or a trustee for: Blue Circle Health; Vertex; Abbott Diabetes Care Received research grant from: Abbott Diabetes Care; Insulet Stock options from: Teladoc; Omada Health

Up to half of patients with type 2 diabetes report poor adherence to their non-insulin medications. In this ReCAP, Dr Anne Peters, director of the University of Southern California Clinical Diabetes Programs in Los Angeles, California, offers clinicians suggestions on how to get their patients to "buy in" to these treatments, many of which do not make them feel any better. Research shows that quality of life, short- and long-term clinical outcomes, and side effects are important factors in treatment adherence. Dr Peters explains that adherence may be improved if patients understand why they need to take a medication, how it might make them feel, what to do about it, and how taking it will fit into their daily pattern. She also points out that access and affordability of the medication regimen are additional factors for which patients may need support to increase treatment adherence.

--

Anne L. Peters, MD, Professor, Department of Clinical Medicine, Clinical Scholar, Keck School of Medicine of the University of Southern California; Director, USC Clinical Diabetes Programs, University of Southern California Westside Center for Diabetes, Los Angeles, California

Anne L. Peters, MD, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or a trustee for: Blue Circle Health; Vertex; Abbott Diabetes Care Received research grant from: Abbott Diabetes Care; Insulet Stock options from: Teladoc; Omada Health

Endocrine therapy (ET) has long been the therapeutic mainstay for first-line treatment of HR+/HER2- breast cancer. Yet, approximately one third of patients exhibit primary or acquired ET resistance, and some patients progress within 2 years after adjuvant ET. Resistance to endocrine therapy is a major challenge for a significant number of patients who go on to develop metastatic breast cancer.

Dr Jennifer Litton from The University of Texas MD Anderson Cancer Center in Houston, Texas, reports on current treatment recommendations and supporting research on the use of endocrine therapy and CDK4/6 inhibitors in both the metastatic and, more recently, the high-risk, early HR+/HER2- breast cancer settings.

Dr Litton also reviews key drivers of endocrine resistance, including somatic mutations such as ESR1. She emphasizes the need for next-generation testing in patients with metastatic HR+/HER2- disease to look for evidence of resistance, which may have implications for the next line of therapy.

--

Professor, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas

Jennifer K. Litton, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The University of Texas MD Anderson Cancer Center

Serve(d) as a speaker or a member of a speakers bureau for: Clinical Care Options; Med Learning Group; Medpage; Medscape; PRIME; Physicians Education Resource; UpToDate

Endocrine therapy (ET) has long been the therapeutic mainstay for first-line treatment of HR+/HER2- breast cancer. Yet, approximately one third of patients exhibit primary or acquired ET resistance, and some patients progress within 2 years after adjuvant ET. Resistance to endocrine therapy is a major challenge for a significant number of patients who go on to develop metastatic breast cancer.

Dr Jennifer Litton from The University of Texas MD Anderson Cancer Center in Houston, Texas, reports on current treatment recommendations and supporting research on the use of endocrine therapy and CDK4/6 inhibitors in both the metastatic and, more recently, the high-risk, early HR+/HER2- breast cancer settings.

Dr Litton also reviews key drivers of endocrine resistance, including somatic mutations such as ESR1. She emphasizes the need for next-generation testing in patients with metastatic HR+/HER2- disease to look for evidence of resistance, which may have implications for the next line of therapy.

--

Professor, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas

Jennifer K. Litton, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The University of Texas MD Anderson Cancer Center

Serve(d) as a speaker or a member of a speakers bureau for: Clinical Care Options; Med Learning Group; Medpage; Medscape; PRIME; Physicians Education Resource; UpToDate

Endocrine therapy (ET) has long been the therapeutic mainstay for first-line treatment of HR+/HER2- breast cancer. Yet, approximately one third of patients exhibit primary or acquired ET resistance, and some patients progress within 2 years after adjuvant ET. Resistance to endocrine therapy is a major challenge for a significant number of patients who go on to develop metastatic breast cancer.

Dr Jennifer Litton from The University of Texas MD Anderson Cancer Center in Houston, Texas, reports on current treatment recommendations and supporting research on the use of endocrine therapy and CDK4/6 inhibitors in both the metastatic and, more recently, the high-risk, early HR+/HER2- breast cancer settings.

Dr Litton also reviews key drivers of endocrine resistance, including somatic mutations such as ESR1. She emphasizes the need for next-generation testing in patients with metastatic HR+/HER2- disease to look for evidence of resistance, which may have implications for the next line of therapy.

--

Professor, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas

Jennifer K. Litton, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The University of Texas MD Anderson Cancer Center

Serve(d) as a speaker or a member of a speakers bureau for: Clinical Care Options; Med Learning Group; Medpage; Medscape; PRIME; Physicians Education Resource; UpToDate

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.

BOSTON – The investigational drug donanemab yielded greater amyloid clearance and amyloid plaque reduction than aducanumab in early, symptomatic Alzheimer’s disease, according to the results of a head-to-head study.

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 – The investigational drug donanemab yielded greater amyloid clearance and amyloid plaque reduction than aducanumab in early, symptomatic Alzheimer’s disease, according to the results of a head-to-head study.

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 – The investigational drug donanemab yielded greater amyloid clearance and amyloid plaque reduction than aducanumab in early, symptomatic Alzheimer’s disease, according to the results of a head-to-head study.

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.

In this supplement to Family Medicine, Charles P Vega, MD, and Pamela R Kushner, MD, discuss failure of the PROMINENT trial and implications for use of fibrates to reduce cardiovascular risk.

Read More 

In this supplement to Family Medicine, Charles P Vega, MD, and Pamela R Kushner, MD, discuss failure of the PROMINENT trial and implications for use of fibrates to reduce cardiovascular risk.

Read More 

In this supplement to Family Medicine, Charles P Vega, MD, and Pamela R Kushner, MD, discuss failure of the PROMINENT trial and implications for use of fibrates to reduce cardiovascular risk.

Read More 

WASHINGTON – A novel program for parents of highly dependent adult children reduces parental burden and anxiety in their offspring, 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 novel program for parents of highly dependent adult children reduces parental burden and anxiety in their offspring, 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 novel program for parents of highly dependent adult children reduces parental burden and anxiety in their offspring, 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.

A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.

Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia

Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.

Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC

Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI  0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.

A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.

Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia

Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.

Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC

Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI  0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.

A cohort study by Minami and colleagues assessed the association between surgery type (lumpectomy vs mastectomy) and change in frailty status in older patients with early-stage breast cancer (BC) undergoing locoregional therapy. The study included 31,084 women, age ≥ 65 years, with ductal carcinoma in situ (n = 9962) or stage I hormone receptor–positive (HR+) and ERBB2+ (human epidermal growth factor receptor 2 positive [HER2+]) BC (n = 21,122), of which 22.6% and 77.4% of patients underwent mastectomy and lumpectomy, respectively. The study showed that older patients who underwent mastectomy vs lumpectomy were more likely to experience worse frailty (adjusted odds ratio 1.31; 95% CI 1.23-1.39). Additionally, women who were robust vs having moderate to severe frailty at baseline, ≥ 75 years vs 65-69 years, or African American/Black vs non-Hispanic White, had significantly higher odds of decline. Given that prior data have shown comparable survival between lumpectomy and mastectomy, careful and thoughtful treatment considerations are needed before deciding to intensify surgical management in this population, even in women who do not appear frail at baseline.

Low-dose tamoxifen continues to prevent BC recurrence in breast noninvasive neoplasia

Low-dose tamoxifen is a treatment option for women with noninvasive BC, especially if the patient was not able to tolerate the standard dose of 20 mg daily. The phase 3 TAM-01 trial included 500 women with intraepithelial neoplasia of the breast who were randomly assigned to receive low-dose tamoxifen (5 mg once daily) or placebo. The 10-year follow-up analysis by Lazzeroni and colleagues showed that treatment with low-dose tamoxifen for 3 years continued to prevent a BC recurrence for at least 7 years after treatment cessation. After a median follow-up of 9.7 years, fewer cases of both invasive and in situ BC (hazard ratio 0.58; log-rank P = .03) and contralateral BC (hazard ratio 0.36; P = .025) were reported in the tamoxifen vs placebo group. These results are meaningful, especially in a setting of an optimal safety profile, where patients on low-dose tamoxifen were experiencing similar menopausal symptoms to placebo, and serious adverse events, such as deep vein thrombosis and pulmonary embolism, were not increased during low-dose tamoxifen therapy. This is different from the threefold increased risk reported with standard dosing.

Worse survival in BRCA1/2 germline mutation carriers receiving ET in HR+/HER2− BC

Inconsistent data have been reported on the prognostic impact of BRCA1/2 mutation in HR+ BC. A retrospective study by Frenel and colleagues included 13,776 patients with metastatic BC (MBC) from the Epidemiological Strategy and Medical Economics (ESME) MBC database, of which 676 and 170 patients were germline BRCA wild-type (gBRCAwt) and germline BRCA mutation (gBRCAm) carriers, respectively. They looked at outcomes and first-line endocrine treatment efficacy in patients with HR+/HER2- MBC, treated in a pre–cyclin-dependent kinase (CDK) 4/6 inhibitors era. The results showed that gBRCAm carriers had shorter overall survival (OS; adjusted hazard ratio [aHR] 1.26; P = .024) and progression-free survival (PFS; aHR 1.21; P = .017) compared with gBRCAwt carriers. Furthermore, among those treated with front-line endocrine therapy, gBRCAm patients had lower adjusted OS (aHR [95% CI] 1.54 [1.03-2.32]) and PFS (aHR [95% CI] 1.58 [1.17-2.12]) compared with gBRCAwt patients. Outcomes were similar for gBRCAm patients who received first-line chemotherapy compared with the gBRCAwt group (OS: aHR [95% CI] 1.12 [0.88-1.41]; first-line PFS: aHR [95% CI] 1.09 [0.90-1.31]). A previous retrospective study by Lambertini and colleagues, focusing on young patients with gBRCAm, also showed a tendency for a worse distant recurrence-free interval (aHR 1.39; 95% CI  0.94-2.05) in patients with HR+ BC. Additional studies are needed, especially in the setting of an evolving treatment landscape that includes CDK4/6 inhibitors and poly-ADP ribose polymerase (PARP) inhibitors.