MDedge Pediatrics

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

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

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

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

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

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

Infant mortality rates rose in 2022 for the first time in more than 20 years, according to a new government report.

The overall mortality rate and the rate for neonatal infants, those younger than 28 days old, rose by 3% from 2021 to 2022, says the Centers for Disease Control and Prevention’s National Center for Health Statistics. The mortality rate for infants older than 28 days rose by 4%.

Meanwhile, infant deaths caused by maternal complications rose by 8% and those caused by bacterial sepsis rose by 14%, the report says.

“We live in a country with significant resources, so the infant mortality rate and the increase are shockingly high,” wrote Sandy Chung, MD, of the American Academy of Pediatrics, to CNN. “As pediatricians who help children grow into healthy adults, any death of any child is one too many. The infant mortality rate in this country in unacceptable.”

Experts say the increase could be a sign of an underlying health care issue, an unusual occurrence, or partly related to the COVID-19 pandemic.

The infant mortality rate rose among mothers aged 25-29 years; for preterm babies; for boys; and in Georgia, Iowa, Missouri, and Texas. The rate declined in Nevada.

“Mortality rates increased significantly among infants of American Indian and Alaska Native non-Hispanic ... and White non-Hispanic women,” the report says.

“Mortality rates for infants of Black women did not increase by much, the report found, but Black infants experienced the highest overall rates of infant mortality: nearly 11 deaths per 1,000 births, or over double the mortality rate of White infants,” CNN wrote.

“We know that for people who live in or near poverty and for certain racial and ethnic groups there are significant challenges with getting access to a doctor or getting treatments,” Dr. Chung wrote. “This can lead to moms and babies showing up for care when they are sicker and more likely have serious outcomes, even death.”

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

Infant mortality rates rose in 2022 for the first time in more than 20 years, according to a new government report.

The overall mortality rate and the rate for neonatal infants, those younger than 28 days old, rose by 3% from 2021 to 2022, says the Centers for Disease Control and Prevention’s National Center for Health Statistics. The mortality rate for infants older than 28 days rose by 4%.

Meanwhile, infant deaths caused by maternal complications rose by 8% and those caused by bacterial sepsis rose by 14%, the report says.

“We live in a country with significant resources, so the infant mortality rate and the increase are shockingly high,” wrote Sandy Chung, MD, of the American Academy of Pediatrics, to CNN. “As pediatricians who help children grow into healthy adults, any death of any child is one too many. The infant mortality rate in this country in unacceptable.”

Experts say the increase could be a sign of an underlying health care issue, an unusual occurrence, or partly related to the COVID-19 pandemic.

The infant mortality rate rose among mothers aged 25-29 years; for preterm babies; for boys; and in Georgia, Iowa, Missouri, and Texas. The rate declined in Nevada.

“Mortality rates increased significantly among infants of American Indian and Alaska Native non-Hispanic ... and White non-Hispanic women,” the report says.

“Mortality rates for infants of Black women did not increase by much, the report found, but Black infants experienced the highest overall rates of infant mortality: nearly 11 deaths per 1,000 births, or over double the mortality rate of White infants,” CNN wrote.

“We know that for people who live in or near poverty and for certain racial and ethnic groups there are significant challenges with getting access to a doctor or getting treatments,” Dr. Chung wrote. “This can lead to moms and babies showing up for care when they are sicker and more likely have serious outcomes, even death.”

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

Infant mortality rates rose in 2022 for the first time in more than 20 years, according to a new government report.

The overall mortality rate and the rate for neonatal infants, those younger than 28 days old, rose by 3% from 2021 to 2022, says the Centers for Disease Control and Prevention’s National Center for Health Statistics. The mortality rate for infants older than 28 days rose by 4%.

Meanwhile, infant deaths caused by maternal complications rose by 8% and those caused by bacterial sepsis rose by 14%, the report says.

“We live in a country with significant resources, so the infant mortality rate and the increase are shockingly high,” wrote Sandy Chung, MD, of the American Academy of Pediatrics, to CNN. “As pediatricians who help children grow into healthy adults, any death of any child is one too many. The infant mortality rate in this country in unacceptable.”

Experts say the increase could be a sign of an underlying health care issue, an unusual occurrence, or partly related to the COVID-19 pandemic.

The infant mortality rate rose among mothers aged 25-29 years; for preterm babies; for boys; and in Georgia, Iowa, Missouri, and Texas. The rate declined in Nevada.

“Mortality rates increased significantly among infants of American Indian and Alaska Native non-Hispanic ... and White non-Hispanic women,” the report says.

“Mortality rates for infants of Black women did not increase by much, the report found, but Black infants experienced the highest overall rates of infant mortality: nearly 11 deaths per 1,000 births, or over double the mortality rate of White infants,” CNN wrote.

“We know that for people who live in or near poverty and for certain racial and ethnic groups there are significant challenges with getting access to a doctor or getting treatments,” Dr. Chung wrote. “This can lead to moms and babies showing up for care when they are sicker and more likely have serious outcomes, even death.”

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

Good news for people struggling with sensory problems after a bout of COVID-19. Although mild cases of the disease often impair the ability to taste and smell, and the problem can drag on for months, a new study from Italy shows that most people return to their senses, as it were, within 3 years.

“In the vast majority of cases, the loss of the sense of smell is not irreversible,” said Paolo Boscolo-Rizzo, MD, a professor of medicine, surgery, and health sciences at the University of Trieste (Italy), and a co-author of the study, published as a research letter in JAMA Otolaryngology–Head & Neck Surgery.

Dr. Boscolo-Rizzo and his colleagues analyzed data from 88 adults with mild COVID-19, which was defined as having no lower respiratory disease and blood oxygen saturation of 94% or greater. Another group of 88 adults who never contracted the virus but sometimes had difficulties with smell and taste were also studied. In both groups, the average age was 49 years, all participants were White, and 58% were women.

The researchers tested participants’ sense of smell with sticks that contained different odors and checked their sense of taste with strips that had different tastes. Over time, fewer people had difficulty distinguishing odors. Three years after developing COVID-19, only 12 people had impaired smell, compared with 36 people at year 1 and 24 people at year 2. And at the 3-year mark, all participants had at least a partial ability to smell. 

The story was similar with sense of taste, with 10 of 88 people reporting impairments 3 years later. By then, people with COVID-19 were no more likely to have trouble with smell or taste than people who did not get the virus. 

A study this past June showed a strong correlation between severity of COVID-19 symptoms and impaired sense of taste and smell and estimated that millions of Americans maintained altered senses. More than 10% of people in the Italian study still had trouble with smell or taste 3 years later.
 

Emerging treatments, psychological concerns

“We’re seeing fewer people with this problem, but there are still people suffering from it,” said Fernando Carnavali, MD, an internal medicine physician and a site director for the Center for Post-COVID Care at the Icahn School of Medicine at Mount Sinai, New York City.

Dr. Carnavali wasn’t part of this study, but he did find the new results encouraging, and he called for similar studies in diverse populations that have experienced COVID-19. He also noted that an impaired sense of smell is distressing.

“It really has a significant psychological impact,” Dr. Carnavali said.

He recalled a patient crying in his office because her inability to smell made it impossible for her to cook. Dr. Carnavali recommended clinicians refer patients facing protracted loss of smell or taste to mental health professionals for support.

Treatments are emerging for COVID-19 smell loss. One approach is to inject platelet-rich plasma into a patient’s nasal cavities to help neurons related to smell repair themselves.

A randomized trial showed platelet-rich plasma significantly outperformed placebo in patients with smell loss up to a year after getting COVID-19.

“I wish more people would do it,” said Zara Patel, MD, an otolaryngologist at Stanford (Calif.) Medicine, who helped conduct that trial. She said some physicians may be nervous about injecting plasma so close to the skull and are therefore hesitant to try this approach. 

Another technique may help to address the olfactory condition known as parosmia, in which patients generally experience a benign odor as rancid, according to otolaryngologist Nyssa Farrell, MD, of Washington University School of Medicine, St. Louis. Dr. Farrell said around two-thirds of patients who contract COVID-19 develop the condition, and the rates of long-term parosmia range from 10%-50% depending on various studies.

“It is almost always foul; this can profoundly affect someone’s quality of life,” impairing their ability to eat or to be intimate with a partner who now smells unpleasant, said Dr. Farrell, who wasn’t associated with this research.

The treatment, called a stellate ganglion block, is provided through a shot into nerves in the neck. People with parosmia associated with COVID-19 often report that this method cures them. Dr. Patel said that may be because their psychological health is improving, not their sense of smell, because the area of the body where the stellate ganglion block is applied is not part of the olfactory system.

Earlier this year, Dr. Farrell and colleagues reported that parosmia linked to COVID-19 is associated with an increased risk for depression, anxiety, and suicidal ideation. 

One coauthor reported receiving grants from Smell and Taste Lab, Takasago, Baia Foods, and Frequency Therapeutics. The other authors reported no relevant financial relationships.

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

Good news for people struggling with sensory problems after a bout of COVID-19. Although mild cases of the disease often impair the ability to taste and smell, and the problem can drag on for months, a new study from Italy shows that most people return to their senses, as it were, within 3 years.

“In the vast majority of cases, the loss of the sense of smell is not irreversible,” said Paolo Boscolo-Rizzo, MD, a professor of medicine, surgery, and health sciences at the University of Trieste (Italy), and a co-author of the study, published as a research letter in JAMA Otolaryngology–Head & Neck Surgery.

Dr. Boscolo-Rizzo and his colleagues analyzed data from 88 adults with mild COVID-19, which was defined as having no lower respiratory disease and blood oxygen saturation of 94% or greater. Another group of 88 adults who never contracted the virus but sometimes had difficulties with smell and taste were also studied. In both groups, the average age was 49 years, all participants were White, and 58% were women.

The researchers tested participants’ sense of smell with sticks that contained different odors and checked their sense of taste with strips that had different tastes. Over time, fewer people had difficulty distinguishing odors. Three years after developing COVID-19, only 12 people had impaired smell, compared with 36 people at year 1 and 24 people at year 2. And at the 3-year mark, all participants had at least a partial ability to smell. 

The story was similar with sense of taste, with 10 of 88 people reporting impairments 3 years later. By then, people with COVID-19 were no more likely to have trouble with smell or taste than people who did not get the virus. 

A study this past June showed a strong correlation between severity of COVID-19 symptoms and impaired sense of taste and smell and estimated that millions of Americans maintained altered senses. More than 10% of people in the Italian study still had trouble with smell or taste 3 years later.
 

Emerging treatments, psychological concerns

“We’re seeing fewer people with this problem, but there are still people suffering from it,” said Fernando Carnavali, MD, an internal medicine physician and a site director for the Center for Post-COVID Care at the Icahn School of Medicine at Mount Sinai, New York City.

Dr. Carnavali wasn’t part of this study, but he did find the new results encouraging, and he called for similar studies in diverse populations that have experienced COVID-19. He also noted that an impaired sense of smell is distressing.

“It really has a significant psychological impact,” Dr. Carnavali said.

He recalled a patient crying in his office because her inability to smell made it impossible for her to cook. Dr. Carnavali recommended clinicians refer patients facing protracted loss of smell or taste to mental health professionals for support.

Treatments are emerging for COVID-19 smell loss. One approach is to inject platelet-rich plasma into a patient’s nasal cavities to help neurons related to smell repair themselves.

A randomized trial showed platelet-rich plasma significantly outperformed placebo in patients with smell loss up to a year after getting COVID-19.

“I wish more people would do it,” said Zara Patel, MD, an otolaryngologist at Stanford (Calif.) Medicine, who helped conduct that trial. She said some physicians may be nervous about injecting plasma so close to the skull and are therefore hesitant to try this approach. 

Another technique may help to address the olfactory condition known as parosmia, in which patients generally experience a benign odor as rancid, according to otolaryngologist Nyssa Farrell, MD, of Washington University School of Medicine, St. Louis. Dr. Farrell said around two-thirds of patients who contract COVID-19 develop the condition, and the rates of long-term parosmia range from 10%-50% depending on various studies.

“It is almost always foul; this can profoundly affect someone’s quality of life,” impairing their ability to eat or to be intimate with a partner who now smells unpleasant, said Dr. Farrell, who wasn’t associated with this research.

The treatment, called a stellate ganglion block, is provided through a shot into nerves in the neck. People with parosmia associated with COVID-19 often report that this method cures them. Dr. Patel said that may be because their psychological health is improving, not their sense of smell, because the area of the body where the stellate ganglion block is applied is not part of the olfactory system.

Earlier this year, Dr. Farrell and colleagues reported that parosmia linked to COVID-19 is associated with an increased risk for depression, anxiety, and suicidal ideation. 

One coauthor reported receiving grants from Smell and Taste Lab, Takasago, Baia Foods, and Frequency Therapeutics. The other authors reported no relevant financial relationships.

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

Good news for people struggling with sensory problems after a bout of COVID-19. Although mild cases of the disease often impair the ability to taste and smell, and the problem can drag on for months, a new study from Italy shows that most people return to their senses, as it were, within 3 years.

“In the vast majority of cases, the loss of the sense of smell is not irreversible,” said Paolo Boscolo-Rizzo, MD, a professor of medicine, surgery, and health sciences at the University of Trieste (Italy), and a co-author of the study, published as a research letter in JAMA Otolaryngology–Head & Neck Surgery.

Dr. Boscolo-Rizzo and his colleagues analyzed data from 88 adults with mild COVID-19, which was defined as having no lower respiratory disease and blood oxygen saturation of 94% or greater. Another group of 88 adults who never contracted the virus but sometimes had difficulties with smell and taste were also studied. In both groups, the average age was 49 years, all participants were White, and 58% were women.

The researchers tested participants’ sense of smell with sticks that contained different odors and checked their sense of taste with strips that had different tastes. Over time, fewer people had difficulty distinguishing odors. Three years after developing COVID-19, only 12 people had impaired smell, compared with 36 people at year 1 and 24 people at year 2. And at the 3-year mark, all participants had at least a partial ability to smell. 

The story was similar with sense of taste, with 10 of 88 people reporting impairments 3 years later. By then, people with COVID-19 were no more likely to have trouble with smell or taste than people who did not get the virus. 

A study this past June showed a strong correlation between severity of COVID-19 symptoms and impaired sense of taste and smell and estimated that millions of Americans maintained altered senses. More than 10% of people in the Italian study still had trouble with smell or taste 3 years later.
 

Emerging treatments, psychological concerns

“We’re seeing fewer people with this problem, but there are still people suffering from it,” said Fernando Carnavali, MD, an internal medicine physician and a site director for the Center for Post-COVID Care at the Icahn School of Medicine at Mount Sinai, New York City.

Dr. Carnavali wasn’t part of this study, but he did find the new results encouraging, and he called for similar studies in diverse populations that have experienced COVID-19. He also noted that an impaired sense of smell is distressing.

“It really has a significant psychological impact,” Dr. Carnavali said.

He recalled a patient crying in his office because her inability to smell made it impossible for her to cook. Dr. Carnavali recommended clinicians refer patients facing protracted loss of smell or taste to mental health professionals for support.

Treatments are emerging for COVID-19 smell loss. One approach is to inject platelet-rich plasma into a patient’s nasal cavities to help neurons related to smell repair themselves.

A randomized trial showed platelet-rich plasma significantly outperformed placebo in patients with smell loss up to a year after getting COVID-19.

“I wish more people would do it,” said Zara Patel, MD, an otolaryngologist at Stanford (Calif.) Medicine, who helped conduct that trial. She said some physicians may be nervous about injecting plasma so close to the skull and are therefore hesitant to try this approach. 

Another technique may help to address the olfactory condition known as parosmia, in which patients generally experience a benign odor as rancid, according to otolaryngologist Nyssa Farrell, MD, of Washington University School of Medicine, St. Louis. Dr. Farrell said around two-thirds of patients who contract COVID-19 develop the condition, and the rates of long-term parosmia range from 10%-50% depending on various studies.

“It is almost always foul; this can profoundly affect someone’s quality of life,” impairing their ability to eat or to be intimate with a partner who now smells unpleasant, said Dr. Farrell, who wasn’t associated with this research.

The treatment, called a stellate ganglion block, is provided through a shot into nerves in the neck. People with parosmia associated with COVID-19 often report that this method cures them. Dr. Patel said that may be because their psychological health is improving, not their sense of smell, because the area of the body where the stellate ganglion block is applied is not part of the olfactory system.

Earlier this year, Dr. Farrell and colleagues reported that parosmia linked to COVID-19 is associated with an increased risk for depression, anxiety, and suicidal ideation. 

One coauthor reported receiving grants from Smell and Taste Lab, Takasago, Baia Foods, and Frequency Therapeutics. The other authors reported no relevant financial relationships.

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

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

The American Heart Association (AHA) has now formally voted to join several other cardiovascular societies to form a new professional certification board for cardiovascular medicine, to be known as the American Board of Cardiovascular Medicine (ABCVM).  

The ABCVM would be independent of the American Board of Internal Medicine (ABIM), the current organization providing maintenance of certification for cardiologists along with 20 other internal medicine subspecialties. The ABIM’s maintenance of certification process has been widely criticized for many years and has been described as “needlessly burdensome and expensive.”

The AHA will be joining the American College of Cardiology (ACC), Heart Failure Society of America (HFSA), Heart Rhythm Society (HRS), and Society for Cardiovascular Angiography & Interventions (SCAI) in forming the ABCVM. 

These four other societies issued a joint statement in September saying that they will apply to the American Board of Medical Specialties (ABMS) to request an independent cardiology board that follows a “new competency-based approach to continuous certification — one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

The new board requirements will “de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills,” the statement noted.

At the time the September statement was issued, the AHA was said to be supportive of the move but was waiting for formal endorsement to join the effort by its board of directors.

That has now happened, with the AHA’s national board of directors voting to provide “full support” for the creation of the proposed ABCVM.

“We enthusiastically join with our colleagues in proposing a new professional certification body to accredit cardiovascular professionals called the American Board of Cardiovascular Medicine,” said the association’s volunteer president Joseph C. Wu, MD. “The new ABCVM will be independent of the ABIM and focus on the specific competency-based trainings and appropriate ongoing certifications that align with and strengthen skills for cardiovascular physicians and enhance quality of care for people with cardiovascular disease,” Wu said.

“The AHA joins the consortium to submit the application to the American Board of Medical Specialties (ABMS) requesting an independent medical board for cardiovascular medicine. The consortium’s robust proposal harnesses the knowledge, skills, and benchmarks appropriate for professional excellence and delivery of effective, high-quality cardiovascular care,” Wu added.

The leaders of the ABCVM will include professional representatives from the consortium of member organizations, with a specific focus on relevant education, trainings, and supports that recognize the increasing specialization in cardiology and the latest advances in the various subspecialties of cardiovascular medicine, the AHA notes in a statement.

Professional certification by ABIM is a condition of employment for physicians practicing in large hospitals or health systems. A dedicated certification board separate from ABIM will help to ensure that cardiovascular professionals are maintaining the expertise appropriate to high-quality care and improved outcomes for their patients, the AHA said.

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

The American Heart Association (AHA) has now formally voted to join several other cardiovascular societies to form a new professional certification board for cardiovascular medicine, to be known as the American Board of Cardiovascular Medicine (ABCVM).  

The ABCVM would be independent of the American Board of Internal Medicine (ABIM), the current organization providing maintenance of certification for cardiologists along with 20 other internal medicine subspecialties. The ABIM’s maintenance of certification process has been widely criticized for many years and has been described as “needlessly burdensome and expensive.”

The AHA will be joining the American College of Cardiology (ACC), Heart Failure Society of America (HFSA), Heart Rhythm Society (HRS), and Society for Cardiovascular Angiography & Interventions (SCAI) in forming the ABCVM. 

These four other societies issued a joint statement in September saying that they will apply to the American Board of Medical Specialties (ABMS) to request an independent cardiology board that follows a “new competency-based approach to continuous certification — one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

The new board requirements will “de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills,” the statement noted.

At the time the September statement was issued, the AHA was said to be supportive of the move but was waiting for formal endorsement to join the effort by its board of directors.

That has now happened, with the AHA’s national board of directors voting to provide “full support” for the creation of the proposed ABCVM.

“We enthusiastically join with our colleagues in proposing a new professional certification body to accredit cardiovascular professionals called the American Board of Cardiovascular Medicine,” said the association’s volunteer president Joseph C. Wu, MD. “The new ABCVM will be independent of the ABIM and focus on the specific competency-based trainings and appropriate ongoing certifications that align with and strengthen skills for cardiovascular physicians and enhance quality of care for people with cardiovascular disease,” Wu said.

“The AHA joins the consortium to submit the application to the American Board of Medical Specialties (ABMS) requesting an independent medical board for cardiovascular medicine. The consortium’s robust proposal harnesses the knowledge, skills, and benchmarks appropriate for professional excellence and delivery of effective, high-quality cardiovascular care,” Wu added.

The leaders of the ABCVM will include professional representatives from the consortium of member organizations, with a specific focus on relevant education, trainings, and supports that recognize the increasing specialization in cardiology and the latest advances in the various subspecialties of cardiovascular medicine, the AHA notes in a statement.

Professional certification by ABIM is a condition of employment for physicians practicing in large hospitals or health systems. A dedicated certification board separate from ABIM will help to ensure that cardiovascular professionals are maintaining the expertise appropriate to high-quality care and improved outcomes for their patients, the AHA said.

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

The American Heart Association (AHA) has now formally voted to join several other cardiovascular societies to form a new professional certification board for cardiovascular medicine, to be known as the American Board of Cardiovascular Medicine (ABCVM).  

The ABCVM would be independent of the American Board of Internal Medicine (ABIM), the current organization providing maintenance of certification for cardiologists along with 20 other internal medicine subspecialties. The ABIM’s maintenance of certification process has been widely criticized for many years and has been described as “needlessly burdensome and expensive.”

The AHA will be joining the American College of Cardiology (ACC), Heart Failure Society of America (HFSA), Heart Rhythm Society (HRS), and Society for Cardiovascular Angiography & Interventions (SCAI) in forming the ABCVM. 

These four other societies issued a joint statement in September saying that they will apply to the American Board of Medical Specialties (ABMS) to request an independent cardiology board that follows a “new competency-based approach to continuous certification — one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

The new board requirements will “de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills,” the statement noted.

At the time the September statement was issued, the AHA was said to be supportive of the move but was waiting for formal endorsement to join the effort by its board of directors.

That has now happened, with the AHA’s national board of directors voting to provide “full support” for the creation of the proposed ABCVM.

“We enthusiastically join with our colleagues in proposing a new professional certification body to accredit cardiovascular professionals called the American Board of Cardiovascular Medicine,” said the association’s volunteer president Joseph C. Wu, MD. “The new ABCVM will be independent of the ABIM and focus on the specific competency-based trainings and appropriate ongoing certifications that align with and strengthen skills for cardiovascular physicians and enhance quality of care for people with cardiovascular disease,” Wu said.

“The AHA joins the consortium to submit the application to the American Board of Medical Specialties (ABMS) requesting an independent medical board for cardiovascular medicine. The consortium’s robust proposal harnesses the knowledge, skills, and benchmarks appropriate for professional excellence and delivery of effective, high-quality cardiovascular care,” Wu added.

The leaders of the ABCVM will include professional representatives from the consortium of member organizations, with a specific focus on relevant education, trainings, and supports that recognize the increasing specialization in cardiology and the latest advances in the various subspecialties of cardiovascular medicine, the AHA notes in a statement.

Professional certification by ABIM is a condition of employment for physicians practicing in large hospitals or health systems. A dedicated certification board separate from ABIM will help to ensure that cardiovascular professionals are maintaining the expertise appropriate to high-quality care and improved outcomes for their patients, the AHA said.

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

Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.

But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.

“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.

Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.

“We now have the potential to change the way genetic epilepsies are treated by addressing the underlying genetic cause of the disease instead of just the seizures,” Dr. Kaye said.
 

Thank COVID?

Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.

Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.

Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.

RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.

Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.

“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.

“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
 

Hope for Dravet syndrome

Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.

Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.

The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.

“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.

Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.

“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.

“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.

“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
 

A promising future

Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”

And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.

Take, for example, a case reported recently in the New England Journal of Medicine.

Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.

One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.

However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”

“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.

The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.

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

Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.

But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.

“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.

Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.

“We now have the potential to change the way genetic epilepsies are treated by addressing the underlying genetic cause of the disease instead of just the seizures,” Dr. Kaye said.
 

Thank COVID?

Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.

Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.

Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.

RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.

Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.

“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.

“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
 

Hope for Dravet syndrome

Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.

Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.

The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.

“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.

Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.

“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.

“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.

“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
 

A promising future

Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”

And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.

Take, for example, a case reported recently in the New England Journal of Medicine.

Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.

One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.

However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”

“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.

The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.

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

Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.

But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.

“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.

Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.

“We now have the potential to change the way genetic epilepsies are treated by addressing the underlying genetic cause of the disease instead of just the seizures,” Dr. Kaye said.
 

Thank COVID?

Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.

Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.

Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.

RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.

Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.

“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.

“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
 

Hope for Dravet syndrome

Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.

Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.

The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.

“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.

Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.

“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.

“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.

“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
 

A promising future

Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”

And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.

Take, for example, a case reported recently in the New England Journal of Medicine.

Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.

One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.

However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”

“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.

The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.

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

Clinicians must monitor children with sickle cell disease for eye complications as much as they do for adults, a new research review suggests.

Earlier research indicated that older patients were more at risk for eye complications from sickle cell disease, but the new study found that a full third of young people aged 10-25 years with sickle cell disease had retinopathy, including nonproliferative retinopathy (33%) and proliferative retinopathy (6%), which can progress to vision loss.

Two patients experienced retinal detachment, while two suffered retinal artery occlusion. One patient with retinal artery occlusion lost their vision and had a final best-corrected visual acuity of 20/60, according to the researchers, who presented their findings at the annual meeting of the American Academy of Ophthalmology.

“Our data underscores the need for patients – including pediatric patients – with sickle cell disease to get routine ophthalmic screenings along with appropriate systemic and ophthalmic treatment,” Mary Ellen Hoehn, MD, a professor of ophthalmology at the University of Tennessee Health Science Center, Memphis, who led the research, said in a press release.

The review covered records for 652 patients with sickle cell disease aged 10-25 years (median age, 14 years), who underwent eye exams over a 12-year period.

Besides looking at rates of retinopathy, Dr. Hoehn’s group studied which treatments were most effective. They found that hydroxyurea and chronic transfusions best lowered retinopathy rates among all genotypes.

“We hope that people will use this information to better care for patients with sickle cell disease, and that more timely ophthalmic screen exams will be performed so that vision-threatening complications from this disease are prevented,” Dr. Hoehn said.

The authors reported no relevant financial relationships.

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

Clinicians must monitor children with sickle cell disease for eye complications as much as they do for adults, a new research review suggests.

Earlier research indicated that older patients were more at risk for eye complications from sickle cell disease, but the new study found that a full third of young people aged 10-25 years with sickle cell disease had retinopathy, including nonproliferative retinopathy (33%) and proliferative retinopathy (6%), which can progress to vision loss.

Two patients experienced retinal detachment, while two suffered retinal artery occlusion. One patient with retinal artery occlusion lost their vision and had a final best-corrected visual acuity of 20/60, according to the researchers, who presented their findings at the annual meeting of the American Academy of Ophthalmology.

“Our data underscores the need for patients – including pediatric patients – with sickle cell disease to get routine ophthalmic screenings along with appropriate systemic and ophthalmic treatment,” Mary Ellen Hoehn, MD, a professor of ophthalmology at the University of Tennessee Health Science Center, Memphis, who led the research, said in a press release.

The review covered records for 652 patients with sickle cell disease aged 10-25 years (median age, 14 years), who underwent eye exams over a 12-year period.

Besides looking at rates of retinopathy, Dr. Hoehn’s group studied which treatments were most effective. They found that hydroxyurea and chronic transfusions best lowered retinopathy rates among all genotypes.

“We hope that people will use this information to better care for patients with sickle cell disease, and that more timely ophthalmic screen exams will be performed so that vision-threatening complications from this disease are prevented,” Dr. Hoehn said.

The authors reported no relevant financial relationships.

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

Clinicians must monitor children with sickle cell disease for eye complications as much as they do for adults, a new research review suggests.

Earlier research indicated that older patients were more at risk for eye complications from sickle cell disease, but the new study found that a full third of young people aged 10-25 years with sickle cell disease had retinopathy, including nonproliferative retinopathy (33%) and proliferative retinopathy (6%), which can progress to vision loss.

Two patients experienced retinal detachment, while two suffered retinal artery occlusion. One patient with retinal artery occlusion lost their vision and had a final best-corrected visual acuity of 20/60, according to the researchers, who presented their findings at the annual meeting of the American Academy of Ophthalmology.

“Our data underscores the need for patients – including pediatric patients – with sickle cell disease to get routine ophthalmic screenings along with appropriate systemic and ophthalmic treatment,” Mary Ellen Hoehn, MD, a professor of ophthalmology at the University of Tennessee Health Science Center, Memphis, who led the research, said in a press release.

The review covered records for 652 patients with sickle cell disease aged 10-25 years (median age, 14 years), who underwent eye exams over a 12-year period.

Besides looking at rates of retinopathy, Dr. Hoehn’s group studied which treatments were most effective. They found that hydroxyurea and chronic transfusions best lowered retinopathy rates among all genotypes.

“We hope that people will use this information to better care for patients with sickle cell disease, and that more timely ophthalmic screen exams will be performed so that vision-threatening complications from this disease are prevented,” Dr. Hoehn said.

The authors reported no relevant financial relationships.

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

Cognitive issues in children with Duchenne muscular dystrophy (DMD) are linked to worse outcomes, but limited access to specialists and limited resources make this problem difficult to address. A new tool from the National Institutes of Health, called NIH Toolbox, could improve that outcome, according to Mathula Thangarajh, MD, PhD, who has conducted research in the field.

“When we talk to families and parents, they are able to identify that even during infancy that [children with DMD] have delayed cognitive function. This includes speech delay, but also language and adaptive skills. We also know that those children with speech delay, which is really a very commonly reported phenotype in up to 50%, go on to have school-based needs. They may repeat [grades] in elementary years, but they also use more resources at school,” said Dr. Thangarajh, who is an assistant professor of neurology at the Children’s Hospital of Richmond at Virginia Commonwealth University, Richmond, during a talk at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

Children’s Hospital of Richmond at Virginia Commonwealth University

A previous natural history study that utilized the Pediatric Quality of Life assessment also showed that DMD patients reported the lowest scores in brain health, including emotional health and school performance.

Other research has shown a correlation between cognitive function and survival in DMD. “This suggests that health maintenance may play an important role [in outcomes],” said Dr. Thangarajh. Another study found a correlation between psychomotor delay that required school-based interventions and earlier loss of ambulation, lower cardiac ejection fraction, and worse pulmonary function. The researchers also found that boys with cognitive delay were diagnosed at an earlier age, and yet had delays in diagnosis and worse motor function, pulmonary health, and cardiac health outcomes. On average, they lost ambulatory ability 2 years earlier.

A study by Dr. Thangarajh’s group showed that patients with speech delay and lower IQ had lower performance in timed tests, including 6-minute walk test distance and scored an average of 2 points lower on the North Star Ambulatory Assessment.
 

A tool for continuous cognitive assessment

The Centers for Disease Control and Prevention–supported DMD CARE guidelines only say that neuropsychological evaluations should be considered at diagnosis, but is essential if concerns arise about developmental progress. However, the Muscular Dystrophy Association has found barriers both in access to specialists, with an average wait time of 1-2 years, and burdensome out-of-pocket costs.

Those issues prompted Dr. Thangarajh to look for an alternative solution. At the time that she embarked on this work, the NIH was interested in technologies to assess neurobehavioral issues across different diseases. The resulting NIH Toolbox iPad app was driven largely by failed clinical trials in dementia, and the aim was to be able to provide continuous assessment over time. “It will allow for assessments across the lifespan, so you can use the same construct from age 3 to 80-plus,” said Dr. Thangarajh. It can also normalize population factors, such as annual household income and mother’s IQ.

She set out to validate the NIH Toolbox in children with DMD. The toolbox includes measures of crystalized cognition and fluid cognition. The former encompasses vocabulary and reading ability, which are strongly predicted by socioeconomic status and maternal IQ. On the other hand, fluid cognition includes cognitive features that develop across the lifespan and is directly related to academic underperformance in DMD patients.

Dr. Thangarajh’s group assessed 30 boys with DMD and found that crystallized cognition was normal, but they had a deficit in fluid cognition. They found deficits within several subdomains of fluid cognition. “This tells us that the NIH Toolbox was able to replicate what we had known in the literature, that these boys really have lower intellectual capacity, but they also have significant weakness in fluid cognition,” she said.

She also wanted to examine changes over time by testing the boys at a 1-year interview. “What we found was that they are not making as much gain in fluid cognition as we would like. They are just making marginal improvements over time. This has implications on how often we should screen them, but also not be over reliant on using school-based resources for them to get tested,” said Dr. Thangarajh.

Her group’s analysis of a dataset of 55 boys provided by PTC Therapeutics revealed a difference by age in a test of working memory. “What we found was that boys who are actually greater than 9 years, compared with those who are less than 9 years, they actually had a reversal of development-based improvement. The older they get, they were not making as much gains as you would expect,” said Dr. Thangarajh.

She went on to discuss psychosocial determinants of cognitive health in DMD. It is known that women who are carriers of the dystrophin mutation can underperform in cognitively stressful tasks, leading her to wonder if this could lead to transgenerational risk to offspring with DMD. Her group tested women who were carriers of the mutation with the NIH Toolbox and found that they had lower fluid cognition than noncarriers. They then tested 65 dyads of mothers and children, and found a correlation, but only when it came to inhibitory control, which required the individual to note the direction of an arrow while ignoring surrounding arrows pointing in various directions.

Next, the researchers examined neighborhoods and their impact on cognitive health, which can be affected by the presence of green spaces, access to public transportation and good nutrition, and other factors. There were significant deficits associated with residence zip codes. “We were pretty shocked. Someone who is not in a socially vulnerable region is scoring slightly below average, but someone who is in a very socially vulnerable neighborhood is only scoring 75 [age-adjusted score] on the NIH toolbox. So with this, we can conclude that carrier women are vulnerable in certain cognitive domains, but also children who come from socially vulnerable [situations] have poor cognitive control. This, again, has implications on how often we should screen and how much we should overly rely on school-based resources for these individuals,” said Dr. Thangarajh.
 

Overcoming a significant barrier

The NIH Toolbox has a lot of potential to improve DMD care, according to Dianna Quan, MD, who is the incoming president of AANEM, and professor of neurology at the University of Colorado at Denver, Aurora. “There’s this huge problem in terms of getting people in to see neuropsychologists and having formal evaluations. I think that’s a huge barrier. If we have people able to access this toolkit, which is simple and easily and universally accessible, how wonderful is that? I think that will be a really great improvement on what’s going on right now. It allows people to easily screen for these cognitive disabilities and make sure that we address them,” Dr. Quan said in an interview.

Asked how the tool could specifically improve care, Dr. Quan suggested that the first step is to understand the contributing factors to cognitive issues, whether they are biological, social, or a combination. “Some of them we can modify, potentially, through addressing the social environment. Some of those biologic factors may also be modifiable with many of the new drug studies that are coming.”

Dr. Thangarajh has received speaker honoraria from NS Pharma and PTC Therapeutics. Dr. Quan has received funding from Alnylam, Pfizer, Cytokinetics, Momenta, and Argenx.

Cognitive issues in children with Duchenne muscular dystrophy (DMD) are linked to worse outcomes, but limited access to specialists and limited resources make this problem difficult to address. A new tool from the National Institutes of Health, called NIH Toolbox, could improve that outcome, according to Mathula Thangarajh, MD, PhD, who has conducted research in the field.

“When we talk to families and parents, they are able to identify that even during infancy that [children with DMD] have delayed cognitive function. This includes speech delay, but also language and adaptive skills. We also know that those children with speech delay, which is really a very commonly reported phenotype in up to 50%, go on to have school-based needs. They may repeat [grades] in elementary years, but they also use more resources at school,” said Dr. Thangarajh, who is an assistant professor of neurology at the Children’s Hospital of Richmond at Virginia Commonwealth University, Richmond, during a talk at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

Children’s Hospital of Richmond at Virginia Commonwealth University

A previous natural history study that utilized the Pediatric Quality of Life assessment also showed that DMD patients reported the lowest scores in brain health, including emotional health and school performance.

Other research has shown a correlation between cognitive function and survival in DMD. “This suggests that health maintenance may play an important role [in outcomes],” said Dr. Thangarajh. Another study found a correlation between psychomotor delay that required school-based interventions and earlier loss of ambulation, lower cardiac ejection fraction, and worse pulmonary function. The researchers also found that boys with cognitive delay were diagnosed at an earlier age, and yet had delays in diagnosis and worse motor function, pulmonary health, and cardiac health outcomes. On average, they lost ambulatory ability 2 years earlier.

A study by Dr. Thangarajh’s group showed that patients with speech delay and lower IQ had lower performance in timed tests, including 6-minute walk test distance and scored an average of 2 points lower on the North Star Ambulatory Assessment.
 

A tool for continuous cognitive assessment

The Centers for Disease Control and Prevention–supported DMD CARE guidelines only say that neuropsychological evaluations should be considered at diagnosis, but is essential if concerns arise about developmental progress. However, the Muscular Dystrophy Association has found barriers both in access to specialists, with an average wait time of 1-2 years, and burdensome out-of-pocket costs.

Those issues prompted Dr. Thangarajh to look for an alternative solution. At the time that she embarked on this work, the NIH was interested in technologies to assess neurobehavioral issues across different diseases. The resulting NIH Toolbox iPad app was driven largely by failed clinical trials in dementia, and the aim was to be able to provide continuous assessment over time. “It will allow for assessments across the lifespan, so you can use the same construct from age 3 to 80-plus,” said Dr. Thangarajh. It can also normalize population factors, such as annual household income and mother’s IQ.

She set out to validate the NIH Toolbox in children with DMD. The toolbox includes measures of crystalized cognition and fluid cognition. The former encompasses vocabulary and reading ability, which are strongly predicted by socioeconomic status and maternal IQ. On the other hand, fluid cognition includes cognitive features that develop across the lifespan and is directly related to academic underperformance in DMD patients.

Dr. Thangarajh’s group assessed 30 boys with DMD and found that crystallized cognition was normal, but they had a deficit in fluid cognition. They found deficits within several subdomains of fluid cognition. “This tells us that the NIH Toolbox was able to replicate what we had known in the literature, that these boys really have lower intellectual capacity, but they also have significant weakness in fluid cognition,” she said.

She also wanted to examine changes over time by testing the boys at a 1-year interview. “What we found was that they are not making as much gain in fluid cognition as we would like. They are just making marginal improvements over time. This has implications on how often we should screen them, but also not be over reliant on using school-based resources for them to get tested,” said Dr. Thangarajh.

Her group’s analysis of a dataset of 55 boys provided by PTC Therapeutics revealed a difference by age in a test of working memory. “What we found was that boys who are actually greater than 9 years, compared with those who are less than 9 years, they actually had a reversal of development-based improvement. The older they get, they were not making as much gains as you would expect,” said Dr. Thangarajh.

She went on to discuss psychosocial determinants of cognitive health in DMD. It is known that women who are carriers of the dystrophin mutation can underperform in cognitively stressful tasks, leading her to wonder if this could lead to transgenerational risk to offspring with DMD. Her group tested women who were carriers of the mutation with the NIH Toolbox and found that they had lower fluid cognition than noncarriers. They then tested 65 dyads of mothers and children, and found a correlation, but only when it came to inhibitory control, which required the individual to note the direction of an arrow while ignoring surrounding arrows pointing in various directions.

Next, the researchers examined neighborhoods and their impact on cognitive health, which can be affected by the presence of green spaces, access to public transportation and good nutrition, and other factors. There were significant deficits associated with residence zip codes. “We were pretty shocked. Someone who is not in a socially vulnerable region is scoring slightly below average, but someone who is in a very socially vulnerable neighborhood is only scoring 75 [age-adjusted score] on the NIH toolbox. So with this, we can conclude that carrier women are vulnerable in certain cognitive domains, but also children who come from socially vulnerable [situations] have poor cognitive control. This, again, has implications on how often we should screen and how much we should overly rely on school-based resources for these individuals,” said Dr. Thangarajh.
 

Overcoming a significant barrier

The NIH Toolbox has a lot of potential to improve DMD care, according to Dianna Quan, MD, who is the incoming president of AANEM, and professor of neurology at the University of Colorado at Denver, Aurora. “There’s this huge problem in terms of getting people in to see neuropsychologists and having formal evaluations. I think that’s a huge barrier. If we have people able to access this toolkit, which is simple and easily and universally accessible, how wonderful is that? I think that will be a really great improvement on what’s going on right now. It allows people to easily screen for these cognitive disabilities and make sure that we address them,” Dr. Quan said in an interview.

Asked how the tool could specifically improve care, Dr. Quan suggested that the first step is to understand the contributing factors to cognitive issues, whether they are biological, social, or a combination. “Some of them we can modify, potentially, through addressing the social environment. Some of those biologic factors may also be modifiable with many of the new drug studies that are coming.”

Dr. Thangarajh has received speaker honoraria from NS Pharma and PTC Therapeutics. Dr. Quan has received funding from Alnylam, Pfizer, Cytokinetics, Momenta, and Argenx.

Cognitive issues in children with Duchenne muscular dystrophy (DMD) are linked to worse outcomes, but limited access to specialists and limited resources make this problem difficult to address. A new tool from the National Institutes of Health, called NIH Toolbox, could improve that outcome, according to Mathula Thangarajh, MD, PhD, who has conducted research in the field.

“When we talk to families and parents, they are able to identify that even during infancy that [children with DMD] have delayed cognitive function. This includes speech delay, but also language and adaptive skills. We also know that those children with speech delay, which is really a very commonly reported phenotype in up to 50%, go on to have school-based needs. They may repeat [grades] in elementary years, but they also use more resources at school,” said Dr. Thangarajh, who is an assistant professor of neurology at the Children’s Hospital of Richmond at Virginia Commonwealth University, Richmond, during a talk at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

Children’s Hospital of Richmond at Virginia Commonwealth University

A previous natural history study that utilized the Pediatric Quality of Life assessment also showed that DMD patients reported the lowest scores in brain health, including emotional health and school performance.

Other research has shown a correlation between cognitive function and survival in DMD. “This suggests that health maintenance may play an important role [in outcomes],” said Dr. Thangarajh. Another study found a correlation between psychomotor delay that required school-based interventions and earlier loss of ambulation, lower cardiac ejection fraction, and worse pulmonary function. The researchers also found that boys with cognitive delay were diagnosed at an earlier age, and yet had delays in diagnosis and worse motor function, pulmonary health, and cardiac health outcomes. On average, they lost ambulatory ability 2 years earlier.

A study by Dr. Thangarajh’s group showed that patients with speech delay and lower IQ had lower performance in timed tests, including 6-minute walk test distance and scored an average of 2 points lower on the North Star Ambulatory Assessment.
 

A tool for continuous cognitive assessment

The Centers for Disease Control and Prevention–supported DMD CARE guidelines only say that neuropsychological evaluations should be considered at diagnosis, but is essential if concerns arise about developmental progress. However, the Muscular Dystrophy Association has found barriers both in access to specialists, with an average wait time of 1-2 years, and burdensome out-of-pocket costs.

Those issues prompted Dr. Thangarajh to look for an alternative solution. At the time that she embarked on this work, the NIH was interested in technologies to assess neurobehavioral issues across different diseases. The resulting NIH Toolbox iPad app was driven largely by failed clinical trials in dementia, and the aim was to be able to provide continuous assessment over time. “It will allow for assessments across the lifespan, so you can use the same construct from age 3 to 80-plus,” said Dr. Thangarajh. It can also normalize population factors, such as annual household income and mother’s IQ.

She set out to validate the NIH Toolbox in children with DMD. The toolbox includes measures of crystalized cognition and fluid cognition. The former encompasses vocabulary and reading ability, which are strongly predicted by socioeconomic status and maternal IQ. On the other hand, fluid cognition includes cognitive features that develop across the lifespan and is directly related to academic underperformance in DMD patients.

Dr. Thangarajh’s group assessed 30 boys with DMD and found that crystallized cognition was normal, but they had a deficit in fluid cognition. They found deficits within several subdomains of fluid cognition. “This tells us that the NIH Toolbox was able to replicate what we had known in the literature, that these boys really have lower intellectual capacity, but they also have significant weakness in fluid cognition,” she said.

She also wanted to examine changes over time by testing the boys at a 1-year interview. “What we found was that they are not making as much gain in fluid cognition as we would like. They are just making marginal improvements over time. This has implications on how often we should screen them, but also not be over reliant on using school-based resources for them to get tested,” said Dr. Thangarajh.

Her group’s analysis of a dataset of 55 boys provided by PTC Therapeutics revealed a difference by age in a test of working memory. “What we found was that boys who are actually greater than 9 years, compared with those who are less than 9 years, they actually had a reversal of development-based improvement. The older they get, they were not making as much gains as you would expect,” said Dr. Thangarajh.

She went on to discuss psychosocial determinants of cognitive health in DMD. It is known that women who are carriers of the dystrophin mutation can underperform in cognitively stressful tasks, leading her to wonder if this could lead to transgenerational risk to offspring with DMD. Her group tested women who were carriers of the mutation with the NIH Toolbox and found that they had lower fluid cognition than noncarriers. They then tested 65 dyads of mothers and children, and found a correlation, but only when it came to inhibitory control, which required the individual to note the direction of an arrow while ignoring surrounding arrows pointing in various directions.

Next, the researchers examined neighborhoods and their impact on cognitive health, which can be affected by the presence of green spaces, access to public transportation and good nutrition, and other factors. There were significant deficits associated with residence zip codes. “We were pretty shocked. Someone who is not in a socially vulnerable region is scoring slightly below average, but someone who is in a very socially vulnerable neighborhood is only scoring 75 [age-adjusted score] on the NIH toolbox. So with this, we can conclude that carrier women are vulnerable in certain cognitive domains, but also children who come from socially vulnerable [situations] have poor cognitive control. This, again, has implications on how often we should screen and how much we should overly rely on school-based resources for these individuals,” said Dr. Thangarajh.
 

Overcoming a significant barrier

The NIH Toolbox has a lot of potential to improve DMD care, according to Dianna Quan, MD, who is the incoming president of AANEM, and professor of neurology at the University of Colorado at Denver, Aurora. “There’s this huge problem in terms of getting people in to see neuropsychologists and having formal evaluations. I think that’s a huge barrier. If we have people able to access this toolkit, which is simple and easily and universally accessible, how wonderful is that? I think that will be a really great improvement on what’s going on right now. It allows people to easily screen for these cognitive disabilities and make sure that we address them,” Dr. Quan said in an interview.

Asked how the tool could specifically improve care, Dr. Quan suggested that the first step is to understand the contributing factors to cognitive issues, whether they are biological, social, or a combination. “Some of them we can modify, potentially, through addressing the social environment. Some of those biologic factors may also be modifiable with many of the new drug studies that are coming.”

Dr. Thangarajh has received speaker honoraria from NS Pharma and PTC Therapeutics. Dr. Quan has received funding from Alnylam, Pfizer, Cytokinetics, Momenta, and Argenx.

Two sets of evidence reports address the primary care physicians’ role in children and adolescents’ oral health and the effectiveness of the fluoride gels and sealants offered at dental offices and schools.

Both were published online in JAMA.

In one report, the United States Preventive Services Task Force (USPSTF) concludes that there is not enough evidence to assess harms versus benefits of routine screening or interventions for oral health conditions, including dental caries, in primary care for asymptomatic children and adolescents aged 5-17 years.

The evidence report on administering fluoride supplements, fluoride gels, sealants and varnish finds evidence that they improve outcomes. The report was done to inform the USPSTF for a new recommendation on primary care screening, dental referral, behavioral counseling, and preventive interventions for oral health in children and adolescents aged 5-17.
 

Primary care physicians’ role

One problem the USPSTF identified in its report was limited evidence on available clinical screening tools or assessments to identify which children have oral health conditions in the primary care setting.

The USPSTF’s team, led by Michael J. Barry, MD, of Harvard Medical School in Boston, calls for more research to fill in the gaps before it can reassess.

Michael S. Reddy, DMD, DMSc, with University of California San Francisco School of Dentistry, Oral Health Affairs, said in an accompanying editorial that the current lack of data should not keep primary care physicians from considering oral health during routine medical exams or keep dentists from finding ways to collaborate with primary care physicians. “Medical primary care must partner with dentistry,” they wrote.

Until there is enough evidence for a USPSTF reevaluation on the topic, primary care clinicians should ask patients about their oral hygiene routines, whether they have any dental symptoms, and when they last saw a dentist, as well as referring to a dentist as necessary, the editorialists wrote.

That works both ways, the editorialists added. “Equally important, oral health professionals are encouraged to collaborate and be a resource for their primary care colleagues. Prevention is one of the best tools clinicians have, and it is promoted by integrated, whole-person health effort, “ wrote Dr. Reddy and colleagues.

When oral health stays separate from medical care, patients are left vulnerable, and referrals between medical and dental offices should be a stronger two-way system, the editorialists said.

“[N]ot every primary care patient has access to a dentist,” they wrote. “Oral health screening and referral by medical primary care clinicians can help ensure that individuals get to the dental chair to receive needed interventions that can benefit both oral and potentially overall health. Likewise, medical challenges and oral mucosal manifestations of chronic health conditions detected at a dental visit should result in medical referral, allowing prompt evaluation and treatment.”
 

Evidence that gels, varnish, sealants are effective

In a companion paper, done to inform the USPSTF, Roger Chou, MD, with Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology at Oregon Health & Science University in Portland, and colleagues found that when administered by a dental professional or in school settings, fluoride supplements, gels and varnish, and resin-based sealants improved health outcomes.

The findings were based on three systematic reviews (20,684 participants) and 19 randomized clinical trials; three nonrandomized trials; and one observational study (total 15,026 participants.)

With fluoride versus placebo or no intervention, researchers found a decrease from baseline in the number of decayed, missing, or filled permanent teeth (DMFT index) or decayed or filled permanent teeth (DFT index). The average difference was −0.73 [95% confidence interval [CI], −1.30 to −0.19]) at 1.5 to 3 years (six trials; n = 1,395).

Fluoride gels were associated with a DMFT- or DFT-prevented fraction of 0.18 (95% CI, 0.09-0.27) at outcomes closest to 3 years (four trials; n = 1,525).

Researchers found an association between fluoride varnish and a DMFT- or DFT-prevented fraction of 0.44 (95% CI, 0.11-0.76) at 1 to 4.5 years (five trials; n = 3,902). The sealants tested were associated with decreased risk of caries in first molars (odds ratio, 0.21 [95% CI, 0.16-0.28]) at 48-54 months (four trials; n = 440).

They noted that the feasibility of administering preventive measures in primary care is unknown; the effectiveness shown here was based on administration in dental and supervised school settings.

Barriers in primary care settings may include lack of training and equipment (particularly for sealants), uncertain reimbursement and lack of acceptance and uptake.
 

USPSTF working to close evidence gaps

Wanda Nicholson, MD, MPH, Prevention and Community Health, George Washington Milken Institute of Public Health in Washington, wrote in an accompanying editorial that to speed necessary research to facilitate recommendations, “the USPSTF and its stakeholders need a transparent, easily implementable communication tool that will systematically describe the research necessary to be directly responsive to the evidence gaps.”

The editorialists noted that the USPSTF in trying to update recommendations often has few, if any, high-quality additional studies to consider since its previous recommendation.

To address that, meetings were conducted in November of 2022 involving USPSTF members, Agency for Healthcare Research and Quality (AHRQ) staff, and leadership from the Office of Disease Prevention and the National Institutes of Health. Members formed a working group “to develop a standardized template for communicating research gaps” according to a framework developed by the National Academies of Sciences, Engineering, and Medicine.

Dr. Nicholson and colleagues wrote, “classifying evidence gaps and calling for specific research needs is a prudent, collaborative step in addressing missing evidence,” particularly for underserved populations.

The authors and editorialists declared no relevant conflicts of interest.

Two sets of evidence reports address the primary care physicians’ role in children and adolescents’ oral health and the effectiveness of the fluoride gels and sealants offered at dental offices and schools.

Both were published online in JAMA.

In one report, the United States Preventive Services Task Force (USPSTF) concludes that there is not enough evidence to assess harms versus benefits of routine screening or interventions for oral health conditions, including dental caries, in primary care for asymptomatic children and adolescents aged 5-17 years.

The evidence report on administering fluoride supplements, fluoride gels, sealants and varnish finds evidence that they improve outcomes. The report was done to inform the USPSTF for a new recommendation on primary care screening, dental referral, behavioral counseling, and preventive interventions for oral health in children and adolescents aged 5-17.
 

Primary care physicians’ role

One problem the USPSTF identified in its report was limited evidence on available clinical screening tools or assessments to identify which children have oral health conditions in the primary care setting.

The USPSTF’s team, led by Michael J. Barry, MD, of Harvard Medical School in Boston, calls for more research to fill in the gaps before it can reassess.

Michael S. Reddy, DMD, DMSc, with University of California San Francisco School of Dentistry, Oral Health Affairs, said in an accompanying editorial that the current lack of data should not keep primary care physicians from considering oral health during routine medical exams or keep dentists from finding ways to collaborate with primary care physicians. “Medical primary care must partner with dentistry,” they wrote.

Until there is enough evidence for a USPSTF reevaluation on the topic, primary care clinicians should ask patients about their oral hygiene routines, whether they have any dental symptoms, and when they last saw a dentist, as well as referring to a dentist as necessary, the editorialists wrote.

That works both ways, the editorialists added. “Equally important, oral health professionals are encouraged to collaborate and be a resource for their primary care colleagues. Prevention is one of the best tools clinicians have, and it is promoted by integrated, whole-person health effort, “ wrote Dr. Reddy and colleagues.

When oral health stays separate from medical care, patients are left vulnerable, and referrals between medical and dental offices should be a stronger two-way system, the editorialists said.

“[N]ot every primary care patient has access to a dentist,” they wrote. “Oral health screening and referral by medical primary care clinicians can help ensure that individuals get to the dental chair to receive needed interventions that can benefit both oral and potentially overall health. Likewise, medical challenges and oral mucosal manifestations of chronic health conditions detected at a dental visit should result in medical referral, allowing prompt evaluation and treatment.”
 

Evidence that gels, varnish, sealants are effective

In a companion paper, done to inform the USPSTF, Roger Chou, MD, with Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology at Oregon Health & Science University in Portland, and colleagues found that when administered by a dental professional or in school settings, fluoride supplements, gels and varnish, and resin-based sealants improved health outcomes.

The findings were based on three systematic reviews (20,684 participants) and 19 randomized clinical trials; three nonrandomized trials; and one observational study (total 15,026 participants.)

With fluoride versus placebo or no intervention, researchers found a decrease from baseline in the number of decayed, missing, or filled permanent teeth (DMFT index) or decayed or filled permanent teeth (DFT index). The average difference was −0.73 [95% confidence interval [CI], −1.30 to −0.19]) at 1.5 to 3 years (six trials; n = 1,395).

Fluoride gels were associated with a DMFT- or DFT-prevented fraction of 0.18 (95% CI, 0.09-0.27) at outcomes closest to 3 years (four trials; n = 1,525).

Researchers found an association between fluoride varnish and a DMFT- or DFT-prevented fraction of 0.44 (95% CI, 0.11-0.76) at 1 to 4.5 years (five trials; n = 3,902). The sealants tested were associated with decreased risk of caries in first molars (odds ratio, 0.21 [95% CI, 0.16-0.28]) at 48-54 months (four trials; n = 440).

They noted that the feasibility of administering preventive measures in primary care is unknown; the effectiveness shown here was based on administration in dental and supervised school settings.

Barriers in primary care settings may include lack of training and equipment (particularly for sealants), uncertain reimbursement and lack of acceptance and uptake.
 

USPSTF working to close evidence gaps

Wanda Nicholson, MD, MPH, Prevention and Community Health, George Washington Milken Institute of Public Health in Washington, wrote in an accompanying editorial that to speed necessary research to facilitate recommendations, “the USPSTF and its stakeholders need a transparent, easily implementable communication tool that will systematically describe the research necessary to be directly responsive to the evidence gaps.”

The editorialists noted that the USPSTF in trying to update recommendations often has few, if any, high-quality additional studies to consider since its previous recommendation.

To address that, meetings were conducted in November of 2022 involving USPSTF members, Agency for Healthcare Research and Quality (AHRQ) staff, and leadership from the Office of Disease Prevention and the National Institutes of Health. Members formed a working group “to develop a standardized template for communicating research gaps” according to a framework developed by the National Academies of Sciences, Engineering, and Medicine.

Dr. Nicholson and colleagues wrote, “classifying evidence gaps and calling for specific research needs is a prudent, collaborative step in addressing missing evidence,” particularly for underserved populations.

The authors and editorialists declared no relevant conflicts of interest.

Two sets of evidence reports address the primary care physicians’ role in children and adolescents’ oral health and the effectiveness of the fluoride gels and sealants offered at dental offices and schools.

Both were published online in JAMA.

In one report, the United States Preventive Services Task Force (USPSTF) concludes that there is not enough evidence to assess harms versus benefits of routine screening or interventions for oral health conditions, including dental caries, in primary care for asymptomatic children and adolescents aged 5-17 years.

The evidence report on administering fluoride supplements, fluoride gels, sealants and varnish finds evidence that they improve outcomes. The report was done to inform the USPSTF for a new recommendation on primary care screening, dental referral, behavioral counseling, and preventive interventions for oral health in children and adolescents aged 5-17.
 

Primary care physicians’ role

One problem the USPSTF identified in its report was limited evidence on available clinical screening tools or assessments to identify which children have oral health conditions in the primary care setting.

The USPSTF’s team, led by Michael J. Barry, MD, of Harvard Medical School in Boston, calls for more research to fill in the gaps before it can reassess.

Michael S. Reddy, DMD, DMSc, with University of California San Francisco School of Dentistry, Oral Health Affairs, said in an accompanying editorial that the current lack of data should not keep primary care physicians from considering oral health during routine medical exams or keep dentists from finding ways to collaborate with primary care physicians. “Medical primary care must partner with dentistry,” they wrote.

Until there is enough evidence for a USPSTF reevaluation on the topic, primary care clinicians should ask patients about their oral hygiene routines, whether they have any dental symptoms, and when they last saw a dentist, as well as referring to a dentist as necessary, the editorialists wrote.

That works both ways, the editorialists added. “Equally important, oral health professionals are encouraged to collaborate and be a resource for their primary care colleagues. Prevention is one of the best tools clinicians have, and it is promoted by integrated, whole-person health effort, “ wrote Dr. Reddy and colleagues.

When oral health stays separate from medical care, patients are left vulnerable, and referrals between medical and dental offices should be a stronger two-way system, the editorialists said.

“[N]ot every primary care patient has access to a dentist,” they wrote. “Oral health screening and referral by medical primary care clinicians can help ensure that individuals get to the dental chair to receive needed interventions that can benefit both oral and potentially overall health. Likewise, medical challenges and oral mucosal manifestations of chronic health conditions detected at a dental visit should result in medical referral, allowing prompt evaluation and treatment.”
 

Evidence that gels, varnish, sealants are effective

In a companion paper, done to inform the USPSTF, Roger Chou, MD, with Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology at Oregon Health & Science University in Portland, and colleagues found that when administered by a dental professional or in school settings, fluoride supplements, gels and varnish, and resin-based sealants improved health outcomes.

The findings were based on three systematic reviews (20,684 participants) and 19 randomized clinical trials; three nonrandomized trials; and one observational study (total 15,026 participants.)

With fluoride versus placebo or no intervention, researchers found a decrease from baseline in the number of decayed, missing, or filled permanent teeth (DMFT index) or decayed or filled permanent teeth (DFT index). The average difference was −0.73 [95% confidence interval [CI], −1.30 to −0.19]) at 1.5 to 3 years (six trials; n = 1,395).

Fluoride gels were associated with a DMFT- or DFT-prevented fraction of 0.18 (95% CI, 0.09-0.27) at outcomes closest to 3 years (four trials; n = 1,525).

Researchers found an association between fluoride varnish and a DMFT- or DFT-prevented fraction of 0.44 (95% CI, 0.11-0.76) at 1 to 4.5 years (five trials; n = 3,902). The sealants tested were associated with decreased risk of caries in first molars (odds ratio, 0.21 [95% CI, 0.16-0.28]) at 48-54 months (four trials; n = 440).

They noted that the feasibility of administering preventive measures in primary care is unknown; the effectiveness shown here was based on administration in dental and supervised school settings.

Barriers in primary care settings may include lack of training and equipment (particularly for sealants), uncertain reimbursement and lack of acceptance and uptake.
 

USPSTF working to close evidence gaps

Wanda Nicholson, MD, MPH, Prevention and Community Health, George Washington Milken Institute of Public Health in Washington, wrote in an accompanying editorial that to speed necessary research to facilitate recommendations, “the USPSTF and its stakeholders need a transparent, easily implementable communication tool that will systematically describe the research necessary to be directly responsive to the evidence gaps.”

The editorialists noted that the USPSTF in trying to update recommendations often has few, if any, high-quality additional studies to consider since its previous recommendation.

To address that, meetings were conducted in November of 2022 involving USPSTF members, Agency for Healthcare Research and Quality (AHRQ) staff, and leadership from the Office of Disease Prevention and the National Institutes of Health. Members formed a working group “to develop a standardized template for communicating research gaps” according to a framework developed by the National Academies of Sciences, Engineering, and Medicine.

Dr. Nicholson and colleagues wrote, “classifying evidence gaps and calling for specific research needs is a prudent, collaborative step in addressing missing evidence,” particularly for underserved populations.

The authors and editorialists declared no relevant conflicts of interest.

Suicide is among the top three causes of death for young people in the United States. According to the Centers for Disease Control and Prevention, the rate of suicide deaths has climbed from 4.4 per 100,000 American 12- to 17-year-olds in 2011 to 6.5 per 100,000 in 2021, an increase of almost 50%. As with accidents and homicides, we hope these are preventable deaths, although the factors contributing to them are complex.

We do know that more than half of the people who die by suicide visit a health care provider within 4 weeks of their death, highlighting an opportunity for screening and intervention.
 

Suicide screening

In 2022, the American Academy of Pediatrics (AAP) recommended that all adolescents get screened for suicide risk annually. Given that less than 1 in 10,000 adolescents commit suicide and that there is no definitive data on how to prevent suicide in any individual, the goal of suicide screening is much broader than preventing suicide. Beyond universal screening, we will review how being open and curious with all of your patients can be the most extraordinary screening instrument.

There is extensive data that tells us that far from causing suicide, asking about suicidal thoughts is protective. When you make suicidal thoughts discussable, you directly counteract the isolation, stigma, and shame that are strong predictors of actual suicide attempts. You model the value of bringing difficult or frightening thoughts to the attention of caring adults, and you model calm listening rather than emotional overreaction for their parents. The resulting connectedness can lower the risk for vulnerable patients and enhance resilience for all of your patients.
 

Who is at greater risk?

We have robust data to guide our understanding of which youth have suicidal ideation, which is distinct from those who attempt suicide, which also may be quite distinct from those who complete. The CDC reports that the rate of suicidal thoughts (“seriously considering suicide”) in high school students climbed from 16% in 2011 to 22% in 2021. In that decade, the number of high schoolers with a suicide plan climbed from 13% to 18%, and those with suicide attempts climbed from 8% to 10%. Girls are at higher risk for suicidal thoughts and attempts, but boys are at greater risk for suicide completion. Black youth were more likely to attempt suicide than were their Asian, Hispanic, or White peers and LGBTQ+ youth are at particular risk; in 2021, they were three times as likely as were their heterosexual peers to have suicidal thoughts and attempts. Youth with psychiatric illness (particularly PTSD, mood or thought disorders), a family history of suicide, a history of risk-taking behavior (including sexual activity, smoking, drinking, and drug use) and those with prior suicide attempts are at the highest risk for suicide. Adding all these risk factors together means that many, if not the majority, of teenagers have risk factors.

Focus on the patient

In your office, though, a public health approach should give way to curiosity about your individual patient. Suicidal thoughts usually follow a substantial stress. Pay attention to exceptional stresses, especially if they have a component of social stigma or isolation. Did your patient report another student for an assault? Are they now being bullied or ostracized by friends? Have they lost an especially important relationship? Some other stresses may seem minor, such as a poor grade on a test. But for a very driven, perfectionistic teenager who believes that a perfect 4.0 GPA is essential to college admission and future success and happiness, one poor grade may feel like a catastrophe.

When your patients tell you about a challenge or setback, slow down and be curious. Listen to the importance they give it. How have they managed it? Are they finding it hard to go to school or back to practice? Do they feel discouraged or even hopeless? Discouragement is a normal response to adversity, but it should be temporary. This approach can make it easy to ask if they have ever wished they were dead, or made a suicide plan or an attempt. When you calmly and supportively learn about their inner experience, it will be easy for young people to be honest with you.

There will be teenagers in your practice who are sensation-seeking and impulsive, and you should pay special attention to this group. They may not be classically depressed, but in the aftermath of a stressful experience that they find humiliating or shameful, they are at risk for an impulsive act that could still be lethal. Be curious with these patients after they feel they have let down their team or their family, or if they have been caught in a crime or cheating, or even if their girlfriend breaks up with them. Find out how they are managing, and where their support comes from. Ask them in a nonjudgmental manner about whether they are having thoughts about death or suicide, and if those thoughts are troubling, frequent, or feel like a relief. What has stopped them from acting on these thoughts? Offer your patient the perspective that such thoughts may be normal in the face of a large stress, but that the pain of stress always subsides, whereas suicide is irreversible.

There will also be patients in your practice who cut themselves. This is sometimes called “nonsuicidal self-injury,” and it often raises concern about suicide risk. While accelerating frequency of self-injury in a teenager who is suicidal can indicate growing risk, this behavior alone is usually a mechanism for regulating emotion. Ask your patient about when they cut themselves. What are the triggers? How do they feel afterward? Are their friends all doing it? Is it only after fighting with their parents? Or does it make their parents worry instead of getting angry? As you learn about the nature of the behavior, you will be able to offer thoughtful guidance about better strategies for stress management or to pursue further assessment and support.
 

Next steps

Speaking comfortably with your patients about suicidal thoughts and behaviors requires that you also feel comfortable with what comes next. As in the ASQ screening instrument recommended by the AAP, you should always follow affirmative answers about suicidal thoughts with more questions. Do they have a plan? Do they have access to lethal means including any guns in the home? Have they ever made an attempt? Are they thinking about killing themselves now? If the thoughts are current, they have access, and they have tried before, it is clear that they need an urgent assessment, probably in an emergency department. But when the thoughts were in the past or have never been connected to plans or intent, there is an opportunity to enhance their connectedness. You can diminish the potential for shame, stigma and isolation by reminding them that such thoughts and feelings are normal in the face of difficulty. They deserve support to help them face and manage their adversity, whether that stress comes from an internal or external source. How do they feel now that they have shared these thoughts with you? Most will describe feeling better, relieved, even hopeful once they are not facing intense thoughts and feelings alone.

You should tell them that you would like to bring their parents into the conversation. You want them to know they can turn to their parents if they are having these thoughts, so they are never alone in facing them. Parents can learn from your model of calm and supportive listening to fully understand the situation before turning together to talk about what might be helpful next steps. It is always prudent to create “speed bumps” between thought and action with impulsive teens, so recommend limiting access to any lethal means (firearms especially). But the strongest protective intervention is for the child to feel confident in and connected to their support network, trusting you and their parents to listen and understand before figuring out together what else is needed to address the situation.

Lastly, recognize that talking about difficult issues with teenagers is among the most stressful and demanding aspects of pediatric primary care. Talk to colleagues, never worry alone, and recognize and manage your own stress. This is among the best ways to model for your patients and their parents that every challenge can be met, but we often need support.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

Suicide is among the top three causes of death for young people in the United States. According to the Centers for Disease Control and Prevention, the rate of suicide deaths has climbed from 4.4 per 100,000 American 12- to 17-year-olds in 2011 to 6.5 per 100,000 in 2021, an increase of almost 50%. As with accidents and homicides, we hope these are preventable deaths, although the factors contributing to them are complex.

We do know that more than half of the people who die by suicide visit a health care provider within 4 weeks of their death, highlighting an opportunity for screening and intervention.
 

Suicide screening

In 2022, the American Academy of Pediatrics (AAP) recommended that all adolescents get screened for suicide risk annually. Given that less than 1 in 10,000 adolescents commit suicide and that there is no definitive data on how to prevent suicide in any individual, the goal of suicide screening is much broader than preventing suicide. Beyond universal screening, we will review how being open and curious with all of your patients can be the most extraordinary screening instrument.

There is extensive data that tells us that far from causing suicide, asking about suicidal thoughts is protective. When you make suicidal thoughts discussable, you directly counteract the isolation, stigma, and shame that are strong predictors of actual suicide attempts. You model the value of bringing difficult or frightening thoughts to the attention of caring adults, and you model calm listening rather than emotional overreaction for their parents. The resulting connectedness can lower the risk for vulnerable patients and enhance resilience for all of your patients.
 

Who is at greater risk?

We have robust data to guide our understanding of which youth have suicidal ideation, which is distinct from those who attempt suicide, which also may be quite distinct from those who complete. The CDC reports that the rate of suicidal thoughts (“seriously considering suicide”) in high school students climbed from 16% in 2011 to 22% in 2021. In that decade, the number of high schoolers with a suicide plan climbed from 13% to 18%, and those with suicide attempts climbed from 8% to 10%. Girls are at higher risk for suicidal thoughts and attempts, but boys are at greater risk for suicide completion. Black youth were more likely to attempt suicide than were their Asian, Hispanic, or White peers and LGBTQ+ youth are at particular risk; in 2021, they were three times as likely as were their heterosexual peers to have suicidal thoughts and attempts. Youth with psychiatric illness (particularly PTSD, mood or thought disorders), a family history of suicide, a history of risk-taking behavior (including sexual activity, smoking, drinking, and drug use) and those with prior suicide attempts are at the highest risk for suicide. Adding all these risk factors together means that many, if not the majority, of teenagers have risk factors.

Focus on the patient

In your office, though, a public health approach should give way to curiosity about your individual patient. Suicidal thoughts usually follow a substantial stress. Pay attention to exceptional stresses, especially if they have a component of social stigma or isolation. Did your patient report another student for an assault? Are they now being bullied or ostracized by friends? Have they lost an especially important relationship? Some other stresses may seem minor, such as a poor grade on a test. But for a very driven, perfectionistic teenager who believes that a perfect 4.0 GPA is essential to college admission and future success and happiness, one poor grade may feel like a catastrophe.

When your patients tell you about a challenge or setback, slow down and be curious. Listen to the importance they give it. How have they managed it? Are they finding it hard to go to school or back to practice? Do they feel discouraged or even hopeless? Discouragement is a normal response to adversity, but it should be temporary. This approach can make it easy to ask if they have ever wished they were dead, or made a suicide plan or an attempt. When you calmly and supportively learn about their inner experience, it will be easy for young people to be honest with you.

There will be teenagers in your practice who are sensation-seeking and impulsive, and you should pay special attention to this group. They may not be classically depressed, but in the aftermath of a stressful experience that they find humiliating or shameful, they are at risk for an impulsive act that could still be lethal. Be curious with these patients after they feel they have let down their team or their family, or if they have been caught in a crime or cheating, or even if their girlfriend breaks up with them. Find out how they are managing, and where their support comes from. Ask them in a nonjudgmental manner about whether they are having thoughts about death or suicide, and if those thoughts are troubling, frequent, or feel like a relief. What has stopped them from acting on these thoughts? Offer your patient the perspective that such thoughts may be normal in the face of a large stress, but that the pain of stress always subsides, whereas suicide is irreversible.

There will also be patients in your practice who cut themselves. This is sometimes called “nonsuicidal self-injury,” and it often raises concern about suicide risk. While accelerating frequency of self-injury in a teenager who is suicidal can indicate growing risk, this behavior alone is usually a mechanism for regulating emotion. Ask your patient about when they cut themselves. What are the triggers? How do they feel afterward? Are their friends all doing it? Is it only after fighting with their parents? Or does it make their parents worry instead of getting angry? As you learn about the nature of the behavior, you will be able to offer thoughtful guidance about better strategies for stress management or to pursue further assessment and support.
 

Next steps

Speaking comfortably with your patients about suicidal thoughts and behaviors requires that you also feel comfortable with what comes next. As in the ASQ screening instrument recommended by the AAP, you should always follow affirmative answers about suicidal thoughts with more questions. Do they have a plan? Do they have access to lethal means including any guns in the home? Have they ever made an attempt? Are they thinking about killing themselves now? If the thoughts are current, they have access, and they have tried before, it is clear that they need an urgent assessment, probably in an emergency department. But when the thoughts were in the past or have never been connected to plans or intent, there is an opportunity to enhance their connectedness. You can diminish the potential for shame, stigma and isolation by reminding them that such thoughts and feelings are normal in the face of difficulty. They deserve support to help them face and manage their adversity, whether that stress comes from an internal or external source. How do they feel now that they have shared these thoughts with you? Most will describe feeling better, relieved, even hopeful once they are not facing intense thoughts and feelings alone.

You should tell them that you would like to bring their parents into the conversation. You want them to know they can turn to their parents if they are having these thoughts, so they are never alone in facing them. Parents can learn from your model of calm and supportive listening to fully understand the situation before turning together to talk about what might be helpful next steps. It is always prudent to create “speed bumps” between thought and action with impulsive teens, so recommend limiting access to any lethal means (firearms especially). But the strongest protective intervention is for the child to feel confident in and connected to their support network, trusting you and their parents to listen and understand before figuring out together what else is needed to address the situation.

Lastly, recognize that talking about difficult issues with teenagers is among the most stressful and demanding aspects of pediatric primary care. Talk to colleagues, never worry alone, and recognize and manage your own stress. This is among the best ways to model for your patients and their parents that every challenge can be met, but we often need support.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

Suicide is among the top three causes of death for young people in the United States. According to the Centers for Disease Control and Prevention, the rate of suicide deaths has climbed from 4.4 per 100,000 American 12- to 17-year-olds in 2011 to 6.5 per 100,000 in 2021, an increase of almost 50%. As with accidents and homicides, we hope these are preventable deaths, although the factors contributing to them are complex.

We do know that more than half of the people who die by suicide visit a health care provider within 4 weeks of their death, highlighting an opportunity for screening and intervention.
 

Suicide screening

In 2022, the American Academy of Pediatrics (AAP) recommended that all adolescents get screened for suicide risk annually. Given that less than 1 in 10,000 adolescents commit suicide and that there is no definitive data on how to prevent suicide in any individual, the goal of suicide screening is much broader than preventing suicide. Beyond universal screening, we will review how being open and curious with all of your patients can be the most extraordinary screening instrument.

There is extensive data that tells us that far from causing suicide, asking about suicidal thoughts is protective. When you make suicidal thoughts discussable, you directly counteract the isolation, stigma, and shame that are strong predictors of actual suicide attempts. You model the value of bringing difficult or frightening thoughts to the attention of caring adults, and you model calm listening rather than emotional overreaction for their parents. The resulting connectedness can lower the risk for vulnerable patients and enhance resilience for all of your patients.
 

Who is at greater risk?

We have robust data to guide our understanding of which youth have suicidal ideation, which is distinct from those who attempt suicide, which also may be quite distinct from those who complete. The CDC reports that the rate of suicidal thoughts (“seriously considering suicide”) in high school students climbed from 16% in 2011 to 22% in 2021. In that decade, the number of high schoolers with a suicide plan climbed from 13% to 18%, and those with suicide attempts climbed from 8% to 10%. Girls are at higher risk for suicidal thoughts and attempts, but boys are at greater risk for suicide completion. Black youth were more likely to attempt suicide than were their Asian, Hispanic, or White peers and LGBTQ+ youth are at particular risk; in 2021, they were three times as likely as were their heterosexual peers to have suicidal thoughts and attempts. Youth with psychiatric illness (particularly PTSD, mood or thought disorders), a family history of suicide, a history of risk-taking behavior (including sexual activity, smoking, drinking, and drug use) and those with prior suicide attempts are at the highest risk for suicide. Adding all these risk factors together means that many, if not the majority, of teenagers have risk factors.

Focus on the patient

In your office, though, a public health approach should give way to curiosity about your individual patient. Suicidal thoughts usually follow a substantial stress. Pay attention to exceptional stresses, especially if they have a component of social stigma or isolation. Did your patient report another student for an assault? Are they now being bullied or ostracized by friends? Have they lost an especially important relationship? Some other stresses may seem minor, such as a poor grade on a test. But for a very driven, perfectionistic teenager who believes that a perfect 4.0 GPA is essential to college admission and future success and happiness, one poor grade may feel like a catastrophe.

When your patients tell you about a challenge or setback, slow down and be curious. Listen to the importance they give it. How have they managed it? Are they finding it hard to go to school or back to practice? Do they feel discouraged or even hopeless? Discouragement is a normal response to adversity, but it should be temporary. This approach can make it easy to ask if they have ever wished they were dead, or made a suicide plan or an attempt. When you calmly and supportively learn about their inner experience, it will be easy for young people to be honest with you.

There will be teenagers in your practice who are sensation-seeking and impulsive, and you should pay special attention to this group. They may not be classically depressed, but in the aftermath of a stressful experience that they find humiliating or shameful, they are at risk for an impulsive act that could still be lethal. Be curious with these patients after they feel they have let down their team or their family, or if they have been caught in a crime or cheating, or even if their girlfriend breaks up with them. Find out how they are managing, and where their support comes from. Ask them in a nonjudgmental manner about whether they are having thoughts about death or suicide, and if those thoughts are troubling, frequent, or feel like a relief. What has stopped them from acting on these thoughts? Offer your patient the perspective that such thoughts may be normal in the face of a large stress, but that the pain of stress always subsides, whereas suicide is irreversible.

There will also be patients in your practice who cut themselves. This is sometimes called “nonsuicidal self-injury,” and it often raises concern about suicide risk. While accelerating frequency of self-injury in a teenager who is suicidal can indicate growing risk, this behavior alone is usually a mechanism for regulating emotion. Ask your patient about when they cut themselves. What are the triggers? How do they feel afterward? Are their friends all doing it? Is it only after fighting with their parents? Or does it make their parents worry instead of getting angry? As you learn about the nature of the behavior, you will be able to offer thoughtful guidance about better strategies for stress management or to pursue further assessment and support.
 

Next steps

Speaking comfortably with your patients about suicidal thoughts and behaviors requires that you also feel comfortable with what comes next. As in the ASQ screening instrument recommended by the AAP, you should always follow affirmative answers about suicidal thoughts with more questions. Do they have a plan? Do they have access to lethal means including any guns in the home? Have they ever made an attempt? Are they thinking about killing themselves now? If the thoughts are current, they have access, and they have tried before, it is clear that they need an urgent assessment, probably in an emergency department. But when the thoughts were in the past or have never been connected to plans or intent, there is an opportunity to enhance their connectedness. You can diminish the potential for shame, stigma and isolation by reminding them that such thoughts and feelings are normal in the face of difficulty. They deserve support to help them face and manage their adversity, whether that stress comes from an internal or external source. How do they feel now that they have shared these thoughts with you? Most will describe feeling better, relieved, even hopeful once they are not facing intense thoughts and feelings alone.

You should tell them that you would like to bring their parents into the conversation. You want them to know they can turn to their parents if they are having these thoughts, so they are never alone in facing them. Parents can learn from your model of calm and supportive listening to fully understand the situation before turning together to talk about what might be helpful next steps. It is always prudent to create “speed bumps” between thought and action with impulsive teens, so recommend limiting access to any lethal means (firearms especially). But the strongest protective intervention is for the child to feel confident in and connected to their support network, trusting you and their parents to listen and understand before figuring out together what else is needed to address the situation.

Lastly, recognize that talking about difficult issues with teenagers is among the most stressful and demanding aspects of pediatric primary care. Talk to colleagues, never worry alone, and recognize and manage your own stress. This is among the best ways to model for your patients and their parents that every challenge can be met, but we often need support.
 

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].