Four years ago in the spring of 2020, physicians and patients coined the term “long COVID” to describe a form of the viral infection from which recovery seemed impossible. (And the old nickname “long-haulers” seems so quaint now.)

What started as a pandemic that killed nearly 3 million people globally in 2020 alone would turn into a chronic disease causing a long list of symptoms — from extreme fatigue, to brain fog, tremors, nausea, headaches, rapid heartbeat, and more.

Today, 6.4% of Americans report symptoms of long COVID, and many have never recovered.

Still, we’ve come a long way, although there’s much we don’t understand about the condition. At the very least, physicians have a greater understanding that long COVID exists and can cause serious long-term symptoms.

While physicians may not have a blanket diagnostic tool that works for all patients with long COVID, they have refined existing tests for more accurate results, said Nisha Viswanathan, MD, director of the University of California Los Angeles Long COVID Program at UCLA Health.

Also, a range of new treatments, now undergoing clinical trials, have emerged that have proved effective in managing long COVID symptoms.

Catecholamine testing, for example, is now commonly used to diagnose long COVID, particularly in those who have dysautonomia, a condition caused by dysfunction of the autonomic nervous system and marked by dizziness, low blood pressure, nausea, and brain fog.

Very high levels of the neurotransmitter, for example, were shown to indicate long COVID in a January 2021 study published in the journal Clinical Medicine.

Certain biomarkers have also been shown indicative of the condition, including low serotonin levels. A study published this year in Cell found lower serotonin levels in patients with long COVID driven by low levels of circulating SARS-CoV-2, the virus that causes the condition.

Still, said Dr. Viswanathan, long COVID is a disease diagnosed by figuring out what a patient does not have — by ruling out other causes — rather than what they do. “It’s still a moving target,” she said, meaning that the disease is always changing based on the variant of acute COVID.
 

Promising Treatments Have Emerged

Dysautonomia, and especially the associated brain fog, fatigue, and dizziness, are now common conditions. As a result, physicians have gotten better at treating them. The vagus nerve is the main nerve of the parasympathetic nervous system that controls everything from digestion to mental health. A February 2022 pilot study suggested a link between vagus nerve dysfunction and some long COVID symptoms.

Vagus nerve stimulation is one form of treatment which involves using a device to stimulate the vagus nerve with electrical impulses. Dr. Viswanathan has been using the treatment in patients with fatigue, brain fog, anxiety, and depression — results, she contends, have been positive.

“This is something tangible that we can offer to patients,” she said.

Curative treatments for long COVID remain elusive, but doctors have many more tools for symptom management than before, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System.

For example, physicians are using beta-blockers to treat postural tachycardia syndrome (POTS), a symptom of long COVID that happens when the heart rate increases rapidly after someone stands up or lies down. Beta-blockers, such as the off-label medication ivabradine, have been used clinically to control heart rate, according to a March 2022 study published in the journal HeartRhythm Case Reports.

“It’s not a cure, but beta-blockers can help patients manage their symptoms,” said Dr. Al-Aly.

Additionally, some patients respond well to low-dose naltrexone for the treatment of extreme fatigue associated with long COVID. A January 2024 article in the journal Clinical Therapeutics found that fatigue symptoms improved in patients taking the medication.

Dr. Al-Aly said doctors treating patients with long COVID are getting better at pinpointing the phenotype or manifestation of the condition and diagnosing a treatment accordingly. Treating long COVID fatigue is not the same as treating POTS or symptoms of headache and joint pain.

It’s still all about the management of symptoms and doctors lack any US Food and Drug Administration–approved medications specifically for the condition.
 

Clinical Trials Exploring New Therapies

Still, a number of large clinical trials currently underway may change that, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

Two clinical trials headed by Dr. Putrino’s lab are looking into repurposing two HIV antivirals to see whether they affect the levels of circulating SARS-CoV-2 virus in the body that may cause long COVID. The hope is that the antivirals Truvada and maraviroc can reduce the «reactivation of latent virus» that, said Dr. Putrino, causes lingering long COVID symptoms.

Ongoing trials are looking into the promise of SARS-CoV-2 monoclonal antibodies, produced from cells made by cloning a unique white blood cell, as a treatment option. The trials are investigating whether these antibodies may similarly target viral reservoirs that are causing persistence of symptoms in some patients.

Other trials are underway through the National Institutes of Health (NIH) RECOVER initiative in which more than 17,000 patients are enrolled, the largest study of its kind, said Grace McComsey, MD.

Dr. McComsey, who leads the study at University Hospitals Health System in Cleveland, said that after following patients for up to 4 years researchers have gathered “a massive repository of information” they hope will help scientists crack the code of this very complex disease.

She and other RECOVER researchers have recently published studies on a variety of findings, reporting in February, for example, that COVID infections may trigger other autoimmune diseases such as rheumatoid arthritis and type 2 diabetes. Another recent finding showed that people with HIV are at a higher risk for complications due to acute COVID-19.
 

Lack of Urgency Holds Back Progress

Still, others like Dr. Al-Aly and Dr. Putrino felt that the initiative isn’t moving fast enough. Dr. Al-Aly said that the NIH needs to “get its act together” and do more for long COVID. In the future, he said that we need to double down on our efforts to expand funding and increase urgency to better understand the mechanism of disease, risk factors, and treatments, as well as societal and economic implications.

“We did trials for COVID-19 vaccines at warp speed, but we’re doing trials for long COVID at a snail’s pace,” he said.

Dr. Al-Aly is concerned about the chronic nature of the disease and how it affects patients down the line. His large-scale study published last month in the journal Science looked specifically at chronic fatigue syndrome triggered by the infection and its long-term impact on patients.

He’s concerned about the practical implications for people who are weighted down with symptoms for multiple years.

“Being fatigued and ill for a few months is one thing, but being at home for 5 years is a totally different ballgame.”

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

Four years ago in the spring of 2020, physicians and patients coined the term “long COVID” to describe a form of the viral infection from which recovery seemed impossible. (And the old nickname “long-haulers” seems so quaint now.)

What started as a pandemic that killed nearly 3 million people globally in 2020 alone would turn into a chronic disease causing a long list of symptoms — from extreme fatigue, to brain fog, tremors, nausea, headaches, rapid heartbeat, and more.

Today, 6.4% of Americans report symptoms of long COVID, and many have never recovered.

Still, we’ve come a long way, although there’s much we don’t understand about the condition. At the very least, physicians have a greater understanding that long COVID exists and can cause serious long-term symptoms.

While physicians may not have a blanket diagnostic tool that works for all patients with long COVID, they have refined existing tests for more accurate results, said Nisha Viswanathan, MD, director of the University of California Los Angeles Long COVID Program at UCLA Health.

Also, a range of new treatments, now undergoing clinical trials, have emerged that have proved effective in managing long COVID symptoms.

Catecholamine testing, for example, is now commonly used to diagnose long COVID, particularly in those who have dysautonomia, a condition caused by dysfunction of the autonomic nervous system and marked by dizziness, low blood pressure, nausea, and brain fog.

Very high levels of the neurotransmitter, for example, were shown to indicate long COVID in a January 2021 study published in the journal Clinical Medicine.

Certain biomarkers have also been shown indicative of the condition, including low serotonin levels. A study published this year in Cell found lower serotonin levels in patients with long COVID driven by low levels of circulating SARS-CoV-2, the virus that causes the condition.

Still, said Dr. Viswanathan, long COVID is a disease diagnosed by figuring out what a patient does not have — by ruling out other causes — rather than what they do. “It’s still a moving target,” she said, meaning that the disease is always changing based on the variant of acute COVID.
 

Promising Treatments Have Emerged

Dysautonomia, and especially the associated brain fog, fatigue, and dizziness, are now common conditions. As a result, physicians have gotten better at treating them. The vagus nerve is the main nerve of the parasympathetic nervous system that controls everything from digestion to mental health. A February 2022 pilot study suggested a link between vagus nerve dysfunction and some long COVID symptoms.

Vagus nerve stimulation is one form of treatment which involves using a device to stimulate the vagus nerve with electrical impulses. Dr. Viswanathan has been using the treatment in patients with fatigue, brain fog, anxiety, and depression — results, she contends, have been positive.

“This is something tangible that we can offer to patients,” she said.

Curative treatments for long COVID remain elusive, but doctors have many more tools for symptom management than before, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System.

For example, physicians are using beta-blockers to treat postural tachycardia syndrome (POTS), a symptom of long COVID that happens when the heart rate increases rapidly after someone stands up or lies down. Beta-blockers, such as the off-label medication ivabradine, have been used clinically to control heart rate, according to a March 2022 study published in the journal HeartRhythm Case Reports.

“It’s not a cure, but beta-blockers can help patients manage their symptoms,” said Dr. Al-Aly.

Additionally, some patients respond well to low-dose naltrexone for the treatment of extreme fatigue associated with long COVID. A January 2024 article in the journal Clinical Therapeutics found that fatigue symptoms improved in patients taking the medication.

Dr. Al-Aly said doctors treating patients with long COVID are getting better at pinpointing the phenotype or manifestation of the condition and diagnosing a treatment accordingly. Treating long COVID fatigue is not the same as treating POTS or symptoms of headache and joint pain.

It’s still all about the management of symptoms and doctors lack any US Food and Drug Administration–approved medications specifically for the condition.
 

Clinical Trials Exploring New Therapies

Still, a number of large clinical trials currently underway may change that, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

Two clinical trials headed by Dr. Putrino’s lab are looking into repurposing two HIV antivirals to see whether they affect the levels of circulating SARS-CoV-2 virus in the body that may cause long COVID. The hope is that the antivirals Truvada and maraviroc can reduce the «reactivation of latent virus» that, said Dr. Putrino, causes lingering long COVID symptoms.

Ongoing trials are looking into the promise of SARS-CoV-2 monoclonal antibodies, produced from cells made by cloning a unique white blood cell, as a treatment option. The trials are investigating whether these antibodies may similarly target viral reservoirs that are causing persistence of symptoms in some patients.

Other trials are underway through the National Institutes of Health (NIH) RECOVER initiative in which more than 17,000 patients are enrolled, the largest study of its kind, said Grace McComsey, MD.

Dr. McComsey, who leads the study at University Hospitals Health System in Cleveland, said that after following patients for up to 4 years researchers have gathered “a massive repository of information” they hope will help scientists crack the code of this very complex disease.

She and other RECOVER researchers have recently published studies on a variety of findings, reporting in February, for example, that COVID infections may trigger other autoimmune diseases such as rheumatoid arthritis and type 2 diabetes. Another recent finding showed that people with HIV are at a higher risk for complications due to acute COVID-19.
 

Lack of Urgency Holds Back Progress

Still, others like Dr. Al-Aly and Dr. Putrino felt that the initiative isn’t moving fast enough. Dr. Al-Aly said that the NIH needs to “get its act together” and do more for long COVID. In the future, he said that we need to double down on our efforts to expand funding and increase urgency to better understand the mechanism of disease, risk factors, and treatments, as well as societal and economic implications.

“We did trials for COVID-19 vaccines at warp speed, but we’re doing trials for long COVID at a snail’s pace,” he said.

Dr. Al-Aly is concerned about the chronic nature of the disease and how it affects patients down the line. His large-scale study published last month in the journal Science looked specifically at chronic fatigue syndrome triggered by the infection and its long-term impact on patients.

He’s concerned about the practical implications for people who are weighted down with symptoms for multiple years.

“Being fatigued and ill for a few months is one thing, but being at home for 5 years is a totally different ballgame.”

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

Four years ago in the spring of 2020, physicians and patients coined the term “long COVID” to describe a form of the viral infection from which recovery seemed impossible. (And the old nickname “long-haulers” seems so quaint now.)

What started as a pandemic that killed nearly 3 million people globally in 2020 alone would turn into a chronic disease causing a long list of symptoms — from extreme fatigue, to brain fog, tremors, nausea, headaches, rapid heartbeat, and more.

Today, 6.4% of Americans report symptoms of long COVID, and many have never recovered.

Still, we’ve come a long way, although there’s much we don’t understand about the condition. At the very least, physicians have a greater understanding that long COVID exists and can cause serious long-term symptoms.

While physicians may not have a blanket diagnostic tool that works for all patients with long COVID, they have refined existing tests for more accurate results, said Nisha Viswanathan, MD, director of the University of California Los Angeles Long COVID Program at UCLA Health.

Also, a range of new treatments, now undergoing clinical trials, have emerged that have proved effective in managing long COVID symptoms.

Catecholamine testing, for example, is now commonly used to diagnose long COVID, particularly in those who have dysautonomia, a condition caused by dysfunction of the autonomic nervous system and marked by dizziness, low blood pressure, nausea, and brain fog.

Very high levels of the neurotransmitter, for example, were shown to indicate long COVID in a January 2021 study published in the journal Clinical Medicine.

Certain biomarkers have also been shown indicative of the condition, including low serotonin levels. A study published this year in Cell found lower serotonin levels in patients with long COVID driven by low levels of circulating SARS-CoV-2, the virus that causes the condition.

Still, said Dr. Viswanathan, long COVID is a disease diagnosed by figuring out what a patient does not have — by ruling out other causes — rather than what they do. “It’s still a moving target,” she said, meaning that the disease is always changing based on the variant of acute COVID.
 

Promising Treatments Have Emerged

Dysautonomia, and especially the associated brain fog, fatigue, and dizziness, are now common conditions. As a result, physicians have gotten better at treating them. The vagus nerve is the main nerve of the parasympathetic nervous system that controls everything from digestion to mental health. A February 2022 pilot study suggested a link between vagus nerve dysfunction and some long COVID symptoms.

Vagus nerve stimulation is one form of treatment which involves using a device to stimulate the vagus nerve with electrical impulses. Dr. Viswanathan has been using the treatment in patients with fatigue, brain fog, anxiety, and depression — results, she contends, have been positive.

“This is something tangible that we can offer to patients,” she said.

Curative treatments for long COVID remain elusive, but doctors have many more tools for symptom management than before, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System.

For example, physicians are using beta-blockers to treat postural tachycardia syndrome (POTS), a symptom of long COVID that happens when the heart rate increases rapidly after someone stands up or lies down. Beta-blockers, such as the off-label medication ivabradine, have been used clinically to control heart rate, according to a March 2022 study published in the journal HeartRhythm Case Reports.

“It’s not a cure, but beta-blockers can help patients manage their symptoms,” said Dr. Al-Aly.

Additionally, some patients respond well to low-dose naltrexone for the treatment of extreme fatigue associated with long COVID. A January 2024 article in the journal Clinical Therapeutics found that fatigue symptoms improved in patients taking the medication.

Dr. Al-Aly said doctors treating patients with long COVID are getting better at pinpointing the phenotype or manifestation of the condition and diagnosing a treatment accordingly. Treating long COVID fatigue is not the same as treating POTS or symptoms of headache and joint pain.

It’s still all about the management of symptoms and doctors lack any US Food and Drug Administration–approved medications specifically for the condition.
 

Clinical Trials Exploring New Therapies

Still, a number of large clinical trials currently underway may change that, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

Two clinical trials headed by Dr. Putrino’s lab are looking into repurposing two HIV antivirals to see whether they affect the levels of circulating SARS-CoV-2 virus in the body that may cause long COVID. The hope is that the antivirals Truvada and maraviroc can reduce the «reactivation of latent virus» that, said Dr. Putrino, causes lingering long COVID symptoms.

Ongoing trials are looking into the promise of SARS-CoV-2 monoclonal antibodies, produced from cells made by cloning a unique white blood cell, as a treatment option. The trials are investigating whether these antibodies may similarly target viral reservoirs that are causing persistence of symptoms in some patients.

Other trials are underway through the National Institutes of Health (NIH) RECOVER initiative in which more than 17,000 patients are enrolled, the largest study of its kind, said Grace McComsey, MD.

Dr. McComsey, who leads the study at University Hospitals Health System in Cleveland, said that after following patients for up to 4 years researchers have gathered “a massive repository of information” they hope will help scientists crack the code of this very complex disease.

She and other RECOVER researchers have recently published studies on a variety of findings, reporting in February, for example, that COVID infections may trigger other autoimmune diseases such as rheumatoid arthritis and type 2 diabetes. Another recent finding showed that people with HIV are at a higher risk for complications due to acute COVID-19.
 

Lack of Urgency Holds Back Progress

Still, others like Dr. Al-Aly and Dr. Putrino felt that the initiative isn’t moving fast enough. Dr. Al-Aly said that the NIH needs to “get its act together” and do more for long COVID. In the future, he said that we need to double down on our efforts to expand funding and increase urgency to better understand the mechanism of disease, risk factors, and treatments, as well as societal and economic implications.

“We did trials for COVID-19 vaccines at warp speed, but we’re doing trials for long COVID at a snail’s pace,” he said.

Dr. Al-Aly is concerned about the chronic nature of the disease and how it affects patients down the line. His large-scale study published last month in the journal Science looked specifically at chronic fatigue syndrome triggered by the infection and its long-term impact on patients.

He’s concerned about the practical implications for people who are weighted down with symptoms for multiple years.

“Being fatigued and ill for a few months is one thing, but being at home for 5 years is a totally different ballgame.”

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

Gut microbiota signatures associated with KRAS mutations in patients with colorectal cancer (CRC) have been identified by researchers.

Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.

“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement. 

The research was recently published online in Microbiology Spectrum. 

The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear. 

To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC. 

The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.

At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group. 

Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.

Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development. 

Similarly, Shewanella has been proven to be a contributor to CRC development.

The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.

In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group. 

Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic. 

The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.

Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.

“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.

Promising Predictive Model

Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC. 

The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote. 

They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings. 

The study had no commercial funding. The authors declared no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.

Gut microbiota signatures associated with KRAS mutations in patients with colorectal cancer (CRC) have been identified by researchers.

Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.

“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement. 

The research was recently published online in Microbiology Spectrum. 

The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear. 

To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC. 

The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.

At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group. 

Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.

Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development. 

Similarly, Shewanella has been proven to be a contributor to CRC development.

The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.

In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group. 

Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic. 

The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.

Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.

“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.

Promising Predictive Model

Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC. 

The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote. 

They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings. 

The study had no commercial funding. The authors declared no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.

Gut microbiota signatures associated with KRAS mutations in patients with colorectal cancer (CRC) have been identified by researchers.

Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.

“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement. 

The research was recently published online in Microbiology Spectrum. 

The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear. 

To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC. 

The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.

At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group. 

Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.

Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development. 

Similarly, Shewanella has been proven to be a contributor to CRC development.

The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.

In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group. 

Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic. 

The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.

Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.

“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.

Promising Predictive Model

Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC. 

The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote. 

They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings. 

The study had no commercial funding. The authors declared no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.

TOPLINE:

Less than 7 hours of sleep per night is common in individuals with type 1 diabetes (T1D) but is tied to poor cardiometabolic health, particularly in adolescents.

METHODOLOGY:

• Sleep is recognized as an important factor in diabetes assessment and treatment by the 2023 American Diabetes Association’s Standards of Medical Care in Diabetes, but it is unclear whether sleep may improve health outcomes across the lifespan in patients with T1D.
• This secondary analysis of the BCQR-T1D crossover trial investigated the link between sleep and cardiometabolic health in 42 adults (age, 19-60 years) and 42 adolescents (age, 12-18 years) with T1D.
• Participants had T1D duration greater than 9 months and received bromocriptine quick-release (BCQR) therapy or placebo for 4 weeks and then switched between the treatments in a separate 4-week period.
• They underwent laboratory testing and anthropometric measurements. Also, continuous glucose monitoring data were collected for a week during each treatment phase along with an accompanying insulin dosing diary.
• Participants were required to wear an actigraphy monitor on the wrist of their nondominant hand for 7 days during each treatment phase to estimate sleep duration.

TAKEAWAY:

• Most adolescents (62%) and adults (74%) with T1D reported less than 7 hours of sleep at baseline.
• Participants with insufficient sleep versus those without insufficient sleep (< 7 vs > 7 hours) had a larger waist circumference and higher mean body mass index, systolic blood pressure, and pulse pressure, as well as lower estimated insulin sensitivity and brachial artery distensibility (P < .05 for all).
• When stratified by age, only adolescents with T1D with insufficient sleep had significant differences in most health outcomes by sleep duration status, except that adults with less than 7 hours of sleep had higher pulse pressure than those with more than 7 hours of sleep.
• Compared with placebo, BCQR slightly improved sleeping parameters in adolescents by delaying their time of waking up and prolonging their time in bed.

IN PRACTICE:

“Sleep may be an important and novel target for improving health in individuals with T1D, particularly when initiated in adolescence or early in diabetes,” the authors wrote.

SOURCE:

Stacey L. Simon, PhD, and Janet K. Snell-Bergeon, PhD, University of Colorado Anschutz Medical Campus, Aurora, led this study, which was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study lacked polysomnography or melatonin assessment to quantify circadian rhythms and subjective sleep quality ratings. It also had no objective measurement of the timing of the daily pills of BCQR, which, when taken in the morning, are hypothesized to reset the circadian rhythm for hypothalamic dopamine and serotonin. The recommended sleep duration of 8 hours for adolescents was not used as the cutoff value due to too few participants who qualified. Also, this study›s findings may be affected by the fact that participants were recruited throughout the year, while adolescents show different sleeping patterns during the academic year compared with school breaks.

DISCLOSURES:

This work was supported by a JDRF grant. Two authors declared receiving equipment, honoraria for lectures, and support for conference travel, which were all unrelated to this study.

A version of this article appeared on Medscape.com.

TOPLINE:

Less than 7 hours of sleep per night is common in individuals with type 1 diabetes (T1D) but is tied to poor cardiometabolic health, particularly in adolescents.

METHODOLOGY:

• Sleep is recognized as an important factor in diabetes assessment and treatment by the 2023 American Diabetes Association’s Standards of Medical Care in Diabetes, but it is unclear whether sleep may improve health outcomes across the lifespan in patients with T1D.
• This secondary analysis of the BCQR-T1D crossover trial investigated the link between sleep and cardiometabolic health in 42 adults (age, 19-60 years) and 42 adolescents (age, 12-18 years) with T1D.
• Participants had T1D duration greater than 9 months and received bromocriptine quick-release (BCQR) therapy or placebo for 4 weeks and then switched between the treatments in a separate 4-week period.
• They underwent laboratory testing and anthropometric measurements. Also, continuous glucose monitoring data were collected for a week during each treatment phase along with an accompanying insulin dosing diary.
• Participants were required to wear an actigraphy monitor on the wrist of their nondominant hand for 7 days during each treatment phase to estimate sleep duration.

TAKEAWAY:

• Most adolescents (62%) and adults (74%) with T1D reported less than 7 hours of sleep at baseline.
• Participants with insufficient sleep versus those without insufficient sleep (< 7 vs > 7 hours) had a larger waist circumference and higher mean body mass index, systolic blood pressure, and pulse pressure, as well as lower estimated insulin sensitivity and brachial artery distensibility (P < .05 for all).
• When stratified by age, only adolescents with T1D with insufficient sleep had significant differences in most health outcomes by sleep duration status, except that adults with less than 7 hours of sleep had higher pulse pressure than those with more than 7 hours of sleep.
• Compared with placebo, BCQR slightly improved sleeping parameters in adolescents by delaying their time of waking up and prolonging their time in bed.

IN PRACTICE:

“Sleep may be an important and novel target for improving health in individuals with T1D, particularly when initiated in adolescence or early in diabetes,” the authors wrote.

SOURCE:

Stacey L. Simon, PhD, and Janet K. Snell-Bergeon, PhD, University of Colorado Anschutz Medical Campus, Aurora, led this study, which was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study lacked polysomnography or melatonin assessment to quantify circadian rhythms and subjective sleep quality ratings. It also had no objective measurement of the timing of the daily pills of BCQR, which, when taken in the morning, are hypothesized to reset the circadian rhythm for hypothalamic dopamine and serotonin. The recommended sleep duration of 8 hours for adolescents was not used as the cutoff value due to too few participants who qualified. Also, this study›s findings may be affected by the fact that participants were recruited throughout the year, while adolescents show different sleeping patterns during the academic year compared with school breaks.

DISCLOSURES:

This work was supported by a JDRF grant. Two authors declared receiving equipment, honoraria for lectures, and support for conference travel, which were all unrelated to this study.

A version of this article appeared on Medscape.com.

TOPLINE:

Less than 7 hours of sleep per night is common in individuals with type 1 diabetes (T1D) but is tied to poor cardiometabolic health, particularly in adolescents.

METHODOLOGY:

• Sleep is recognized as an important factor in diabetes assessment and treatment by the 2023 American Diabetes Association’s Standards of Medical Care in Diabetes, but it is unclear whether sleep may improve health outcomes across the lifespan in patients with T1D.
• This secondary analysis of the BCQR-T1D crossover trial investigated the link between sleep and cardiometabolic health in 42 adults (age, 19-60 years) and 42 adolescents (age, 12-18 years) with T1D.
• Participants had T1D duration greater than 9 months and received bromocriptine quick-release (BCQR) therapy or placebo for 4 weeks and then switched between the treatments in a separate 4-week period.
• They underwent laboratory testing and anthropometric measurements. Also, continuous glucose monitoring data were collected for a week during each treatment phase along with an accompanying insulin dosing diary.
• Participants were required to wear an actigraphy monitor on the wrist of their nondominant hand for 7 days during each treatment phase to estimate sleep duration.

TAKEAWAY:

• Most adolescents (62%) and adults (74%) with T1D reported less than 7 hours of sleep at baseline.
• Participants with insufficient sleep versus those without insufficient sleep (< 7 vs > 7 hours) had a larger waist circumference and higher mean body mass index, systolic blood pressure, and pulse pressure, as well as lower estimated insulin sensitivity and brachial artery distensibility (P < .05 for all).
• When stratified by age, only adolescents with T1D with insufficient sleep had significant differences in most health outcomes by sleep duration status, except that adults with less than 7 hours of sleep had higher pulse pressure than those with more than 7 hours of sleep.
• Compared with placebo, BCQR slightly improved sleeping parameters in adolescents by delaying their time of waking up and prolonging their time in bed.

IN PRACTICE:

“Sleep may be an important and novel target for improving health in individuals with T1D, particularly when initiated in adolescence or early in diabetes,” the authors wrote.

SOURCE:

Stacey L. Simon, PhD, and Janet K. Snell-Bergeon, PhD, University of Colorado Anschutz Medical Campus, Aurora, led this study, which was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study lacked polysomnography or melatonin assessment to quantify circadian rhythms and subjective sleep quality ratings. It also had no objective measurement of the timing of the daily pills of BCQR, which, when taken in the morning, are hypothesized to reset the circadian rhythm for hypothalamic dopamine and serotonin. The recommended sleep duration of 8 hours for adolescents was not used as the cutoff value due to too few participants who qualified. Also, this study›s findings may be affected by the fact that participants were recruited throughout the year, while adolescents show different sleeping patterns during the academic year compared with school breaks.

DISCLOSURES:

This work was supported by a JDRF grant. Two authors declared receiving equipment, honoraria for lectures, and support for conference travel, which were all unrelated to this study.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent study suggests that younger breast cancer survivors with a germline pathogenic variant or those with an initial diagnosis of in situ vs invasive primary breast cancer have a significantly higher risk for a second primary breast cancer.

METHODOLOGY:

• Women who are diagnosed with breast cancer at age 40 or younger are about two to three times more likely to develop second primary breast cancer compared with women who are older when first diagnosed.
• However, data are lacking on whether certain factors increase a woman’s risk for a second primary breast cancer.
• To classify the risk of developing a second primary breast cancer, the researchers evaluated a main cohort of 685 patients with stages 0-III breast cancer who were diagnosed at age 40 years or younger and had undergone unilateral mastectomy or lumpectomy as primary surgery between August 2006 and June 2015. The team also analyzed data on 547 younger women who had a bilateral mastectomy.
• The researchers assessed various breast cancer risk factors, including self-reported ethnicity, race, age, family history of breast or ovarian cancer, germline genetics, tumor stage, grade, and receptor status.
• The primary outcome was the diagnosis of a second primary breast cancer that occurred at least 6 months after the initial diagnosis of primary breast cancer.

TAKEAWAY:

• Among the 685 main study participants, 17 (2.5%) developed a second primary breast cancer (15 contralateral and 2 ipsilateral) over a median of 4.2 years since their primary diagnosis. The 5- and 10-year cumulative incidence of a second primary breast cancer was 1.5% and 2.6%, respectively.
• Overall, only 33 women were positive for a germline pathogenic variant, and having a pathogenic variant was associated with a fourfold higher risk for second primary breast cancer compared with noncarriers at 5 years (5.5% vs 1.3%) and at 10 years (8.9% vs 2.2%). These findings were held in multivariate models.
• Patients initially diagnosed with in situ disease had more than a fivefold higher risk for second primary breast cancer compared with those initially diagnosed with invasive disease — 6.2% vs 1.2% at 5 years and 10.4% vs 2.1% at 10 years (hazard ratio, 5.25; P = .004). These findings were held in multivariate models (adjusted sub-hazard ratio [sHR], 5.61; 95% CI, 1.52-20.70) and among women without a pathogenic variant (adjusted sHR, 5.67; 95% CI, 1.54-20.90).
• The researchers also found a low risk for contralateral breast cancer among women without pathogenic variants, which could inform surgical decision-making.

IN PRACTICE:

Although the number of women positive for a germline pathogenic variant was small (n = 33) and “results should be interpreted cautiously,” the analysis signals “the importance of genetic testing” in younger breast cancer survivors to gauge their risk for a second primary breast cancer, the authors concluded. The authors added that their “finding of a higher risk of [second primary breast cancer] among those diagnosed with in situ primary [breast cancer] merits further investigation.”

SOURCE:

This study, led by Kristen D. Brantley, PhD, from Harvard T. H. Chan School of Public Health, Boston, was published online in JAMA Oncology.

LIMITATIONS:

A small number of second breast cancer events limited the authors’ ability to assess the effects of multiple risk factors together. Data on risk factors might be incomplete. About 9% of participants completed abbreviated questionnaires that did not include information on body mass index, alcohol, smoking, and family history. Frequencies of pathogenic variants besides BRCA1 and BRCA2 may be underestimated.

DISCLOSURES:

This study received no external funding. Four authors reported receiving grants or royalties outside this work. Other reported no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent study suggests that younger breast cancer survivors with a germline pathogenic variant or those with an initial diagnosis of in situ vs invasive primary breast cancer have a significantly higher risk for a second primary breast cancer.

METHODOLOGY:

• Women who are diagnosed with breast cancer at age 40 or younger are about two to three times more likely to develop second primary breast cancer compared with women who are older when first diagnosed.
• However, data are lacking on whether certain factors increase a woman’s risk for a second primary breast cancer.
• To classify the risk of developing a second primary breast cancer, the researchers evaluated a main cohort of 685 patients with stages 0-III breast cancer who were diagnosed at age 40 years or younger and had undergone unilateral mastectomy or lumpectomy as primary surgery between August 2006 and June 2015. The team also analyzed data on 547 younger women who had a bilateral mastectomy.
• The researchers assessed various breast cancer risk factors, including self-reported ethnicity, race, age, family history of breast or ovarian cancer, germline genetics, tumor stage, grade, and receptor status.
• The primary outcome was the diagnosis of a second primary breast cancer that occurred at least 6 months after the initial diagnosis of primary breast cancer.

TAKEAWAY:

• Among the 685 main study participants, 17 (2.5%) developed a second primary breast cancer (15 contralateral and 2 ipsilateral) over a median of 4.2 years since their primary diagnosis. The 5- and 10-year cumulative incidence of a second primary breast cancer was 1.5% and 2.6%, respectively.
• Overall, only 33 women were positive for a germline pathogenic variant, and having a pathogenic variant was associated with a fourfold higher risk for second primary breast cancer compared with noncarriers at 5 years (5.5% vs 1.3%) and at 10 years (8.9% vs 2.2%). These findings were held in multivariate models.
• Patients initially diagnosed with in situ disease had more than a fivefold higher risk for second primary breast cancer compared with those initially diagnosed with invasive disease — 6.2% vs 1.2% at 5 years and 10.4% vs 2.1% at 10 years (hazard ratio, 5.25; P = .004). These findings were held in multivariate models (adjusted sub-hazard ratio [sHR], 5.61; 95% CI, 1.52-20.70) and among women without a pathogenic variant (adjusted sHR, 5.67; 95% CI, 1.54-20.90).
• The researchers also found a low risk for contralateral breast cancer among women without pathogenic variants, which could inform surgical decision-making.

IN PRACTICE:

Although the number of women positive for a germline pathogenic variant was small (n = 33) and “results should be interpreted cautiously,” the analysis signals “the importance of genetic testing” in younger breast cancer survivors to gauge their risk for a second primary breast cancer, the authors concluded. The authors added that their “finding of a higher risk of [second primary breast cancer] among those diagnosed with in situ primary [breast cancer] merits further investigation.”

SOURCE:

This study, led by Kristen D. Brantley, PhD, from Harvard T. H. Chan School of Public Health, Boston, was published online in JAMA Oncology.

LIMITATIONS:

A small number of second breast cancer events limited the authors’ ability to assess the effects of multiple risk factors together. Data on risk factors might be incomplete. About 9% of participants completed abbreviated questionnaires that did not include information on body mass index, alcohol, smoking, and family history. Frequencies of pathogenic variants besides BRCA1 and BRCA2 may be underestimated.

DISCLOSURES:

This study received no external funding. Four authors reported receiving grants or royalties outside this work. Other reported no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent study suggests that younger breast cancer survivors with a germline pathogenic variant or those with an initial diagnosis of in situ vs invasive primary breast cancer have a significantly higher risk for a second primary breast cancer.

METHODOLOGY:

• Women who are diagnosed with breast cancer at age 40 or younger are about two to three times more likely to develop second primary breast cancer compared with women who are older when first diagnosed.
• However, data are lacking on whether certain factors increase a woman’s risk for a second primary breast cancer.
• To classify the risk of developing a second primary breast cancer, the researchers evaluated a main cohort of 685 patients with stages 0-III breast cancer who were diagnosed at age 40 years or younger and had undergone unilateral mastectomy or lumpectomy as primary surgery between August 2006 and June 2015. The team also analyzed data on 547 younger women who had a bilateral mastectomy.
• The researchers assessed various breast cancer risk factors, including self-reported ethnicity, race, age, family history of breast or ovarian cancer, germline genetics, tumor stage, grade, and receptor status.
• The primary outcome was the diagnosis of a second primary breast cancer that occurred at least 6 months after the initial diagnosis of primary breast cancer.

TAKEAWAY:

• Among the 685 main study participants, 17 (2.5%) developed a second primary breast cancer (15 contralateral and 2 ipsilateral) over a median of 4.2 years since their primary diagnosis. The 5- and 10-year cumulative incidence of a second primary breast cancer was 1.5% and 2.6%, respectively.
• Overall, only 33 women were positive for a germline pathogenic variant, and having a pathogenic variant was associated with a fourfold higher risk for second primary breast cancer compared with noncarriers at 5 years (5.5% vs 1.3%) and at 10 years (8.9% vs 2.2%). These findings were held in multivariate models.
• Patients initially diagnosed with in situ disease had more than a fivefold higher risk for second primary breast cancer compared with those initially diagnosed with invasive disease — 6.2% vs 1.2% at 5 years and 10.4% vs 2.1% at 10 years (hazard ratio, 5.25; P = .004). These findings were held in multivariate models (adjusted sub-hazard ratio [sHR], 5.61; 95% CI, 1.52-20.70) and among women without a pathogenic variant (adjusted sHR, 5.67; 95% CI, 1.54-20.90).
• The researchers also found a low risk for contralateral breast cancer among women without pathogenic variants, which could inform surgical decision-making.

IN PRACTICE:

Although the number of women positive for a germline pathogenic variant was small (n = 33) and “results should be interpreted cautiously,” the analysis signals “the importance of genetic testing” in younger breast cancer survivors to gauge their risk for a second primary breast cancer, the authors concluded. The authors added that their “finding of a higher risk of [second primary breast cancer] among those diagnosed with in situ primary [breast cancer] merits further investigation.”

SOURCE:

This study, led by Kristen D. Brantley, PhD, from Harvard T. H. Chan School of Public Health, Boston, was published online in JAMA Oncology.

LIMITATIONS:

A small number of second breast cancer events limited the authors’ ability to assess the effects of multiple risk factors together. Data on risk factors might be incomplete. About 9% of participants completed abbreviated questionnaires that did not include information on body mass index, alcohol, smoking, and family history. Frequencies of pathogenic variants besides BRCA1 and BRCA2 may be underestimated.

DISCLOSURES:

This study received no external funding. Four authors reported receiving grants or royalties outside this work. Other reported no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

Because of climate change, heat waves, storms, heavy rainfalls, and floods are now occurring in areas that seldom experienced these phenomena before. “Extreme weather events are rare, but in terms of their extent, duration, and scale, they are unusual. And they are increasing due to climate change,” said Andrea Elmer, MD, an internal medicine and pulmonology specialist at the DKD Helios Clinic in Wiesbaden, Germany. She spoke at the Congress of the German Society for Pneumology and Respiratory Medicine.

Dr. Elmer referred to the 2023 status report by the Robert Koch Institute and the 2023 Synthesis Report by the Intergovernmental Panel on Climate Change, in which the likelihood of extreme weather events was acknowledged to be significantly higher than previously recognized. “Knowing about such extreme weather events is important to assess the consequences for our patients and to identify possible medical care needs,” said Dr. Elmer. She focused on the effects of platanus (plane tree) cough and thunderstorm asthma.
 

Platanus Cough

The severe symptoms of 40 students at a comprehensive school in Wiesbaden, including shortness of breath, coughing, and irritated eyes, led to a major operation involving the fire brigade and police on May 11, 2022. The symptoms worsened when the children left the building and waited in the schoolyard. Initially, a chemical attack with irritant gas was suspected because the school is located near an industrial area. There were no indications of a pollen cloud.

Eventually, doctors and firefighters found that the symptoms were caused by platanus cough, which is induced by the fine star-shaped hair found on young platanus leaves, bark, young branches, and buds. If strong winds move the leaves after prolonged dryness, these trichomes can break off when touched, creating platanus dust.

At that time, there were unusual climatic conditions. The temperature was 29 °C, it was dry, and wind gusts reached 50 km/h. The schoolyard was enclosed and densely planted with tall, old plane trees. Initial symptoms occurred in classrooms with open windows.

Twenty-five children had to be admitted to the hospital. Treatment included lorazepam and salbutamol. All students had normal oxygen levels, and the symptoms were reversed.
 

Cough or Allergy?

The clinical differential diagnosis for an allergy is quite simple, said Dr. Elmer. Platanus cough mainly shows symptoms of irritation, a feeling of a foreign body, and scratching in the eyes, throat, and nose. Coughing can also occur. In an allergy, there is often a runny nose and itching in the eyes and nose. Such allergic symptoms do not occur with platanus cough.

It should also be noted that the sensitization rates for a platanus allergy in Germany range between 5% and 11%. “Having so many platanus allergy sufferers in one place was relatively unlikely,” said Dr. Elmer.

She expects an increase in cases of platanus cough, especially in cities with dense construction, such as in narrow schoolyards. High concentrations of platanus dust can occur, especially when it is warm, dry, and windy. “Platanus cough does not occur every time we walk under plane trees. It strongly depends on warmth, dryness, and wind,” said Dr. Elmer.

Patients can protect themselves by avoiding skin and mucous membrane contact under appropriate climatic conditions and by wearing protective glasses and masks. Leaves and branches should not be swept but vacuumed. “Under no circumstances should plane trees be cut down. We need trees, especially in cities,” said Dr. Elmer. Moreover, the trichomes act as biofilters for air pollutants. In critical environments such as schoolyards, seasonal spraying of plane trees with a mixture of apple pectin and water can prevent the star hair from breaking off.
 

Thunderstorm Asthma

For patients with asthma, wildfires, storms, heavy rainfall, and thunderstorms can lead to exacerbations. Emergency room visits and hospital admissions generally increase after extreme weather events.

A study examining the consequences of the fires in California from 2004 to 2009, for example, reported that hospital visits related to asthma increased by 10.3%. Those related to respiratory problems increased by 3.3%. Infants and children up to age 5 years were most affected.

Thunderstorms are increasing because of global warming. Thunderstorm asthma arises under specific meteorological conditions. It typically occurs in patients with aeroallergies (eg, to pollen and fungal spores) in combination with thunderstorms and lightning. Large pollen grains, which normally remain in the upper airways, ascend into higher atmospheric layers and break apart due to updrafts. These very small particles are pushed back to ground level by downdrafts, enter the lower airways, and cause acute asthma.

Worldwide, cases of thunderstorm asthma are rare. About 30 events have been documented. Thunderstorm asthma was first observed in 1983 in Birmingham, England. Fungal spores were the trigger.

The most significant incident so far was a severe thunderstorm on November 21, 2016, in Melbourne, Australia. Worldwide attention was drawn to the storm because of an unusually high number of asthma cases. Within 30 hours, 3365 patients were admitted to emergency rooms. “This is also a high burden for a city with 4.6 million inhabitants,” said Dr. Elmer. Of the patients in Melbourne, 35 were admitted to the intensive care unit and 5 patients died.

Dr. Elmer calculated the corresponding number of patients for Wiesbaden and Mainz. “Assuming a population of 500,000 in this region, that would be 400 patients in emergency rooms within 30 hours, which would be a significant number.”

Such events are mainly observed in Australia, where two events per decade are expected. However, due to climate change, the risk could also increase in Europe, leading to more cases of thunderstorm asthma.
 

Risk Factors

The following environmental factors increase the risk:

• High pollen concentrations in the days before a thunderstorm
• Precipitation and high humidity, thunderstorms, and lightning
• Sudden temperature changes
• Increases in aeroallergen biomass and extreme weather events because of climate change

In Australia, grass pollen was often the trigger for thunderstorm asthma. In the United Kingdom, it was fungal spores. In Italy, olive pollen has a similar potential.

Patients with preexisting asthma, uncontrolled asthma, and high serum-specific immunoglobulin E levels are at risk. The risk is also increased for patients with poor compliance with inhaled steroid (ICS) therapy and for patients who have previously been hospitalized because of their asthma.

Patients with hay fever (ie, seasonal allergic rhinitis) have a significantly higher risk. As Dr. Elmer observed, 88% of patients in the emergency room in Melbourne had seasonal allergic rhinitis. “Fifty-seven percent of the patients in the emergency room did not have previously known asthma, but more than half showed symptoms indicating latent asthma. These patients had latent asthma but had not yet been diagnosed.”

Dr. Elmer emphasized how important it is not to underestimate mild asthma, which should be treated. For patients with hay fever, hyposensitization should be considered.
 

Reducing Risk

Many factors must come together for thunderstorm asthma to develop, according to Dr. Elmer. Because this convergence is difficult to predict, however, preparation and risk reduction are important. They consist of individual precautions and public health strategies.

The following steps can be taken at the individual level:

• Identify risk groups, including patients with allergic rhinitis and high serum-specific immunoglobulin E levels. Patients with hay fever benefit from hyposensitization.
• Avoid outdoor activities on risky days.
• Diagnose asthma, and do not underestimate mild asthma. Improve therapy compliance with ICS therapy and use maintenance and reliever therapy. This way, the patient automatically increases the steroid dose with increased symptoms and is better protected against exacerbations.
• Improve health literacy and understanding of asthma.

Thunderstorm asthma also affects healthcare professionals, Dr. Elmer warned. In Melbourne, 25% of responders themselves showed symptoms. Therefore, expect that some of these clinicians will also be unavailable.

Other steps are appropriate at the public health level. In addition to monitoring local pollen concentrations, one must identify risk groups, especially people working outdoors. “It is very difficult to predict an epidemic of thunderstorm asthma,” said Dr. Elmer. Therefore, it is important to increase awareness of the phenomenon and to develop an early warning system with emergency plans for patients and the healthcare system.

“Allergen immunotherapy is protective,” she added. “This has been well studied, and for Melbourne, it has been demonstrated. Patients with allergic rhinitis who had received immunotherapy were protected. These patients did not have to visit the emergency room. This shows that we can do something, and we should hyposensitize,” Dr. Elmer concluded.
 

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Because of climate change, heat waves, storms, heavy rainfalls, and floods are now occurring in areas that seldom experienced these phenomena before. “Extreme weather events are rare, but in terms of their extent, duration, and scale, they are unusual. And they are increasing due to climate change,” said Andrea Elmer, MD, an internal medicine and pulmonology specialist at the DKD Helios Clinic in Wiesbaden, Germany. She spoke at the Congress of the German Society for Pneumology and Respiratory Medicine.

Dr. Elmer referred to the 2023 status report by the Robert Koch Institute and the 2023 Synthesis Report by the Intergovernmental Panel on Climate Change, in which the likelihood of extreme weather events was acknowledged to be significantly higher than previously recognized. “Knowing about such extreme weather events is important to assess the consequences for our patients and to identify possible medical care needs,” said Dr. Elmer. She focused on the effects of platanus (plane tree) cough and thunderstorm asthma.
 

Platanus Cough

The severe symptoms of 40 students at a comprehensive school in Wiesbaden, including shortness of breath, coughing, and irritated eyes, led to a major operation involving the fire brigade and police on May 11, 2022. The symptoms worsened when the children left the building and waited in the schoolyard. Initially, a chemical attack with irritant gas was suspected because the school is located near an industrial area. There were no indications of a pollen cloud.

Eventually, doctors and firefighters found that the symptoms were caused by platanus cough, which is induced by the fine star-shaped hair found on young platanus leaves, bark, young branches, and buds. If strong winds move the leaves after prolonged dryness, these trichomes can break off when touched, creating platanus dust.

At that time, there were unusual climatic conditions. The temperature was 29 °C, it was dry, and wind gusts reached 50 km/h. The schoolyard was enclosed and densely planted with tall, old plane trees. Initial symptoms occurred in classrooms with open windows.

Twenty-five children had to be admitted to the hospital. Treatment included lorazepam and salbutamol. All students had normal oxygen levels, and the symptoms were reversed.
 

Cough or Allergy?

The clinical differential diagnosis for an allergy is quite simple, said Dr. Elmer. Platanus cough mainly shows symptoms of irritation, a feeling of a foreign body, and scratching in the eyes, throat, and nose. Coughing can also occur. In an allergy, there is often a runny nose and itching in the eyes and nose. Such allergic symptoms do not occur with platanus cough.

It should also be noted that the sensitization rates for a platanus allergy in Germany range between 5% and 11%. “Having so many platanus allergy sufferers in one place was relatively unlikely,” said Dr. Elmer.

She expects an increase in cases of platanus cough, especially in cities with dense construction, such as in narrow schoolyards. High concentrations of platanus dust can occur, especially when it is warm, dry, and windy. “Platanus cough does not occur every time we walk under plane trees. It strongly depends on warmth, dryness, and wind,” said Dr. Elmer.

Patients can protect themselves by avoiding skin and mucous membrane contact under appropriate climatic conditions and by wearing protective glasses and masks. Leaves and branches should not be swept but vacuumed. “Under no circumstances should plane trees be cut down. We need trees, especially in cities,” said Dr. Elmer. Moreover, the trichomes act as biofilters for air pollutants. In critical environments such as schoolyards, seasonal spraying of plane trees with a mixture of apple pectin and water can prevent the star hair from breaking off.
 

Thunderstorm Asthma

For patients with asthma, wildfires, storms, heavy rainfall, and thunderstorms can lead to exacerbations. Emergency room visits and hospital admissions generally increase after extreme weather events.

A study examining the consequences of the fires in California from 2004 to 2009, for example, reported that hospital visits related to asthma increased by 10.3%. Those related to respiratory problems increased by 3.3%. Infants and children up to age 5 years were most affected.

Thunderstorms are increasing because of global warming. Thunderstorm asthma arises under specific meteorological conditions. It typically occurs in patients with aeroallergies (eg, to pollen and fungal spores) in combination with thunderstorms and lightning. Large pollen grains, which normally remain in the upper airways, ascend into higher atmospheric layers and break apart due to updrafts. These very small particles are pushed back to ground level by downdrafts, enter the lower airways, and cause acute asthma.

Worldwide, cases of thunderstorm asthma are rare. About 30 events have been documented. Thunderstorm asthma was first observed in 1983 in Birmingham, England. Fungal spores were the trigger.

The most significant incident so far was a severe thunderstorm on November 21, 2016, in Melbourne, Australia. Worldwide attention was drawn to the storm because of an unusually high number of asthma cases. Within 30 hours, 3365 patients were admitted to emergency rooms. “This is also a high burden for a city with 4.6 million inhabitants,” said Dr. Elmer. Of the patients in Melbourne, 35 were admitted to the intensive care unit and 5 patients died.

Dr. Elmer calculated the corresponding number of patients for Wiesbaden and Mainz. “Assuming a population of 500,000 in this region, that would be 400 patients in emergency rooms within 30 hours, which would be a significant number.”

Such events are mainly observed in Australia, where two events per decade are expected. However, due to climate change, the risk could also increase in Europe, leading to more cases of thunderstorm asthma.
 

Risk Factors

The following environmental factors increase the risk:

• High pollen concentrations in the days before a thunderstorm
• Precipitation and high humidity, thunderstorms, and lightning
• Sudden temperature changes
• Increases in aeroallergen biomass and extreme weather events because of climate change

In Australia, grass pollen was often the trigger for thunderstorm asthma. In the United Kingdom, it was fungal spores. In Italy, olive pollen has a similar potential.

Patients with preexisting asthma, uncontrolled asthma, and high serum-specific immunoglobulin E levels are at risk. The risk is also increased for patients with poor compliance with inhaled steroid (ICS) therapy and for patients who have previously been hospitalized because of their asthma.

Patients with hay fever (ie, seasonal allergic rhinitis) have a significantly higher risk. As Dr. Elmer observed, 88% of patients in the emergency room in Melbourne had seasonal allergic rhinitis. “Fifty-seven percent of the patients in the emergency room did not have previously known asthma, but more than half showed symptoms indicating latent asthma. These patients had latent asthma but had not yet been diagnosed.”

Dr. Elmer emphasized how important it is not to underestimate mild asthma, which should be treated. For patients with hay fever, hyposensitization should be considered.
 

Reducing Risk

Many factors must come together for thunderstorm asthma to develop, according to Dr. Elmer. Because this convergence is difficult to predict, however, preparation and risk reduction are important. They consist of individual precautions and public health strategies.

The following steps can be taken at the individual level:

• Identify risk groups, including patients with allergic rhinitis and high serum-specific immunoglobulin E levels. Patients with hay fever benefit from hyposensitization.
• Avoid outdoor activities on risky days.
• Diagnose asthma, and do not underestimate mild asthma. Improve therapy compliance with ICS therapy and use maintenance and reliever therapy. This way, the patient automatically increases the steroid dose with increased symptoms and is better protected against exacerbations.
• Improve health literacy and understanding of asthma.

Thunderstorm asthma also affects healthcare professionals, Dr. Elmer warned. In Melbourne, 25% of responders themselves showed symptoms. Therefore, expect that some of these clinicians will also be unavailable.

Other steps are appropriate at the public health level. In addition to monitoring local pollen concentrations, one must identify risk groups, especially people working outdoors. “It is very difficult to predict an epidemic of thunderstorm asthma,” said Dr. Elmer. Therefore, it is important to increase awareness of the phenomenon and to develop an early warning system with emergency plans for patients and the healthcare system.

“Allergen immunotherapy is protective,” she added. “This has been well studied, and for Melbourne, it has been demonstrated. Patients with allergic rhinitis who had received immunotherapy were protected. These patients did not have to visit the emergency room. This shows that we can do something, and we should hyposensitize,” Dr. Elmer concluded.
 

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Because of climate change, heat waves, storms, heavy rainfalls, and floods are now occurring in areas that seldom experienced these phenomena before. “Extreme weather events are rare, but in terms of their extent, duration, and scale, they are unusual. And they are increasing due to climate change,” said Andrea Elmer, MD, an internal medicine and pulmonology specialist at the DKD Helios Clinic in Wiesbaden, Germany. She spoke at the Congress of the German Society for Pneumology and Respiratory Medicine.

Dr. Elmer referred to the 2023 status report by the Robert Koch Institute and the 2023 Synthesis Report by the Intergovernmental Panel on Climate Change, in which the likelihood of extreme weather events was acknowledged to be significantly higher than previously recognized. “Knowing about such extreme weather events is important to assess the consequences for our patients and to identify possible medical care needs,” said Dr. Elmer. She focused on the effects of platanus (plane tree) cough and thunderstorm asthma.
 

Platanus Cough

The severe symptoms of 40 students at a comprehensive school in Wiesbaden, including shortness of breath, coughing, and irritated eyes, led to a major operation involving the fire brigade and police on May 11, 2022. The symptoms worsened when the children left the building and waited in the schoolyard. Initially, a chemical attack with irritant gas was suspected because the school is located near an industrial area. There were no indications of a pollen cloud.

Eventually, doctors and firefighters found that the symptoms were caused by platanus cough, which is induced by the fine star-shaped hair found on young platanus leaves, bark, young branches, and buds. If strong winds move the leaves after prolonged dryness, these trichomes can break off when touched, creating platanus dust.

At that time, there were unusual climatic conditions. The temperature was 29 °C, it was dry, and wind gusts reached 50 km/h. The schoolyard was enclosed and densely planted with tall, old plane trees. Initial symptoms occurred in classrooms with open windows.

Twenty-five children had to be admitted to the hospital. Treatment included lorazepam and salbutamol. All students had normal oxygen levels, and the symptoms were reversed.
 

Cough or Allergy?

The clinical differential diagnosis for an allergy is quite simple, said Dr. Elmer. Platanus cough mainly shows symptoms of irritation, a feeling of a foreign body, and scratching in the eyes, throat, and nose. Coughing can also occur. In an allergy, there is often a runny nose and itching in the eyes and nose. Such allergic symptoms do not occur with platanus cough.

It should also be noted that the sensitization rates for a platanus allergy in Germany range between 5% and 11%. “Having so many platanus allergy sufferers in one place was relatively unlikely,” said Dr. Elmer.

She expects an increase in cases of platanus cough, especially in cities with dense construction, such as in narrow schoolyards. High concentrations of platanus dust can occur, especially when it is warm, dry, and windy. “Platanus cough does not occur every time we walk under plane trees. It strongly depends on warmth, dryness, and wind,” said Dr. Elmer.

Patients can protect themselves by avoiding skin and mucous membrane contact under appropriate climatic conditions and by wearing protective glasses and masks. Leaves and branches should not be swept but vacuumed. “Under no circumstances should plane trees be cut down. We need trees, especially in cities,” said Dr. Elmer. Moreover, the trichomes act as biofilters for air pollutants. In critical environments such as schoolyards, seasonal spraying of plane trees with a mixture of apple pectin and water can prevent the star hair from breaking off.
 

Thunderstorm Asthma

For patients with asthma, wildfires, storms, heavy rainfall, and thunderstorms can lead to exacerbations. Emergency room visits and hospital admissions generally increase after extreme weather events.

A study examining the consequences of the fires in California from 2004 to 2009, for example, reported that hospital visits related to asthma increased by 10.3%. Those related to respiratory problems increased by 3.3%. Infants and children up to age 5 years were most affected.

Thunderstorms are increasing because of global warming. Thunderstorm asthma arises under specific meteorological conditions. It typically occurs in patients with aeroallergies (eg, to pollen and fungal spores) in combination with thunderstorms and lightning. Large pollen grains, which normally remain in the upper airways, ascend into higher atmospheric layers and break apart due to updrafts. These very small particles are pushed back to ground level by downdrafts, enter the lower airways, and cause acute asthma.

Worldwide, cases of thunderstorm asthma are rare. About 30 events have been documented. Thunderstorm asthma was first observed in 1983 in Birmingham, England. Fungal spores were the trigger.

The most significant incident so far was a severe thunderstorm on November 21, 2016, in Melbourne, Australia. Worldwide attention was drawn to the storm because of an unusually high number of asthma cases. Within 30 hours, 3365 patients were admitted to emergency rooms. “This is also a high burden for a city with 4.6 million inhabitants,” said Dr. Elmer. Of the patients in Melbourne, 35 were admitted to the intensive care unit and 5 patients died.

Dr. Elmer calculated the corresponding number of patients for Wiesbaden and Mainz. “Assuming a population of 500,000 in this region, that would be 400 patients in emergency rooms within 30 hours, which would be a significant number.”

Such events are mainly observed in Australia, where two events per decade are expected. However, due to climate change, the risk could also increase in Europe, leading to more cases of thunderstorm asthma.
 

Risk Factors

The following environmental factors increase the risk:

• High pollen concentrations in the days before a thunderstorm
• Precipitation and high humidity, thunderstorms, and lightning
• Sudden temperature changes
• Increases in aeroallergen biomass and extreme weather events because of climate change

In Australia, grass pollen was often the trigger for thunderstorm asthma. In the United Kingdom, it was fungal spores. In Italy, olive pollen has a similar potential.

Patients with preexisting asthma, uncontrolled asthma, and high serum-specific immunoglobulin E levels are at risk. The risk is also increased for patients with poor compliance with inhaled steroid (ICS) therapy and for patients who have previously been hospitalized because of their asthma.

Patients with hay fever (ie, seasonal allergic rhinitis) have a significantly higher risk. As Dr. Elmer observed, 88% of patients in the emergency room in Melbourne had seasonal allergic rhinitis. “Fifty-seven percent of the patients in the emergency room did not have previously known asthma, but more than half showed symptoms indicating latent asthma. These patients had latent asthma but had not yet been diagnosed.”

Dr. Elmer emphasized how important it is not to underestimate mild asthma, which should be treated. For patients with hay fever, hyposensitization should be considered.
 

Reducing Risk

Many factors must come together for thunderstorm asthma to develop, according to Dr. Elmer. Because this convergence is difficult to predict, however, preparation and risk reduction are important. They consist of individual precautions and public health strategies.

The following steps can be taken at the individual level:

• Identify risk groups, including patients with allergic rhinitis and high serum-specific immunoglobulin E levels. Patients with hay fever benefit from hyposensitization.
• Avoid outdoor activities on risky days.
• Diagnose asthma, and do not underestimate mild asthma. Improve therapy compliance with ICS therapy and use maintenance and reliever therapy. This way, the patient automatically increases the steroid dose with increased symptoms and is better protected against exacerbations.
• Improve health literacy and understanding of asthma.

Thunderstorm asthma also affects healthcare professionals, Dr. Elmer warned. In Melbourne, 25% of responders themselves showed symptoms. Therefore, expect that some of these clinicians will also be unavailable.

Other steps are appropriate at the public health level. In addition to monitoring local pollen concentrations, one must identify risk groups, especially people working outdoors. “It is very difficult to predict an epidemic of thunderstorm asthma,” said Dr. Elmer. Therefore, it is important to increase awareness of the phenomenon and to develop an early warning system with emergency plans for patients and the healthcare system.

“Allergen immunotherapy is protective,” she added. “This has been well studied, and for Melbourne, it has been demonstrated. Patients with allergic rhinitis who had received immunotherapy were protected. These patients did not have to visit the emergency room. This shows that we can do something, and we should hyposensitize,” Dr. Elmer concluded.
 

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

DENVER — An interim analysis of an ongoing extension study supports the long-term safety and efficacy of the oral calcitonin gene-related peptide (CGRP) receptor antagonist atogepant (Qulipta, AbbVie) to prevent chronic and episodic migraine.

The data show that 70% of patients treated with atogepant 60 mg daily achieved at least a 50% reduction in monthly migraine days at weeks 13-16 and this was maintained over 48 weeks of treatment. 

“This is the first long-term study for assessing the safety and efficacy of a drug belonging to the gepant class, atogepant, used in the prevention of migraine in persons with episodic migraine who did not benefit from several previous preventive treatments or with chronic migraine,” said study investigator Cristina Tassorelli, MD, professor and chair of neurology, University of Pavia, Italy. 

“It shows consistency of efficacy over 48 weeks and confirms the known safety profile of atogepant reported in randomized controlled trials, without detecting any new signal with the open-label use over 1 year,” Dr. Tassorelli said.

The results were reported at the 2024 annual meeting of the American Academy of Neurology by Sait Ashina, MD, with the Comprehensive Headache Center at Beth Israel Deaconess Medical Center in Boston.
 

Novel Longer-Term Data

The extension study includes more than 500 patients who completed the phase 3 PROGRESS or ELEVATE randomized placebo-controlled trials of atogepant 60 mg once daily for prevention of episodic or chronic migraine. It will run for 156 weeks. 

Dr. Ashina reported safety and tolerability data at 52 weeks of treatment and efficacy data between 13 and 48 weeks of treatment. The mean duration of atogepant exposure was 496.5 days, and the mean number of migraine days at baseline was 14.5. 

With atogepant, monthly migraine days improved on average by 8.5 days at weeks 13-16, and this was consistent over 48 weeks, Dr. Ashina reported. Similar improvements were observed for monthly headache days and monthly acute medication use days.

In addition, 70% of patients achieved a 50% or greater reduction in monthly migraine days at weeks 13-16, and this was consistent during the 48 weeks of open-label treatment.

Overall safety results were consistent with the known safety profile of atogepant. “A small percentage of subjects (< 6%) discontinue the treatment because of side effects,” Dr. Tassorelli said. 

The most common treatment-emergent adverse events (≥ 5% of participants) were COVID-19 (28.7%), nasopharyngitis (10.9%), and constipation (8.2%).

As the first report of 1-year atogepant data, the results are “very encouraging” for patients and clinicians, Dr. Ashina said in wrapping up his presentation. 
 

Important Advance, but Not Transformative

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, noted that “[w]hile the anti-CGRP medications represent an important advancement in migraine treatment, the data suggests they have not necessarily transformed the landscape as dramatically as some may have expected. 

“The efficacy of the anti-CGRP drugs appears to be generally similar to previous preventive and mostly genericized treatments, offering modest but meaningful improvements in migraine frequency and severity for many patients,” Dr. Lakhan said.

“In terms of safety, the anti-CGRPs do seem to have a somewhat cleaner profile compared to earlier migraine preventives, which is certainly a positive. However, the long-term data is still emerging, so the full safety picture is not yet clear,” Dr. Lakhan added. 

“These medications are also associated with significantly higher overall healthcare costs compared to other treatment approaches. The substantial cost implications, both for patients and the healthcare system, deserve careful consideration as we assess their overall value and role in migraine care going forward,” Dr. Lakhan said.

Funding was provided by AbbVie. Several investigators have disclosed financial relationships with the company. Dr. Lakhan has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — An interim analysis of an ongoing extension study supports the long-term safety and efficacy of the oral calcitonin gene-related peptide (CGRP) receptor antagonist atogepant (Qulipta, AbbVie) to prevent chronic and episodic migraine.

The data show that 70% of patients treated with atogepant 60 mg daily achieved at least a 50% reduction in monthly migraine days at weeks 13-16 and this was maintained over 48 weeks of treatment. 

“This is the first long-term study for assessing the safety and efficacy of a drug belonging to the gepant class, atogepant, used in the prevention of migraine in persons with episodic migraine who did not benefit from several previous preventive treatments or with chronic migraine,” said study investigator Cristina Tassorelli, MD, professor and chair of neurology, University of Pavia, Italy. 

“It shows consistency of efficacy over 48 weeks and confirms the known safety profile of atogepant reported in randomized controlled trials, without detecting any new signal with the open-label use over 1 year,” Dr. Tassorelli said.

The results were reported at the 2024 annual meeting of the American Academy of Neurology by Sait Ashina, MD, with the Comprehensive Headache Center at Beth Israel Deaconess Medical Center in Boston.
 

Novel Longer-Term Data

The extension study includes more than 500 patients who completed the phase 3 PROGRESS or ELEVATE randomized placebo-controlled trials of atogepant 60 mg once daily for prevention of episodic or chronic migraine. It will run for 156 weeks. 

Dr. Ashina reported safety and tolerability data at 52 weeks of treatment and efficacy data between 13 and 48 weeks of treatment. The mean duration of atogepant exposure was 496.5 days, and the mean number of migraine days at baseline was 14.5. 

With atogepant, monthly migraine days improved on average by 8.5 days at weeks 13-16, and this was consistent over 48 weeks, Dr. Ashina reported. Similar improvements were observed for monthly headache days and monthly acute medication use days.

In addition, 70% of patients achieved a 50% or greater reduction in monthly migraine days at weeks 13-16, and this was consistent during the 48 weeks of open-label treatment.

Overall safety results were consistent with the known safety profile of atogepant. “A small percentage of subjects (< 6%) discontinue the treatment because of side effects,” Dr. Tassorelli said. 

The most common treatment-emergent adverse events (≥ 5% of participants) were COVID-19 (28.7%), nasopharyngitis (10.9%), and constipation (8.2%).

As the first report of 1-year atogepant data, the results are “very encouraging” for patients and clinicians, Dr. Ashina said in wrapping up his presentation. 
 

Important Advance, but Not Transformative

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, noted that “[w]hile the anti-CGRP medications represent an important advancement in migraine treatment, the data suggests they have not necessarily transformed the landscape as dramatically as some may have expected. 

“The efficacy of the anti-CGRP drugs appears to be generally similar to previous preventive and mostly genericized treatments, offering modest but meaningful improvements in migraine frequency and severity for many patients,” Dr. Lakhan said.

“In terms of safety, the anti-CGRPs do seem to have a somewhat cleaner profile compared to earlier migraine preventives, which is certainly a positive. However, the long-term data is still emerging, so the full safety picture is not yet clear,” Dr. Lakhan added. 

“These medications are also associated with significantly higher overall healthcare costs compared to other treatment approaches. The substantial cost implications, both for patients and the healthcare system, deserve careful consideration as we assess their overall value and role in migraine care going forward,” Dr. Lakhan said.

Funding was provided by AbbVie. Several investigators have disclosed financial relationships with the company. Dr. Lakhan has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — An interim analysis of an ongoing extension study supports the long-term safety and efficacy of the oral calcitonin gene-related peptide (CGRP) receptor antagonist atogepant (Qulipta, AbbVie) to prevent chronic and episodic migraine.

The data show that 70% of patients treated with atogepant 60 mg daily achieved at least a 50% reduction in monthly migraine days at weeks 13-16 and this was maintained over 48 weeks of treatment. 

“This is the first long-term study for assessing the safety and efficacy of a drug belonging to the gepant class, atogepant, used in the prevention of migraine in persons with episodic migraine who did not benefit from several previous preventive treatments or with chronic migraine,” said study investigator Cristina Tassorelli, MD, professor and chair of neurology, University of Pavia, Italy. 

“It shows consistency of efficacy over 48 weeks and confirms the known safety profile of atogepant reported in randomized controlled trials, without detecting any new signal with the open-label use over 1 year,” Dr. Tassorelli said.

The results were reported at the 2024 annual meeting of the American Academy of Neurology by Sait Ashina, MD, with the Comprehensive Headache Center at Beth Israel Deaconess Medical Center in Boston.
 

Novel Longer-Term Data

The extension study includes more than 500 patients who completed the phase 3 PROGRESS or ELEVATE randomized placebo-controlled trials of atogepant 60 mg once daily for prevention of episodic or chronic migraine. It will run for 156 weeks. 

Dr. Ashina reported safety and tolerability data at 52 weeks of treatment and efficacy data between 13 and 48 weeks of treatment. The mean duration of atogepant exposure was 496.5 days, and the mean number of migraine days at baseline was 14.5. 

With atogepant, monthly migraine days improved on average by 8.5 days at weeks 13-16, and this was consistent over 48 weeks, Dr. Ashina reported. Similar improvements were observed for monthly headache days and monthly acute medication use days.

In addition, 70% of patients achieved a 50% or greater reduction in monthly migraine days at weeks 13-16, and this was consistent during the 48 weeks of open-label treatment.

Overall safety results were consistent with the known safety profile of atogepant. “A small percentage of subjects (< 6%) discontinue the treatment because of side effects,” Dr. Tassorelli said. 

The most common treatment-emergent adverse events (≥ 5% of participants) were COVID-19 (28.7%), nasopharyngitis (10.9%), and constipation (8.2%).

As the first report of 1-year atogepant data, the results are “very encouraging” for patients and clinicians, Dr. Ashina said in wrapping up his presentation. 
 

Important Advance, but Not Transformative

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, noted that “[w]hile the anti-CGRP medications represent an important advancement in migraine treatment, the data suggests they have not necessarily transformed the landscape as dramatically as some may have expected. 

“The efficacy of the anti-CGRP drugs appears to be generally similar to previous preventive and mostly genericized treatments, offering modest but meaningful improvements in migraine frequency and severity for many patients,” Dr. Lakhan said.

“In terms of safety, the anti-CGRPs do seem to have a somewhat cleaner profile compared to earlier migraine preventives, which is certainly a positive. However, the long-term data is still emerging, so the full safety picture is not yet clear,” Dr. Lakhan added. 

“These medications are also associated with significantly higher overall healthcare costs compared to other treatment approaches. The substantial cost implications, both for patients and the healthcare system, deserve careful consideration as we assess their overall value and role in migraine care going forward,” Dr. Lakhan said.

Funding was provided by AbbVie. Several investigators have disclosed financial relationships with the company. Dr. Lakhan has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Is picky eating a problem? Well, yes and no. We have all had parents come to us with concerns about their child’s picky eating. At this point in history, we may feel grateful not to be facing another of the myriad of our child patients who are seriously overweight. So, should we just tell parents to not worry about it?

About 18% of young children are picky eaters; 7% of older children, even adolescents, are still picky eaters. The lack of variety eaten can limit growth and nutrition — in particular iron, and vitamins A and C — and limit them socially at older ages because people think they’re weird because they don’t eat typical foods. The crying, tantrums, gagging, even vomiting at the sight of certain foods that may be part of picky eating is hard on families and may make them all less welcome as guests/friends. We know that if eating issues are not addressed early, they tend to persist. For example, the fruit variety eaten is actually higher at 27 months than it is at 60 months without intervention. The fruit variety eaten at 2 years of age actually predicts what the child will eat when they’re 6-8 years old. About 40% of irregular eaters at age 5 are still irregular eaters at age 14.
 

Practical Advice for Dealing With Picky Eating

There are some things you may not know about this common condition that could change your approach. Infants in the first year of life will naturally turn away from the bottle or breast when sated. But babies need to learn to eat solids, and it is actually stressful. Pushing food out is their first response. If progressively more textured foods are not provided between 6 and 10 months of age, the baby may struggle with accepting solids subsequently. Babies around 8 months want to grab everything, including the spoon, and want to feed themselves. If parents push the spoon and thwart participation, refusal to be fed — the so-called Battle of the Spoon, the most common reason for stalled weight gain at this age — may ensue. Instead, caregivers need to give the baby his/her own spoon to hold, and allow finger feeding, no matter how messy! The parent’s job is to provide healthy food in reasonable amounts, and the child’s job is to eat what they want of it.

But, often suddenly, typically around 21 months, children may become picky. What happened? This is an age of perceiving differences and developing a strong sense of autonomy. Foods recently eaten without protest may now be dramatically rejected. Whole food categories or textures (think slimy) may be refused, especially vegetables and meat. Food cut in their preferred shape, their favorite brand, or delivered in the same cup may be demanded with alternatives refused. Foods that touch together on the plate or are covered with sauce may cause a tantrum. Some of this pickiness may reflect sensitive or intense temperament. Some food preferences are cultural (borscht?), or familial (no fruit), but others are nearly universal because of the heightened sensitivity of taste at this age (spinach, for example, as it contains oxalic acid).

Young children refusing foods can have their autonomy honored by providing only healthy foods on a low table to eat as they please without commentary, but continue seating them with family for meals, allowing exit (no return) from that meal if they choose. The desire to be social and removal of pressure results in eating regular meals within a week in most cases.

Any of these new reactions may persist for years. In most cases, picky eaters get adequate nutrition and grow fine without any intervention. Removing the power struggle or parental discord is generally more important than getting the child to accept a few more foods. Keep in mind that children may have picky eating because mealtime interactions are aversive or in order to get attention or a special menu — both reinforcers to avoid.

But there are some ways food selectivity can be reduced. Modeling eating a variety of foods can make a difference but is best done without comment (seen as pressure). Seeing heroes or peers eat the food that might otherwise be undesired by a picky eater (recall Popeye, who ate his spinach), is based on this. Having a peer come over who will eat that specific food (Mikey likes it!) can be very helpful.

There are other practices that can improve picky eating and are good general feeding advice. Maintaining three meals and three snacks, always at the table with adult company, can reduce grazing on perhaps tasty and filling foods or drinks (milk being the worst) that replace the drive for eating less desired foods once seated. Providing the child a multivitamin can help parents avoid showing panic or pressure when working to increase food variety. All the foods prepared for the family should be put on the plate to increase exposure, along with at least one item the child is known to eat. Family meals have many benefits (eg, language development), and it has been shown that children who sit at a meal for 20-30 minutes eat significantly more undesired fruits and vegetables than those seated for less time. Boredom helps with exploration!

Sometimes a new brand or new way of preparing a food that they currently won’t eat, or sprinkling a new food on a currently accepted food (eg, chocolate on a fruit) will encourage eating it. Adding a food similar to one they are already eating may help.

It is wise to avoid supplements, however. While nutritionally sound and supportive of growth, supplements are usually calorie dense, and they remove the drive to eat at meals, as well as not providing the variety of components needed to reduce selectivity.
 

Advice for Severe Cases

If picky eating is severe or growth is impaired, and the eating pattern does not respond to these adjustments and parent counseling, more may be needed. One of the main things known to increase the variety eaten is repeated tasting. Looks are not enough. A proven method includes giving praise and sticker rewards for eating a little piece of the same undesired vegetable/food presented to them each day for at least 14 days in a row. This method may expand the range of foods eaten as well as the range of those liked. Even a microscopic amount, the size of a grain of rice of an undesired food, if ingested regularly and repeatedly, will increase acceptance!

A feeding program for serious problems with food selectivity at Penn State has the child given A) a pea-sized amount of an undesired food and B) a bite-sized amount of an accepted food. The child is required to eat A in order to get B, plus a small drink. This is done repeatedly for about 10 minutes. If the child does not eat anything, they don’t get anything more until the next meal. An alternative to this is insisting on one bite per meal or one bite per day of an undesired food. One can also mix in, in increasing amounts, an undesired liquid into a desired liquid. While families travel far for this special program when selectivity is extreme, the “praise and sticker” method has been shown effective done at home.

In extreme cases of food selectivity or refusal, we need to consider medical problems as a potential cause, especially if choking, gagging, or vomiting occur or if there is poor weight gain or complications such as rash, abdominal pain, or diarrhea. An episode of food poisoning or an allergic reaction (anaphylaxis can present as diarrhea) can trigger onset of a lifelong aversion to that food. Omitting foods that have sickened a person is reasonable. Gastroesophageal reflux and eosinophilic esophagitis, oral-motor incoordination and choking, dental caries, tracheo-esophageal fistulas with aspiration, constipation, sensory issues, and sometimes lactose intolerance all may cause food refusal through the conditioned responses to the discomfort. Children with autism often have a combination of these factors producing severe food selectivity for which the above methods can be helpful.

Parents everywhere take feeding their children as one of their highest priorities. Along with empathy for their concern, understanding potential contributing factors and some practical prevention and intervention steps for picky eating can help you partner on what can be a long journey. On a positive note, you can reassure parents that studies also show that picky eaters are less likely to go on to be overweight!
 

Dr. Howard is assistant professor of pediatrics at The Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Is picky eating a problem? Well, yes and no. We have all had parents come to us with concerns about their child’s picky eating. At this point in history, we may feel grateful not to be facing another of the myriad of our child patients who are seriously overweight. So, should we just tell parents to not worry about it?

About 18% of young children are picky eaters; 7% of older children, even adolescents, are still picky eaters. The lack of variety eaten can limit growth and nutrition — in particular iron, and vitamins A and C — and limit them socially at older ages because people think they’re weird because they don’t eat typical foods. The crying, tantrums, gagging, even vomiting at the sight of certain foods that may be part of picky eating is hard on families and may make them all less welcome as guests/friends. We know that if eating issues are not addressed early, they tend to persist. For example, the fruit variety eaten is actually higher at 27 months than it is at 60 months without intervention. The fruit variety eaten at 2 years of age actually predicts what the child will eat when they’re 6-8 years old. About 40% of irregular eaters at age 5 are still irregular eaters at age 14.
 

Practical Advice for Dealing With Picky Eating

There are some things you may not know about this common condition that could change your approach. Infants in the first year of life will naturally turn away from the bottle or breast when sated. But babies need to learn to eat solids, and it is actually stressful. Pushing food out is their first response. If progressively more textured foods are not provided between 6 and 10 months of age, the baby may struggle with accepting solids subsequently. Babies around 8 months want to grab everything, including the spoon, and want to feed themselves. If parents push the spoon and thwart participation, refusal to be fed — the so-called Battle of the Spoon, the most common reason for stalled weight gain at this age — may ensue. Instead, caregivers need to give the baby his/her own spoon to hold, and allow finger feeding, no matter how messy! The parent’s job is to provide healthy food in reasonable amounts, and the child’s job is to eat what they want of it.

But, often suddenly, typically around 21 months, children may become picky. What happened? This is an age of perceiving differences and developing a strong sense of autonomy. Foods recently eaten without protest may now be dramatically rejected. Whole food categories or textures (think slimy) may be refused, especially vegetables and meat. Food cut in their preferred shape, their favorite brand, or delivered in the same cup may be demanded with alternatives refused. Foods that touch together on the plate or are covered with sauce may cause a tantrum. Some of this pickiness may reflect sensitive or intense temperament. Some food preferences are cultural (borscht?), or familial (no fruit), but others are nearly universal because of the heightened sensitivity of taste at this age (spinach, for example, as it contains oxalic acid).

Young children refusing foods can have their autonomy honored by providing only healthy foods on a low table to eat as they please without commentary, but continue seating them with family for meals, allowing exit (no return) from that meal if they choose. The desire to be social and removal of pressure results in eating regular meals within a week in most cases.

Any of these new reactions may persist for years. In most cases, picky eaters get adequate nutrition and grow fine without any intervention. Removing the power struggle or parental discord is generally more important than getting the child to accept a few more foods. Keep in mind that children may have picky eating because mealtime interactions are aversive or in order to get attention or a special menu — both reinforcers to avoid.

But there are some ways food selectivity can be reduced. Modeling eating a variety of foods can make a difference but is best done without comment (seen as pressure). Seeing heroes or peers eat the food that might otherwise be undesired by a picky eater (recall Popeye, who ate his spinach), is based on this. Having a peer come over who will eat that specific food (Mikey likes it!) can be very helpful.

There are other practices that can improve picky eating and are good general feeding advice. Maintaining three meals and three snacks, always at the table with adult company, can reduce grazing on perhaps tasty and filling foods or drinks (milk being the worst) that replace the drive for eating less desired foods once seated. Providing the child a multivitamin can help parents avoid showing panic or pressure when working to increase food variety. All the foods prepared for the family should be put on the plate to increase exposure, along with at least one item the child is known to eat. Family meals have many benefits (eg, language development), and it has been shown that children who sit at a meal for 20-30 minutes eat significantly more undesired fruits and vegetables than those seated for less time. Boredom helps with exploration!

Sometimes a new brand or new way of preparing a food that they currently won’t eat, or sprinkling a new food on a currently accepted food (eg, chocolate on a fruit) will encourage eating it. Adding a food similar to one they are already eating may help.

It is wise to avoid supplements, however. While nutritionally sound and supportive of growth, supplements are usually calorie dense, and they remove the drive to eat at meals, as well as not providing the variety of components needed to reduce selectivity.
 

Advice for Severe Cases

If picky eating is severe or growth is impaired, and the eating pattern does not respond to these adjustments and parent counseling, more may be needed. One of the main things known to increase the variety eaten is repeated tasting. Looks are not enough. A proven method includes giving praise and sticker rewards for eating a little piece of the same undesired vegetable/food presented to them each day for at least 14 days in a row. This method may expand the range of foods eaten as well as the range of those liked. Even a microscopic amount, the size of a grain of rice of an undesired food, if ingested regularly and repeatedly, will increase acceptance!

A feeding program for serious problems with food selectivity at Penn State has the child given A) a pea-sized amount of an undesired food and B) a bite-sized amount of an accepted food. The child is required to eat A in order to get B, plus a small drink. This is done repeatedly for about 10 minutes. If the child does not eat anything, they don’t get anything more until the next meal. An alternative to this is insisting on one bite per meal or one bite per day of an undesired food. One can also mix in, in increasing amounts, an undesired liquid into a desired liquid. While families travel far for this special program when selectivity is extreme, the “praise and sticker” method has been shown effective done at home.

In extreme cases of food selectivity or refusal, we need to consider medical problems as a potential cause, especially if choking, gagging, or vomiting occur or if there is poor weight gain or complications such as rash, abdominal pain, or diarrhea. An episode of food poisoning or an allergic reaction (anaphylaxis can present as diarrhea) can trigger onset of a lifelong aversion to that food. Omitting foods that have sickened a person is reasonable. Gastroesophageal reflux and eosinophilic esophagitis, oral-motor incoordination and choking, dental caries, tracheo-esophageal fistulas with aspiration, constipation, sensory issues, and sometimes lactose intolerance all may cause food refusal through the conditioned responses to the discomfort. Children with autism often have a combination of these factors producing severe food selectivity for which the above methods can be helpful.

Parents everywhere take feeding their children as one of their highest priorities. Along with empathy for their concern, understanding potential contributing factors and some practical prevention and intervention steps for picky eating can help you partner on what can be a long journey. On a positive note, you can reassure parents that studies also show that picky eaters are less likely to go on to be overweight!
 

Dr. Howard is assistant professor of pediatrics at The Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Is picky eating a problem? Well, yes and no. We have all had parents come to us with concerns about their child’s picky eating. At this point in history, we may feel grateful not to be facing another of the myriad of our child patients who are seriously overweight. So, should we just tell parents to not worry about it?

About 18% of young children are picky eaters; 7% of older children, even adolescents, are still picky eaters. The lack of variety eaten can limit growth and nutrition — in particular iron, and vitamins A and C — and limit them socially at older ages because people think they’re weird because they don’t eat typical foods. The crying, tantrums, gagging, even vomiting at the sight of certain foods that may be part of picky eating is hard on families and may make them all less welcome as guests/friends. We know that if eating issues are not addressed early, they tend to persist. For example, the fruit variety eaten is actually higher at 27 months than it is at 60 months without intervention. The fruit variety eaten at 2 years of age actually predicts what the child will eat when they’re 6-8 years old. About 40% of irregular eaters at age 5 are still irregular eaters at age 14.
 

Practical Advice for Dealing With Picky Eating

There are some things you may not know about this common condition that could change your approach. Infants in the first year of life will naturally turn away from the bottle or breast when sated. But babies need to learn to eat solids, and it is actually stressful. Pushing food out is their first response. If progressively more textured foods are not provided between 6 and 10 months of age, the baby may struggle with accepting solids subsequently. Babies around 8 months want to grab everything, including the spoon, and want to feed themselves. If parents push the spoon and thwart participation, refusal to be fed — the so-called Battle of the Spoon, the most common reason for stalled weight gain at this age — may ensue. Instead, caregivers need to give the baby his/her own spoon to hold, and allow finger feeding, no matter how messy! The parent’s job is to provide healthy food in reasonable amounts, and the child’s job is to eat what they want of it.

But, often suddenly, typically around 21 months, children may become picky. What happened? This is an age of perceiving differences and developing a strong sense of autonomy. Foods recently eaten without protest may now be dramatically rejected. Whole food categories or textures (think slimy) may be refused, especially vegetables and meat. Food cut in their preferred shape, their favorite brand, or delivered in the same cup may be demanded with alternatives refused. Foods that touch together on the plate or are covered with sauce may cause a tantrum. Some of this pickiness may reflect sensitive or intense temperament. Some food preferences are cultural (borscht?), or familial (no fruit), but others are nearly universal because of the heightened sensitivity of taste at this age (spinach, for example, as it contains oxalic acid).

Young children refusing foods can have their autonomy honored by providing only healthy foods on a low table to eat as they please without commentary, but continue seating them with family for meals, allowing exit (no return) from that meal if they choose. The desire to be social and removal of pressure results in eating regular meals within a week in most cases.

Any of these new reactions may persist for years. In most cases, picky eaters get adequate nutrition and grow fine without any intervention. Removing the power struggle or parental discord is generally more important than getting the child to accept a few more foods. Keep in mind that children may have picky eating because mealtime interactions are aversive or in order to get attention or a special menu — both reinforcers to avoid.

But there are some ways food selectivity can be reduced. Modeling eating a variety of foods can make a difference but is best done without comment (seen as pressure). Seeing heroes or peers eat the food that might otherwise be undesired by a picky eater (recall Popeye, who ate his spinach), is based on this. Having a peer come over who will eat that specific food (Mikey likes it!) can be very helpful.

There are other practices that can improve picky eating and are good general feeding advice. Maintaining three meals and three snacks, always at the table with adult company, can reduce grazing on perhaps tasty and filling foods or drinks (milk being the worst) that replace the drive for eating less desired foods once seated. Providing the child a multivitamin can help parents avoid showing panic or pressure when working to increase food variety. All the foods prepared for the family should be put on the plate to increase exposure, along with at least one item the child is known to eat. Family meals have many benefits (eg, language development), and it has been shown that children who sit at a meal for 20-30 minutes eat significantly more undesired fruits and vegetables than those seated for less time. Boredom helps with exploration!

Sometimes a new brand or new way of preparing a food that they currently won’t eat, or sprinkling a new food on a currently accepted food (eg, chocolate on a fruit) will encourage eating it. Adding a food similar to one they are already eating may help.

It is wise to avoid supplements, however. While nutritionally sound and supportive of growth, supplements are usually calorie dense, and they remove the drive to eat at meals, as well as not providing the variety of components needed to reduce selectivity.
 

Advice for Severe Cases

If picky eating is severe or growth is impaired, and the eating pattern does not respond to these adjustments and parent counseling, more may be needed. One of the main things known to increase the variety eaten is repeated tasting. Looks are not enough. A proven method includes giving praise and sticker rewards for eating a little piece of the same undesired vegetable/food presented to them each day for at least 14 days in a row. This method may expand the range of foods eaten as well as the range of those liked. Even a microscopic amount, the size of a grain of rice of an undesired food, if ingested regularly and repeatedly, will increase acceptance!

A feeding program for serious problems with food selectivity at Penn State has the child given A) a pea-sized amount of an undesired food and B) a bite-sized amount of an accepted food. The child is required to eat A in order to get B, plus a small drink. This is done repeatedly for about 10 minutes. If the child does not eat anything, they don’t get anything more until the next meal. An alternative to this is insisting on one bite per meal or one bite per day of an undesired food. One can also mix in, in increasing amounts, an undesired liquid into a desired liquid. While families travel far for this special program when selectivity is extreme, the “praise and sticker” method has been shown effective done at home.

In extreme cases of food selectivity or refusal, we need to consider medical problems as a potential cause, especially if choking, gagging, or vomiting occur or if there is poor weight gain or complications such as rash, abdominal pain, or diarrhea. An episode of food poisoning or an allergic reaction (anaphylaxis can present as diarrhea) can trigger onset of a lifelong aversion to that food. Omitting foods that have sickened a person is reasonable. Gastroesophageal reflux and eosinophilic esophagitis, oral-motor incoordination and choking, dental caries, tracheo-esophageal fistulas with aspiration, constipation, sensory issues, and sometimes lactose intolerance all may cause food refusal through the conditioned responses to the discomfort. Children with autism often have a combination of these factors producing severe food selectivity for which the above methods can be helpful.

Parents everywhere take feeding their children as one of their highest priorities. Along with empathy for their concern, understanding potential contributing factors and some practical prevention and intervention steps for picky eating can help you partner on what can be a long journey. On a positive note, you can reassure parents that studies also show that picky eaters are less likely to go on to be overweight!
 

Dr. Howard is assistant professor of pediatrics at The Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

On May 5, 2023, the director of the Centers for Disease Control and Prevention (CDC), Rochelle Walensky, in announcing her resignation after more than 2 years of dedicated service, wrote that she “took on this role … with the goal of leaving behind the dark days of the pandemic and moving the CDC — and public health — forward into a much better and more trusted place.”

Three times in the past 3 years I have written a Beyond the White Coat column emphasizing the importance of trust. Trust in the expertise of scientists. Trust in the integrity of medical research and public health institutions. Trust in the commitment of providers — doctors, nurses, therapists, and first responders — to shepherd us through the pandemic and other medical crises in our lives. This column is take four.

All human institutions have human imperfections. However, imperfect humans working together in community are more productive and more reliable than nihilism and political polarization. Underlying all of healthcare are compassion and honesty. Honesty means the truth, the whole truth, and nothing but the truth. Honesty is such a simple concept in the moral formation of children, but the concept has evolved aberrantly in the world of woke adults. There appear to be irresistible temptations to shade that truth for political gain. The dominant current mutation is the half-truth. One tells the part of the truth that appears to advance one’s own political aspirations and at the same time one omits or censors other viewpoints.

On April 17, 2023, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the American Psychiatric Association wrote an open letter to Congressional leaders advocating for transgender female students’ participation in girl’s and women’s sports. The letter was written “On behalf of the more than 165,000” members of those organizations, though public opinion polls show a majority of those members likely oppose the opinion expressed. The letter goes on to extol the benefits that sports might bring to transgender students, but it contains not one word acknowledging the negative impact that participation has on others. That is a half-truth.

The same half-truth methodology distorts dialogue about various therapies for gender dysphoria in children and young adults.

In April 2022, U.S. Assistant Secretary for Health Rachel Levine in an NPR interview declared that, “There is no argument about the value and importance of gender-affirming care.” That might be a half-truth, since I could not locate U.S. specialists who dare to go on record questioning the party line of the World Professional Association for Transgender Health. However, Dr. Levine’s dismissal of any dissent is bizarre since in the prior 2 years multiple countries, including Australia, New Zealand, Sweden, Finland, and the United Kingdom had all issued reports questioning and even rescinding the practices that evolved since the 2012 WPATH guidance. Their main concerns included 1) the marked increase in incidence of gender dysphoria first manifesting in tween and early teenage girls, 2) the inadequate access to mental health screening before considering transitioning, 3) the long-term risks of puberty blockers particularly to bone density, and 4) the low quality of evidence supporting a measurable reduction in suicide rates. There may be reasonable counterarguments to each of those concerns, but a high ranking U.S. government official labeling all those international reports as “no argument” does not produce high quality decision making and does not foster the public’s trust.

Indeed, the public in many cases has decided its elected legislators are more trustworthy on these topics than the medical organizations. As I wrote the first draft of this column, the Missouri state legislators had passed a bill banning gender-affirming health care for transgender minors. They also passed a bill preventing participation of transgender females in women’s sports. Per reckoning by CBS News in the summer of 2023, 16 states had recently enacted laws restricting gender-affirming care and 22 states had restricted transgender participation in sports.

In 2022, I wrote a column claiming that suppressing viewpoints and debate leads to exploding spaceships. I believe the current legislative carnage is just such an explosion. It harms children.

The AAP has experts in advocacy. I am no expert in political advocacy. Perhaps politics has to be played by different rules where half-truths are normalized. Criminal law and advertising use those rules. But this explosion of vitriol and legislative intrusion into medicine should prompt everyone to reassess the use of one-sided advocacy in public and professional circles in healthcare. I want to be associated with a profession that uses evidence-based medicine that is not corrupted with political agendas. I want to be associated with a profession known for telling the whole truth.

In a society that is increasingly polarized, I want to embrace the advice of John Stuart Mill, a 19th century English philosopher best known for utilitarianism, which is often expressed as “the greatest good for the greatest number.” Mr. Mill also wrote on social theory, liberty, and even some early feminist theory. His 1859 work, On Liberty, chapter II, asserts: “He who knows only his own side of the case, knows little of that. His reasons may be good, and no one may have been able to refute them. But if he is equally unable to refute the reasons on the opposite side; if he does not so much as know what they are, he has no ground for preferring either opinion.”

Mr. Mill did not like half-truths.
 

It’s About Trust

My column is not the instrument to debate the use of hormones as puberty blockers or the fairness of transgender women participating in women’s sports. Those judgments will be rendered by others. I may report on those deliberations, but my column’s emphasis is on how professionals, and their organizations, go about making those determinations

For instance, the National Health Service in the United Kingdom spent 2 years reassessing transgender care for children and in October 2022 released a draft proposal to reduce and limit the aggressive therapies. On June 9, 2023, the NHS fully enacted those changes. Puberty blockers for gender dysphoria would be used only in experimental trials. In April 2024 the NHS began implementing those changes, joining other European countries that have imposed similar restrictions.

Similarly, the debate about transgender participation in women’s sports has continued to rage for years. On April 8, 2024, the National Association of Intercollegiate Athletics passed a resolution that bans almost all transgender participation in NAIA-regulated intercollegiate women’s sports. Dance and cheerleading are exceptions. Participation is still permissible at the intramural level. The NCAA has different rules.

Go to those sources to learn more substance for those debates. This column is about trust.

A major problem currently facing medicine is the public’s trust in expertise. That trust had been seriously weakened before the pandemic and was repeatedly wounded during the pandemic with arguments over masks, vaccines, and shutdowns. It needs repair.

A parent bringing a baby to a pediatrician’s office needs to trust that physician for the relationship to work. This is especially true for pediatric hospitalists that do not have the opportunity that office-based pediatricians have to build rapport with a family over years. At a recent university conference on diversity, equity, and inclusivity, one female rabbi stated, “I cannot be rabbi to everybody.” I agreed, but as a medical professional, sometimes I must be.

Telling half-truths harms the public’s trust in their personal physicians and in the medical establishment. Once people suspect an organization is making decisions based on ideology rather than science, credibility is lost and difficult to recover.

Let us stop telling half-truths. Let us stop suppressing dialogue. Truth can never be completely captured by humans, but if one side of an issue is suppressed by cancel culture, censorship, accusations of homophobia, or threat of cultural war, the search for truth is severely impaired.

Let us, as medical professionals, adopt Stephen Covey’s habit number 5, “Seek first to understand, then to be understood.” Empower voices. Listen to all stakeholders. And when we finally do speak, remember John Stuart Mill and tell the whole truth.
 

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

On May 5, 2023, the director of the Centers for Disease Control and Prevention (CDC), Rochelle Walensky, in announcing her resignation after more than 2 years of dedicated service, wrote that she “took on this role … with the goal of leaving behind the dark days of the pandemic and moving the CDC — and public health — forward into a much better and more trusted place.”

Three times in the past 3 years I have written a Beyond the White Coat column emphasizing the importance of trust. Trust in the expertise of scientists. Trust in the integrity of medical research and public health institutions. Trust in the commitment of providers — doctors, nurses, therapists, and first responders — to shepherd us through the pandemic and other medical crises in our lives. This column is take four.

All human institutions have human imperfections. However, imperfect humans working together in community are more productive and more reliable than nihilism and political polarization. Underlying all of healthcare are compassion and honesty. Honesty means the truth, the whole truth, and nothing but the truth. Honesty is such a simple concept in the moral formation of children, but the concept has evolved aberrantly in the world of woke adults. There appear to be irresistible temptations to shade that truth for political gain. The dominant current mutation is the half-truth. One tells the part of the truth that appears to advance one’s own political aspirations and at the same time one omits or censors other viewpoints.

On April 17, 2023, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the American Psychiatric Association wrote an open letter to Congressional leaders advocating for transgender female students’ participation in girl’s and women’s sports. The letter was written “On behalf of the more than 165,000” members of those organizations, though public opinion polls show a majority of those members likely oppose the opinion expressed. The letter goes on to extol the benefits that sports might bring to transgender students, but it contains not one word acknowledging the negative impact that participation has on others. That is a half-truth.

The same half-truth methodology distorts dialogue about various therapies for gender dysphoria in children and young adults.

In April 2022, U.S. Assistant Secretary for Health Rachel Levine in an NPR interview declared that, “There is no argument about the value and importance of gender-affirming care.” That might be a half-truth, since I could not locate U.S. specialists who dare to go on record questioning the party line of the World Professional Association for Transgender Health. However, Dr. Levine’s dismissal of any dissent is bizarre since in the prior 2 years multiple countries, including Australia, New Zealand, Sweden, Finland, and the United Kingdom had all issued reports questioning and even rescinding the practices that evolved since the 2012 WPATH guidance. Their main concerns included 1) the marked increase in incidence of gender dysphoria first manifesting in tween and early teenage girls, 2) the inadequate access to mental health screening before considering transitioning, 3) the long-term risks of puberty blockers particularly to bone density, and 4) the low quality of evidence supporting a measurable reduction in suicide rates. There may be reasonable counterarguments to each of those concerns, but a high ranking U.S. government official labeling all those international reports as “no argument” does not produce high quality decision making and does not foster the public’s trust.

Indeed, the public in many cases has decided its elected legislators are more trustworthy on these topics than the medical organizations. As I wrote the first draft of this column, the Missouri state legislators had passed a bill banning gender-affirming health care for transgender minors. They also passed a bill preventing participation of transgender females in women’s sports. Per reckoning by CBS News in the summer of 2023, 16 states had recently enacted laws restricting gender-affirming care and 22 states had restricted transgender participation in sports.

In 2022, I wrote a column claiming that suppressing viewpoints and debate leads to exploding spaceships. I believe the current legislative carnage is just such an explosion. It harms children.

The AAP has experts in advocacy. I am no expert in political advocacy. Perhaps politics has to be played by different rules where half-truths are normalized. Criminal law and advertising use those rules. But this explosion of vitriol and legislative intrusion into medicine should prompt everyone to reassess the use of one-sided advocacy in public and professional circles in healthcare. I want to be associated with a profession that uses evidence-based medicine that is not corrupted with political agendas. I want to be associated with a profession known for telling the whole truth.

In a society that is increasingly polarized, I want to embrace the advice of John Stuart Mill, a 19th century English philosopher best known for utilitarianism, which is often expressed as “the greatest good for the greatest number.” Mr. Mill also wrote on social theory, liberty, and even some early feminist theory. His 1859 work, On Liberty, chapter II, asserts: “He who knows only his own side of the case, knows little of that. His reasons may be good, and no one may have been able to refute them. But if he is equally unable to refute the reasons on the opposite side; if he does not so much as know what they are, he has no ground for preferring either opinion.”

Mr. Mill did not like half-truths.
 

It’s About Trust

My column is not the instrument to debate the use of hormones as puberty blockers or the fairness of transgender women participating in women’s sports. Those judgments will be rendered by others. I may report on those deliberations, but my column’s emphasis is on how professionals, and their organizations, go about making those determinations

For instance, the National Health Service in the United Kingdom spent 2 years reassessing transgender care for children and in October 2022 released a draft proposal to reduce and limit the aggressive therapies. On June 9, 2023, the NHS fully enacted those changes. Puberty blockers for gender dysphoria would be used only in experimental trials. In April 2024 the NHS began implementing those changes, joining other European countries that have imposed similar restrictions.

Similarly, the debate about transgender participation in women’s sports has continued to rage for years. On April 8, 2024, the National Association of Intercollegiate Athletics passed a resolution that bans almost all transgender participation in NAIA-regulated intercollegiate women’s sports. Dance and cheerleading are exceptions. Participation is still permissible at the intramural level. The NCAA has different rules.

Go to those sources to learn more substance for those debates. This column is about trust.

A major problem currently facing medicine is the public’s trust in expertise. That trust had been seriously weakened before the pandemic and was repeatedly wounded during the pandemic with arguments over masks, vaccines, and shutdowns. It needs repair.

A parent bringing a baby to a pediatrician’s office needs to trust that physician for the relationship to work. This is especially true for pediatric hospitalists that do not have the opportunity that office-based pediatricians have to build rapport with a family over years. At a recent university conference on diversity, equity, and inclusivity, one female rabbi stated, “I cannot be rabbi to everybody.” I agreed, but as a medical professional, sometimes I must be.

Telling half-truths harms the public’s trust in their personal physicians and in the medical establishment. Once people suspect an organization is making decisions based on ideology rather than science, credibility is lost and difficult to recover.

Let us stop telling half-truths. Let us stop suppressing dialogue. Truth can never be completely captured by humans, but if one side of an issue is suppressed by cancel culture, censorship, accusations of homophobia, or threat of cultural war, the search for truth is severely impaired.

Let us, as medical professionals, adopt Stephen Covey’s habit number 5, “Seek first to understand, then to be understood.” Empower voices. Listen to all stakeholders. And when we finally do speak, remember John Stuart Mill and tell the whole truth.
 

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

On May 5, 2023, the director of the Centers for Disease Control and Prevention (CDC), Rochelle Walensky, in announcing her resignation after more than 2 years of dedicated service, wrote that she “took on this role … with the goal of leaving behind the dark days of the pandemic and moving the CDC — and public health — forward into a much better and more trusted place.”

Three times in the past 3 years I have written a Beyond the White Coat column emphasizing the importance of trust. Trust in the expertise of scientists. Trust in the integrity of medical research and public health institutions. Trust in the commitment of providers — doctors, nurses, therapists, and first responders — to shepherd us through the pandemic and other medical crises in our lives. This column is take four.

All human institutions have human imperfections. However, imperfect humans working together in community are more productive and more reliable than nihilism and political polarization. Underlying all of healthcare are compassion and honesty. Honesty means the truth, the whole truth, and nothing but the truth. Honesty is such a simple concept in the moral formation of children, but the concept has evolved aberrantly in the world of woke adults. There appear to be irresistible temptations to shade that truth for political gain. The dominant current mutation is the half-truth. One tells the part of the truth that appears to advance one’s own political aspirations and at the same time one omits or censors other viewpoints.

On April 17, 2023, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the American Psychiatric Association wrote an open letter to Congressional leaders advocating for transgender female students’ participation in girl’s and women’s sports. The letter was written “On behalf of the more than 165,000” members of those organizations, though public opinion polls show a majority of those members likely oppose the opinion expressed. The letter goes on to extol the benefits that sports might bring to transgender students, but it contains not one word acknowledging the negative impact that participation has on others. That is a half-truth.

The same half-truth methodology distorts dialogue about various therapies for gender dysphoria in children and young adults.

In April 2022, U.S. Assistant Secretary for Health Rachel Levine in an NPR interview declared that, “There is no argument about the value and importance of gender-affirming care.” That might be a half-truth, since I could not locate U.S. specialists who dare to go on record questioning the party line of the World Professional Association for Transgender Health. However, Dr. Levine’s dismissal of any dissent is bizarre since in the prior 2 years multiple countries, including Australia, New Zealand, Sweden, Finland, and the United Kingdom had all issued reports questioning and even rescinding the practices that evolved since the 2012 WPATH guidance. Their main concerns included 1) the marked increase in incidence of gender dysphoria first manifesting in tween and early teenage girls, 2) the inadequate access to mental health screening before considering transitioning, 3) the long-term risks of puberty blockers particularly to bone density, and 4) the low quality of evidence supporting a measurable reduction in suicide rates. There may be reasonable counterarguments to each of those concerns, but a high ranking U.S. government official labeling all those international reports as “no argument” does not produce high quality decision making and does not foster the public’s trust.

Indeed, the public in many cases has decided its elected legislators are more trustworthy on these topics than the medical organizations. As I wrote the first draft of this column, the Missouri state legislators had passed a bill banning gender-affirming health care for transgender minors. They also passed a bill preventing participation of transgender females in women’s sports. Per reckoning by CBS News in the summer of 2023, 16 states had recently enacted laws restricting gender-affirming care and 22 states had restricted transgender participation in sports.

In 2022, I wrote a column claiming that suppressing viewpoints and debate leads to exploding spaceships. I believe the current legislative carnage is just such an explosion. It harms children.

The AAP has experts in advocacy. I am no expert in political advocacy. Perhaps politics has to be played by different rules where half-truths are normalized. Criminal law and advertising use those rules. But this explosion of vitriol and legislative intrusion into medicine should prompt everyone to reassess the use of one-sided advocacy in public and professional circles in healthcare. I want to be associated with a profession that uses evidence-based medicine that is not corrupted with political agendas. I want to be associated with a profession known for telling the whole truth.

In a society that is increasingly polarized, I want to embrace the advice of John Stuart Mill, a 19th century English philosopher best known for utilitarianism, which is often expressed as “the greatest good for the greatest number.” Mr. Mill also wrote on social theory, liberty, and even some early feminist theory. His 1859 work, On Liberty, chapter II, asserts: “He who knows only his own side of the case, knows little of that. His reasons may be good, and no one may have been able to refute them. But if he is equally unable to refute the reasons on the opposite side; if he does not so much as know what they are, he has no ground for preferring either opinion.”

Mr. Mill did not like half-truths.
 

It’s About Trust

My column is not the instrument to debate the use of hormones as puberty blockers or the fairness of transgender women participating in women’s sports. Those judgments will be rendered by others. I may report on those deliberations, but my column’s emphasis is on how professionals, and their organizations, go about making those determinations

For instance, the National Health Service in the United Kingdom spent 2 years reassessing transgender care for children and in October 2022 released a draft proposal to reduce and limit the aggressive therapies. On June 9, 2023, the NHS fully enacted those changes. Puberty blockers for gender dysphoria would be used only in experimental trials. In April 2024 the NHS began implementing those changes, joining other European countries that have imposed similar restrictions.

Similarly, the debate about transgender participation in women’s sports has continued to rage for years. On April 8, 2024, the National Association of Intercollegiate Athletics passed a resolution that bans almost all transgender participation in NAIA-regulated intercollegiate women’s sports. Dance and cheerleading are exceptions. Participation is still permissible at the intramural level. The NCAA has different rules.

Go to those sources to learn more substance for those debates. This column is about trust.

A major problem currently facing medicine is the public’s trust in expertise. That trust had been seriously weakened before the pandemic and was repeatedly wounded during the pandemic with arguments over masks, vaccines, and shutdowns. It needs repair.

A parent bringing a baby to a pediatrician’s office needs to trust that physician for the relationship to work. This is especially true for pediatric hospitalists that do not have the opportunity that office-based pediatricians have to build rapport with a family over years. At a recent university conference on diversity, equity, and inclusivity, one female rabbi stated, “I cannot be rabbi to everybody.” I agreed, but as a medical professional, sometimes I must be.

Telling half-truths harms the public’s trust in their personal physicians and in the medical establishment. Once people suspect an organization is making decisions based on ideology rather than science, credibility is lost and difficult to recover.

Let us stop telling half-truths. Let us stop suppressing dialogue. Truth can never be completely captured by humans, but if one side of an issue is suppressed by cancel culture, censorship, accusations of homophobia, or threat of cultural war, the search for truth is severely impaired.

Let us, as medical professionals, adopt Stephen Covey’s habit number 5, “Seek first to understand, then to be understood.” Empower voices. Listen to all stakeholders. And when we finally do speak, remember John Stuart Mill and tell the whole truth.
 

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

Imagine going to see your physician and being mistreated for who you are. For LGBTQ patients, this is an everyday reality. According to a new Kaiser Family Foundation report, 33% of LGBT adults experienced unfair or disrespectful treatment from their physician or other healthcare provider compared with only 15% of their non-LGBT counterparts.¹ LGBTQ children and adolescents are also more likely to experience discrimination from their physicians or other healthcare providers compared with their non-LGBTQ counterparts.

Statistics such as this underscore the importance of ensuring our offices and staff are as welcoming as possible to our LGBTQ patients. When patients feel unwelcome, it can have serious consequences for their health. In a 2022 report, the Center for American Progress found that 23% of LGBTQ patients, and 37% of transgender patients, postponed medically necessary care out of fear that they would experience discrimination in the healthcare setting.² This compares with 7% of their non-LGBTQ counterparts. In addition, 7% of LGBTQ patients said that their provider refused to see them due to their actual or perceived sexual orientation. While this may not be a problem in major urban areas where there are many physicians or other healthcare providers to see, in rural areas this could lead to loss of access to medically necessary care or require long travel times.

UT Southwestern Medical Center

This is not just an adult care problem. In their 2023 LGBTQ+ Youth Report, the Human Rights Campaign found that only 35.9% of LGBTQ+ youth were out to some or all of their doctors and 35.8% of transgender youth were out to some or all of their doctors.³ This could be due to fear of discrimination from their physician, in addition to possible concerns about loss of confidentiality if the physician were to tell their parent about their sexual orientation and/or gender identity. As of the time of the writing of this article, no state requires a physician to “out” their minor patients to their parent(s) or guardian(s). Therefore, it is important to respect the trust that your patient places in your confidentiality. As their physician, you may be the only adult to know about a patient’s sexual orientation and/or gender identity. Research shows that acceptance of one’s gender identity by at least one healthcare professional reduces the odds of a past-year suicide attempt by 32%.⁴

As of the time of the writing of this article, 10 states have laws that allow medical professionals to decline services to patients who are, or are perceived to be, LGBTQ based on their sincerely held religious beliefs. These laws directly conflict with our ethical obligations as physicians to care for all patients, regardless of their race, gender, culture, sexuality, gender identity, or religion. In fact, the American Medical Association Code of Medical Ethics states that physicians must “respect basic civil liberties and not discriminate against individuals in deciding whether to enter into a professional relationship with a new patient” and “take care that their actions do not discriminate against or unduly burden individual patients or populations of patients and do not adversely affect patient or public trust.” This requires all of us to examine our implicit biases and treat all patients with the dignity and respect that they deserve.
 

Dr. Cooper is assistant professor of pediatrics at University of Texas Southwestern, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas.

References

1. Montero A et al. LGBT Adults’ Experiences With Discrimination and Health Care Disparities: Findings From the KFF Survey of Racism, Discrimination, and Health. KFF 2024 Apr 2.

2. Medina C and Mahowald L. Discrimination and Barriers to Well-Being: The State of the LGBTQI+ Community in 2022. Center for American Progress. 2023, Jan 12.

3. Goldberg SK et al. 2023 LGBTQ+ Youth Report. Human Rights Campaign Foundation. 2023 Aug.

4. Price MN and Green AE. Association of Gender Identity Acceptance With Fewer Suicide Attempts Among Transgender and Nonbinary Youth. Transgend Health. 2023 Feb 8;8(1):56-63. doi: 10.1089/trgh.2021.0079.

Imagine going to see your physician and being mistreated for who you are. For LGBTQ patients, this is an everyday reality. According to a new Kaiser Family Foundation report, 33% of LGBT adults experienced unfair or disrespectful treatment from their physician or other healthcare provider compared with only 15% of their non-LGBT counterparts.¹ LGBTQ children and adolescents are also more likely to experience discrimination from their physicians or other healthcare providers compared with their non-LGBTQ counterparts.

Statistics such as this underscore the importance of ensuring our offices and staff are as welcoming as possible to our LGBTQ patients. When patients feel unwelcome, it can have serious consequences for their health. In a 2022 report, the Center for American Progress found that 23% of LGBTQ patients, and 37% of transgender patients, postponed medically necessary care out of fear that they would experience discrimination in the healthcare setting.² This compares with 7% of their non-LGBTQ counterparts. In addition, 7% of LGBTQ patients said that their provider refused to see them due to their actual or perceived sexual orientation. While this may not be a problem in major urban areas where there are many physicians or other healthcare providers to see, in rural areas this could lead to loss of access to medically necessary care or require long travel times.

UT Southwestern Medical Center

This is not just an adult care problem. In their 2023 LGBTQ+ Youth Report, the Human Rights Campaign found that only 35.9% of LGBTQ+ youth were out to some or all of their doctors and 35.8% of transgender youth were out to some or all of their doctors.³ This could be due to fear of discrimination from their physician, in addition to possible concerns about loss of confidentiality if the physician were to tell their parent about their sexual orientation and/or gender identity. As of the time of the writing of this article, no state requires a physician to “out” their minor patients to their parent(s) or guardian(s). Therefore, it is important to respect the trust that your patient places in your confidentiality. As their physician, you may be the only adult to know about a patient’s sexual orientation and/or gender identity. Research shows that acceptance of one’s gender identity by at least one healthcare professional reduces the odds of a past-year suicide attempt by 32%.⁴

As of the time of the writing of this article, 10 states have laws that allow medical professionals to decline services to patients who are, or are perceived to be, LGBTQ based on their sincerely held religious beliefs. These laws directly conflict with our ethical obligations as physicians to care for all patients, regardless of their race, gender, culture, sexuality, gender identity, or religion. In fact, the American Medical Association Code of Medical Ethics states that physicians must “respect basic civil liberties and not discriminate against individuals in deciding whether to enter into a professional relationship with a new patient” and “take care that their actions do not discriminate against or unduly burden individual patients or populations of patients and do not adversely affect patient or public trust.” This requires all of us to examine our implicit biases and treat all patients with the dignity and respect that they deserve.
 

Dr. Cooper is assistant professor of pediatrics at University of Texas Southwestern, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas.

References

1. Montero A et al. LGBT Adults’ Experiences With Discrimination and Health Care Disparities: Findings From the KFF Survey of Racism, Discrimination, and Health. KFF 2024 Apr 2.

2. Medina C and Mahowald L. Discrimination and Barriers to Well-Being: The State of the LGBTQI+ Community in 2022. Center for American Progress. 2023, Jan 12.

3. Goldberg SK et al. 2023 LGBTQ+ Youth Report. Human Rights Campaign Foundation. 2023 Aug.

4. Price MN and Green AE. Association of Gender Identity Acceptance With Fewer Suicide Attempts Among Transgender and Nonbinary Youth. Transgend Health. 2023 Feb 8;8(1):56-63. doi: 10.1089/trgh.2021.0079.

Imagine going to see your physician and being mistreated for who you are. For LGBTQ patients, this is an everyday reality. According to a new Kaiser Family Foundation report, 33% of LGBT adults experienced unfair or disrespectful treatment from their physician or other healthcare provider compared with only 15% of their non-LGBT counterparts.¹ LGBTQ children and adolescents are also more likely to experience discrimination from their physicians or other healthcare providers compared with their non-LGBTQ counterparts.

Statistics such as this underscore the importance of ensuring our offices and staff are as welcoming as possible to our LGBTQ patients. When patients feel unwelcome, it can have serious consequences for their health. In a 2022 report, the Center for American Progress found that 23% of LGBTQ patients, and 37% of transgender patients, postponed medically necessary care out of fear that they would experience discrimination in the healthcare setting.² This compares with 7% of their non-LGBTQ counterparts. In addition, 7% of LGBTQ patients said that their provider refused to see them due to their actual or perceived sexual orientation. While this may not be a problem in major urban areas where there are many physicians or other healthcare providers to see, in rural areas this could lead to loss of access to medically necessary care or require long travel times.

UT Southwestern Medical Center

This is not just an adult care problem. In their 2023 LGBTQ+ Youth Report, the Human Rights Campaign found that only 35.9% of LGBTQ+ youth were out to some or all of their doctors and 35.8% of transgender youth were out to some or all of their doctors.³ This could be due to fear of discrimination from their physician, in addition to possible concerns about loss of confidentiality if the physician were to tell their parent about their sexual orientation and/or gender identity. As of the time of the writing of this article, no state requires a physician to “out” their minor patients to their parent(s) or guardian(s). Therefore, it is important to respect the trust that your patient places in your confidentiality. As their physician, you may be the only adult to know about a patient’s sexual orientation and/or gender identity. Research shows that acceptance of one’s gender identity by at least one healthcare professional reduces the odds of a past-year suicide attempt by 32%.⁴

As of the time of the writing of this article, 10 states have laws that allow medical professionals to decline services to patients who are, or are perceived to be, LGBTQ based on their sincerely held religious beliefs. These laws directly conflict with our ethical obligations as physicians to care for all patients, regardless of their race, gender, culture, sexuality, gender identity, or religion. In fact, the American Medical Association Code of Medical Ethics states that physicians must “respect basic civil liberties and not discriminate against individuals in deciding whether to enter into a professional relationship with a new patient” and “take care that their actions do not discriminate against or unduly burden individual patients or populations of patients and do not adversely affect patient or public trust.” This requires all of us to examine our implicit biases and treat all patients with the dignity and respect that they deserve.
 

Dr. Cooper is assistant professor of pediatrics at University of Texas Southwestern, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas.

References

1. Montero A et al. LGBT Adults’ Experiences With Discrimination and Health Care Disparities: Findings From the KFF Survey of Racism, Discrimination, and Health. KFF 2024 Apr 2.

2. Medina C and Mahowald L. Discrimination and Barriers to Well-Being: The State of the LGBTQI+ Community in 2022. Center for American Progress. 2023, Jan 12.

3. Goldberg SK et al. 2023 LGBTQ+ Youth Report. Human Rights Campaign Foundation. 2023 Aug.

4. Price MN and Green AE. Association of Gender Identity Acceptance With Fewer Suicide Attempts Among Transgender and Nonbinary Youth. Transgend Health. 2023 Feb 8;8(1):56-63. doi: 10.1089/trgh.2021.0079.