Mixed Topics

TOPLINE:

The efficacy of clascoterone cream 1% for treating acne vulgaris appears to increase over time after 12 weeks of use and up to 1 year.

METHODOLOGY:

• A 1% cream formulation of clascoterone, a topical androgen receptor inhibitor, is approved for the treatment of acne vulgaris in patients aged 12 years and older based on results from two identical phase 3 12-week trials, NCT02608450 and NCT02608476, and a long-term extension (LTE) study.
• The purpose of the current study was to evaluate the integrated efficacy of clascoterone cream 1% (Winlevi) in the intention-to-treat population of patients from all three trials.
• In the pivotal trials, investigators randomized patients with acne 1:1 to receive clascoterone cream 1% or vehicle twice daily for 12 weeks. Participants were eligible to enter the LTE study, in which patients applied clascoterone to the face, and if they wanted to, the trunk for up to 9 more months.
• To assess combined efficacy, researchers evaluated the proportion of patients who achieved an Investigator’s Global Assessment (IGA) of 0 or 1.

TAKEAWAY:

• Of the 1143 patients from the pivotal trials who completed 12 weeks of treatment, 576 were in the clascoterone group and 567 were in the vehicle group. Of the 600 patients who entered the LTE study, 311 were in the clascoterone group and 289 were in the vehicle group. Of these, 343 completed the LTE study.
• At week 12, the proportion of patients who achieved treatment success was higher in the clascoterone group than in the vehicle group (19.9% vs 7.7%, respectively; P < .0001).
• In the LTE study, the proportion of patients previously treated with clascoterone who achieved a facial IGA of 0/1 increased from 13.5% at extension day 0 to 29.9% at extension day 274, while the proportion of patients previously treated with vehicle and switched to clascoterone who achieved a facial IGA of 0/1 increased from 6.2% at extension day 0 to 30.4% at extension day 274.
• Similarly, the proportion of patients in the LTE study with a truncal IGA of 0/1 increased from 4.9% at extension day 0 to 31.7% on extension day 274.

IN PRACTICE:

“Clinicians may consider counseling patients that treatment persistence is required to maximize the efficacy of clascoterone treatment,” the authors concluded.

SOURCE:

Lawrence F. Eichenfield, MD, of the departments of dermatology and pediatrics at the University of California and Rady Children’s Hospital, San Diego, California, led the research. The study was published in the January 2024 issue of the Journal of Drugs in Dermatology.

LIMITATIONS:

There was a high patient discontinuation rate before and during the LET study. Also, no assessment was made as to how clascoterone affected patients’ quality of life.

DISCLOSURES:

Clascoterone manufacturer Cassiopea funded the studies. Dr. Eichenfield and fellow investigators Adelaide A. Hebert, MD, and Linda Stein Gold, MD, received compensation from Cassiopea as advisers and disclosed ties to many other pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The efficacy of clascoterone cream 1% for treating acne vulgaris appears to increase over time after 12 weeks of use and up to 1 year.

METHODOLOGY:

• A 1% cream formulation of clascoterone, a topical androgen receptor inhibitor, is approved for the treatment of acne vulgaris in patients aged 12 years and older based on results from two identical phase 3 12-week trials, NCT02608450 and NCT02608476, and a long-term extension (LTE) study.
• The purpose of the current study was to evaluate the integrated efficacy of clascoterone cream 1% (Winlevi) in the intention-to-treat population of patients from all three trials.
• In the pivotal trials, investigators randomized patients with acne 1:1 to receive clascoterone cream 1% or vehicle twice daily for 12 weeks. Participants were eligible to enter the LTE study, in which patients applied clascoterone to the face, and if they wanted to, the trunk for up to 9 more months.
• To assess combined efficacy, researchers evaluated the proportion of patients who achieved an Investigator’s Global Assessment (IGA) of 0 or 1.

TAKEAWAY:

• Of the 1143 patients from the pivotal trials who completed 12 weeks of treatment, 576 were in the clascoterone group and 567 were in the vehicle group. Of the 600 patients who entered the LTE study, 311 were in the clascoterone group and 289 were in the vehicle group. Of these, 343 completed the LTE study.
• At week 12, the proportion of patients who achieved treatment success was higher in the clascoterone group than in the vehicle group (19.9% vs 7.7%, respectively; P < .0001).
• In the LTE study, the proportion of patients previously treated with clascoterone who achieved a facial IGA of 0/1 increased from 13.5% at extension day 0 to 29.9% at extension day 274, while the proportion of patients previously treated with vehicle and switched to clascoterone who achieved a facial IGA of 0/1 increased from 6.2% at extension day 0 to 30.4% at extension day 274.
• Similarly, the proportion of patients in the LTE study with a truncal IGA of 0/1 increased from 4.9% at extension day 0 to 31.7% on extension day 274.

IN PRACTICE:

“Clinicians may consider counseling patients that treatment persistence is required to maximize the efficacy of clascoterone treatment,” the authors concluded.

SOURCE:

Lawrence F. Eichenfield, MD, of the departments of dermatology and pediatrics at the University of California and Rady Children’s Hospital, San Diego, California, led the research. The study was published in the January 2024 issue of the Journal of Drugs in Dermatology.

LIMITATIONS:

There was a high patient discontinuation rate before and during the LET study. Also, no assessment was made as to how clascoterone affected patients’ quality of life.

DISCLOSURES:

Clascoterone manufacturer Cassiopea funded the studies. Dr. Eichenfield and fellow investigators Adelaide A. Hebert, MD, and Linda Stein Gold, MD, received compensation from Cassiopea as advisers and disclosed ties to many other pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The efficacy of clascoterone cream 1% for treating acne vulgaris appears to increase over time after 12 weeks of use and up to 1 year.

METHODOLOGY:

• A 1% cream formulation of clascoterone, a topical androgen receptor inhibitor, is approved for the treatment of acne vulgaris in patients aged 12 years and older based on results from two identical phase 3 12-week trials, NCT02608450 and NCT02608476, and a long-term extension (LTE) study.
• The purpose of the current study was to evaluate the integrated efficacy of clascoterone cream 1% (Winlevi) in the intention-to-treat population of patients from all three trials.
• In the pivotal trials, investigators randomized patients with acne 1:1 to receive clascoterone cream 1% or vehicle twice daily for 12 weeks. Participants were eligible to enter the LTE study, in which patients applied clascoterone to the face, and if they wanted to, the trunk for up to 9 more months.
• To assess combined efficacy, researchers evaluated the proportion of patients who achieved an Investigator’s Global Assessment (IGA) of 0 or 1.

TAKEAWAY:

• Of the 1143 patients from the pivotal trials who completed 12 weeks of treatment, 576 were in the clascoterone group and 567 were in the vehicle group. Of the 600 patients who entered the LTE study, 311 were in the clascoterone group and 289 were in the vehicle group. Of these, 343 completed the LTE study.
• At week 12, the proportion of patients who achieved treatment success was higher in the clascoterone group than in the vehicle group (19.9% vs 7.7%, respectively; P < .0001).
• In the LTE study, the proportion of patients previously treated with clascoterone who achieved a facial IGA of 0/1 increased from 13.5% at extension day 0 to 29.9% at extension day 274, while the proportion of patients previously treated with vehicle and switched to clascoterone who achieved a facial IGA of 0/1 increased from 6.2% at extension day 0 to 30.4% at extension day 274.
• Similarly, the proportion of patients in the LTE study with a truncal IGA of 0/1 increased from 4.9% at extension day 0 to 31.7% on extension day 274.

IN PRACTICE:

“Clinicians may consider counseling patients that treatment persistence is required to maximize the efficacy of clascoterone treatment,” the authors concluded.

SOURCE:

Lawrence F. Eichenfield, MD, of the departments of dermatology and pediatrics at the University of California and Rady Children’s Hospital, San Diego, California, led the research. The study was published in the January 2024 issue of the Journal of Drugs in Dermatology.

LIMITATIONS:

There was a high patient discontinuation rate before and during the LET study. Also, no assessment was made as to how clascoterone affected patients’ quality of life.

DISCLOSURES:

Clascoterone manufacturer Cassiopea funded the studies. Dr. Eichenfield and fellow investigators Adelaide A. Hebert, MD, and Linda Stein Gold, MD, received compensation from Cassiopea as advisers and disclosed ties to many other pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

Nearly 10% of survivors of head, neck, esophageal, and gastric cancers experienced active substance use disorders, based on data from more than 6,000 individuals.

The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.

“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.

In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.

The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.

Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).

Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.

Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).

The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
 

Limitations and Implications

The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.

“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.

“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
 

Integrated care is needed

“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.

Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
 

Recognize risk factors

“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.

The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
 

Individualize risk assessment

“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.

As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.

The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.

Nearly 10% of survivors of head, neck, esophageal, and gastric cancers experienced active substance use disorders, based on data from more than 6,000 individuals.

The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.

“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.

In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.

The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.

Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).

Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.

Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).

The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
 

Limitations and Implications

The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.

“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.

“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
 

Integrated care is needed

“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.

Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
 

Recognize risk factors

“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.

The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
 

Individualize risk assessment

“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.

As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.

The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.

Nearly 10% of survivors of head, neck, esophageal, and gastric cancers experienced active substance use disorders, based on data from more than 6,000 individuals.

The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.

“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.

In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.

The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.

Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).

Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.

Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).

The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
 

Limitations and Implications

The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.

“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.

“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
 

Integrated care is needed

“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.

Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
 

Recognize risk factors

“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.

The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
 

Individualize risk assessment

“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.

As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.

The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

About 60% of US physicians who served as panel and task force members for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) received more than $14 million in undisclosed industry funding, a new study shows. 

Most payments were for food and beverages, travel, and consulting fees. But more than one third of contributors received compensation for services other than consulting, such as serving on a pharmaceutical company’s speakers bureau, which medical ethicists say is particularly problematic. 

Often referred to as the bible of psychiatric disorders, the DSM-5-TR was released in 2022 by the American Psychiatric Association (APA) and includes changes that were made online since the DSM-5 was first published in 2013.

An APA spokesperson said that DSM-5-TR decision-makers were unable to participate if they had received more than $5000 in industry payments and that all 186 individuals who worked on the text revision were required to disclose all sources of income prior to their participation. 

“The APA implemented and enforced a rigorous process for DSM-5-TR that required transparency by all contributors of their personal and professional interests, followed by an independent review to ensure that personal and professional interests did not bias any results,” the spokesperson said.

However, having industry funding did not preclude contributors’ participation, and investigators note that none of the disclosures were published in the manual or shared publicly. 

“The point is not to point fingers at the APA or individual members of the APA but rather to provide hopefully a small piece of research data that would help the APA look at the larger systemic issue of conflicts of interest,” said the study’s lead investigator Lisa Cosgrove, PhD, professor of counseling and faculty fellow in the Applied Ethics Center at the University of Massachusetts Boston. 

The findings were published online in The BMJ .

A Deep Dive

The work builds on the investigators’ earlier research into financial conflicts among DSM contributors. The lack of a centralized database of industry payments made the group›s prior studies far more complicated and time-consuming. 

For this project, investigators drew on the Open Payments database, which launched in 2014. It collects and publishes data on payments by pharmaceutical and medical device companies to physicians and other healthcare professionals for research, meals, travel, gifts, speaking fees, and other expenses. The program was established as part of the Affordable Care Act and is run by the Centers for Medicare & Medicaid Services. 

Investigators analyzed industry payments made to DSM-5-TR contributors between 2016 and 2019, just before work on the text revision began. Of the 168 individuals listed as contributors to the manual, 92 met the inclusion criteria of being a US-based physician with industry payments tracked in Open Payments.

Fifty-five of those physicians, or 59.8%, had financial ties to industry. The most common type of payment was for food and beverages (90.9%), travel (69.1%), and consulting (69.1%). Nineteen panel members received $1.8 million for “compensation for services other than consulting, including serving as faculty or as a speaker at a venue other than a continuing education program.”

The greatest proportion of compensation by category of payment was for research funding (71%).

Investigators found that every DSM-5-TR panel included at least one member with industry ties. The panels with the highest number of members with a recent history of industry funding were those for neurodevelopmental disorders; bipolar disorders; obsessive-compulsive disorders; neurocognitive disorders; medication induced movement disorders; and disruptive, impulse control, and conduct disorders. More than 70% of members on those panels had received industry funding. 

The total payments received by all contributors was more than $14.2 million, with a range from just under $14 per physician to $2.7 million per physician. The researchers note that the percentage of panel members with industry support was similar between DSM-5-TR and DSM-5.

“What we also see that’s consistent with our 2016 study and 2012 study is the panels for which the members had the most financial ties to industry were those for which pharmaceutical interventions are the first line of therapy,” Dr. Cosgrove said.

No Public Disclosure

For DSM-5, the APA instituted a new disclosure policy for contributors and reported those disclosures on its website. 

This time, the association spokesperson said that DSM-5-TR chairs and the DSM Steering Committee who reviewed all proposed changes were required to have no industry-related income above $5000 and that “in fact, many had no industry income.”

Other DSM-5-TR contributors had to submit “extensive” disclosure forms and report “any relationships they or close relations had with industry (very broadly defined) and sources of income,” the spokesperson added. They were also asked to report other nonfinancial interests that they or close relatives had that could potentially bias their work. 

The APA’s standing Conflict of Interest Committee reviewed all disclosure forms and flagged those with disclosures that could impact content. Text written by individuals with flagged disclosures received additional review, the spokesperson said. 

“If any possible bias was noted in the text content, such as for a potential commercial advantage with a diagnostic instrument, that content was deleted,” the spokesperson said.

However, the real sticking point for medical ethicists is that unlike with the DSM-5, the APA did not share DSM-5-TR contributors’ disclosures publicly. 

Commenting on the research, Bernard Lo, MD, professor emeritus of medicine and director emeritus of the Program in Medical Ethics Emeritus at University of California, San Francisco, said that the lack of public disclosure is critical.

“Part of the report should be, ‘Here are the conflicts of interest reported by the members of the panel,’” said Dr. Lo, adding that publishing disclosures is standard in all of APA’s peer-reviewed journals. “Failure to do that in the DSM-5-TR is unacceptable from an ethical and transparency point of view.”

Loss of Public Trust?

In her previous research and in this new study, Dr. Cosgrove recommends the APA follow the 2011 report Clinical Practice Guidelines We Can Trust. Published by the Institute of Medicine (IOM, now called the National Academy of Medicine), that report updated and streamlined a 2009 conflicts of interest guideline, which Dr. Lo coauthored. 

“The IOM recommends that the whole guideline development group be free of industry ties,” Dr. Cosgrove said. “At a minimum, the chair should not have ties and the majority of folks should not have ties to industry.”

Some have argued that banning all contributors with industry ties would shrink the expert pool that develops the DSM and other guidelines. Dr. Cosgrove disagrees with that assertion.

“There are hundreds of experts in all medical disciplines that do not have industry ties,” Dr. Cosgrove said. “The ‘most experts have industry ties’ is a spurious and unsupported argument.”

The APA also should ban contributors who receive industry funding as key opinion leaders, known as KOLs, such as members of pharmaceutical companies’ speakers bureaus, Dr. Lo said. 

“Certain types of funding relationships with industry are more fraught with ethical problems,” including KOLs, who Dr. Lo said are “basically salespeople trying to increase sales of a product.” 

“It really compromises their scientific objectivity and should exclude someone from any practice guideline body,” Dr. Lo said. “This failure to adequately address conflicts of interest doesn’t promote transparency and it doesn’t promote public trust in the diagnostic criteria.”

The Larger Issue

Removing financial conflicts of interest is a start, but it wouldn’t address the larger issue in medicine, said Allen Frances, MD, who chaired the DSM-4 task force and has been an outspoken critic of the DSM-5. 

“The financial conflicts of interest may play a role with some people, I’m not denying that,” said Dr. Frances, a professor and chair emeritus of psychiatry at Duke University, Durham, North Carolina. “But that’s a much smaller problem than the fact that any individual from any professional association that has an intense interest in any given diagnosis will always be on the side of expanding that diagnosis and expanding the treatment for it.”

Though financial conflicts of interest can be addressed, Frances believes that professionals’ “intellectual and emotional conflicts” are much harder to overcome. 

“People who spend their careers working on any diagnosis are terribly biased by virtue of their attachment to their work,” he said. 

The solution is for guidelines in psychiatry and all medical fields to be developed by a truly multidisciplinary “neutral board” that includes broad representation of primary care physicians. 

Specialists would be involved in the development of the guidelines but would not have a final say in what diagnoses or treatments are included or excluded. 

“80% of psychiatric meds are prescribed by primary care doctors, not psychiatrists,” he said. “So, when you’re making a suggestion for a change in psychiatry, you’re making that suggestion primarily for primary care doctor and have to be thinking about, How will this change play in primary care, which the experts never do.”

The study was unfunded. Dr. Allen reported no relevant disclosures. Dr. Lo served as a paid member of the Takeda Pharmaceuticals Ethics Advisory Committee.

A version of this article appeared on Medscape.com.

About 60% of US physicians who served as panel and task force members for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) received more than $14 million in undisclosed industry funding, a new study shows. 

Most payments were for food and beverages, travel, and consulting fees. But more than one third of contributors received compensation for services other than consulting, such as serving on a pharmaceutical company’s speakers bureau, which medical ethicists say is particularly problematic. 

Often referred to as the bible of psychiatric disorders, the DSM-5-TR was released in 2022 by the American Psychiatric Association (APA) and includes changes that were made online since the DSM-5 was first published in 2013.

An APA spokesperson said that DSM-5-TR decision-makers were unable to participate if they had received more than $5000 in industry payments and that all 186 individuals who worked on the text revision were required to disclose all sources of income prior to their participation. 

“The APA implemented and enforced a rigorous process for DSM-5-TR that required transparency by all contributors of their personal and professional interests, followed by an independent review to ensure that personal and professional interests did not bias any results,” the spokesperson said.

However, having industry funding did not preclude contributors’ participation, and investigators note that none of the disclosures were published in the manual or shared publicly. 

“The point is not to point fingers at the APA or individual members of the APA but rather to provide hopefully a small piece of research data that would help the APA look at the larger systemic issue of conflicts of interest,” said the study’s lead investigator Lisa Cosgrove, PhD, professor of counseling and faculty fellow in the Applied Ethics Center at the University of Massachusetts Boston. 

The findings were published online in The BMJ .

A Deep Dive

The work builds on the investigators’ earlier research into financial conflicts among DSM contributors. The lack of a centralized database of industry payments made the group›s prior studies far more complicated and time-consuming. 

For this project, investigators drew on the Open Payments database, which launched in 2014. It collects and publishes data on payments by pharmaceutical and medical device companies to physicians and other healthcare professionals for research, meals, travel, gifts, speaking fees, and other expenses. The program was established as part of the Affordable Care Act and is run by the Centers for Medicare & Medicaid Services. 

Investigators analyzed industry payments made to DSM-5-TR contributors between 2016 and 2019, just before work on the text revision began. Of the 168 individuals listed as contributors to the manual, 92 met the inclusion criteria of being a US-based physician with industry payments tracked in Open Payments.

Fifty-five of those physicians, or 59.8%, had financial ties to industry. The most common type of payment was for food and beverages (90.9%), travel (69.1%), and consulting (69.1%). Nineteen panel members received $1.8 million for “compensation for services other than consulting, including serving as faculty or as a speaker at a venue other than a continuing education program.”

The greatest proportion of compensation by category of payment was for research funding (71%).

Investigators found that every DSM-5-TR panel included at least one member with industry ties. The panels with the highest number of members with a recent history of industry funding were those for neurodevelopmental disorders; bipolar disorders; obsessive-compulsive disorders; neurocognitive disorders; medication induced movement disorders; and disruptive, impulse control, and conduct disorders. More than 70% of members on those panels had received industry funding. 

The total payments received by all contributors was more than $14.2 million, with a range from just under $14 per physician to $2.7 million per physician. The researchers note that the percentage of panel members with industry support was similar between DSM-5-TR and DSM-5.

“What we also see that’s consistent with our 2016 study and 2012 study is the panels for which the members had the most financial ties to industry were those for which pharmaceutical interventions are the first line of therapy,” Dr. Cosgrove said.

No Public Disclosure

For DSM-5, the APA instituted a new disclosure policy for contributors and reported those disclosures on its website. 

This time, the association spokesperson said that DSM-5-TR chairs and the DSM Steering Committee who reviewed all proposed changes were required to have no industry-related income above $5000 and that “in fact, many had no industry income.”

Other DSM-5-TR contributors had to submit “extensive” disclosure forms and report “any relationships they or close relations had with industry (very broadly defined) and sources of income,” the spokesperson added. They were also asked to report other nonfinancial interests that they or close relatives had that could potentially bias their work. 

The APA’s standing Conflict of Interest Committee reviewed all disclosure forms and flagged those with disclosures that could impact content. Text written by individuals with flagged disclosures received additional review, the spokesperson said. 

“If any possible bias was noted in the text content, such as for a potential commercial advantage with a diagnostic instrument, that content was deleted,” the spokesperson said.

However, the real sticking point for medical ethicists is that unlike with the DSM-5, the APA did not share DSM-5-TR contributors’ disclosures publicly. 

Commenting on the research, Bernard Lo, MD, professor emeritus of medicine and director emeritus of the Program in Medical Ethics Emeritus at University of California, San Francisco, said that the lack of public disclosure is critical.

“Part of the report should be, ‘Here are the conflicts of interest reported by the members of the panel,’” said Dr. Lo, adding that publishing disclosures is standard in all of APA’s peer-reviewed journals. “Failure to do that in the DSM-5-TR is unacceptable from an ethical and transparency point of view.”

Loss of Public Trust?

In her previous research and in this new study, Dr. Cosgrove recommends the APA follow the 2011 report Clinical Practice Guidelines We Can Trust. Published by the Institute of Medicine (IOM, now called the National Academy of Medicine), that report updated and streamlined a 2009 conflicts of interest guideline, which Dr. Lo coauthored. 

“The IOM recommends that the whole guideline development group be free of industry ties,” Dr. Cosgrove said. “At a minimum, the chair should not have ties and the majority of folks should not have ties to industry.”

Some have argued that banning all contributors with industry ties would shrink the expert pool that develops the DSM and other guidelines. Dr. Cosgrove disagrees with that assertion.

“There are hundreds of experts in all medical disciplines that do not have industry ties,” Dr. Cosgrove said. “The ‘most experts have industry ties’ is a spurious and unsupported argument.”

The APA also should ban contributors who receive industry funding as key opinion leaders, known as KOLs, such as members of pharmaceutical companies’ speakers bureaus, Dr. Lo said. 

“Certain types of funding relationships with industry are more fraught with ethical problems,” including KOLs, who Dr. Lo said are “basically salespeople trying to increase sales of a product.” 

“It really compromises their scientific objectivity and should exclude someone from any practice guideline body,” Dr. Lo said. “This failure to adequately address conflicts of interest doesn’t promote transparency and it doesn’t promote public trust in the diagnostic criteria.”

The Larger Issue

Removing financial conflicts of interest is a start, but it wouldn’t address the larger issue in medicine, said Allen Frances, MD, who chaired the DSM-4 task force and has been an outspoken critic of the DSM-5. 

“The financial conflicts of interest may play a role with some people, I’m not denying that,” said Dr. Frances, a professor and chair emeritus of psychiatry at Duke University, Durham, North Carolina. “But that’s a much smaller problem than the fact that any individual from any professional association that has an intense interest in any given diagnosis will always be on the side of expanding that diagnosis and expanding the treatment for it.”

Though financial conflicts of interest can be addressed, Frances believes that professionals’ “intellectual and emotional conflicts” are much harder to overcome. 

“People who spend their careers working on any diagnosis are terribly biased by virtue of their attachment to their work,” he said. 

The solution is for guidelines in psychiatry and all medical fields to be developed by a truly multidisciplinary “neutral board” that includes broad representation of primary care physicians. 

Specialists would be involved in the development of the guidelines but would not have a final say in what diagnoses or treatments are included or excluded. 

“80% of psychiatric meds are prescribed by primary care doctors, not psychiatrists,” he said. “So, when you’re making a suggestion for a change in psychiatry, you’re making that suggestion primarily for primary care doctor and have to be thinking about, How will this change play in primary care, which the experts never do.”

The study was unfunded. Dr. Allen reported no relevant disclosures. Dr. Lo served as a paid member of the Takeda Pharmaceuticals Ethics Advisory Committee.

A version of this article appeared on Medscape.com.

About 60% of US physicians who served as panel and task force members for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) received more than $14 million in undisclosed industry funding, a new study shows. 

Most payments were for food and beverages, travel, and consulting fees. But more than one third of contributors received compensation for services other than consulting, such as serving on a pharmaceutical company’s speakers bureau, which medical ethicists say is particularly problematic. 

Often referred to as the bible of psychiatric disorders, the DSM-5-TR was released in 2022 by the American Psychiatric Association (APA) and includes changes that were made online since the DSM-5 was first published in 2013.

An APA spokesperson said that DSM-5-TR decision-makers were unable to participate if they had received more than $5000 in industry payments and that all 186 individuals who worked on the text revision were required to disclose all sources of income prior to their participation. 

“The APA implemented and enforced a rigorous process for DSM-5-TR that required transparency by all contributors of their personal and professional interests, followed by an independent review to ensure that personal and professional interests did not bias any results,” the spokesperson said.

However, having industry funding did not preclude contributors’ participation, and investigators note that none of the disclosures were published in the manual or shared publicly. 

“The point is not to point fingers at the APA or individual members of the APA but rather to provide hopefully a small piece of research data that would help the APA look at the larger systemic issue of conflicts of interest,” said the study’s lead investigator Lisa Cosgrove, PhD, professor of counseling and faculty fellow in the Applied Ethics Center at the University of Massachusetts Boston. 

The findings were published online in The BMJ .

A Deep Dive

The work builds on the investigators’ earlier research into financial conflicts among DSM contributors. The lack of a centralized database of industry payments made the group›s prior studies far more complicated and time-consuming. 

For this project, investigators drew on the Open Payments database, which launched in 2014. It collects and publishes data on payments by pharmaceutical and medical device companies to physicians and other healthcare professionals for research, meals, travel, gifts, speaking fees, and other expenses. The program was established as part of the Affordable Care Act and is run by the Centers for Medicare & Medicaid Services. 

Investigators analyzed industry payments made to DSM-5-TR contributors between 2016 and 2019, just before work on the text revision began. Of the 168 individuals listed as contributors to the manual, 92 met the inclusion criteria of being a US-based physician with industry payments tracked in Open Payments.

Fifty-five of those physicians, or 59.8%, had financial ties to industry. The most common type of payment was for food and beverages (90.9%), travel (69.1%), and consulting (69.1%). Nineteen panel members received $1.8 million for “compensation for services other than consulting, including serving as faculty or as a speaker at a venue other than a continuing education program.”

The greatest proportion of compensation by category of payment was for research funding (71%).

Investigators found that every DSM-5-TR panel included at least one member with industry ties. The panels with the highest number of members with a recent history of industry funding were those for neurodevelopmental disorders; bipolar disorders; obsessive-compulsive disorders; neurocognitive disorders; medication induced movement disorders; and disruptive, impulse control, and conduct disorders. More than 70% of members on those panels had received industry funding. 

The total payments received by all contributors was more than $14.2 million, with a range from just under $14 per physician to $2.7 million per physician. The researchers note that the percentage of panel members with industry support was similar between DSM-5-TR and DSM-5.

“What we also see that’s consistent with our 2016 study and 2012 study is the panels for which the members had the most financial ties to industry were those for which pharmaceutical interventions are the first line of therapy,” Dr. Cosgrove said.

No Public Disclosure

For DSM-5, the APA instituted a new disclosure policy for contributors and reported those disclosures on its website. 

This time, the association spokesperson said that DSM-5-TR chairs and the DSM Steering Committee who reviewed all proposed changes were required to have no industry-related income above $5000 and that “in fact, many had no industry income.”

Other DSM-5-TR contributors had to submit “extensive” disclosure forms and report “any relationships they or close relations had with industry (very broadly defined) and sources of income,” the spokesperson added. They were also asked to report other nonfinancial interests that they or close relatives had that could potentially bias their work. 

The APA’s standing Conflict of Interest Committee reviewed all disclosure forms and flagged those with disclosures that could impact content. Text written by individuals with flagged disclosures received additional review, the spokesperson said. 

“If any possible bias was noted in the text content, such as for a potential commercial advantage with a diagnostic instrument, that content was deleted,” the spokesperson said.

However, the real sticking point for medical ethicists is that unlike with the DSM-5, the APA did not share DSM-5-TR contributors’ disclosures publicly. 

Commenting on the research, Bernard Lo, MD, professor emeritus of medicine and director emeritus of the Program in Medical Ethics Emeritus at University of California, San Francisco, said that the lack of public disclosure is critical.

“Part of the report should be, ‘Here are the conflicts of interest reported by the members of the panel,’” said Dr. Lo, adding that publishing disclosures is standard in all of APA’s peer-reviewed journals. “Failure to do that in the DSM-5-TR is unacceptable from an ethical and transparency point of view.”

Loss of Public Trust?

In her previous research and in this new study, Dr. Cosgrove recommends the APA follow the 2011 report Clinical Practice Guidelines We Can Trust. Published by the Institute of Medicine (IOM, now called the National Academy of Medicine), that report updated and streamlined a 2009 conflicts of interest guideline, which Dr. Lo coauthored. 

“The IOM recommends that the whole guideline development group be free of industry ties,” Dr. Cosgrove said. “At a minimum, the chair should not have ties and the majority of folks should not have ties to industry.”

Some have argued that banning all contributors with industry ties would shrink the expert pool that develops the DSM and other guidelines. Dr. Cosgrove disagrees with that assertion.

“There are hundreds of experts in all medical disciplines that do not have industry ties,” Dr. Cosgrove said. “The ‘most experts have industry ties’ is a spurious and unsupported argument.”

The APA also should ban contributors who receive industry funding as key opinion leaders, known as KOLs, such as members of pharmaceutical companies’ speakers bureaus, Dr. Lo said. 

“Certain types of funding relationships with industry are more fraught with ethical problems,” including KOLs, who Dr. Lo said are “basically salespeople trying to increase sales of a product.” 

“It really compromises their scientific objectivity and should exclude someone from any practice guideline body,” Dr. Lo said. “This failure to adequately address conflicts of interest doesn’t promote transparency and it doesn’t promote public trust in the diagnostic criteria.”

The Larger Issue

Removing financial conflicts of interest is a start, but it wouldn’t address the larger issue in medicine, said Allen Frances, MD, who chaired the DSM-4 task force and has been an outspoken critic of the DSM-5. 

“The financial conflicts of interest may play a role with some people, I’m not denying that,” said Dr. Frances, a professor and chair emeritus of psychiatry at Duke University, Durham, North Carolina. “But that’s a much smaller problem than the fact that any individual from any professional association that has an intense interest in any given diagnosis will always be on the side of expanding that diagnosis and expanding the treatment for it.”

Though financial conflicts of interest can be addressed, Frances believes that professionals’ “intellectual and emotional conflicts” are much harder to overcome. 

“People who spend their careers working on any diagnosis are terribly biased by virtue of their attachment to their work,” he said. 

The solution is for guidelines in psychiatry and all medical fields to be developed by a truly multidisciplinary “neutral board” that includes broad representation of primary care physicians. 

Specialists would be involved in the development of the guidelines but would not have a final say in what diagnoses or treatments are included or excluded. 

“80% of psychiatric meds are prescribed by primary care doctors, not psychiatrists,” he said. “So, when you’re making a suggestion for a change in psychiatry, you’re making that suggestion primarily for primary care doctor and have to be thinking about, How will this change play in primary care, which the experts never do.”

The study was unfunded. Dr. Allen reported no relevant disclosures. Dr. Lo served as a paid member of the Takeda Pharmaceuticals Ethics Advisory Committee.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

I don’t rightly remember when I first learned of restless legs syndrome (RLS). It was many decades ago, and I recognized that once in a while, I would be restless during sleep, tossing and turning, seeking a favorable sleeping position. I felt like I just needed to move my legs around; my gastrocnemii and hamstrings might cramp; and my torso skin might strangely “crawl” a bit, but then normal sleep would return. I never sought medical care for it and used no treatment, except moving my legs when indicated.

My trusty LLM (large language model), Bard, tells me that there are about 53,000 articles about RLS in English, of which, some 20,000 are in the primary source, peer reviewed literature. Count this as one more article. Will it make a difference? Read on and see.

For many centuries (since Sir Thomas Willis in 1672), the symptoms now grouped and categorized as RLS have been recognized and reported but were often dismissed as bizarre and unexplained. The name was applied in 1948 by Dr Karl-Axel Ekborn.

In the 1960s, in sleep labs, RLS became better studied and characterized.

Mayo Clinic describes RLS as “… compelling, unpleasant sensations in the legs or feet ... both sides of the body ... within the limb rather than on the skin ... crawling, creeping, pulling, throbbing, aching, itching, electric ... difficult to explain …” Not numbness, but a consistent desire to move the legs.

When I read about it many decades ago, I realized that I may have RLS. But then many months would pass with no recurrence, so I dismissed it as just another of those “symptoms of unknown origin” that my late friend Clifton Meador has written about so eloquently.

I am sure that a lot of people experience this, don’t understand it, and don’t consider it important enough to do anything about. Between 1% and 15% (a wide range) of Americans are believed to be affected by RLS. The cause is unknown, but it seems to run in families. It may be autosomal dominant, but no causative genes have been confirmed.
 

Treatment of RLS

Many pharmacologic and physical treatments have been tried with some success for some patients, but over time, these treatments have mostly failed.

We know how Big Pharma often operates. A company owns a drug, preferably under patent protection, but without an apparent profitable indication. They need to find a medical condition, ideally one with troublesome symptoms, that the drug might ameliorate to some degree. Armed with a plausible candidate symptom, the company embarks upon a campaign to find people who might want to take the drug. Mass communications, such as direct-to-consumer advertising, can identify large numbers of people who match to pretty much any symptoms, although many of these people never suspected they had a disease, much less a treatable one.

I figured long ago that RLS was just another of those nonspecific entities experienced by many people, making them good candidates for disease mongering.

In 2005, the marketing of GlaxoSmithKline’s (GSK’s) dopamine agonist drug Requip (ropinirole) was approved by the FDA. GSK had already undertaken an intensive promotional campaign for Requip, issuing press releases, advertising to doctors in medical journals, and advertising directly to consumers. To increase general awareness of RLS, GSK’s campaign told consumers that a “new survey reveals that a common yet underrecognized disorder-restless legs syndrome—is keeping Americans awake at night.” GSK was accused of “disease mongering,” trying to turn ordinary people into patients who needed specific drugs.

Within a year, sales of the drug had doubled, climbing from $165 million in 2005 to nearly $330 million in 2006. Soon, 4.4 million prescriptions were written annually for the drug, with sales reported to be nearly $491 million. However, the focus on RLS faded rapidly as the Requip television commercials were pulled from the airwaves following approval of generic ropinirole.

And Requip had competition. Boehringer Ingelheim manufactures pramipexole (brand name Mirapex) another dopamine agonist. Gabapentin enacarbil (marketed as Horizant by UCB Pharma) is also approved for RLS, and Pfizer’s pregabalin (brand name Lyrica) is used off-label to manage symptoms of RLS. Janssen Pharmaceuticals manufactures rotigotine, (brand name Neupro), a dopamine agonist delivered via a transdermal patch.

It is safe to say that RLS is a real clinical entity composed of clearly recognizable symptoms, with no cure and no ending, unless it is associated with iron-deficiency anemia. However, as a disease, it seems to lack etiology, pathology, pathogenesis, pathophysiology, diagnostic findings on physical examination, laboratory tests, or imaging, and any clear strategy for prevention.

Pharmacologic treatments include dopaminergic agents, benzodiazepines, opioids, anticonvulsants, alpha 2–adrenergic agonists and iron salts. Yes, you read that right; RLS is treated with a broad array of different drugs, which is usually a sign that nothing works very well. Some agents work for a while, but none seem to be the definitive solution.

Same for the physical interventions: sleep hygiene, exercise, hot or cold bathing, limb massage, vibratory or electrical stimulation of the feet, stopping caffeine before bedtime. Try everything and see if something works.
 

Taking the Sugar Challenge

Could the culprit be sugar?

Lacking clarity of scientific understanding of RLS or its treatment from an extensive clinical literature, after ascertaining that RLS is real, one might look for real-world evidence, including well-performed N-of-1 trials.

I am an antisugar guy. Read my prior Medscape columns. I practice what I preach, but sugar does taste good.

Early in November 2023, after a healthy, conservative dinner at home with some wine, I enjoyed a mini Dove bar for dessert. But I didn’t stop there.

Mini Dove bars contain 11 grams sugar. It was also just a few days after Halloween. Having had fewer trick-or-treaters than expected, we had leftovers. Snickers, Milky Ways, Twix mini bars, each with at least 20 grams of sugar.

I ate several of these not long before bedtime. Lo and behold, in the dark of that night, and continuing off and on for a few fitful hours, I had bad RLS. Shifting, tossing, turning, compulsively seeking a new sleeping position only to have to soon move again. Plus, I had repetitive leg cramps and that creepy-crawly skin sensation. An altogether unpleasant experience. Sound sleep eventually arrived, and there were no recurrences over subsequent weeks.

The classic way to determine whether a drug is causing a reaction, condition, or disease is to apply the challenge-dechallenge-rechallenge testing method.

Give the drug, the patient demonstrates the disease finding. Remove the drug, the problem disappears. Rinse and repeat three times. We pathologists first worked this out for drug-induced liver disease, such as steatosis, in the late 1960s. Blinding or double blinding in these N-of-1 situations would be nice but often not practical.

Siwert de Groot, in the Netherlands, published a very convincing use of this technique in 2023: Big-time sugar consumption for a week, then low intake of sugar for the following week, repeated three times on one patient.

Very elaborate RLS symptom reporting. I’m pretty convinced from my unintentional challenge and single dechallenge that my unusually high sugar intake resulted in RLS. I will not undergo a rechallenge, although it might be fun to binge on sucrose and see what happens.

If you are serious about identifying or treating RLS, I suggest that you incorporate the International Restless Legs Study Group Severity Rating Scale into your practice, and begin the systematic use of the dechallenge-rechallenge exclusion process for your patients with RLS. Start with sugar and see what happens. Keep records and let the world know what you discover. Be your own clinical investigator. Social media offers you abundant opportunity to share your results, whatever they may be.

How many millions of dollars would Big Pharma lose if patients with RLS just said no to sugar and it worked? Of course, humans being humans, many would probably prefer to continue to gorge on sugar, gain weight, develop diabetes, and then take medications to control their RLS symptoms. But patients ought to at least be given an informed choice.

I will be watching for your reports.

Dr. Lundberg had no disclosures.

A version of this article appeared on Medscape.com.

I don’t rightly remember when I first learned of restless legs syndrome (RLS). It was many decades ago, and I recognized that once in a while, I would be restless during sleep, tossing and turning, seeking a favorable sleeping position. I felt like I just needed to move my legs around; my gastrocnemii and hamstrings might cramp; and my torso skin might strangely “crawl” a bit, but then normal sleep would return. I never sought medical care for it and used no treatment, except moving my legs when indicated.

My trusty LLM (large language model), Bard, tells me that there are about 53,000 articles about RLS in English, of which, some 20,000 are in the primary source, peer reviewed literature. Count this as one more article. Will it make a difference? Read on and see.

For many centuries (since Sir Thomas Willis in 1672), the symptoms now grouped and categorized as RLS have been recognized and reported but were often dismissed as bizarre and unexplained. The name was applied in 1948 by Dr Karl-Axel Ekborn.

In the 1960s, in sleep labs, RLS became better studied and characterized.

Mayo Clinic describes RLS as “… compelling, unpleasant sensations in the legs or feet ... both sides of the body ... within the limb rather than on the skin ... crawling, creeping, pulling, throbbing, aching, itching, electric ... difficult to explain …” Not numbness, but a consistent desire to move the legs.

When I read about it many decades ago, I realized that I may have RLS. But then many months would pass with no recurrence, so I dismissed it as just another of those “symptoms of unknown origin” that my late friend Clifton Meador has written about so eloquently.

I am sure that a lot of people experience this, don’t understand it, and don’t consider it important enough to do anything about. Between 1% and 15% (a wide range) of Americans are believed to be affected by RLS. The cause is unknown, but it seems to run in families. It may be autosomal dominant, but no causative genes have been confirmed.
 

Treatment of RLS

Many pharmacologic and physical treatments have been tried with some success for some patients, but over time, these treatments have mostly failed.

We know how Big Pharma often operates. A company owns a drug, preferably under patent protection, but without an apparent profitable indication. They need to find a medical condition, ideally one with troublesome symptoms, that the drug might ameliorate to some degree. Armed with a plausible candidate symptom, the company embarks upon a campaign to find people who might want to take the drug. Mass communications, such as direct-to-consumer advertising, can identify large numbers of people who match to pretty much any symptoms, although many of these people never suspected they had a disease, much less a treatable one.

I figured long ago that RLS was just another of those nonspecific entities experienced by many people, making them good candidates for disease mongering.

In 2005, the marketing of GlaxoSmithKline’s (GSK’s) dopamine agonist drug Requip (ropinirole) was approved by the FDA. GSK had already undertaken an intensive promotional campaign for Requip, issuing press releases, advertising to doctors in medical journals, and advertising directly to consumers. To increase general awareness of RLS, GSK’s campaign told consumers that a “new survey reveals that a common yet underrecognized disorder-restless legs syndrome—is keeping Americans awake at night.” GSK was accused of “disease mongering,” trying to turn ordinary people into patients who needed specific drugs.

Within a year, sales of the drug had doubled, climbing from $165 million in 2005 to nearly $330 million in 2006. Soon, 4.4 million prescriptions were written annually for the drug, with sales reported to be nearly $491 million. However, the focus on RLS faded rapidly as the Requip television commercials were pulled from the airwaves following approval of generic ropinirole.

And Requip had competition. Boehringer Ingelheim manufactures pramipexole (brand name Mirapex) another dopamine agonist. Gabapentin enacarbil (marketed as Horizant by UCB Pharma) is also approved for RLS, and Pfizer’s pregabalin (brand name Lyrica) is used off-label to manage symptoms of RLS. Janssen Pharmaceuticals manufactures rotigotine, (brand name Neupro), a dopamine agonist delivered via a transdermal patch.

It is safe to say that RLS is a real clinical entity composed of clearly recognizable symptoms, with no cure and no ending, unless it is associated with iron-deficiency anemia. However, as a disease, it seems to lack etiology, pathology, pathogenesis, pathophysiology, diagnostic findings on physical examination, laboratory tests, or imaging, and any clear strategy for prevention.

Pharmacologic treatments include dopaminergic agents, benzodiazepines, opioids, anticonvulsants, alpha 2–adrenergic agonists and iron salts. Yes, you read that right; RLS is treated with a broad array of different drugs, which is usually a sign that nothing works very well. Some agents work for a while, but none seem to be the definitive solution.

Same for the physical interventions: sleep hygiene, exercise, hot or cold bathing, limb massage, vibratory or electrical stimulation of the feet, stopping caffeine before bedtime. Try everything and see if something works.
 

Taking the Sugar Challenge

Could the culprit be sugar?

Lacking clarity of scientific understanding of RLS or its treatment from an extensive clinical literature, after ascertaining that RLS is real, one might look for real-world evidence, including well-performed N-of-1 trials.

I am an antisugar guy. Read my prior Medscape columns. I practice what I preach, but sugar does taste good.

Early in November 2023, after a healthy, conservative dinner at home with some wine, I enjoyed a mini Dove bar for dessert. But I didn’t stop there.

Mini Dove bars contain 11 grams sugar. It was also just a few days after Halloween. Having had fewer trick-or-treaters than expected, we had leftovers. Snickers, Milky Ways, Twix mini bars, each with at least 20 grams of sugar.

I ate several of these not long before bedtime. Lo and behold, in the dark of that night, and continuing off and on for a few fitful hours, I had bad RLS. Shifting, tossing, turning, compulsively seeking a new sleeping position only to have to soon move again. Plus, I had repetitive leg cramps and that creepy-crawly skin sensation. An altogether unpleasant experience. Sound sleep eventually arrived, and there were no recurrences over subsequent weeks.

The classic way to determine whether a drug is causing a reaction, condition, or disease is to apply the challenge-dechallenge-rechallenge testing method.

Give the drug, the patient demonstrates the disease finding. Remove the drug, the problem disappears. Rinse and repeat three times. We pathologists first worked this out for drug-induced liver disease, such as steatosis, in the late 1960s. Blinding or double blinding in these N-of-1 situations would be nice but often not practical.

Siwert de Groot, in the Netherlands, published a very convincing use of this technique in 2023: Big-time sugar consumption for a week, then low intake of sugar for the following week, repeated three times on one patient.

Very elaborate RLS symptom reporting. I’m pretty convinced from my unintentional challenge and single dechallenge that my unusually high sugar intake resulted in RLS. I will not undergo a rechallenge, although it might be fun to binge on sucrose and see what happens.

If you are serious about identifying or treating RLS, I suggest that you incorporate the International Restless Legs Study Group Severity Rating Scale into your practice, and begin the systematic use of the dechallenge-rechallenge exclusion process for your patients with RLS. Start with sugar and see what happens. Keep records and let the world know what you discover. Be your own clinical investigator. Social media offers you abundant opportunity to share your results, whatever they may be.

How many millions of dollars would Big Pharma lose if patients with RLS just said no to sugar and it worked? Of course, humans being humans, many would probably prefer to continue to gorge on sugar, gain weight, develop diabetes, and then take medications to control their RLS symptoms. But patients ought to at least be given an informed choice.

I will be watching for your reports.

Dr. Lundberg had no disclosures.

A version of this article appeared on Medscape.com.

I don’t rightly remember when I first learned of restless legs syndrome (RLS). It was many decades ago, and I recognized that once in a while, I would be restless during sleep, tossing and turning, seeking a favorable sleeping position. I felt like I just needed to move my legs around; my gastrocnemii and hamstrings might cramp; and my torso skin might strangely “crawl” a bit, but then normal sleep would return. I never sought medical care for it and used no treatment, except moving my legs when indicated.

My trusty LLM (large language model), Bard, tells me that there are about 53,000 articles about RLS in English, of which, some 20,000 are in the primary source, peer reviewed literature. Count this as one more article. Will it make a difference? Read on and see.

For many centuries (since Sir Thomas Willis in 1672), the symptoms now grouped and categorized as RLS have been recognized and reported but were often dismissed as bizarre and unexplained. The name was applied in 1948 by Dr Karl-Axel Ekborn.

In the 1960s, in sleep labs, RLS became better studied and characterized.

Mayo Clinic describes RLS as “… compelling, unpleasant sensations in the legs or feet ... both sides of the body ... within the limb rather than on the skin ... crawling, creeping, pulling, throbbing, aching, itching, electric ... difficult to explain …” Not numbness, but a consistent desire to move the legs.

When I read about it many decades ago, I realized that I may have RLS. But then many months would pass with no recurrence, so I dismissed it as just another of those “symptoms of unknown origin” that my late friend Clifton Meador has written about so eloquently.

I am sure that a lot of people experience this, don’t understand it, and don’t consider it important enough to do anything about. Between 1% and 15% (a wide range) of Americans are believed to be affected by RLS. The cause is unknown, but it seems to run in families. It may be autosomal dominant, but no causative genes have been confirmed.
 

Treatment of RLS

Many pharmacologic and physical treatments have been tried with some success for some patients, but over time, these treatments have mostly failed.

We know how Big Pharma often operates. A company owns a drug, preferably under patent protection, but without an apparent profitable indication. They need to find a medical condition, ideally one with troublesome symptoms, that the drug might ameliorate to some degree. Armed with a plausible candidate symptom, the company embarks upon a campaign to find people who might want to take the drug. Mass communications, such as direct-to-consumer advertising, can identify large numbers of people who match to pretty much any symptoms, although many of these people never suspected they had a disease, much less a treatable one.

I figured long ago that RLS was just another of those nonspecific entities experienced by many people, making them good candidates for disease mongering.

In 2005, the marketing of GlaxoSmithKline’s (GSK’s) dopamine agonist drug Requip (ropinirole) was approved by the FDA. GSK had already undertaken an intensive promotional campaign for Requip, issuing press releases, advertising to doctors in medical journals, and advertising directly to consumers. To increase general awareness of RLS, GSK’s campaign told consumers that a “new survey reveals that a common yet underrecognized disorder-restless legs syndrome—is keeping Americans awake at night.” GSK was accused of “disease mongering,” trying to turn ordinary people into patients who needed specific drugs.

Within a year, sales of the drug had doubled, climbing from $165 million in 2005 to nearly $330 million in 2006. Soon, 4.4 million prescriptions were written annually for the drug, with sales reported to be nearly $491 million. However, the focus on RLS faded rapidly as the Requip television commercials were pulled from the airwaves following approval of generic ropinirole.

And Requip had competition. Boehringer Ingelheim manufactures pramipexole (brand name Mirapex) another dopamine agonist. Gabapentin enacarbil (marketed as Horizant by UCB Pharma) is also approved for RLS, and Pfizer’s pregabalin (brand name Lyrica) is used off-label to manage symptoms of RLS. Janssen Pharmaceuticals manufactures rotigotine, (brand name Neupro), a dopamine agonist delivered via a transdermal patch.

It is safe to say that RLS is a real clinical entity composed of clearly recognizable symptoms, with no cure and no ending, unless it is associated with iron-deficiency anemia. However, as a disease, it seems to lack etiology, pathology, pathogenesis, pathophysiology, diagnostic findings on physical examination, laboratory tests, or imaging, and any clear strategy for prevention.

Pharmacologic treatments include dopaminergic agents, benzodiazepines, opioids, anticonvulsants, alpha 2–adrenergic agonists and iron salts. Yes, you read that right; RLS is treated with a broad array of different drugs, which is usually a sign that nothing works very well. Some agents work for a while, but none seem to be the definitive solution.

Same for the physical interventions: sleep hygiene, exercise, hot or cold bathing, limb massage, vibratory or electrical stimulation of the feet, stopping caffeine before bedtime. Try everything and see if something works.
 

Taking the Sugar Challenge

Could the culprit be sugar?

Lacking clarity of scientific understanding of RLS or its treatment from an extensive clinical literature, after ascertaining that RLS is real, one might look for real-world evidence, including well-performed N-of-1 trials.

I am an antisugar guy. Read my prior Medscape columns. I practice what I preach, but sugar does taste good.

Early in November 2023, after a healthy, conservative dinner at home with some wine, I enjoyed a mini Dove bar for dessert. But I didn’t stop there.

Mini Dove bars contain 11 grams sugar. It was also just a few days after Halloween. Having had fewer trick-or-treaters than expected, we had leftovers. Snickers, Milky Ways, Twix mini bars, each with at least 20 grams of sugar.

I ate several of these not long before bedtime. Lo and behold, in the dark of that night, and continuing off and on for a few fitful hours, I had bad RLS. Shifting, tossing, turning, compulsively seeking a new sleeping position only to have to soon move again. Plus, I had repetitive leg cramps and that creepy-crawly skin sensation. An altogether unpleasant experience. Sound sleep eventually arrived, and there were no recurrences over subsequent weeks.

The classic way to determine whether a drug is causing a reaction, condition, or disease is to apply the challenge-dechallenge-rechallenge testing method.

Give the drug, the patient demonstrates the disease finding. Remove the drug, the problem disappears. Rinse and repeat three times. We pathologists first worked this out for drug-induced liver disease, such as steatosis, in the late 1960s. Blinding or double blinding in these N-of-1 situations would be nice but often not practical.

Siwert de Groot, in the Netherlands, published a very convincing use of this technique in 2023: Big-time sugar consumption for a week, then low intake of sugar for the following week, repeated three times on one patient.

Very elaborate RLS symptom reporting. I’m pretty convinced from my unintentional challenge and single dechallenge that my unusually high sugar intake resulted in RLS. I will not undergo a rechallenge, although it might be fun to binge on sucrose and see what happens.

If you are serious about identifying or treating RLS, I suggest that you incorporate the International Restless Legs Study Group Severity Rating Scale into your practice, and begin the systematic use of the dechallenge-rechallenge exclusion process for your patients with RLS. Start with sugar and see what happens. Keep records and let the world know what you discover. Be your own clinical investigator. Social media offers you abundant opportunity to share your results, whatever they may be.

How many millions of dollars would Big Pharma lose if patients with RLS just said no to sugar and it worked? Of course, humans being humans, many would probably prefer to continue to gorge on sugar, gain weight, develop diabetes, and then take medications to control their RLS symptoms. But patients ought to at least be given an informed choice.

I will be watching for your reports.

Dr. Lundberg had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Among women diagnosed with rosacea, the impact of pregnancy on the disease is unpredictable.

METHODOLOGY:

• Few data beyond case reports exist about the course of rosacea during pregnancy.
• Researchers conducted a telephone survey of 39 women with a diagnosis of rosacea in the electronic medical records prior to the onset of pregnancy who had been admitted to Oregon Health & Science University for labor and delivery from June 27, 2015, to June 27, 2020.
• Patient global assessment of clear (0), mild (1), moderate (2), or severe (3) rosacea was rated across five timepoints: 1-3 months preconception; first, second, and third trimesters; and 6 weeks postpartum.

TAKEAWAY:

• The mean age of the survey participants was 35.5 years, the mean gestational age at delivery was 39.4 weeks, and most had singleton pregnancies.
• All but one study participant (97.4%) reported symptoms of erythematotelangiectatic rosacea, while 26 (67%) reported symptoms of papulopustular rosacea.
• Nearly half of the participants (19, 48.7%) said their rosacea worsened during pregnancy, 13 (33.3%) reported no change in rosacea severity during pregnancy, and 7 (17.9%) reported that their rosacea improved during pregnancy.
• Before conceiving, the mean rosacea severity score among participants was mild (1.10; 95% CI, 0.92-1.29) and did not change significantly over time, a reflection of individual variations. In addition, 83.3% of participants did not use prescription rosacea treatments prior to pregnancy, and 89.6% did not use them during pregnancy.

IN PRACTICE:

“Rosacea, like acne, lacks a predictable group effect, and instead, each individual may have a different response to the physiologic changes of pregnancy,” the authors concluded.

SOURCE:

Genevieve Benedetti, MD, MPP, of the Department of Dermatology at Oregon Health & Science University, Portland, Oregon, led the research, published as a research letter in the International Journal of Women’s Dermatology.

LIMITATIONS:

The small sample size, single-center design, and overall prevalence of mild disease limit the ability to detect change.

DISCLOSURES:

The researchers reported having no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Among women diagnosed with rosacea, the impact of pregnancy on the disease is unpredictable.

METHODOLOGY:

• Few data beyond case reports exist about the course of rosacea during pregnancy.
• Researchers conducted a telephone survey of 39 women with a diagnosis of rosacea in the electronic medical records prior to the onset of pregnancy who had been admitted to Oregon Health & Science University for labor and delivery from June 27, 2015, to June 27, 2020.
• Patient global assessment of clear (0), mild (1), moderate (2), or severe (3) rosacea was rated across five timepoints: 1-3 months preconception; first, second, and third trimesters; and 6 weeks postpartum.

TAKEAWAY:

• The mean age of the survey participants was 35.5 years, the mean gestational age at delivery was 39.4 weeks, and most had singleton pregnancies.
• All but one study participant (97.4%) reported symptoms of erythematotelangiectatic rosacea, while 26 (67%) reported symptoms of papulopustular rosacea.
• Nearly half of the participants (19, 48.7%) said their rosacea worsened during pregnancy, 13 (33.3%) reported no change in rosacea severity during pregnancy, and 7 (17.9%) reported that their rosacea improved during pregnancy.
• Before conceiving, the mean rosacea severity score among participants was mild (1.10; 95% CI, 0.92-1.29) and did not change significantly over time, a reflection of individual variations. In addition, 83.3% of participants did not use prescription rosacea treatments prior to pregnancy, and 89.6% did not use them during pregnancy.

IN PRACTICE:

“Rosacea, like acne, lacks a predictable group effect, and instead, each individual may have a different response to the physiologic changes of pregnancy,” the authors concluded.

SOURCE:

Genevieve Benedetti, MD, MPP, of the Department of Dermatology at Oregon Health & Science University, Portland, Oregon, led the research, published as a research letter in the International Journal of Women’s Dermatology.

LIMITATIONS:

The small sample size, single-center design, and overall prevalence of mild disease limit the ability to detect change.

DISCLOSURES:

The researchers reported having no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Among women diagnosed with rosacea, the impact of pregnancy on the disease is unpredictable.

METHODOLOGY:

• Few data beyond case reports exist about the course of rosacea during pregnancy.
• Researchers conducted a telephone survey of 39 women with a diagnosis of rosacea in the electronic medical records prior to the onset of pregnancy who had been admitted to Oregon Health & Science University for labor and delivery from June 27, 2015, to June 27, 2020.
• Patient global assessment of clear (0), mild (1), moderate (2), or severe (3) rosacea was rated across five timepoints: 1-3 months preconception; first, second, and third trimesters; and 6 weeks postpartum.

TAKEAWAY:

• The mean age of the survey participants was 35.5 years, the mean gestational age at delivery was 39.4 weeks, and most had singleton pregnancies.
• All but one study participant (97.4%) reported symptoms of erythematotelangiectatic rosacea, while 26 (67%) reported symptoms of papulopustular rosacea.
• Nearly half of the participants (19, 48.7%) said their rosacea worsened during pregnancy, 13 (33.3%) reported no change in rosacea severity during pregnancy, and 7 (17.9%) reported that their rosacea improved during pregnancy.
• Before conceiving, the mean rosacea severity score among participants was mild (1.10; 95% CI, 0.92-1.29) and did not change significantly over time, a reflection of individual variations. In addition, 83.3% of participants did not use prescription rosacea treatments prior to pregnancy, and 89.6% did not use them during pregnancy.

IN PRACTICE:

“Rosacea, like acne, lacks a predictable group effect, and instead, each individual may have a different response to the physiologic changes of pregnancy,” the authors concluded.

SOURCE:

Genevieve Benedetti, MD, MPP, of the Department of Dermatology at Oregon Health & Science University, Portland, Oregon, led the research, published as a research letter in the International Journal of Women’s Dermatology.

LIMITATIONS:

The small sample size, single-center design, and overall prevalence of mild disease limit the ability to detect change.

DISCLOSURES:

The researchers reported having no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.

Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.

Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.

First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!

Leslie A. Hulvershorn, MD, MSc: Thank you.

Christopher J. Hammond, MD, PhD: Thank you.

Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?

Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.

When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.

If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.

What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.

Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.

Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?

Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.

Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.

You referred, Chris, to the safety aspect. If you look at social media, the press, and the conversations where cannabis is talked about, there’s no risk, right? This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?

Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.

In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.

Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.

There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.

Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.

Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.

If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.

There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.

Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.

I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.

Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.

The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.

The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.

After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.

Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.

What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?

Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.

Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.

You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.

I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”

I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.

The safest advice, I think, is no use. That’s never going to be bad advice.

Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.

There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.

The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.

There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.

I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.

There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.

Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?

Dr. Hammond: Absolutely not.

Dr. Strakowski: Thank you.

Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.

There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.

They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.

Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.

These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.

It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.

Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.

I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.

Dr. Hammond: Yes, it sets a dangerous precedent.

Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.

I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.

I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.

Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:

• Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
• Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press

Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:

• Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit

Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:

• Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.

Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.

Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.

First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!

Leslie A. Hulvershorn, MD, MSc: Thank you.

Christopher J. Hammond, MD, PhD: Thank you.

Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?

Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.

When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.

If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.

What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.

Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.

Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?

Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.

Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.

You referred, Chris, to the safety aspect. If you look at social media, the press, and the conversations where cannabis is talked about, there’s no risk, right? This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?

Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.

In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.

Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.

There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.

Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.

Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.

If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.

There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.

Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.

I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.

Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.

The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.

The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.

After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.

Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.

What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?

Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.

Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.

You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.

I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”

I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.

The safest advice, I think, is no use. That’s never going to be bad advice.

Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.

There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.

The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.

There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.

I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.

There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.

Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?

Dr. Hammond: Absolutely not.

Dr. Strakowski: Thank you.

Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.

There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.

They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.

Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.

These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.

It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.

Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.

I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.

Dr. Hammond: Yes, it sets a dangerous precedent.

Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.

I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.

I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.

Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:

• Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
• Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press

Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:

• Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit

Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:

• Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.

Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.

Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.

First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!

Leslie A. Hulvershorn, MD, MSc: Thank you.

Christopher J. Hammond, MD, PhD: Thank you.

Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?

Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.

When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.

If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.

What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.

Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.

Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?

Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.

Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.

You referred, Chris, to the safety aspect. If you look at social media, the press, and the conversations where cannabis is talked about, there’s no risk, right? This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?

Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.

In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.

Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.

There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.

Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.

Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.

If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.

There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.

Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.

I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.

Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.

The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.

The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.

After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.

Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.

What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?

Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.

Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.

You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.

I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”

I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.

The safest advice, I think, is no use. That’s never going to be bad advice.

Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.

There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.

The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.

There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.

I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.

There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.

Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?

Dr. Hammond: Absolutely not.

Dr. Strakowski: Thank you.

Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.

There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.

They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.

Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.

These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.

It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.

Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.

I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.

Dr. Hammond: Yes, it sets a dangerous precedent.

Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.

I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.

I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.

Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:

• Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
• Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press

Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:

• Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit

Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:

• Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.