News

COPENHAGEN — Growing evidence supports the use of highly effective disease-modifying therapies for children with multiple sclerosis (MS). However, only few of these medications are licensed for pediatric use, indicating it may be time to reconsider the standard treatment approach for this patient population.

Treatments for pediatric-onset MS have mostly been used off-label until the recent approvals of fingolimod, dimethyl fumarate, and teriflunomide. Typically, children with MS start with moderately effective therapies, while more potent options are reserved for those who don’t respond.

However, recent research suggests this may not be the most effective treatment strategy for this patient population. Several studies suggesting impressive treatment responses to highly effective therapies (HETs) in children were presented at the 2024 ECTRIMS annual meeting.

In one study, initiating monoclonal antibody treatment during childhood was associated with reduced disability into early adulthood and beyond.

“Our findings are a strong argument for rethinking current treatment guidelines,” said study investigator Sifat Sharmin, PhD, The University of Melbourne, Australia.

“By allowing earlier access to highly effective treatments, we can significantly enhance the quality of life for children with MS and reduce the burden of long-term disability,” she added.

In another presentation, Yael Hacohen, MD, Great Ormond Street Hospital, London, England, noted that the use of these more effective monoclonal antibody therapies in children with MS has been associated with some improvements in Expanded Disability Status Scale (EDSS) scores after 2 or 3 years of treatment.

Maybe this is a sign that “this is a population that can repair, in contrast to adult patients,” she wondered.

MS is primarily a disease of adults, but pediatric MS accounts for up to 5% of all cases. Children with MS tend to have much more active disease than adults, Dr. Hacohen explained. However, they also tend to recover from attacks more quickly with little disability, which sometimes causes diagnostic delays.

A pediatrician or family doctor will often dismiss pins and needles or blurred vision that only lasts a couple of days and won’t send the patient for an MRI, she said. But on MRI, pediatric patients with MS often have multiple lesions, even though they may have had very few symptoms. The EDSS may not change very much, but there can still be significant brain atrophy.

Over the past 20 years, there’s been an explosion of new disease-modifying treatments for MS, but these high-efficacy treatments, such as antibody therapies, are often not prescribed until the patient reaches the age of 18 years, both Dr. Sharmin and Dr. Hacohen pointed out.

“We need to get some of these medications approved for use in children,” Dr. Hacohen said.
 

Slowed Disability

In her presentation, Dr. Sharmin reported an observational study that included 282 patients younger than 18 years at MS onset identified from the French MS Registry, the Italian MS Register, and the Global MSBase Registry.

Of these, 110 (39%) had initiated therapy with ocrelizumab, rituximab, or natalizumab early in the disease course between ages 12 and 17 years and 172 (61%) had initiated treatment with one of these agents at ages 20-22 years.

The primary outcome was the difference in EDSS scores from baseline (at age 18 years) to ages 23-27 years between those who had started treatment with one of these agents early and those who had started late.

At the baseline of age 18 years, the median EDSS score was 1.5 in the early group and 1.3 in the late group. Median follow-up time was 10.8 years.

The data were adjusted for baseline differences in factors such as sex, age at symptom onset, time from onset to clinically definite MS, and the number of relapses (using inverse probability treatment weighting based on propensity scores).

Results showed that between ages 23 and 27 years, disability was a 0.57 step lower in the early group than in the late group. The mean absolute differences in EDSS from baseline were 0.40 in the early group and 0.95 in the late group. This benefit of early treatment persisted throughout the rest of the follow-up period.

The substantially lower risk of progressing to higher disability levels in the early treatment group was particularly evident in the moderate disability range, where further progression was reduced by up to 97%, Dr. Sharmin noted.

“Starting these highly effective therapies, before the onset of significant neurological impairments, appears crucial for preserving neurological function in children with relapsing-remitting MS over the long term,” she said.

These findings highlight the critical importance of early intervention in pediatric-onset MS, she concluded.

The researchers are planning further work to generate more evidence to support the proactive treatment of pediatric-onset MS, with a particular focus on assessing the long-term risks for immunosuppressive therapies in this population.
 

Ocrelizumab Experience in Children

Dr. Hacohen reported on a UK cohort of children with MS treated with ocrelizumab, with 66 patients having more than 12 months of follow-up. Of these, only four patients had relapses, and there was no evidence of disease activity in 94% patients.

“We’ve stopped doing relapse clinic because they really don’t relapse,” Dr. Hacohen reported.

“This has completely changed our practice in pediatric MS,” she said. Twice a year, patients come in to have pre-infusion bloods and clinical assessments and then return a month later for treatment.

“They only have to come to the hospital for 4 days a year, and the rest of the time, they can forget they have MS,” said Dr. Hacohen.

In terms of complications, one patient in the UK cohort developed enterovirus meningitis but recovered completely, and two patients had hypogammaglobulinemia and were changed to an extended interval or to a different agent.

Dr. Hacohen cautioned that hypogammaglobulinemia — a condition in which immunoglobulin levels are below normal — is “something that hypothetically we should maybe be more worried about in the pediatric population, particularly as these patients are more likely to be on anti-CD20 therapies for a much longer time.”

She said this complication tends to happen after about 4 or 5 years of treatment. “If we start seeing IgG levels dropping, we need to come up with a plan about extending the dosing interval. We need clinical trials to look at this.”

Dr. Hacohen also drew attention to the issue of vaccinations not being effective in patients on anti-CD20 antibody therapy, which could be a particular problem in children.

However, given that vaccinations do seem to be effective in patients taking natalizumab, pediatric patients with highly active disease could receive the drug for 3-6 months while receiving vaccines and then switched over to ocrelizumab, she said.

Giving natalizumab for such a short period is not believed to have a high risk of developing JCV antibodies, she added.

In another presentation, Brenda Banwell, MD, Johns Hopkins Children’s Center, Baltimore, reported new data from an early study (OPERETTA 1) with ocrelizumab in pediatric relapsing-remitting MS showing a safety profile similar to that observed in adults. The suggested dose is 300 mg for children under 35 kg and 600 mg for adults over 35 kg, administered every 24 weeks. These doses will be further investigated in the ongoing phase III OPERETTA 2 trial.

Dr. Sharmin received a postdoctoral fellowship from MS Australia. The OPERETTA studies were sponsored by F. Hoffmann-La Roche. Dr. Banwell served as a consultant to Roche. Dr. Hacohen reported no relevant disclosures.
 

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

COPENHAGEN — Growing evidence supports the use of highly effective disease-modifying therapies for children with multiple sclerosis (MS). However, only few of these medications are licensed for pediatric use, indicating it may be time to reconsider the standard treatment approach for this patient population.

Treatments for pediatric-onset MS have mostly been used off-label until the recent approvals of fingolimod, dimethyl fumarate, and teriflunomide. Typically, children with MS start with moderately effective therapies, while more potent options are reserved for those who don’t respond.

However, recent research suggests this may not be the most effective treatment strategy for this patient population. Several studies suggesting impressive treatment responses to highly effective therapies (HETs) in children were presented at the 2024 ECTRIMS annual meeting.

In one study, initiating monoclonal antibody treatment during childhood was associated with reduced disability into early adulthood and beyond.

“Our findings are a strong argument for rethinking current treatment guidelines,” said study investigator Sifat Sharmin, PhD, The University of Melbourne, Australia.

“By allowing earlier access to highly effective treatments, we can significantly enhance the quality of life for children with MS and reduce the burden of long-term disability,” she added.

In another presentation, Yael Hacohen, MD, Great Ormond Street Hospital, London, England, noted that the use of these more effective monoclonal antibody therapies in children with MS has been associated with some improvements in Expanded Disability Status Scale (EDSS) scores after 2 or 3 years of treatment.

Maybe this is a sign that “this is a population that can repair, in contrast to adult patients,” she wondered.

MS is primarily a disease of adults, but pediatric MS accounts for up to 5% of all cases. Children with MS tend to have much more active disease than adults, Dr. Hacohen explained. However, they also tend to recover from attacks more quickly with little disability, which sometimes causes diagnostic delays.

A pediatrician or family doctor will often dismiss pins and needles or blurred vision that only lasts a couple of days and won’t send the patient for an MRI, she said. But on MRI, pediatric patients with MS often have multiple lesions, even though they may have had very few symptoms. The EDSS may not change very much, but there can still be significant brain atrophy.

Over the past 20 years, there’s been an explosion of new disease-modifying treatments for MS, but these high-efficacy treatments, such as antibody therapies, are often not prescribed until the patient reaches the age of 18 years, both Dr. Sharmin and Dr. Hacohen pointed out.

“We need to get some of these medications approved for use in children,” Dr. Hacohen said.
 

Slowed Disability

In her presentation, Dr. Sharmin reported an observational study that included 282 patients younger than 18 years at MS onset identified from the French MS Registry, the Italian MS Register, and the Global MSBase Registry.

Of these, 110 (39%) had initiated therapy with ocrelizumab, rituximab, or natalizumab early in the disease course between ages 12 and 17 years and 172 (61%) had initiated treatment with one of these agents at ages 20-22 years.

The primary outcome was the difference in EDSS scores from baseline (at age 18 years) to ages 23-27 years between those who had started treatment with one of these agents early and those who had started late.

At the baseline of age 18 years, the median EDSS score was 1.5 in the early group and 1.3 in the late group. Median follow-up time was 10.8 years.

The data were adjusted for baseline differences in factors such as sex, age at symptom onset, time from onset to clinically definite MS, and the number of relapses (using inverse probability treatment weighting based on propensity scores).

Results showed that between ages 23 and 27 years, disability was a 0.57 step lower in the early group than in the late group. The mean absolute differences in EDSS from baseline were 0.40 in the early group and 0.95 in the late group. This benefit of early treatment persisted throughout the rest of the follow-up period.

The substantially lower risk of progressing to higher disability levels in the early treatment group was particularly evident in the moderate disability range, where further progression was reduced by up to 97%, Dr. Sharmin noted.

“Starting these highly effective therapies, before the onset of significant neurological impairments, appears crucial for preserving neurological function in children with relapsing-remitting MS over the long term,” she said.

These findings highlight the critical importance of early intervention in pediatric-onset MS, she concluded.

The researchers are planning further work to generate more evidence to support the proactive treatment of pediatric-onset MS, with a particular focus on assessing the long-term risks for immunosuppressive therapies in this population.
 

Ocrelizumab Experience in Children

Dr. Hacohen reported on a UK cohort of children with MS treated with ocrelizumab, with 66 patients having more than 12 months of follow-up. Of these, only four patients had relapses, and there was no evidence of disease activity in 94% patients.

“We’ve stopped doing relapse clinic because they really don’t relapse,” Dr. Hacohen reported.

“This has completely changed our practice in pediatric MS,” she said. Twice a year, patients come in to have pre-infusion bloods and clinical assessments and then return a month later for treatment.

“They only have to come to the hospital for 4 days a year, and the rest of the time, they can forget they have MS,” said Dr. Hacohen.

In terms of complications, one patient in the UK cohort developed enterovirus meningitis but recovered completely, and two patients had hypogammaglobulinemia and were changed to an extended interval or to a different agent.

Dr. Hacohen cautioned that hypogammaglobulinemia — a condition in which immunoglobulin levels are below normal — is “something that hypothetically we should maybe be more worried about in the pediatric population, particularly as these patients are more likely to be on anti-CD20 therapies for a much longer time.”

She said this complication tends to happen after about 4 or 5 years of treatment. “If we start seeing IgG levels dropping, we need to come up with a plan about extending the dosing interval. We need clinical trials to look at this.”

Dr. Hacohen also drew attention to the issue of vaccinations not being effective in patients on anti-CD20 antibody therapy, which could be a particular problem in children.

However, given that vaccinations do seem to be effective in patients taking natalizumab, pediatric patients with highly active disease could receive the drug for 3-6 months while receiving vaccines and then switched over to ocrelizumab, she said.

Giving natalizumab for such a short period is not believed to have a high risk of developing JCV antibodies, she added.

In another presentation, Brenda Banwell, MD, Johns Hopkins Children’s Center, Baltimore, reported new data from an early study (OPERETTA 1) with ocrelizumab in pediatric relapsing-remitting MS showing a safety profile similar to that observed in adults. The suggested dose is 300 mg for children under 35 kg and 600 mg for adults over 35 kg, administered every 24 weeks. These doses will be further investigated in the ongoing phase III OPERETTA 2 trial.

Dr. Sharmin received a postdoctoral fellowship from MS Australia. The OPERETTA studies were sponsored by F. Hoffmann-La Roche. Dr. Banwell served as a consultant to Roche. Dr. Hacohen reported no relevant disclosures.
 

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

COPENHAGEN — Growing evidence supports the use of highly effective disease-modifying therapies for children with multiple sclerosis (MS). However, only few of these medications are licensed for pediatric use, indicating it may be time to reconsider the standard treatment approach for this patient population.

Treatments for pediatric-onset MS have mostly been used off-label until the recent approvals of fingolimod, dimethyl fumarate, and teriflunomide. Typically, children with MS start with moderately effective therapies, while more potent options are reserved for those who don’t respond.

However, recent research suggests this may not be the most effective treatment strategy for this patient population. Several studies suggesting impressive treatment responses to highly effective therapies (HETs) in children were presented at the 2024 ECTRIMS annual meeting.

In one study, initiating monoclonal antibody treatment during childhood was associated with reduced disability into early adulthood and beyond.

“Our findings are a strong argument for rethinking current treatment guidelines,” said study investigator Sifat Sharmin, PhD, The University of Melbourne, Australia.

“By allowing earlier access to highly effective treatments, we can significantly enhance the quality of life for children with MS and reduce the burden of long-term disability,” she added.

In another presentation, Yael Hacohen, MD, Great Ormond Street Hospital, London, England, noted that the use of these more effective monoclonal antibody therapies in children with MS has been associated with some improvements in Expanded Disability Status Scale (EDSS) scores after 2 or 3 years of treatment.

Maybe this is a sign that “this is a population that can repair, in contrast to adult patients,” she wondered.

MS is primarily a disease of adults, but pediatric MS accounts for up to 5% of all cases. Children with MS tend to have much more active disease than adults, Dr. Hacohen explained. However, they also tend to recover from attacks more quickly with little disability, which sometimes causes diagnostic delays.

A pediatrician or family doctor will often dismiss pins and needles or blurred vision that only lasts a couple of days and won’t send the patient for an MRI, she said. But on MRI, pediatric patients with MS often have multiple lesions, even though they may have had very few symptoms. The EDSS may not change very much, but there can still be significant brain atrophy.

Over the past 20 years, there’s been an explosion of new disease-modifying treatments for MS, but these high-efficacy treatments, such as antibody therapies, are often not prescribed until the patient reaches the age of 18 years, both Dr. Sharmin and Dr. Hacohen pointed out.

“We need to get some of these medications approved for use in children,” Dr. Hacohen said.
 

Slowed Disability

In her presentation, Dr. Sharmin reported an observational study that included 282 patients younger than 18 years at MS onset identified from the French MS Registry, the Italian MS Register, and the Global MSBase Registry.

Of these, 110 (39%) had initiated therapy with ocrelizumab, rituximab, or natalizumab early in the disease course between ages 12 and 17 years and 172 (61%) had initiated treatment with one of these agents at ages 20-22 years.

The primary outcome was the difference in EDSS scores from baseline (at age 18 years) to ages 23-27 years between those who had started treatment with one of these agents early and those who had started late.

At the baseline of age 18 years, the median EDSS score was 1.5 in the early group and 1.3 in the late group. Median follow-up time was 10.8 years.

The data were adjusted for baseline differences in factors such as sex, age at symptom onset, time from onset to clinically definite MS, and the number of relapses (using inverse probability treatment weighting based on propensity scores).

Results showed that between ages 23 and 27 years, disability was a 0.57 step lower in the early group than in the late group. The mean absolute differences in EDSS from baseline were 0.40 in the early group and 0.95 in the late group. This benefit of early treatment persisted throughout the rest of the follow-up period.

The substantially lower risk of progressing to higher disability levels in the early treatment group was particularly evident in the moderate disability range, where further progression was reduced by up to 97%, Dr. Sharmin noted.

“Starting these highly effective therapies, before the onset of significant neurological impairments, appears crucial for preserving neurological function in children with relapsing-remitting MS over the long term,” she said.

These findings highlight the critical importance of early intervention in pediatric-onset MS, she concluded.

The researchers are planning further work to generate more evidence to support the proactive treatment of pediatric-onset MS, with a particular focus on assessing the long-term risks for immunosuppressive therapies in this population.
 

Ocrelizumab Experience in Children

Dr. Hacohen reported on a UK cohort of children with MS treated with ocrelizumab, with 66 patients having more than 12 months of follow-up. Of these, only four patients had relapses, and there was no evidence of disease activity in 94% patients.

“We’ve stopped doing relapse clinic because they really don’t relapse,” Dr. Hacohen reported.

“This has completely changed our practice in pediatric MS,” she said. Twice a year, patients come in to have pre-infusion bloods and clinical assessments and then return a month later for treatment.

“They only have to come to the hospital for 4 days a year, and the rest of the time, they can forget they have MS,” said Dr. Hacohen.

In terms of complications, one patient in the UK cohort developed enterovirus meningitis but recovered completely, and two patients had hypogammaglobulinemia and were changed to an extended interval or to a different agent.

Dr. Hacohen cautioned that hypogammaglobulinemia — a condition in which immunoglobulin levels are below normal — is “something that hypothetically we should maybe be more worried about in the pediatric population, particularly as these patients are more likely to be on anti-CD20 therapies for a much longer time.”

She said this complication tends to happen after about 4 or 5 years of treatment. “If we start seeing IgG levels dropping, we need to come up with a plan about extending the dosing interval. We need clinical trials to look at this.”

Dr. Hacohen also drew attention to the issue of vaccinations not being effective in patients on anti-CD20 antibody therapy, which could be a particular problem in children.

However, given that vaccinations do seem to be effective in patients taking natalizumab, pediatric patients with highly active disease could receive the drug for 3-6 months while receiving vaccines and then switched over to ocrelizumab, she said.

Giving natalizumab for such a short period is not believed to have a high risk of developing JCV antibodies, she added.

In another presentation, Brenda Banwell, MD, Johns Hopkins Children’s Center, Baltimore, reported new data from an early study (OPERETTA 1) with ocrelizumab in pediatric relapsing-remitting MS showing a safety profile similar to that observed in adults. The suggested dose is 300 mg for children under 35 kg and 600 mg for adults over 35 kg, administered every 24 weeks. These doses will be further investigated in the ongoing phase III OPERETTA 2 trial.

Dr. Sharmin received a postdoctoral fellowship from MS Australia. The OPERETTA studies were sponsored by F. Hoffmann-La Roche. Dr. Banwell served as a consultant to Roche. Dr. Hacohen reported no relevant disclosures.
 

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

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

PHILADELPHIA — The investigational agent ecopipam reduces tic severity in children and adolescents with Tourette syndrome without exacerbating common psychiatric comorbidities, results of a new analysis suggest.

As previously reported, the first-in-class dopamine-1 (D1) receptor antagonist reduced the primary endpoint of tic severity scores by 30% compared with placebo among 149 patients in the 12-week, phase 2b D1AMOND trial. 

What was unknown, however, is whether ecopipam would affect the comorbidities of attention-deficit/hyperactivity disorder (ADHD), anxiety, obsessive-compulsive disorder (OCD), and depression that were present in two thirds of participants.

The two key findings in this post hoc analysis were “first, that patients with a nonmotor diagnosis like depression or ADHD did not do any worse in terms of tic efficacy; and second, we didn’t find any evidence that any of the nonmotor symptoms of Tourette’s got worse with ecopipam,” said study investigator Donald Gilbert, MD, professor of pediatrics and neurology at University of Cincinnati Children’s Hospital Medical Center.

Dr. Gilbert presented the results at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024. 
 

No Worsening of ADHD Symptoms

Tourette syndrome affects approximately 1 in 160 children between 5 and 17 years of age in the United States, data from the Tourette Association of America show. Research has shown that 85% of patients with Tourette syndrome will have a co-occurring psychiatric condition. 

Guidelines recommend Comprehensive Behavioral Intervention for Tics (CBIT) as first-line treatment for Tourette syndrome, but cost and access are barriers. The only currently approved medications to treat Tourette syndrome are antipsychotics that act on the D2 receptor, but their use is limited by the potential for weight gain, metabolic changes, drug-induced movement disorders, and risk for suicidality, said Dr. Gilbert. 

The D1AMOND study randomly assigned patients aged 6-17 years with Tourette syndrome and a Yale Global Tic Severity Total Tic Scale score of at least 20 to receive a target steady-state dose of 2 mg/kg/d of oral ecopipam or placebo for a 4-week titration period, followed by an 8-week treatment phase before being tapered off the study drug. 

Patients were allowed to remain on medications without D2-receptor blocking activity for anxiety, OCD, and ADHD if the dosage was stable for 4 weeks before screening and not specifically prescribed for tics. 

A mixed model for repeated measures was used to assess changes in several scales administered at baseline and at weeks 4, 6, 8, and 12: the Swanson, Nolan, and Pelham Teacher and Parent Rating Scale (SNAP-IV); Pediatric Anxiety Rating Scale; Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), and Children’s Depression Rating Scale–Revised (CDRS-R). 

In patients with a co-occurring psychiatric condition, no significant differences were found over time between ecopipam and placebo in terms of SNAP-IV (-4.4; P = .45), Pediatric Anxiety Rating Scale (1.0; P = .62), CDRS-R (-3.2; P = .65), or CY-BOCS (-0.7; P = .76) scores.

For ADHD, the most frequent comorbidity, scores trended lower in the ecopipam group but were not significantly different from those in the placebo group. “We found no evidence that ecopipam worsened ADHD symptoms,” Dr. Gilbert said.
 

No Weight Gain

Suicidal ideation was reported during the dosing period in eight patients in the placebo group and none in the ecopipam group. One patient treated with ecopipam had multiple depressive episodes and dropped out of the study on day 79. Ecopipam was discontinued in another patient because of anxiety. 

Notably, there was more weight gain in the placebo group than in the ecopipam group (2.4 kg vs 1.8 kg) by 12 weeks. No shifts from baseline were seen in blood glucose, A1c, total cholesterol, or triglycerides in either group. 

The lack of weight gain with ecopipam is important, Dr. Gilbert stressed. “Medicines that block D2 so often cause weight gain, and a lot of our patients, unfortunately, can be heavier already,” he explained. “We don’t want to make that worse or put them at a long-term risk of type 2 diabetes.”  

For patients with more severe disease, we really “do need something else besides D2-blockers in our tool kit,” he added. 

Commenting on the study, Tanya Simuni, MD, co-moderator of the session and director of the Parkinson’s Disease and Movement Disorders Center, Northwestern Feinberg School of Medicine, Chicago, said the aim of assessing D1-directed medications is to reduce the negative impact of traditional antipsychotics with a theoretical benefit on hyperkinetic movement.

But the most important thing that they’ve shown is that “there was no negative effect, no liability for the nonmotor manifestations of Tourette’s. That is important because Tourette’s is not a pure motor syndrome, and psychiatric manifestations in a lot of cases are associated with more disease-related quality of life impairment compared to the motor manifestations,” said Dr. Simuni.

That said, she noted, the “ideal drug would be the one that would have benefit for both motor and nonmotor domains.” 
 

Multiple Agents in the Pipeline 

“The neuropharmacology of Tourette syndrome has long remained stagnant, and most existing treatments often fail to balance efficacy with tolerability, underscoring the urgent need for newer therapeutics,” Christos Ganos, MD, professor of neurology, University of Toronto, said in a press release.

He noted that three studies have been published on ecopipam since 2014: an 8-week, open-label trial in adults with Tourette syndrome, a 4-week, placebo-controlled crossover trial in 38 children with Tourette syndrome, and the 12-week D1AMOND trial.

“These studies demonstrated clinically meaningful reductions in tics, without relevant safety concerns or changes in Tourette syndrome-typical neuropsychiatric measures, as also shown by the abstract highlighted here,” Dr. Ganos said. 

“This emerging body of research provides a solid foundation for introducing ecopipam as a novel pharmacological agent to treat tics and may motivate further work, both on the pathophysiology and pharmacotherapy of tic disorders and their associations.”

A single-arm, phase 3 trial is currently underway at 58 centers in North America and Europe investigating the long-term safety and tolerability of ecopipam over 24 months in 150 children, adolescents, and adults with Tourette syndrome. The study is expected to be completed in 2027.

Several other new medications are also under investigation including the vesicular monoamine transporter (VMAT2) inhibitors tetrabenazine, deutetrabenazine, and valbenazine; the PEDE10A inhibitor gemlapodect; the allopregnanolone antagonist sepranolone; and SCI-110, which combines dronabinol (the synthetic form of tetrahydrocannabinol) and the endocannabinoid palmitoylethanolamide.

The study was funded by Emalex Biosciences. Dr. Gilbert’s institution received research support from Emalex Biosciences and PTC Therapeutics. Dr. Gilbert has received publishing royalties from a healthcare-related publication; compensation for serving as a medical expert with Teladoc; Advanced Medical; and the National Vaccine Injury Compensation Program, US Department of Health and Human Services. Simuni reports no relevant conflicts of interest. Dr. Ganos has received honoraria for educational activities from the Movement Disorder Society and academic research support from VolkswagenStiftung. 
 

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

PHILADELPHIA — The investigational agent ecopipam reduces tic severity in children and adolescents with Tourette syndrome without exacerbating common psychiatric comorbidities, results of a new analysis suggest.

As previously reported, the first-in-class dopamine-1 (D1) receptor antagonist reduced the primary endpoint of tic severity scores by 30% compared with placebo among 149 patients in the 12-week, phase 2b D1AMOND trial. 

What was unknown, however, is whether ecopipam would affect the comorbidities of attention-deficit/hyperactivity disorder (ADHD), anxiety, obsessive-compulsive disorder (OCD), and depression that were present in two thirds of participants.

The two key findings in this post hoc analysis were “first, that patients with a nonmotor diagnosis like depression or ADHD did not do any worse in terms of tic efficacy; and second, we didn’t find any evidence that any of the nonmotor symptoms of Tourette’s got worse with ecopipam,” said study investigator Donald Gilbert, MD, professor of pediatrics and neurology at University of Cincinnati Children’s Hospital Medical Center.

Dr. Gilbert presented the results at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024. 
 

No Worsening of ADHD Symptoms

Tourette syndrome affects approximately 1 in 160 children between 5 and 17 years of age in the United States, data from the Tourette Association of America show. Research has shown that 85% of patients with Tourette syndrome will have a co-occurring psychiatric condition. 

Guidelines recommend Comprehensive Behavioral Intervention for Tics (CBIT) as first-line treatment for Tourette syndrome, but cost and access are barriers. The only currently approved medications to treat Tourette syndrome are antipsychotics that act on the D2 receptor, but their use is limited by the potential for weight gain, metabolic changes, drug-induced movement disorders, and risk for suicidality, said Dr. Gilbert. 

The D1AMOND study randomly assigned patients aged 6-17 years with Tourette syndrome and a Yale Global Tic Severity Total Tic Scale score of at least 20 to receive a target steady-state dose of 2 mg/kg/d of oral ecopipam or placebo for a 4-week titration period, followed by an 8-week treatment phase before being tapered off the study drug. 

Patients were allowed to remain on medications without D2-receptor blocking activity for anxiety, OCD, and ADHD if the dosage was stable for 4 weeks before screening and not specifically prescribed for tics. 

A mixed model for repeated measures was used to assess changes in several scales administered at baseline and at weeks 4, 6, 8, and 12: the Swanson, Nolan, and Pelham Teacher and Parent Rating Scale (SNAP-IV); Pediatric Anxiety Rating Scale; Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), and Children’s Depression Rating Scale–Revised (CDRS-R). 

In patients with a co-occurring psychiatric condition, no significant differences were found over time between ecopipam and placebo in terms of SNAP-IV (-4.4; P = .45), Pediatric Anxiety Rating Scale (1.0; P = .62), CDRS-R (-3.2; P = .65), or CY-BOCS (-0.7; P = .76) scores.

For ADHD, the most frequent comorbidity, scores trended lower in the ecopipam group but were not significantly different from those in the placebo group. “We found no evidence that ecopipam worsened ADHD symptoms,” Dr. Gilbert said.
 

No Weight Gain

Suicidal ideation was reported during the dosing period in eight patients in the placebo group and none in the ecopipam group. One patient treated with ecopipam had multiple depressive episodes and dropped out of the study on day 79. Ecopipam was discontinued in another patient because of anxiety. 

Notably, there was more weight gain in the placebo group than in the ecopipam group (2.4 kg vs 1.8 kg) by 12 weeks. No shifts from baseline were seen in blood glucose, A1c, total cholesterol, or triglycerides in either group. 

The lack of weight gain with ecopipam is important, Dr. Gilbert stressed. “Medicines that block D2 so often cause weight gain, and a lot of our patients, unfortunately, can be heavier already,” he explained. “We don’t want to make that worse or put them at a long-term risk of type 2 diabetes.”  

For patients with more severe disease, we really “do need something else besides D2-blockers in our tool kit,” he added. 

Commenting on the study, Tanya Simuni, MD, co-moderator of the session and director of the Parkinson’s Disease and Movement Disorders Center, Northwestern Feinberg School of Medicine, Chicago, said the aim of assessing D1-directed medications is to reduce the negative impact of traditional antipsychotics with a theoretical benefit on hyperkinetic movement.

But the most important thing that they’ve shown is that “there was no negative effect, no liability for the nonmotor manifestations of Tourette’s. That is important because Tourette’s is not a pure motor syndrome, and psychiatric manifestations in a lot of cases are associated with more disease-related quality of life impairment compared to the motor manifestations,” said Dr. Simuni.

That said, she noted, the “ideal drug would be the one that would have benefit for both motor and nonmotor domains.” 
 

Multiple Agents in the Pipeline 

“The neuropharmacology of Tourette syndrome has long remained stagnant, and most existing treatments often fail to balance efficacy with tolerability, underscoring the urgent need for newer therapeutics,” Christos Ganos, MD, professor of neurology, University of Toronto, said in a press release.

He noted that three studies have been published on ecopipam since 2014: an 8-week, open-label trial in adults with Tourette syndrome, a 4-week, placebo-controlled crossover trial in 38 children with Tourette syndrome, and the 12-week D1AMOND trial.

“These studies demonstrated clinically meaningful reductions in tics, without relevant safety concerns or changes in Tourette syndrome-typical neuropsychiatric measures, as also shown by the abstract highlighted here,” Dr. Ganos said. 

“This emerging body of research provides a solid foundation for introducing ecopipam as a novel pharmacological agent to treat tics and may motivate further work, both on the pathophysiology and pharmacotherapy of tic disorders and their associations.”

A single-arm, phase 3 trial is currently underway at 58 centers in North America and Europe investigating the long-term safety and tolerability of ecopipam over 24 months in 150 children, adolescents, and adults with Tourette syndrome. The study is expected to be completed in 2027.

Several other new medications are also under investigation including the vesicular monoamine transporter (VMAT2) inhibitors tetrabenazine, deutetrabenazine, and valbenazine; the PEDE10A inhibitor gemlapodect; the allopregnanolone antagonist sepranolone; and SCI-110, which combines dronabinol (the synthetic form of tetrahydrocannabinol) and the endocannabinoid palmitoylethanolamide.

The study was funded by Emalex Biosciences. Dr. Gilbert’s institution received research support from Emalex Biosciences and PTC Therapeutics. Dr. Gilbert has received publishing royalties from a healthcare-related publication; compensation for serving as a medical expert with Teladoc; Advanced Medical; and the National Vaccine Injury Compensation Program, US Department of Health and Human Services. Simuni reports no relevant conflicts of interest. Dr. Ganos has received honoraria for educational activities from the Movement Disorder Society and academic research support from VolkswagenStiftung. 
 

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

PHILADELPHIA — The investigational agent ecopipam reduces tic severity in children and adolescents with Tourette syndrome without exacerbating common psychiatric comorbidities, results of a new analysis suggest.

As previously reported, the first-in-class dopamine-1 (D1) receptor antagonist reduced the primary endpoint of tic severity scores by 30% compared with placebo among 149 patients in the 12-week, phase 2b D1AMOND trial. 

What was unknown, however, is whether ecopipam would affect the comorbidities of attention-deficit/hyperactivity disorder (ADHD), anxiety, obsessive-compulsive disorder (OCD), and depression that were present in two thirds of participants.

The two key findings in this post hoc analysis were “first, that patients with a nonmotor diagnosis like depression or ADHD did not do any worse in terms of tic efficacy; and second, we didn’t find any evidence that any of the nonmotor symptoms of Tourette’s got worse with ecopipam,” said study investigator Donald Gilbert, MD, professor of pediatrics and neurology at University of Cincinnati Children’s Hospital Medical Center.

Dr. Gilbert presented the results at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024. 
 

No Worsening of ADHD Symptoms

Tourette syndrome affects approximately 1 in 160 children between 5 and 17 years of age in the United States, data from the Tourette Association of America show. Research has shown that 85% of patients with Tourette syndrome will have a co-occurring psychiatric condition. 

Guidelines recommend Comprehensive Behavioral Intervention for Tics (CBIT) as first-line treatment for Tourette syndrome, but cost and access are barriers. The only currently approved medications to treat Tourette syndrome are antipsychotics that act on the D2 receptor, but their use is limited by the potential for weight gain, metabolic changes, drug-induced movement disorders, and risk for suicidality, said Dr. Gilbert. 

The D1AMOND study randomly assigned patients aged 6-17 years with Tourette syndrome and a Yale Global Tic Severity Total Tic Scale score of at least 20 to receive a target steady-state dose of 2 mg/kg/d of oral ecopipam or placebo for a 4-week titration period, followed by an 8-week treatment phase before being tapered off the study drug. 

Patients were allowed to remain on medications without D2-receptor blocking activity for anxiety, OCD, and ADHD if the dosage was stable for 4 weeks before screening and not specifically prescribed for tics. 

A mixed model for repeated measures was used to assess changes in several scales administered at baseline and at weeks 4, 6, 8, and 12: the Swanson, Nolan, and Pelham Teacher and Parent Rating Scale (SNAP-IV); Pediatric Anxiety Rating Scale; Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), and Children’s Depression Rating Scale–Revised (CDRS-R). 

In patients with a co-occurring psychiatric condition, no significant differences were found over time between ecopipam and placebo in terms of SNAP-IV (-4.4; P = .45), Pediatric Anxiety Rating Scale (1.0; P = .62), CDRS-R (-3.2; P = .65), or CY-BOCS (-0.7; P = .76) scores.

For ADHD, the most frequent comorbidity, scores trended lower in the ecopipam group but were not significantly different from those in the placebo group. “We found no evidence that ecopipam worsened ADHD symptoms,” Dr. Gilbert said.
 

No Weight Gain

Suicidal ideation was reported during the dosing period in eight patients in the placebo group and none in the ecopipam group. One patient treated with ecopipam had multiple depressive episodes and dropped out of the study on day 79. Ecopipam was discontinued in another patient because of anxiety. 

Notably, there was more weight gain in the placebo group than in the ecopipam group (2.4 kg vs 1.8 kg) by 12 weeks. No shifts from baseline were seen in blood glucose, A1c, total cholesterol, or triglycerides in either group. 

The lack of weight gain with ecopipam is important, Dr. Gilbert stressed. “Medicines that block D2 so often cause weight gain, and a lot of our patients, unfortunately, can be heavier already,” he explained. “We don’t want to make that worse or put them at a long-term risk of type 2 diabetes.”  

For patients with more severe disease, we really “do need something else besides D2-blockers in our tool kit,” he added. 

Commenting on the study, Tanya Simuni, MD, co-moderator of the session and director of the Parkinson’s Disease and Movement Disorders Center, Northwestern Feinberg School of Medicine, Chicago, said the aim of assessing D1-directed medications is to reduce the negative impact of traditional antipsychotics with a theoretical benefit on hyperkinetic movement.

But the most important thing that they’ve shown is that “there was no negative effect, no liability for the nonmotor manifestations of Tourette’s. That is important because Tourette’s is not a pure motor syndrome, and psychiatric manifestations in a lot of cases are associated with more disease-related quality of life impairment compared to the motor manifestations,” said Dr. Simuni.

That said, she noted, the “ideal drug would be the one that would have benefit for both motor and nonmotor domains.” 
 

Multiple Agents in the Pipeline 

“The neuropharmacology of Tourette syndrome has long remained stagnant, and most existing treatments often fail to balance efficacy with tolerability, underscoring the urgent need for newer therapeutics,” Christos Ganos, MD, professor of neurology, University of Toronto, said in a press release.

He noted that three studies have been published on ecopipam since 2014: an 8-week, open-label trial in adults with Tourette syndrome, a 4-week, placebo-controlled crossover trial in 38 children with Tourette syndrome, and the 12-week D1AMOND trial.

“These studies demonstrated clinically meaningful reductions in tics, without relevant safety concerns or changes in Tourette syndrome-typical neuropsychiatric measures, as also shown by the abstract highlighted here,” Dr. Ganos said. 

“This emerging body of research provides a solid foundation for introducing ecopipam as a novel pharmacological agent to treat tics and may motivate further work, both on the pathophysiology and pharmacotherapy of tic disorders and their associations.”

A single-arm, phase 3 trial is currently underway at 58 centers in North America and Europe investigating the long-term safety and tolerability of ecopipam over 24 months in 150 children, adolescents, and adults with Tourette syndrome. The study is expected to be completed in 2027.

Several other new medications are also under investigation including the vesicular monoamine transporter (VMAT2) inhibitors tetrabenazine, deutetrabenazine, and valbenazine; the PEDE10A inhibitor gemlapodect; the allopregnanolone antagonist sepranolone; and SCI-110, which combines dronabinol (the synthetic form of tetrahydrocannabinol) and the endocannabinoid palmitoylethanolamide.

The study was funded by Emalex Biosciences. Dr. Gilbert’s institution received research support from Emalex Biosciences and PTC Therapeutics. Dr. Gilbert has received publishing royalties from a healthcare-related publication; compensation for serving as a medical expert with Teladoc; Advanced Medical; and the National Vaccine Injury Compensation Program, US Department of Health and Human Services. Simuni reports no relevant conflicts of interest. Dr. Ganos has received honoraria for educational activities from the Movement Disorder Society and academic research support from VolkswagenStiftung. 
 

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

MADRID — Individuals with type 2 diabetes and/or obesity plus one or more metabolic risk factors are at a higher risk for metabolic dysfunction–associated steatotic liver disease (MASLD) with fibrosis and progression to more severe liver disease, stated new European guidelines that provide recommendations for diagnosis and management.

“The availability of improved treatment options underlines the need to identify at-risk individuals with MASLD early, as we now possess the tools to positively influence the course of the diseases, which is expected to prevent relevant clinical events,” stated the clinical practice guidelines, updated for the first time since 2016.

“Now we have guidelines that tell clinicians how to monitor the liver,” said Amalia Gastaldelli, PhD, research director at the Institute of Clinical Physiology of the National Research Council in Pisa, Italy, and a member of the panel that developed the guidelines.

Dr. Gastaldelli moderated a session focused on the guidelines at the annual meeting of the European Association for the Study of Diabetes (EASD). In an interview after the session, Dr. Gastaldelli, who leads a cardiometabolic risk research group, stressed the importance of the liver’s role in the body and the need for diabetes specialists to start paying more attention to this vital organ.

“It’s an important organ for monitoring because liver disease is silent, and the patient doesn’t feel unwell until disease is severe,” she said. “Diabetologists already monitor the eye, the heart, the kidney, and so on, but the liver is often neglected,” she said. A 2024 study found that the global pooled prevalence of MASLD among patients with type 2 diabetes was 65.33%.

Dr. Gastaldelli noted the importance of liver status in diabetes care. The liver makes triglycerides and very-low-density lipoprotein cholesterol, which are all major risk factors for atherosclerosis and cardiovascular disease (CVD), she said, as well as producing glucose, which in excess can lead to hyperglycemia.

The guidelines were jointly written by EASD, the European Association for the Study of the Liver, and the European Association for the Study of Obesity, and published in Diabetologia, The Journal of Hepatology, and Obesity Facts.
 

A Metabolic Condition

In the EASD meeting session, Dr. Gastaldelli discussed the reasons for, and implications of, shifting the name from nonalcoholic fatty liver disease (NAFLD) to MASLD.

“The name change focuses on the fact that this is a metabolic disease, while NAFLD had no mention of this and was considered stigmatizing by patients, especially in relation to the words ‘fatty’ and ‘nonalcoholic,’” she said.

According to the guidelines, MASLD is defined as liver steatosis in the presence of one or more cardiometabolic risk factor(s) and the absence of excess alcohol intake.

MASLD has become the most common chronic liver disease and includes isolated steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), MASH-related fibrosis, and cirrhosis.

In the overarching group of steatotic liver disease, a totally new intermediate category has been added: MASLD with moderate (increased) alcohol intake (MetALD), which represents MASLD in people who consume greater amounts of alcohol per week (140-350 g/week and 210-420 g/week for women and men, respectively).

The change in the nomenclature has been incremental and regional, Dr. Gastaldelli said. “The definition first changed from NAFLD to MAFLD, which recognizes the importance of metabolism in the pathophysiology of this disease but does not take into account alcohol intake. MAFLD is still used in Asia, Australasia, and North Africa, while Europe and the Americas have endorsed MASLD.”
 

Case-Finding and Diagnosis

Identifying MASLD cases in people at risk remains incidental, largely because it is a silent disease and is symptom-free until it becomes severe, said Dr. Gastaldelli.

The guideline recognizes that individuals with type 2 diabetes or obesity with additional metabolic risk factor(s) are at a higher risk for MASLD with fibrosis and progression to MASH.

Assessment strategies for severe liver fibrosis in MASLD include the use of noninvasive tests in people who have cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes or obesity or in the presence of one or more metabolic risk factors.

Dr. Gastaldelli noted that type 2 diabetes, metabolic syndrome, and obesity, including abdominal obesity identified by large waist circumference, are the major risk factors and should be warning signs.

“We need to consider abdominal obesity too — we’ve published data in relatively lean people, body mass index < 25, with MASH but without diabetes. Most of the patients accumulated fat viscerally and in the liver and had hypertriglyceridemia and hypercholesterolemia,” she said.

“The guidelines reflect this because the definition of MASLD includes steatosis plus at least one metabolic factor — waist circumference, for example, which is related to visceral fat, hyperlipidemia, or hyperglycemia. Of note, in both pharmacological and diet-induced weight loss, the decrease in liver fat was associated with the decrease in visceral fat.” 

The noninvasive biomarker test, Fibrosis-4 (FIB-4) may be used to assess the risk for liver fibrosis. The FIB-4 index is calculated using a patient’s age and results of three blood tests — aspartate aminotransferase, alanine aminotransferase, and platelet count.

Advanced fibrosis (grade F3-F4) “is a major risk factor for severe outcomes,” said Dr. Gastaldelli. A FIB-4 test result below 1.3 indicates low risk for advanced liver fibrosis, 1.30-2.67 indicates intermediate risk, and above 2.67 indicates high risk.

“When fibrosis increases, then liver enzymes increase and the platelets decrease,” said Dr. Gastaldelli. “It is not a perfect tool, and we need to add in age because at a young age, it is prone to false negatives and when very old — false positives. It’s important to take a global view, especially if the patient has persistent high liver enzymes, but FIB-4 is low.” 

“And if they have more than one metabolic risk factor, proceed with more tests, for example, transient elastography,” she advised. Imaging techniques such as transient elastography may rule out or rule in advanced fibrosis, which is predictive of liver-related outcomes.

“However, imaging techniques only diagnose steatosis and fibrosis, and right now, MASH can only be diagnosed with liver biopsy because we do not have any markers of liver inflammation and ballooning. In the future, noninvasive tests based on imaging and blood tests will be used to identify patients with MASH,” she added.
 

Management of MASLD — Lifestyle and Treatment

“Pharmacological treatments are designed for [patients] with MASH and fibrosis grade F2 or F3, but not MASLD,” Dr. Gastaldelli said. As such, lifestyle interventions are the mainstay of management — including weight loss, dietary changes, physical exercise, and low to no alcohol consumption. “Eating good-quality food and reducing calories are both important because the metabolism responds differently to different nutrients,” Dr. Gastaldelli said.

“In particular, the guidelines advise dietary management because some foods carry liver toxicity, for example, sugary foods with sucrose/fructose especially,” she said, adding that, “complex carbohydrates are less harmful than refined carbohydrates. Processed foods should be avoided if possible because they contain sugars, [as well as] saturated fats and hydrogenated fat, which is particularly bad for the liver. Olive oil is better than butter or margarine, which are rich in saturated fat, and fish and white meat are preferable.”

She added that a diet to help manage type 2 diabetes was not so dissimilar because sugar again needs to be reduced. 

If a patient has severe obesity (and MASLD), data show that bariatric surgery is beneficial. “It not only helps weight loss, but it improves liver histology and has been shown to improve or resolve type 2 diabetes and reduce CVD risk. Importantly, regarding fibrosis, nutritional management after the bariatric surgery is the most important thing,” said Dr. Gastaldelli.

Optimal management of comorbidities — including the use of incretin-based therapies such as semaglutide or tirzepatide for type 2 diabetes or obesity, if indicated — is advised, according to the guidelines.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been shown to have a beneficial effect on MASH, said Dr. Gastaldelli. “They have not shown effectiveness in the resolution of fibrosis, but this might take longer to manifest. However, if the medication is started early enough, it may prevent severe fibrosis. Significant weight loss, both with lifestyle and pharmacological treatment, should lead to an improvement in the liver too.”

There are currently no drugs available in Europe for the treatment of noncirrhotic MASH and severe fibrosis (stage ≥ 2). Resmetirom is the first approved MASH-targeted treatment in noncirrhotic MASH and significant liver fibrosis, with histological effectiveness on steatohepatitis and fibrosis, together with an acceptable safety and tolerability profile, but, for the moment, this agent is only available in United States.

Finally, turning to MASH-related cirrhosis, the guidelines advise adaptations of metabolic drugs, nutritional counseling, and surveillance for portal hypertension and hepatocellular carcinoma, as well as liver transplantation in decompensated cirrhosis.

After the session, this news organization spoke to Tushy Kailayanathan, MBBS BSc, medical director of the liver MRI company, Perspectum, who reviewed the limitations of the FIB-4 test. The FIB-4 test identifies those with advanced fibrosis in the liver, for example, patients with hepatitis C, she noted; however, “it performs worse in type 2 diabetic patients and in the elderly. There is little clinical guidance on the adjustment of FIB-4 thresholds needed for these high cardiometabolic risk groups. The priority patients are missed by FIB-4 because those individuals with early and active disease may not yet have progressed to advanced disease detected by FIB-4.”

These individuals are exactly those amenable to primary care prevention strategies, said Dr. Kailayanathan. Because of the nature of early and active liver disease in patients with high cardiometabolic risk, it would make sense to shift some diagnostic protocols into primary care.

“These individuals are exactly those amenable to primary care prevention strategies at annual diabetic review because they are likely to have modifiable cardiometabolic risk factors such as metabolic syndrome and would benefit from lifestyle and therapeutic intervention, including GLP-1 RAs and SGLT2is [sodium-glucose cotransporter-2 inhibitors],” she said. “Case-finding and detection of early-stage MASLD is a priority in diabetics, and there is an unmet need for accurate biomarkers to measure liver fat and inflammation early.”

Dr. Gastaldelli has been on the advisory board or consulting for Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Fractyl, Pfizer, Merck-MSD, MetaDeq and a speaker for Eli Lilly, Novo Nordisk, and Pfizer. Dr. Kailayanathan is medical director at Perspectum, a UK-based company involved in liver imaging technology.

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

MADRID — Individuals with type 2 diabetes and/or obesity plus one or more metabolic risk factors are at a higher risk for metabolic dysfunction–associated steatotic liver disease (MASLD) with fibrosis and progression to more severe liver disease, stated new European guidelines that provide recommendations for diagnosis and management.

“The availability of improved treatment options underlines the need to identify at-risk individuals with MASLD early, as we now possess the tools to positively influence the course of the diseases, which is expected to prevent relevant clinical events,” stated the clinical practice guidelines, updated for the first time since 2016.

“Now we have guidelines that tell clinicians how to monitor the liver,” said Amalia Gastaldelli, PhD, research director at the Institute of Clinical Physiology of the National Research Council in Pisa, Italy, and a member of the panel that developed the guidelines.

Dr. Gastaldelli moderated a session focused on the guidelines at the annual meeting of the European Association for the Study of Diabetes (EASD). In an interview after the session, Dr. Gastaldelli, who leads a cardiometabolic risk research group, stressed the importance of the liver’s role in the body and the need for diabetes specialists to start paying more attention to this vital organ.

“It’s an important organ for monitoring because liver disease is silent, and the patient doesn’t feel unwell until disease is severe,” she said. “Diabetologists already monitor the eye, the heart, the kidney, and so on, but the liver is often neglected,” she said. A 2024 study found that the global pooled prevalence of MASLD among patients with type 2 diabetes was 65.33%.

Dr. Gastaldelli noted the importance of liver status in diabetes care. The liver makes triglycerides and very-low-density lipoprotein cholesterol, which are all major risk factors for atherosclerosis and cardiovascular disease (CVD), she said, as well as producing glucose, which in excess can lead to hyperglycemia.

The guidelines were jointly written by EASD, the European Association for the Study of the Liver, and the European Association for the Study of Obesity, and published in Diabetologia, The Journal of Hepatology, and Obesity Facts.
 

A Metabolic Condition

In the EASD meeting session, Dr. Gastaldelli discussed the reasons for, and implications of, shifting the name from nonalcoholic fatty liver disease (NAFLD) to MASLD.

“The name change focuses on the fact that this is a metabolic disease, while NAFLD had no mention of this and was considered stigmatizing by patients, especially in relation to the words ‘fatty’ and ‘nonalcoholic,’” she said.

According to the guidelines, MASLD is defined as liver steatosis in the presence of one or more cardiometabolic risk factor(s) and the absence of excess alcohol intake.

MASLD has become the most common chronic liver disease and includes isolated steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), MASH-related fibrosis, and cirrhosis.

In the overarching group of steatotic liver disease, a totally new intermediate category has been added: MASLD with moderate (increased) alcohol intake (MetALD), which represents MASLD in people who consume greater amounts of alcohol per week (140-350 g/week and 210-420 g/week for women and men, respectively).

The change in the nomenclature has been incremental and regional, Dr. Gastaldelli said. “The definition first changed from NAFLD to MAFLD, which recognizes the importance of metabolism in the pathophysiology of this disease but does not take into account alcohol intake. MAFLD is still used in Asia, Australasia, and North Africa, while Europe and the Americas have endorsed MASLD.”
 

Case-Finding and Diagnosis

Identifying MASLD cases in people at risk remains incidental, largely because it is a silent disease and is symptom-free until it becomes severe, said Dr. Gastaldelli.

The guideline recognizes that individuals with type 2 diabetes or obesity with additional metabolic risk factor(s) are at a higher risk for MASLD with fibrosis and progression to MASH.

Assessment strategies for severe liver fibrosis in MASLD include the use of noninvasive tests in people who have cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes or obesity or in the presence of one or more metabolic risk factors.

Dr. Gastaldelli noted that type 2 diabetes, metabolic syndrome, and obesity, including abdominal obesity identified by large waist circumference, are the major risk factors and should be warning signs.

“We need to consider abdominal obesity too — we’ve published data in relatively lean people, body mass index < 25, with MASH but without diabetes. Most of the patients accumulated fat viscerally and in the liver and had hypertriglyceridemia and hypercholesterolemia,” she said.

“The guidelines reflect this because the definition of MASLD includes steatosis plus at least one metabolic factor — waist circumference, for example, which is related to visceral fat, hyperlipidemia, or hyperglycemia. Of note, in both pharmacological and diet-induced weight loss, the decrease in liver fat was associated with the decrease in visceral fat.” 

The noninvasive biomarker test, Fibrosis-4 (FIB-4) may be used to assess the risk for liver fibrosis. The FIB-4 index is calculated using a patient’s age and results of three blood tests — aspartate aminotransferase, alanine aminotransferase, and platelet count.

Advanced fibrosis (grade F3-F4) “is a major risk factor for severe outcomes,” said Dr. Gastaldelli. A FIB-4 test result below 1.3 indicates low risk for advanced liver fibrosis, 1.30-2.67 indicates intermediate risk, and above 2.67 indicates high risk.

“When fibrosis increases, then liver enzymes increase and the platelets decrease,” said Dr. Gastaldelli. “It is not a perfect tool, and we need to add in age because at a young age, it is prone to false negatives and when very old — false positives. It’s important to take a global view, especially if the patient has persistent high liver enzymes, but FIB-4 is low.” 

“And if they have more than one metabolic risk factor, proceed with more tests, for example, transient elastography,” she advised. Imaging techniques such as transient elastography may rule out or rule in advanced fibrosis, which is predictive of liver-related outcomes.

“However, imaging techniques only diagnose steatosis and fibrosis, and right now, MASH can only be diagnosed with liver biopsy because we do not have any markers of liver inflammation and ballooning. In the future, noninvasive tests based on imaging and blood tests will be used to identify patients with MASH,” she added.
 

Management of MASLD — Lifestyle and Treatment

“Pharmacological treatments are designed for [patients] with MASH and fibrosis grade F2 or F3, but not MASLD,” Dr. Gastaldelli said. As such, lifestyle interventions are the mainstay of management — including weight loss, dietary changes, physical exercise, and low to no alcohol consumption. “Eating good-quality food and reducing calories are both important because the metabolism responds differently to different nutrients,” Dr. Gastaldelli said.

“In particular, the guidelines advise dietary management because some foods carry liver toxicity, for example, sugary foods with sucrose/fructose especially,” she said, adding that, “complex carbohydrates are less harmful than refined carbohydrates. Processed foods should be avoided if possible because they contain sugars, [as well as] saturated fats and hydrogenated fat, which is particularly bad for the liver. Olive oil is better than butter or margarine, which are rich in saturated fat, and fish and white meat are preferable.”

She added that a diet to help manage type 2 diabetes was not so dissimilar because sugar again needs to be reduced. 

If a patient has severe obesity (and MASLD), data show that bariatric surgery is beneficial. “It not only helps weight loss, but it improves liver histology and has been shown to improve or resolve type 2 diabetes and reduce CVD risk. Importantly, regarding fibrosis, nutritional management after the bariatric surgery is the most important thing,” said Dr. Gastaldelli.

Optimal management of comorbidities — including the use of incretin-based therapies such as semaglutide or tirzepatide for type 2 diabetes or obesity, if indicated — is advised, according to the guidelines.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been shown to have a beneficial effect on MASH, said Dr. Gastaldelli. “They have not shown effectiveness in the resolution of fibrosis, but this might take longer to manifest. However, if the medication is started early enough, it may prevent severe fibrosis. Significant weight loss, both with lifestyle and pharmacological treatment, should lead to an improvement in the liver too.”

There are currently no drugs available in Europe for the treatment of noncirrhotic MASH and severe fibrosis (stage ≥ 2). Resmetirom is the first approved MASH-targeted treatment in noncirrhotic MASH and significant liver fibrosis, with histological effectiveness on steatohepatitis and fibrosis, together with an acceptable safety and tolerability profile, but, for the moment, this agent is only available in United States.

Finally, turning to MASH-related cirrhosis, the guidelines advise adaptations of metabolic drugs, nutritional counseling, and surveillance for portal hypertension and hepatocellular carcinoma, as well as liver transplantation in decompensated cirrhosis.

After the session, this news organization spoke to Tushy Kailayanathan, MBBS BSc, medical director of the liver MRI company, Perspectum, who reviewed the limitations of the FIB-4 test. The FIB-4 test identifies those with advanced fibrosis in the liver, for example, patients with hepatitis C, she noted; however, “it performs worse in type 2 diabetic patients and in the elderly. There is little clinical guidance on the adjustment of FIB-4 thresholds needed for these high cardiometabolic risk groups. The priority patients are missed by FIB-4 because those individuals with early and active disease may not yet have progressed to advanced disease detected by FIB-4.”

These individuals are exactly those amenable to primary care prevention strategies, said Dr. Kailayanathan. Because of the nature of early and active liver disease in patients with high cardiometabolic risk, it would make sense to shift some diagnostic protocols into primary care.

“These individuals are exactly those amenable to primary care prevention strategies at annual diabetic review because they are likely to have modifiable cardiometabolic risk factors such as metabolic syndrome and would benefit from lifestyle and therapeutic intervention, including GLP-1 RAs and SGLT2is [sodium-glucose cotransporter-2 inhibitors],” she said. “Case-finding and detection of early-stage MASLD is a priority in diabetics, and there is an unmet need for accurate biomarkers to measure liver fat and inflammation early.”

Dr. Gastaldelli has been on the advisory board or consulting for Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Fractyl, Pfizer, Merck-MSD, MetaDeq and a speaker for Eli Lilly, Novo Nordisk, and Pfizer. Dr. Kailayanathan is medical director at Perspectum, a UK-based company involved in liver imaging technology.

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

MADRID — Individuals with type 2 diabetes and/or obesity plus one or more metabolic risk factors are at a higher risk for metabolic dysfunction–associated steatotic liver disease (MASLD) with fibrosis and progression to more severe liver disease, stated new European guidelines that provide recommendations for diagnosis and management.

“The availability of improved treatment options underlines the need to identify at-risk individuals with MASLD early, as we now possess the tools to positively influence the course of the diseases, which is expected to prevent relevant clinical events,” stated the clinical practice guidelines, updated for the first time since 2016.

“Now we have guidelines that tell clinicians how to monitor the liver,” said Amalia Gastaldelli, PhD, research director at the Institute of Clinical Physiology of the National Research Council in Pisa, Italy, and a member of the panel that developed the guidelines.

Dr. Gastaldelli moderated a session focused on the guidelines at the annual meeting of the European Association for the Study of Diabetes (EASD). In an interview after the session, Dr. Gastaldelli, who leads a cardiometabolic risk research group, stressed the importance of the liver’s role in the body and the need for diabetes specialists to start paying more attention to this vital organ.

“It’s an important organ for monitoring because liver disease is silent, and the patient doesn’t feel unwell until disease is severe,” she said. “Diabetologists already monitor the eye, the heart, the kidney, and so on, but the liver is often neglected,” she said. A 2024 study found that the global pooled prevalence of MASLD among patients with type 2 diabetes was 65.33%.

Dr. Gastaldelli noted the importance of liver status in diabetes care. The liver makes triglycerides and very-low-density lipoprotein cholesterol, which are all major risk factors for atherosclerosis and cardiovascular disease (CVD), she said, as well as producing glucose, which in excess can lead to hyperglycemia.

The guidelines were jointly written by EASD, the European Association for the Study of the Liver, and the European Association for the Study of Obesity, and published in Diabetologia, The Journal of Hepatology, and Obesity Facts.
 

A Metabolic Condition

In the EASD meeting session, Dr. Gastaldelli discussed the reasons for, and implications of, shifting the name from nonalcoholic fatty liver disease (NAFLD) to MASLD.

“The name change focuses on the fact that this is a metabolic disease, while NAFLD had no mention of this and was considered stigmatizing by patients, especially in relation to the words ‘fatty’ and ‘nonalcoholic,’” she said.

According to the guidelines, MASLD is defined as liver steatosis in the presence of one or more cardiometabolic risk factor(s) and the absence of excess alcohol intake.

MASLD has become the most common chronic liver disease and includes isolated steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), MASH-related fibrosis, and cirrhosis.

In the overarching group of steatotic liver disease, a totally new intermediate category has been added: MASLD with moderate (increased) alcohol intake (MetALD), which represents MASLD in people who consume greater amounts of alcohol per week (140-350 g/week and 210-420 g/week for women and men, respectively).

The change in the nomenclature has been incremental and regional, Dr. Gastaldelli said. “The definition first changed from NAFLD to MAFLD, which recognizes the importance of metabolism in the pathophysiology of this disease but does not take into account alcohol intake. MAFLD is still used in Asia, Australasia, and North Africa, while Europe and the Americas have endorsed MASLD.”
 

Case-Finding and Diagnosis

Identifying MASLD cases in people at risk remains incidental, largely because it is a silent disease and is symptom-free until it becomes severe, said Dr. Gastaldelli.

The guideline recognizes that individuals with type 2 diabetes or obesity with additional metabolic risk factor(s) are at a higher risk for MASLD with fibrosis and progression to MASH.

Assessment strategies for severe liver fibrosis in MASLD include the use of noninvasive tests in people who have cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes or obesity or in the presence of one or more metabolic risk factors.

Dr. Gastaldelli noted that type 2 diabetes, metabolic syndrome, and obesity, including abdominal obesity identified by large waist circumference, are the major risk factors and should be warning signs.

“We need to consider abdominal obesity too — we’ve published data in relatively lean people, body mass index < 25, with MASH but without diabetes. Most of the patients accumulated fat viscerally and in the liver and had hypertriglyceridemia and hypercholesterolemia,” she said.

“The guidelines reflect this because the definition of MASLD includes steatosis plus at least one metabolic factor — waist circumference, for example, which is related to visceral fat, hyperlipidemia, or hyperglycemia. Of note, in both pharmacological and diet-induced weight loss, the decrease in liver fat was associated with the decrease in visceral fat.” 

The noninvasive biomarker test, Fibrosis-4 (FIB-4) may be used to assess the risk for liver fibrosis. The FIB-4 index is calculated using a patient’s age and results of three blood tests — aspartate aminotransferase, alanine aminotransferase, and platelet count.

Advanced fibrosis (grade F3-F4) “is a major risk factor for severe outcomes,” said Dr. Gastaldelli. A FIB-4 test result below 1.3 indicates low risk for advanced liver fibrosis, 1.30-2.67 indicates intermediate risk, and above 2.67 indicates high risk.

“When fibrosis increases, then liver enzymes increase and the platelets decrease,” said Dr. Gastaldelli. “It is not a perfect tool, and we need to add in age because at a young age, it is prone to false negatives and when very old — false positives. It’s important to take a global view, especially if the patient has persistent high liver enzymes, but FIB-4 is low.” 

“And if they have more than one metabolic risk factor, proceed with more tests, for example, transient elastography,” she advised. Imaging techniques such as transient elastography may rule out or rule in advanced fibrosis, which is predictive of liver-related outcomes.

“However, imaging techniques only diagnose steatosis and fibrosis, and right now, MASH can only be diagnosed with liver biopsy because we do not have any markers of liver inflammation and ballooning. In the future, noninvasive tests based on imaging and blood tests will be used to identify patients with MASH,” she added.
 

Management of MASLD — Lifestyle and Treatment

“Pharmacological treatments are designed for [patients] with MASH and fibrosis grade F2 or F3, but not MASLD,” Dr. Gastaldelli said. As such, lifestyle interventions are the mainstay of management — including weight loss, dietary changes, physical exercise, and low to no alcohol consumption. “Eating good-quality food and reducing calories are both important because the metabolism responds differently to different nutrients,” Dr. Gastaldelli said.

“In particular, the guidelines advise dietary management because some foods carry liver toxicity, for example, sugary foods with sucrose/fructose especially,” she said, adding that, “complex carbohydrates are less harmful than refined carbohydrates. Processed foods should be avoided if possible because they contain sugars, [as well as] saturated fats and hydrogenated fat, which is particularly bad for the liver. Olive oil is better than butter or margarine, which are rich in saturated fat, and fish and white meat are preferable.”

She added that a diet to help manage type 2 diabetes was not so dissimilar because sugar again needs to be reduced. 

If a patient has severe obesity (and MASLD), data show that bariatric surgery is beneficial. “It not only helps weight loss, but it improves liver histology and has been shown to improve or resolve type 2 diabetes and reduce CVD risk. Importantly, regarding fibrosis, nutritional management after the bariatric surgery is the most important thing,” said Dr. Gastaldelli.

Optimal management of comorbidities — including the use of incretin-based therapies such as semaglutide or tirzepatide for type 2 diabetes or obesity, if indicated — is advised, according to the guidelines.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been shown to have a beneficial effect on MASH, said Dr. Gastaldelli. “They have not shown effectiveness in the resolution of fibrosis, but this might take longer to manifest. However, if the medication is started early enough, it may prevent severe fibrosis. Significant weight loss, both with lifestyle and pharmacological treatment, should lead to an improvement in the liver too.”

There are currently no drugs available in Europe for the treatment of noncirrhotic MASH and severe fibrosis (stage ≥ 2). Resmetirom is the first approved MASH-targeted treatment in noncirrhotic MASH and significant liver fibrosis, with histological effectiveness on steatohepatitis and fibrosis, together with an acceptable safety and tolerability profile, but, for the moment, this agent is only available in United States.

Finally, turning to MASH-related cirrhosis, the guidelines advise adaptations of metabolic drugs, nutritional counseling, and surveillance for portal hypertension and hepatocellular carcinoma, as well as liver transplantation in decompensated cirrhosis.

After the session, this news organization spoke to Tushy Kailayanathan, MBBS BSc, medical director of the liver MRI company, Perspectum, who reviewed the limitations of the FIB-4 test. The FIB-4 test identifies those with advanced fibrosis in the liver, for example, patients with hepatitis C, she noted; however, “it performs worse in type 2 diabetic patients and in the elderly. There is little clinical guidance on the adjustment of FIB-4 thresholds needed for these high cardiometabolic risk groups. The priority patients are missed by FIB-4 because those individuals with early and active disease may not yet have progressed to advanced disease detected by FIB-4.”

These individuals are exactly those amenable to primary care prevention strategies, said Dr. Kailayanathan. Because of the nature of early and active liver disease in patients with high cardiometabolic risk, it would make sense to shift some diagnostic protocols into primary care.

“These individuals are exactly those amenable to primary care prevention strategies at annual diabetic review because they are likely to have modifiable cardiometabolic risk factors such as metabolic syndrome and would benefit from lifestyle and therapeutic intervention, including GLP-1 RAs and SGLT2is [sodium-glucose cotransporter-2 inhibitors],” she said. “Case-finding and detection of early-stage MASLD is a priority in diabetics, and there is an unmet need for accurate biomarkers to measure liver fat and inflammation early.”

Dr. Gastaldelli has been on the advisory board or consulting for Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Fractyl, Pfizer, Merck-MSD, MetaDeq and a speaker for Eli Lilly, Novo Nordisk, and Pfizer. Dr. Kailayanathan is medical director at Perspectum, a UK-based company involved in liver imaging technology.

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

A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.

The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options. 

Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication. 

Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February. 

“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News. 

Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.

“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
 

Moving the Field Forward

The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology. 

They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.

Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.

Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.

Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.

Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems. 

“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said. 

“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”

Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America. 

Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
 

Clinical Implications

Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.

MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future. 

The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.

Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided. 

Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes. 

Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them. 

The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.

The sources in this story reported no relevant financial conflicts of interest.
 

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

A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.

The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options. 

Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication. 

Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February. 

“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News. 

Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.

“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
 

Moving the Field Forward

The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology. 

They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.

Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.

Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.

Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.

Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems. 

“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said. 

“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”

Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America. 

Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
 

Clinical Implications

Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.

MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future. 

The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.

Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided. 

Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes. 

Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them. 

The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.

The sources in this story reported no relevant financial conflicts of interest.
 

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

A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.

The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options. 

Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication. 

Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February. 

“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News. 

Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.

“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
 

Moving the Field Forward

The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology. 

They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.

Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.

Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.

Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.

Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems. 

“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said. 

“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”

Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America. 

Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
 

Clinical Implications

Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.

MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future. 

The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.

Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided. 

Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes. 

Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them. 

The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.

The sources in this story reported no relevant financial conflicts of interest.
 

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

TOPLINE:

Women with hyperandrogenic polycystic ovary syndrome (PCOS) have lower pregnancy (29.9%) and live birth rates (20.1%) than those with nonhyperandrogenic PCOS (40.2% and 33.1%, respectively).

METHODOLOGY:

• Researchers conducted a retrospective cohort study of 1376 participants from the PPCOS I and II trials, all meeting National Institutes of Health diagnostic criteria for PCOS.
• Participants were categorized into hyperandrogenic (A and B) and nonhyperandrogenic (D) PCOS phenotypes on the basis of medical interviews, demographics, physical examinations, and laboratory data.
• Outcomes of interest included clinical pregnancy, pregnancy loss, live birth, obstetric complications, and neonatal outcomes.
• Fasting blood samples were analyzed for hormonal assays, and Homeostatic Model Assessment for Insulin Resistance scores were calculated using fasting glucose and insulin values.

TAKEAWAY:

• Participants with hyperandrogenic PCOS had higher body mass index (35.5 ± 8.9 vs 31.9 ± 9.3; P < .001) and fasting insulin levels (21.6 ± 27.7 vs 14.7 ± 15.0 μIU/mL; P < .001) than those with nonhyperandrogenic PCOS.
• Participants with hyperandrogenic PCOS had lower odds of achieving pregnancy (odds ratio [OR], 0.63; 95% CI, 0.44-0.92) and live birth (OR, 0.51; 95% CI, 0.34-0.76) than those with nonhyperandrogenic PCOS.
• No significant differences were found in pregnancy loss rates (23.9% vs 32.3%, P = .06) or neonatal outcomes between the two groups.
• The study lacked the power to detect differences in neonatal outcomes because of the low prevalence of these outcomes.

IN PRACTICE:

“Patients with nonhyperandrogenic PCOS may represent a different disease process with unique morbidities and outcomes and could be counseled differently than hyperandrogenic PCOS,” wrote the authors of the study.

SOURCE:

The study was led by Jessica L. Chan, MD, MSCE, Cedars-Sinai Medical Center in Los Angeles, California. It was published online in Obstetrics & Gynecology.

LIMITATIONS:

The primary limitation of this study was that it is a secondary analysis of previously collected randomized controlled trial data, which may affect the availability of certain information. Additionally, the lower number of participants in the nonhyperandrogenic PCOS group could affect the power of the results. The study was underpowered to detect statistically significant differences in neonatal outcomes because of their low prevalence.

DISCLOSURES:

The study was supported by a grant from the ASRM/NICHD/Duke Clinical Research/Reproductive Scientist Training Program. One coauthor disclosed receiving payments from Celmatix, Ferring Pharmaceuticals, Exeltis, Organon, and Monsanto; another disclosed receiving payments from Ferring Pharmaceuticals. Additional disclosures are noted in the original article.

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

TOPLINE:

Women with hyperandrogenic polycystic ovary syndrome (PCOS) have lower pregnancy (29.9%) and live birth rates (20.1%) than those with nonhyperandrogenic PCOS (40.2% and 33.1%, respectively).

METHODOLOGY:

• Researchers conducted a retrospective cohort study of 1376 participants from the PPCOS I and II trials, all meeting National Institutes of Health diagnostic criteria for PCOS.
• Participants were categorized into hyperandrogenic (A and B) and nonhyperandrogenic (D) PCOS phenotypes on the basis of medical interviews, demographics, physical examinations, and laboratory data.
• Outcomes of interest included clinical pregnancy, pregnancy loss, live birth, obstetric complications, and neonatal outcomes.
• Fasting blood samples were analyzed for hormonal assays, and Homeostatic Model Assessment for Insulin Resistance scores were calculated using fasting glucose and insulin values.

TAKEAWAY:

• Participants with hyperandrogenic PCOS had higher body mass index (35.5 ± 8.9 vs 31.9 ± 9.3; P < .001) and fasting insulin levels (21.6 ± 27.7 vs 14.7 ± 15.0 μIU/mL; P < .001) than those with nonhyperandrogenic PCOS.
• Participants with hyperandrogenic PCOS had lower odds of achieving pregnancy (odds ratio [OR], 0.63; 95% CI, 0.44-0.92) and live birth (OR, 0.51; 95% CI, 0.34-0.76) than those with nonhyperandrogenic PCOS.
• No significant differences were found in pregnancy loss rates (23.9% vs 32.3%, P = .06) or neonatal outcomes between the two groups.
• The study lacked the power to detect differences in neonatal outcomes because of the low prevalence of these outcomes.

IN PRACTICE:

“Patients with nonhyperandrogenic PCOS may represent a different disease process with unique morbidities and outcomes and could be counseled differently than hyperandrogenic PCOS,” wrote the authors of the study.

SOURCE:

The study was led by Jessica L. Chan, MD, MSCE, Cedars-Sinai Medical Center in Los Angeles, California. It was published online in Obstetrics & Gynecology.

LIMITATIONS:

The primary limitation of this study was that it is a secondary analysis of previously collected randomized controlled trial data, which may affect the availability of certain information. Additionally, the lower number of participants in the nonhyperandrogenic PCOS group could affect the power of the results. The study was underpowered to detect statistically significant differences in neonatal outcomes because of their low prevalence.

DISCLOSURES:

The study was supported by a grant from the ASRM/NICHD/Duke Clinical Research/Reproductive Scientist Training Program. One coauthor disclosed receiving payments from Celmatix, Ferring Pharmaceuticals, Exeltis, Organon, and Monsanto; another disclosed receiving payments from Ferring Pharmaceuticals. Additional disclosures are noted in the original article.

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

TOPLINE:

Women with hyperandrogenic polycystic ovary syndrome (PCOS) have lower pregnancy (29.9%) and live birth rates (20.1%) than those with nonhyperandrogenic PCOS (40.2% and 33.1%, respectively).

METHODOLOGY:

• Researchers conducted a retrospective cohort study of 1376 participants from the PPCOS I and II trials, all meeting National Institutes of Health diagnostic criteria for PCOS.
• Participants were categorized into hyperandrogenic (A and B) and nonhyperandrogenic (D) PCOS phenotypes on the basis of medical interviews, demographics, physical examinations, and laboratory data.
• Outcomes of interest included clinical pregnancy, pregnancy loss, live birth, obstetric complications, and neonatal outcomes.
• Fasting blood samples were analyzed for hormonal assays, and Homeostatic Model Assessment for Insulin Resistance scores were calculated using fasting glucose and insulin values.

TAKEAWAY:

• Participants with hyperandrogenic PCOS had higher body mass index (35.5 ± 8.9 vs 31.9 ± 9.3; P < .001) and fasting insulin levels (21.6 ± 27.7 vs 14.7 ± 15.0 μIU/mL; P < .001) than those with nonhyperandrogenic PCOS.
• Participants with hyperandrogenic PCOS had lower odds of achieving pregnancy (odds ratio [OR], 0.63; 95% CI, 0.44-0.92) and live birth (OR, 0.51; 95% CI, 0.34-0.76) than those with nonhyperandrogenic PCOS.
• No significant differences were found in pregnancy loss rates (23.9% vs 32.3%, P = .06) or neonatal outcomes between the two groups.
• The study lacked the power to detect differences in neonatal outcomes because of the low prevalence of these outcomes.

IN PRACTICE:

“Patients with nonhyperandrogenic PCOS may represent a different disease process with unique morbidities and outcomes and could be counseled differently than hyperandrogenic PCOS,” wrote the authors of the study.

SOURCE:

The study was led by Jessica L. Chan, MD, MSCE, Cedars-Sinai Medical Center in Los Angeles, California. It was published online in Obstetrics & Gynecology.

LIMITATIONS:

The primary limitation of this study was that it is a secondary analysis of previously collected randomized controlled trial data, which may affect the availability of certain information. Additionally, the lower number of participants in the nonhyperandrogenic PCOS group could affect the power of the results. The study was underpowered to detect statistically significant differences in neonatal outcomes because of their low prevalence.

DISCLOSURES:

The study was supported by a grant from the ASRM/NICHD/Duke Clinical Research/Reproductive Scientist Training Program. One coauthor disclosed receiving payments from Celmatix, Ferring Pharmaceuticals, Exeltis, Organon, and Monsanto; another disclosed receiving payments from Ferring Pharmaceuticals. Additional disclosures are noted in the original article.

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

TOPLINE:

Accounting for racial disparities, including in the quality of family history data, enhanced the predictive performance of a colorectal cancer (CRC) risk prediction model.

METHODOLOGY:

• The medical community is reevaluating the use of race adjustments in clinical algorithms due to concerns about the exacerbation of health disparities, especially as reported family history data are known to vary by race.
• To understand how adjusting for race affects the accuracy of CRC prediction algorithms, researchers studied data from community health centers across 12 states as part of the Southern Community Cohort Study.
• Researchers compared two screening algorithms that modeled 10-year CRC risk: A race-blind algorithm and a race-adjusted algorithm that included Black race as a main effect and an interaction with family history.
• The primary outcome was the development of CRC within 10 years of enrollment, assessed using data collected from surveys at enrollment and follow-ups, cancer registry data, and National Death Index reports.
• The researchers compared the algorithms’ predictive performance using such measures as area under the receiver operating characteristic curve (AUC) and calibration and also assessed how adjusting for race changed the proportion of Black participants identified as being at high risk for CRC.

TAKEAWAY:

• The study sample included 77,836 adults aged 40-74 years with no history of CRC at baseline.
• Despite having higher cancer rates, Black participants were more likely to report unknown family history (odds ratio [OR], 1.69; P < .001) and less likely to report known positive family history (OR, 0.68; P < .001) than White participants.
• The interaction term between race and family history was 0.56, indicating that reported family history was less predictive of CRC risk in Black participants than in White participants (P = .010).
• Compared with the race-blinded algorithm, the race-adjusted algorithm increased the fraction of Black participants among the predicted high-risk group (66.1% vs 74.4%; P < .001), potentially enhancing access to screening.
• The race-adjusted algorithm improved the goodness of fit (P < .001) and showed a small improvement in AUC among Black participants (0.611 vs 0.608; P = .006).

IN PRACTICE:

“Our analysis found that removing race from colorectal screening predictors could reduce the number of Black patients recommended for screening, which would work against efforts to reduce disparities in colorectal cancer screening and outcomes,” the authors wrote.

SOURCE:

The study, led by Anna Zink, PhD, the University of Chicago Booth School of Business, Chicago, was published online in Proceedings of the National Academy of Sciences of the USA .

LIMITATIONS:

The study did not report any limitations.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health. The authors declared no conflicts of interest.

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

TOPLINE:

Accounting for racial disparities, including in the quality of family history data, enhanced the predictive performance of a colorectal cancer (CRC) risk prediction model.

METHODOLOGY:

• The medical community is reevaluating the use of race adjustments in clinical algorithms due to concerns about the exacerbation of health disparities, especially as reported family history data are known to vary by race.
• To understand how adjusting for race affects the accuracy of CRC prediction algorithms, researchers studied data from community health centers across 12 states as part of the Southern Community Cohort Study.
• Researchers compared two screening algorithms that modeled 10-year CRC risk: A race-blind algorithm and a race-adjusted algorithm that included Black race as a main effect and an interaction with family history.
• The primary outcome was the development of CRC within 10 years of enrollment, assessed using data collected from surveys at enrollment and follow-ups, cancer registry data, and National Death Index reports.
• The researchers compared the algorithms’ predictive performance using such measures as area under the receiver operating characteristic curve (AUC) and calibration and also assessed how adjusting for race changed the proportion of Black participants identified as being at high risk for CRC.

TAKEAWAY:

• The study sample included 77,836 adults aged 40-74 years with no history of CRC at baseline.
• Despite having higher cancer rates, Black participants were more likely to report unknown family history (odds ratio [OR], 1.69; P < .001) and less likely to report known positive family history (OR, 0.68; P < .001) than White participants.
• The interaction term between race and family history was 0.56, indicating that reported family history was less predictive of CRC risk in Black participants than in White participants (P = .010).
• Compared with the race-blinded algorithm, the race-adjusted algorithm increased the fraction of Black participants among the predicted high-risk group (66.1% vs 74.4%; P < .001), potentially enhancing access to screening.
• The race-adjusted algorithm improved the goodness of fit (P < .001) and showed a small improvement in AUC among Black participants (0.611 vs 0.608; P = .006).

IN PRACTICE:

“Our analysis found that removing race from colorectal screening predictors could reduce the number of Black patients recommended for screening, which would work against efforts to reduce disparities in colorectal cancer screening and outcomes,” the authors wrote.

SOURCE:

The study, led by Anna Zink, PhD, the University of Chicago Booth School of Business, Chicago, was published online in Proceedings of the National Academy of Sciences of the USA .

LIMITATIONS:

The study did not report any limitations.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health. The authors declared no conflicts of interest.

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

TOPLINE:

Accounting for racial disparities, including in the quality of family history data, enhanced the predictive performance of a colorectal cancer (CRC) risk prediction model.

METHODOLOGY:

• The medical community is reevaluating the use of race adjustments in clinical algorithms due to concerns about the exacerbation of health disparities, especially as reported family history data are known to vary by race.
• To understand how adjusting for race affects the accuracy of CRC prediction algorithms, researchers studied data from community health centers across 12 states as part of the Southern Community Cohort Study.
• Researchers compared two screening algorithms that modeled 10-year CRC risk: A race-blind algorithm and a race-adjusted algorithm that included Black race as a main effect and an interaction with family history.
• The primary outcome was the development of CRC within 10 years of enrollment, assessed using data collected from surveys at enrollment and follow-ups, cancer registry data, and National Death Index reports.
• The researchers compared the algorithms’ predictive performance using such measures as area under the receiver operating characteristic curve (AUC) and calibration and also assessed how adjusting for race changed the proportion of Black participants identified as being at high risk for CRC.

TAKEAWAY:

• The study sample included 77,836 adults aged 40-74 years with no history of CRC at baseline.
• Despite having higher cancer rates, Black participants were more likely to report unknown family history (odds ratio [OR], 1.69; P < .001) and less likely to report known positive family history (OR, 0.68; P < .001) than White participants.
• The interaction term between race and family history was 0.56, indicating that reported family history was less predictive of CRC risk in Black participants than in White participants (P = .010).
• Compared with the race-blinded algorithm, the race-adjusted algorithm increased the fraction of Black participants among the predicted high-risk group (66.1% vs 74.4%; P < .001), potentially enhancing access to screening.
• The race-adjusted algorithm improved the goodness of fit (P < .001) and showed a small improvement in AUC among Black participants (0.611 vs 0.608; P = .006).

IN PRACTICE:

“Our analysis found that removing race from colorectal screening predictors could reduce the number of Black patients recommended for screening, which would work against efforts to reduce disparities in colorectal cancer screening and outcomes,” the authors wrote.

SOURCE:

The study, led by Anna Zink, PhD, the University of Chicago Booth School of Business, Chicago, was published online in Proceedings of the National Academy of Sciences of the USA .

LIMITATIONS:

The study did not report any limitations.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health. The authors declared no conflicts of interest.

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

There’s a new morning ritual in Pinedale, Wyoming, a town of about 2000, nestled against the Wind River Mountains.

Friends and neighbors in the oil- and gas-rich community “take their morning coffee and pull up” to watch workers building the county’s first hospital, said Kari DeWitt, the project’s public relations director.

“I think it’s just gratitude,” Ms. DeWitt said.

Sublette County is the only one in Wyoming — where counties span thousands of square miles — without a hospital. The 10-bed, 40,000-square-foot hospital, with a similarly sized attached long-term care facility, is slated to open by the summer of 2025.

Ms. DeWitt, who also is executive director of the Sublette County Health Foundation, has an office at the town’s health clinic with a window view of the construction.

Pinedale’s residents have good reason to be excited. New full-service hospitals with inpatient beds are rare in rural America, where declining population has spurred decades of downsizing and closures. Yet, a few communities in Wyoming and others in Kansas and Georgia are defying the trend.

“To be honest with you, it even seems strange to me,” said Wyoming Hospital Association President Eric Boley. Small rural “hospitals are really struggling all across the country,” he said.

There is no official tally of new hospitals being built in rural America, but industry experts such as Mr. Boley said they’re rare. Typically, health-related construction projects in rural areas are for smaller urgent care centers or stand-alone emergency facilities or are replacements for old hospitals.

About half of rural hospitals lost money in the prior year, according to Chartis, a health analytics and consulting firm. And nearly 150 rural hospitals have closed or converted to smaller operations since 2010, according to data collected by the University of North Carolina’s Cecil G. Sheps Center for Health Services Research.

To stem the tide of closures, Congress created a new rural emergency hospital designation that allowed struggling hospitals to close their inpatient units and provide only outpatient and emergency services. Since January 2023, when the program took effect, 32 of the more than 1700 eligible rural hospitals — from Georgia to New Mexico — have joined the program, according to data from the Centers for Medicare & Medicaid Services.

Tony Breitlow is healthcare studio director for EUA, which has extensive experience working for rural health care systems. Mr. Breitlow said his national architecture and engineering firm’s work expands, replaces, or revamps older buildings, many of which were constructed during the middle of the last century.

The work, Mr. Breitlow said, is part of health care “systems figuring out how to remain robust and viable.”

Freeman Health System, based in Joplin, Missouri, announced plans last year to build a new 50-bed hospital across the state line in Kansas. Paula Baker, Freeman’s president and chief executive, said the system is building for patients in the southeastern corner of the state who travel 45 minutes or more to its bigger Joplin facilities for care.

Freeman’s new hospital, with construction on the building expected to begin in the spring, will be less than 10 miles away from an older, 64-bed hospital that has existed for decades. Kansas is one of more than a dozen states with no “certificate of need” law that would require health providers to obtain approval from the state before offering new services or building or expanding facilities.

Ms. Baker also said Freeman plans to operate emergency services and a small 10-bed outpost in Fort Scott, Kansas, opening early next year in a corner of a hospital that closed in late 2018. Residents there “cried, they cheered, they hugged me,” Ms. Baker said, adding that the “level of appreciation and gratitude that they felt and they displayed was overwhelming to me.”

Michael Topchik, executive director of the Chartis Center for Rural Health, said regional healthcare systems in the Upper Midwest have been particularly active in competing for patients by, among other things, building new hospitals.

And while private corporate money can drive construction, many rural hospital projects tap government programs, especially those supported by the US Department of Agriculture, Mr. Topchik said. That, he said, “surprises a lot of people.”

Since 2021, the USDA’s rural Community Facilities Programs have awarded $2.24 billion in loans and grants to 68 rural hospitals for work that was not related to an emergency or disaster, according to data analyzed by KFF Health News and confirmed by the agency. The federal program is funded through what is often known as the farm bill, which faces a September congressional renewal deadline.

Nearly all the projects are replacements or expansions and updates of older facilities.

The USDA confirmed that three new or planned Wyoming hospitals received federal funding. Hospital projects in Riverton and Saratoga received loans of $37.2 million and $18.3 million, respectively. Pinedale’s hospital received a $29.2 million loan from the agency.

Wyoming’s new construction is rare in a state where more than 80% of rural hospitals reported losses in the third quarter of 2023, according to Chartis. The state association’s Mr. Boley said he worries about several hospitals that have less than 10 days’ cash on hand “day and night.”

Pinedale’s project loan was approved after the community submitted a feasibility study to the USDA that included local clinics and a long-term care facility. “It’s pretty remote and right up in the mountains,” Mr. Boley said.

Pinedale’s Ms. DeWitt said the community was missing key services, such as blood transfusions, which are often necessary when there is a trauma like a car crash or if a pregnant woman faces severe complications. Local ambulances drove 94,000 miles last year, she said.

Ms. DeWitt began working to raise support for the new hospital after her own pregnancy-related trauma in 2014. She was bleeding heavily and arrived at the local health clinic believing it operated like a hospital.

“It was shocking to hear, ‘No, we’re not a hospital. We can’t do blood transfusions. We’re just going to have to pray you live for the next 45 minutes,’ ” Ms. DeWitt said.

Ms. DeWitt had to be airlifted to Idaho, where she delivered a few minutes after landing. When the hospital financing went on the ballot in 2020, Ms. DeWitt — fully recovered, with healthy grade-schoolers at home — began making five calls a night to rally support for a county tax increase to help fund the hospital.

“By improving health care, I think we improve everybody’s chances of survival. You know, it’s pretty basic,” Ms. DeWitt said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

There’s a new morning ritual in Pinedale, Wyoming, a town of about 2000, nestled against the Wind River Mountains.

Friends and neighbors in the oil- and gas-rich community “take their morning coffee and pull up” to watch workers building the county’s first hospital, said Kari DeWitt, the project’s public relations director.

“I think it’s just gratitude,” Ms. DeWitt said.

Sublette County is the only one in Wyoming — where counties span thousands of square miles — without a hospital. The 10-bed, 40,000-square-foot hospital, with a similarly sized attached long-term care facility, is slated to open by the summer of 2025.

Ms. DeWitt, who also is executive director of the Sublette County Health Foundation, has an office at the town’s health clinic with a window view of the construction.

Pinedale’s residents have good reason to be excited. New full-service hospitals with inpatient beds are rare in rural America, where declining population has spurred decades of downsizing and closures. Yet, a few communities in Wyoming and others in Kansas and Georgia are defying the trend.

“To be honest with you, it even seems strange to me,” said Wyoming Hospital Association President Eric Boley. Small rural “hospitals are really struggling all across the country,” he said.

There is no official tally of new hospitals being built in rural America, but industry experts such as Mr. Boley said they’re rare. Typically, health-related construction projects in rural areas are for smaller urgent care centers or stand-alone emergency facilities or are replacements for old hospitals.

About half of rural hospitals lost money in the prior year, according to Chartis, a health analytics and consulting firm. And nearly 150 rural hospitals have closed or converted to smaller operations since 2010, according to data collected by the University of North Carolina’s Cecil G. Sheps Center for Health Services Research.

To stem the tide of closures, Congress created a new rural emergency hospital designation that allowed struggling hospitals to close their inpatient units and provide only outpatient and emergency services. Since January 2023, when the program took effect, 32 of the more than 1700 eligible rural hospitals — from Georgia to New Mexico — have joined the program, according to data from the Centers for Medicare & Medicaid Services.

Tony Breitlow is healthcare studio director for EUA, which has extensive experience working for rural health care systems. Mr. Breitlow said his national architecture and engineering firm’s work expands, replaces, or revamps older buildings, many of which were constructed during the middle of the last century.

The work, Mr. Breitlow said, is part of health care “systems figuring out how to remain robust and viable.”

Freeman Health System, based in Joplin, Missouri, announced plans last year to build a new 50-bed hospital across the state line in Kansas. Paula Baker, Freeman’s president and chief executive, said the system is building for patients in the southeastern corner of the state who travel 45 minutes or more to its bigger Joplin facilities for care.

Freeman’s new hospital, with construction on the building expected to begin in the spring, will be less than 10 miles away from an older, 64-bed hospital that has existed for decades. Kansas is one of more than a dozen states with no “certificate of need” law that would require health providers to obtain approval from the state before offering new services or building or expanding facilities.

Ms. Baker also said Freeman plans to operate emergency services and a small 10-bed outpost in Fort Scott, Kansas, opening early next year in a corner of a hospital that closed in late 2018. Residents there “cried, they cheered, they hugged me,” Ms. Baker said, adding that the “level of appreciation and gratitude that they felt and they displayed was overwhelming to me.”

Michael Topchik, executive director of the Chartis Center for Rural Health, said regional healthcare systems in the Upper Midwest have been particularly active in competing for patients by, among other things, building new hospitals.

And while private corporate money can drive construction, many rural hospital projects tap government programs, especially those supported by the US Department of Agriculture, Mr. Topchik said. That, he said, “surprises a lot of people.”

Since 2021, the USDA’s rural Community Facilities Programs have awarded $2.24 billion in loans and grants to 68 rural hospitals for work that was not related to an emergency or disaster, according to data analyzed by KFF Health News and confirmed by the agency. The federal program is funded through what is often known as the farm bill, which faces a September congressional renewal deadline.

Nearly all the projects are replacements or expansions and updates of older facilities.

The USDA confirmed that three new or planned Wyoming hospitals received federal funding. Hospital projects in Riverton and Saratoga received loans of $37.2 million and $18.3 million, respectively. Pinedale’s hospital received a $29.2 million loan from the agency.

Wyoming’s new construction is rare in a state where more than 80% of rural hospitals reported losses in the third quarter of 2023, according to Chartis. The state association’s Mr. Boley said he worries about several hospitals that have less than 10 days’ cash on hand “day and night.”

Pinedale’s project loan was approved after the community submitted a feasibility study to the USDA that included local clinics and a long-term care facility. “It’s pretty remote and right up in the mountains,” Mr. Boley said.

Pinedale’s Ms. DeWitt said the community was missing key services, such as blood transfusions, which are often necessary when there is a trauma like a car crash or if a pregnant woman faces severe complications. Local ambulances drove 94,000 miles last year, she said.

Ms. DeWitt began working to raise support for the new hospital after her own pregnancy-related trauma in 2014. She was bleeding heavily and arrived at the local health clinic believing it operated like a hospital.

“It was shocking to hear, ‘No, we’re not a hospital. We can’t do blood transfusions. We’re just going to have to pray you live for the next 45 minutes,’ ” Ms. DeWitt said.

Ms. DeWitt had to be airlifted to Idaho, where she delivered a few minutes after landing. When the hospital financing went on the ballot in 2020, Ms. DeWitt — fully recovered, with healthy grade-schoolers at home — began making five calls a night to rally support for a county tax increase to help fund the hospital.

“By improving health care, I think we improve everybody’s chances of survival. You know, it’s pretty basic,” Ms. DeWitt said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

There’s a new morning ritual in Pinedale, Wyoming, a town of about 2000, nestled against the Wind River Mountains.

Friends and neighbors in the oil- and gas-rich community “take their morning coffee and pull up” to watch workers building the county’s first hospital, said Kari DeWitt, the project’s public relations director.

“I think it’s just gratitude,” Ms. DeWitt said.

Sublette County is the only one in Wyoming — where counties span thousands of square miles — without a hospital. The 10-bed, 40,000-square-foot hospital, with a similarly sized attached long-term care facility, is slated to open by the summer of 2025.

Ms. DeWitt, who also is executive director of the Sublette County Health Foundation, has an office at the town’s health clinic with a window view of the construction.

Pinedale’s residents have good reason to be excited. New full-service hospitals with inpatient beds are rare in rural America, where declining population has spurred decades of downsizing and closures. Yet, a few communities in Wyoming and others in Kansas and Georgia are defying the trend.

“To be honest with you, it even seems strange to me,” said Wyoming Hospital Association President Eric Boley. Small rural “hospitals are really struggling all across the country,” he said.

There is no official tally of new hospitals being built in rural America, but industry experts such as Mr. Boley said they’re rare. Typically, health-related construction projects in rural areas are for smaller urgent care centers or stand-alone emergency facilities or are replacements for old hospitals.

About half of rural hospitals lost money in the prior year, according to Chartis, a health analytics and consulting firm. And nearly 150 rural hospitals have closed or converted to smaller operations since 2010, according to data collected by the University of North Carolina’s Cecil G. Sheps Center for Health Services Research.

To stem the tide of closures, Congress created a new rural emergency hospital designation that allowed struggling hospitals to close their inpatient units and provide only outpatient and emergency services. Since January 2023, when the program took effect, 32 of the more than 1700 eligible rural hospitals — from Georgia to New Mexico — have joined the program, according to data from the Centers for Medicare & Medicaid Services.

Tony Breitlow is healthcare studio director for EUA, which has extensive experience working for rural health care systems. Mr. Breitlow said his national architecture and engineering firm’s work expands, replaces, or revamps older buildings, many of which were constructed during the middle of the last century.

The work, Mr. Breitlow said, is part of health care “systems figuring out how to remain robust and viable.”

Freeman Health System, based in Joplin, Missouri, announced plans last year to build a new 50-bed hospital across the state line in Kansas. Paula Baker, Freeman’s president and chief executive, said the system is building for patients in the southeastern corner of the state who travel 45 minutes or more to its bigger Joplin facilities for care.

Freeman’s new hospital, with construction on the building expected to begin in the spring, will be less than 10 miles away from an older, 64-bed hospital that has existed for decades. Kansas is one of more than a dozen states with no “certificate of need” law that would require health providers to obtain approval from the state before offering new services or building or expanding facilities.

Ms. Baker also said Freeman plans to operate emergency services and a small 10-bed outpost in Fort Scott, Kansas, opening early next year in a corner of a hospital that closed in late 2018. Residents there “cried, they cheered, they hugged me,” Ms. Baker said, adding that the “level of appreciation and gratitude that they felt and they displayed was overwhelming to me.”

Michael Topchik, executive director of the Chartis Center for Rural Health, said regional healthcare systems in the Upper Midwest have been particularly active in competing for patients by, among other things, building new hospitals.

And while private corporate money can drive construction, many rural hospital projects tap government programs, especially those supported by the US Department of Agriculture, Mr. Topchik said. That, he said, “surprises a lot of people.”

Since 2021, the USDA’s rural Community Facilities Programs have awarded $2.24 billion in loans and grants to 68 rural hospitals for work that was not related to an emergency or disaster, according to data analyzed by KFF Health News and confirmed by the agency. The federal program is funded through what is often known as the farm bill, which faces a September congressional renewal deadline.

Nearly all the projects are replacements or expansions and updates of older facilities.

The USDA confirmed that three new or planned Wyoming hospitals received federal funding. Hospital projects in Riverton and Saratoga received loans of $37.2 million and $18.3 million, respectively. Pinedale’s hospital received a $29.2 million loan from the agency.

Wyoming’s new construction is rare in a state where more than 80% of rural hospitals reported losses in the third quarter of 2023, according to Chartis. The state association’s Mr. Boley said he worries about several hospitals that have less than 10 days’ cash on hand “day and night.”

Pinedale’s project loan was approved after the community submitted a feasibility study to the USDA that included local clinics and a long-term care facility. “It’s pretty remote and right up in the mountains,” Mr. Boley said.

Pinedale’s Ms. DeWitt said the community was missing key services, such as blood transfusions, which are often necessary when there is a trauma like a car crash or if a pregnant woman faces severe complications. Local ambulances drove 94,000 miles last year, she said.

Ms. DeWitt began working to raise support for the new hospital after her own pregnancy-related trauma in 2014. She was bleeding heavily and arrived at the local health clinic believing it operated like a hospital.

“It was shocking to hear, ‘No, we’re not a hospital. We can’t do blood transfusions. We’re just going to have to pray you live for the next 45 minutes,’ ” Ms. DeWitt said.

Ms. DeWitt had to be airlifted to Idaho, where she delivered a few minutes after landing. When the hospital financing went on the ballot in 2020, Ms. DeWitt — fully recovered, with healthy grade-schoolers at home — began making five calls a night to rally support for a county tax increase to help fund the hospital.

“By improving health care, I think we improve everybody’s chances of survival. You know, it’s pretty basic,” Ms. DeWitt said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Journal CHEST®

Association Between Healthy Behaviors and Health Care Resource Use With Subsequent Positive Airway Pressure Therapy Adherence in OSA

By Launois, MD, PhD, and colleagues

One of the pitfalls in the interpretation of the effect of treatment adherence on health outcomes is the healthy-adherer effect (HAE) bias. Healthy-adherer bias occurs when patients who are treatment-adherent tend to actively seek out preventative care and engage in other healthy behaviors. Incomplete adjustment for such behaviors can lead to spurious inferences regarding study outcomes because healthy behaviors are associated with a reduced risk of many poor health outcomes.

This study demonstrates that HAE proxies (adherence to CV active drugs, no history of smoking, or sleepiness-related car accidents) were associated with subsequent PAP adherence after adjustment for confounders. PAP-adherent patients used less health care resources before PAP initiation. Unfortunately, the study did not measure other healthy behaviors (nutrition, physical activity, psychosocial support) that could also potentially explain HAE. Until the HAE associated with PAP adherence is better understood, clinicians should use caution when interpreting the association of PAP adherence with CV health outcomes and health care resource use.

CHEST

CHEST® Critical Care

Circulating Biomarkers of Endothelial Dysfunction Associated With Ventilatory Ratio and Mortality in ARDS Resulting From SARS-CoV-2 Infection Treated With Anti-inflammatory Therapies

By Alladina, MD, and colleagues

Practitioners in the intensive care unit have become increasingly aware that the population of patients with ARDS is highly heterogenous not only in terms of the inciting factors of their condition but also in terms of their respiratory physiology. Calfee and co-workers opened new horizons for us with their 2014 descriptions of two phenotypes of ARDS based upon biological markers that had different clinical outcome profiles. The work by Alladina et al adds to this body of knowledge by studying biomarkers from patients with COVID-ARDS who were receiving anti-inflammatory therapies. These researchers demonstrated that in such patients, endothelial biomarkers, particularly NEDD9, were associated with 60-day mortality. Increased understanding of biologic phenotypes in ARDS patients may facilitate the application of precision medicine to patients with this condition, improving outcome prediction and allowing practitioners to target specific treatments to selected patients.

CHEST

CHEST® Pulmonary

Association of Short-Term Increases in Ambient Fine Particulate Matter With Hospitalization for Asthma or COPD During Wildfire Season and Other Time Periods

By Horne, PhD, MStat, MPH, and colleagues

Trigger avoidance is one the most important interventions in the control of symptoms and prevention of exacerbations in chronic airways diseases. Nevertheless, trigger avoidance is at times not possible. This is the case with wildfire smoke and other environmental irritants—an increasing global health problem. Using data from 11 hospitals along the Utah’s Wasatch Front, the study by Horne and colleagues shows a clear association between a short-term increase in ambient fine particulate matter exposure resulting from wildfires and a surge in asthma exacerbations. This effect was also seen in patients with COPD but to a lesser degree. The study is limited by its observational design and because measurements of pollution levels were performed regionally and not at individual patient level. Yet this study offers valuable insights on the effects of environmental exposures in patients with chronic airways diseases and the consequences to our health care systems. Futures studies are still needed to assess the long-term consequences of sustained exposures to these irritants in patients with respiratory conditions.

CHEST

Journal CHEST®

Association Between Healthy Behaviors and Health Care Resource Use With Subsequent Positive Airway Pressure Therapy Adherence in OSA

By Launois, MD, PhD, and colleagues

One of the pitfalls in the interpretation of the effect of treatment adherence on health outcomes is the healthy-adherer effect (HAE) bias. Healthy-adherer bias occurs when patients who are treatment-adherent tend to actively seek out preventative care and engage in other healthy behaviors. Incomplete adjustment for such behaviors can lead to spurious inferences regarding study outcomes because healthy behaviors are associated with a reduced risk of many poor health outcomes.

This study demonstrates that HAE proxies (adherence to CV active drugs, no history of smoking, or sleepiness-related car accidents) were associated with subsequent PAP adherence after adjustment for confounders. PAP-adherent patients used less health care resources before PAP initiation. Unfortunately, the study did not measure other healthy behaviors (nutrition, physical activity, psychosocial support) that could also potentially explain HAE. Until the HAE associated with PAP adherence is better understood, clinicians should use caution when interpreting the association of PAP adherence with CV health outcomes and health care resource use.

CHEST

CHEST® Critical Care

Circulating Biomarkers of Endothelial Dysfunction Associated With Ventilatory Ratio and Mortality in ARDS Resulting From SARS-CoV-2 Infection Treated With Anti-inflammatory Therapies

By Alladina, MD, and colleagues

Practitioners in the intensive care unit have become increasingly aware that the population of patients with ARDS is highly heterogenous not only in terms of the inciting factors of their condition but also in terms of their respiratory physiology. Calfee and co-workers opened new horizons for us with their 2014 descriptions of two phenotypes of ARDS based upon biological markers that had different clinical outcome profiles. The work by Alladina et al adds to this body of knowledge by studying biomarkers from patients with COVID-ARDS who were receiving anti-inflammatory therapies. These researchers demonstrated that in such patients, endothelial biomarkers, particularly NEDD9, were associated with 60-day mortality. Increased understanding of biologic phenotypes in ARDS patients may facilitate the application of precision medicine to patients with this condition, improving outcome prediction and allowing practitioners to target specific treatments to selected patients.

CHEST

CHEST® Pulmonary

Association of Short-Term Increases in Ambient Fine Particulate Matter With Hospitalization for Asthma or COPD During Wildfire Season and Other Time Periods

By Horne, PhD, MStat, MPH, and colleagues

Trigger avoidance is one the most important interventions in the control of symptoms and prevention of exacerbations in chronic airways diseases. Nevertheless, trigger avoidance is at times not possible. This is the case with wildfire smoke and other environmental irritants—an increasing global health problem. Using data from 11 hospitals along the Utah’s Wasatch Front, the study by Horne and colleagues shows a clear association between a short-term increase in ambient fine particulate matter exposure resulting from wildfires and a surge in asthma exacerbations. This effect was also seen in patients with COPD but to a lesser degree. The study is limited by its observational design and because measurements of pollution levels were performed regionally and not at individual patient level. Yet this study offers valuable insights on the effects of environmental exposures in patients with chronic airways diseases and the consequences to our health care systems. Futures studies are still needed to assess the long-term consequences of sustained exposures to these irritants in patients with respiratory conditions.

CHEST

Journal CHEST®

Association Between Healthy Behaviors and Health Care Resource Use With Subsequent Positive Airway Pressure Therapy Adherence in OSA

By Launois, MD, PhD, and colleagues

One of the pitfalls in the interpretation of the effect of treatment adherence on health outcomes is the healthy-adherer effect (HAE) bias. Healthy-adherer bias occurs when patients who are treatment-adherent tend to actively seek out preventative care and engage in other healthy behaviors. Incomplete adjustment for such behaviors can lead to spurious inferences regarding study outcomes because healthy behaviors are associated with a reduced risk of many poor health outcomes.

This study demonstrates that HAE proxies (adherence to CV active drugs, no history of smoking, or sleepiness-related car accidents) were associated with subsequent PAP adherence after adjustment for confounders. PAP-adherent patients used less health care resources before PAP initiation. Unfortunately, the study did not measure other healthy behaviors (nutrition, physical activity, psychosocial support) that could also potentially explain HAE. Until the HAE associated with PAP adherence is better understood, clinicians should use caution when interpreting the association of PAP adherence with CV health outcomes and health care resource use.

CHEST

CHEST® Critical Care

Circulating Biomarkers of Endothelial Dysfunction Associated With Ventilatory Ratio and Mortality in ARDS Resulting From SARS-CoV-2 Infection Treated With Anti-inflammatory Therapies

By Alladina, MD, and colleagues

Practitioners in the intensive care unit have become increasingly aware that the population of patients with ARDS is highly heterogenous not only in terms of the inciting factors of their condition but also in terms of their respiratory physiology. Calfee and co-workers opened new horizons for us with their 2014 descriptions of two phenotypes of ARDS based upon biological markers that had different clinical outcome profiles. The work by Alladina et al adds to this body of knowledge by studying biomarkers from patients with COVID-ARDS who were receiving anti-inflammatory therapies. These researchers demonstrated that in such patients, endothelial biomarkers, particularly NEDD9, were associated with 60-day mortality. Increased understanding of biologic phenotypes in ARDS patients may facilitate the application of precision medicine to patients with this condition, improving outcome prediction and allowing practitioners to target specific treatments to selected patients.

CHEST

CHEST® Pulmonary

Association of Short-Term Increases in Ambient Fine Particulate Matter With Hospitalization for Asthma or COPD During Wildfire Season and Other Time Periods

By Horne, PhD, MStat, MPH, and colleagues

Trigger avoidance is one the most important interventions in the control of symptoms and prevention of exacerbations in chronic airways diseases. Nevertheless, trigger avoidance is at times not possible. This is the case with wildfire smoke and other environmental irritants—an increasing global health problem. Using data from 11 hospitals along the Utah’s Wasatch Front, the study by Horne and colleagues shows a clear association between a short-term increase in ambient fine particulate matter exposure resulting from wildfires and a surge in asthma exacerbations. This effect was also seen in patients with COPD but to a lesser degree. The study is limited by its observational design and because measurements of pollution levels were performed regionally and not at individual patient level. Yet this study offers valuable insights on the effects of environmental exposures in patients with chronic airways diseases and the consequences to our health care systems. Futures studies are still needed to assess the long-term consequences of sustained exposures to these irritants in patients with respiratory conditions.

CHEST

Earlier this year, Representative Greg Murphy, MD, along with several cosponsors, introduced H.R. 7725, the Embracing Anti-Discrimination, Unbiased Curricula, and Advancing Truth in Education (EDUCATE) Act.

If enacted, the EDUCATE Act would cut off federal funding to medical schools that force students or faculty to adopt specific beliefs; discriminate based on race or ethnicity; or have diversity, equity, and inclusion (DEI) offices or any functional equivalent. The bill would also require accreditation agencies to check that their standards do not push these practices, while still allowing instruction about health issues tied to race or collecting data for research.

In response to the introduction of this act, CHEST published a statement in support of DEI practices and their necessary role within the practice of health care and medical training programs.

It is our belief that health care requires a solid patient-provider therapeutic alliance to achieve successful outcomes, and decades of scientific research have shown that a lack of clinician diversity worsens health disparities. For patients from historically underserved communities, having clinicians who share similar lived experiences almost always leads to significant improvements in patient outcomes. If identity concordance is not feasible, clinicians with considerable exposure to diverse patient populations, equitable approaches to care, and inclusive perspectives on health gained through continuing, comprehensive medical education and professional training can also positively impact outcomes.

Research indicates that a diverse medical workforce improves cultural competence and can help clinicians better meet the needs of patients from diverse backgrounds and ethnicities and that the benefits of diverse learning environments enhance the educational experience of all participants. Racial and ethnic health inequities illuminate the greatest gaps and worst patient outcomes, especially when compounded by disparities related to gender identity, ability, language, immigration status, sexual orientation, age, socioeconomics, and other social drivers of health. Research also shows that nearly one-fifth of Latine Americans avoid medical care due to concern about experiencing discrimination, Black Americans have significantly lower life expectancies, and Asian Americans are the only racial group to experience cancer as a leading cause of death. It is also well documented that communities experiencing disproportionately high rates of COVID-19 infection, hospitalization, and mortality when compared with White Americans include Black, Latine, Asian, Native Hawaiian, and Native Americans.

“In 2023, the CHEST organization shared its organizational values: community, inclusivity, innovation, advocacy, and integrity,” said CHEST President, Jack D. Buckley, MD, MPH, FCCP. “In strong accordance with these values and with our mission to champion the prevention, diagnosis, and treatment of chest diseases and advance the best patient outcomes, CHEST is firmly committed to the necessity of diversity, equity, and inclusion in health care research, education, and delivery.”

Guided by our core values, CHEST is relentlessly committed to improving the professional’s experience and patient outcomes equally. This commitment compels us to work toward eliminating disparities in the medical field. According to the most recent US Census projections, by 2045, White Americans will no longer be considered a racial majority, with Black, Latine, and Asian Americans continuing to rise. It is incumbent upon us to ensure that our clinician workforce reflects the diversity of its local and national communities.

The underrepresentation of physicians from racially diverse backgrounds is factually clear. Black physicians comprise 5% of the current physician workforce despite Black Americans representing 13% of the population.¹ Similarly, while Native Americans comprise 3% of the United States population, Native American physicians account for less than 1% of the physician workforce, with less than 10% of medical schools reporting total enrollment of more than four Native American students.² Where gender is concerned, women make up about 36% of the physician workforce, a professional disparity that is further exacerbated given the intersections of race and gender, resulting in a significant impact on the current workforce.³ Allowing disinformation to influence the future of medical education and patient care directly contradicts our mission as clinicians dedicated to improving the health of all people.

If physician representation and patient outcomes are linked, as research shows, the lack of diverse medical school representation has dire consequences for matriculation, job recruitment, retention, and promotion. Without supportive policies, programs, and equity-focused curriculums in medical education, we will never close the gap on professional disparities, which means we will similarly never close the gap on health disparities.

Our commitment to our members, all health care professionals, and the field of medicine means that we will stand firm in our defense of DEI today and every day until we have achieved optimal, equitable health for all people in all places. CHEST is committed to an intersectional approach to equitable health care education and delivery. We strive to design solutions that center the most impacted and radiate support outward, ensuring our interventions benefit all others experiencing discrimination.

Read more about CHEST’s commitment to diversity and other advocacy work on the CHEST website.

References

1. AAMC. Figure 18. Percentage of all active physicians by race/ethnicity, 2018. AAMC; 2019. https://www.aamc.org/data-reports/workforce/data/figure-18-percentage-all-active-physicians-race/ethnicity-2018#:~:text=Diversity%20in%20Medicine%3A%20Facts%20and%20Figures%202019,-Diversity%20in%20Medicine&text=Among%20active%20physicians%2C%2056.2%25%20identified,as%20Black%20or%20African%20American

2. Murphy B. New effort to help Native American pre-meds pursue physician dreams. AMA. January 13, 2022. https://www.ama-assn.org/education/medical-school-diversity/new-effort-help-native-american-pre-meds-pursue-physician-dreams

3. AAMC. U.S. Physician Workforce Data Dashboard. AAMC; 2023. https://www.aamc.org/data-reports/report/us-physician-workforce-data-dashboard

Earlier this year, Representative Greg Murphy, MD, along with several cosponsors, introduced H.R. 7725, the Embracing Anti-Discrimination, Unbiased Curricula, and Advancing Truth in Education (EDUCATE) Act.

If enacted, the EDUCATE Act would cut off federal funding to medical schools that force students or faculty to adopt specific beliefs; discriminate based on race or ethnicity; or have diversity, equity, and inclusion (DEI) offices or any functional equivalent. The bill would also require accreditation agencies to check that their standards do not push these practices, while still allowing instruction about health issues tied to race or collecting data for research.

In response to the introduction of this act, CHEST published a statement in support of DEI practices and their necessary role within the practice of health care and medical training programs.

It is our belief that health care requires a solid patient-provider therapeutic alliance to achieve successful outcomes, and decades of scientific research have shown that a lack of clinician diversity worsens health disparities. For patients from historically underserved communities, having clinicians who share similar lived experiences almost always leads to significant improvements in patient outcomes. If identity concordance is not feasible, clinicians with considerable exposure to diverse patient populations, equitable approaches to care, and inclusive perspectives on health gained through continuing, comprehensive medical education and professional training can also positively impact outcomes.

Research indicates that a diverse medical workforce improves cultural competence and can help clinicians better meet the needs of patients from diverse backgrounds and ethnicities and that the benefits of diverse learning environments enhance the educational experience of all participants. Racial and ethnic health inequities illuminate the greatest gaps and worst patient outcomes, especially when compounded by disparities related to gender identity, ability, language, immigration status, sexual orientation, age, socioeconomics, and other social drivers of health. Research also shows that nearly one-fifth of Latine Americans avoid medical care due to concern about experiencing discrimination, Black Americans have significantly lower life expectancies, and Asian Americans are the only racial group to experience cancer as a leading cause of death. It is also well documented that communities experiencing disproportionately high rates of COVID-19 infection, hospitalization, and mortality when compared with White Americans include Black, Latine, Asian, Native Hawaiian, and Native Americans.

“In 2023, the CHEST organization shared its organizational values: community, inclusivity, innovation, advocacy, and integrity,” said CHEST President, Jack D. Buckley, MD, MPH, FCCP. “In strong accordance with these values and with our mission to champion the prevention, diagnosis, and treatment of chest diseases and advance the best patient outcomes, CHEST is firmly committed to the necessity of diversity, equity, and inclusion in health care research, education, and delivery.”

Guided by our core values, CHEST is relentlessly committed to improving the professional’s experience and patient outcomes equally. This commitment compels us to work toward eliminating disparities in the medical field. According to the most recent US Census projections, by 2045, White Americans will no longer be considered a racial majority, with Black, Latine, and Asian Americans continuing to rise. It is incumbent upon us to ensure that our clinician workforce reflects the diversity of its local and national communities.

The underrepresentation of physicians from racially diverse backgrounds is factually clear. Black physicians comprise 5% of the current physician workforce despite Black Americans representing 13% of the population.¹ Similarly, while Native Americans comprise 3% of the United States population, Native American physicians account for less than 1% of the physician workforce, with less than 10% of medical schools reporting total enrollment of more than four Native American students.² Where gender is concerned, women make up about 36% of the physician workforce, a professional disparity that is further exacerbated given the intersections of race and gender, resulting in a significant impact on the current workforce.³ Allowing disinformation to influence the future of medical education and patient care directly contradicts our mission as clinicians dedicated to improving the health of all people.

If physician representation and patient outcomes are linked, as research shows, the lack of diverse medical school representation has dire consequences for matriculation, job recruitment, retention, and promotion. Without supportive policies, programs, and equity-focused curriculums in medical education, we will never close the gap on professional disparities, which means we will similarly never close the gap on health disparities.

Our commitment to our members, all health care professionals, and the field of medicine means that we will stand firm in our defense of DEI today and every day until we have achieved optimal, equitable health for all people in all places. CHEST is committed to an intersectional approach to equitable health care education and delivery. We strive to design solutions that center the most impacted and radiate support outward, ensuring our interventions benefit all others experiencing discrimination.

Read more about CHEST’s commitment to diversity and other advocacy work on the CHEST website.

References

1. AAMC. Figure 18. Percentage of all active physicians by race/ethnicity, 2018. AAMC; 2019. https://www.aamc.org/data-reports/workforce/data/figure-18-percentage-all-active-physicians-race/ethnicity-2018#:~:text=Diversity%20in%20Medicine%3A%20Facts%20and%20Figures%202019,-Diversity%20in%20Medicine&text=Among%20active%20physicians%2C%2056.2%25%20identified,as%20Black%20or%20African%20American

2. Murphy B. New effort to help Native American pre-meds pursue physician dreams. AMA. January 13, 2022. https://www.ama-assn.org/education/medical-school-diversity/new-effort-help-native-american-pre-meds-pursue-physician-dreams

3. AAMC. U.S. Physician Workforce Data Dashboard. AAMC; 2023. https://www.aamc.org/data-reports/report/us-physician-workforce-data-dashboard

Earlier this year, Representative Greg Murphy, MD, along with several cosponsors, introduced H.R. 7725, the Embracing Anti-Discrimination, Unbiased Curricula, and Advancing Truth in Education (EDUCATE) Act.

If enacted, the EDUCATE Act would cut off federal funding to medical schools that force students or faculty to adopt specific beliefs; discriminate based on race or ethnicity; or have diversity, equity, and inclusion (DEI) offices or any functional equivalent. The bill would also require accreditation agencies to check that their standards do not push these practices, while still allowing instruction about health issues tied to race or collecting data for research.

In response to the introduction of this act, CHEST published a statement in support of DEI practices and their necessary role within the practice of health care and medical training programs.

It is our belief that health care requires a solid patient-provider therapeutic alliance to achieve successful outcomes, and decades of scientific research have shown that a lack of clinician diversity worsens health disparities. For patients from historically underserved communities, having clinicians who share similar lived experiences almost always leads to significant improvements in patient outcomes. If identity concordance is not feasible, clinicians with considerable exposure to diverse patient populations, equitable approaches to care, and inclusive perspectives on health gained through continuing, comprehensive medical education and professional training can also positively impact outcomes.

Research indicates that a diverse medical workforce improves cultural competence and can help clinicians better meet the needs of patients from diverse backgrounds and ethnicities and that the benefits of diverse learning environments enhance the educational experience of all participants. Racial and ethnic health inequities illuminate the greatest gaps and worst patient outcomes, especially when compounded by disparities related to gender identity, ability, language, immigration status, sexual orientation, age, socioeconomics, and other social drivers of health. Research also shows that nearly one-fifth of Latine Americans avoid medical care due to concern about experiencing discrimination, Black Americans have significantly lower life expectancies, and Asian Americans are the only racial group to experience cancer as a leading cause of death. It is also well documented that communities experiencing disproportionately high rates of COVID-19 infection, hospitalization, and mortality when compared with White Americans include Black, Latine, Asian, Native Hawaiian, and Native Americans.

“In 2023, the CHEST organization shared its organizational values: community, inclusivity, innovation, advocacy, and integrity,” said CHEST President, Jack D. Buckley, MD, MPH, FCCP. “In strong accordance with these values and with our mission to champion the prevention, diagnosis, and treatment of chest diseases and advance the best patient outcomes, CHEST is firmly committed to the necessity of diversity, equity, and inclusion in health care research, education, and delivery.”

Guided by our core values, CHEST is relentlessly committed to improving the professional’s experience and patient outcomes equally. This commitment compels us to work toward eliminating disparities in the medical field. According to the most recent US Census projections, by 2045, White Americans will no longer be considered a racial majority, with Black, Latine, and Asian Americans continuing to rise. It is incumbent upon us to ensure that our clinician workforce reflects the diversity of its local and national communities.

The underrepresentation of physicians from racially diverse backgrounds is factually clear. Black physicians comprise 5% of the current physician workforce despite Black Americans representing 13% of the population.¹ Similarly, while Native Americans comprise 3% of the United States population, Native American physicians account for less than 1% of the physician workforce, with less than 10% of medical schools reporting total enrollment of more than four Native American students.² Where gender is concerned, women make up about 36% of the physician workforce, a professional disparity that is further exacerbated given the intersections of race and gender, resulting in a significant impact on the current workforce.³ Allowing disinformation to influence the future of medical education and patient care directly contradicts our mission as clinicians dedicated to improving the health of all people.

If physician representation and patient outcomes are linked, as research shows, the lack of diverse medical school representation has dire consequences for matriculation, job recruitment, retention, and promotion. Without supportive policies, programs, and equity-focused curriculums in medical education, we will never close the gap on professional disparities, which means we will similarly never close the gap on health disparities.

Our commitment to our members, all health care professionals, and the field of medicine means that we will stand firm in our defense of DEI today and every day until we have achieved optimal, equitable health for all people in all places. CHEST is committed to an intersectional approach to equitable health care education and delivery. We strive to design solutions that center the most impacted and radiate support outward, ensuring our interventions benefit all others experiencing discrimination.

Read more about CHEST’s commitment to diversity and other advocacy work on the CHEST website.

References

1. AAMC. Figure 18. Percentage of all active physicians by race/ethnicity, 2018. AAMC; 2019. https://www.aamc.org/data-reports/workforce/data/figure-18-percentage-all-active-physicians-race/ethnicity-2018#:~:text=Diversity%20in%20Medicine%3A%20Facts%20and%20Figures%202019,-Diversity%20in%20Medicine&text=Among%20active%20physicians%2C%2056.2%25%20identified,as%20Black%20or%20African%20American

2. Murphy B. New effort to help Native American pre-meds pursue physician dreams. AMA. January 13, 2022. https://www.ama-assn.org/education/medical-school-diversity/new-effort-help-native-american-pre-meds-pursue-physician-dreams

3. AAMC. U.S. Physician Workforce Data Dashboard. AAMC; 2023. https://www.aamc.org/data-reports/report/us-physician-workforce-data-dashboard