From the Journals

TOPLINE:

People with central obesity (CO), characterized by excess fat around the abdomen, are at a greater risk for pelvic organ prolapse (POP), particularly those who are younger than 60 years or without a history of hysterectomy. Also, women who have overweight but do not have CO are at greater risk.

METHODOLOGY:

• Researchers conducted a prospective cohort study to estimate the association between CO and general obesity and the risk for POP in individuals using the UK Biobank.
• A total of 251,143 participants (median age, 57 years) without preexisting POP were included, of whom 60.9% were postmenopausal and 17.2% had undergone hysterectomy before enrollment.
• Participants were followed for a median duration of 13.8 years, and POP cases were identified using International Classification of Diseases, 10th Revision (ICD-10) codes.
• Waist circumference, height, and body weight were measured at enrollment for the calculation of waist/height ratio and body mass index (BMI); CO was defined as a waist/height ratio ≥ 0.5.
• The relative risk of POP for the various combinations of waist/height ratio and BMI was evaluated against the reference group (waist/height ratio < 0.5; BMI < 25) using Cox proportional hazards models.

TAKEAWAY:

• During the follow-up period, 9781 cases of POP were identified, of which 71.2% occurred in a single pelvic compartment.
• Around 21.7% of all POP cases were attributable to CO; 2% were attributable to being overweight without CO.
• The risk for POP was 48% higher in individuals with CO regardless of BMI (hazard ratio [HR], 1.48; 95% CI, 1.41-1.56) and 23% higher in those who had overweight without CO (HR, 1.23; 95% CI, 1.14-1.34).
• The association between POP and CO was further strengthened in individuals who were younger than 60 years and those without a history of hysterectomy.

IN PRACTICE:

“We found that waist/height ratio combined with BMI could help differentiate individuals with varying risks of prolapse more accurately. Among individuals within the same BMI category, waist/height ratio can vary, with those having a higher ratio generally facing a greater risk of POP, compared with those with a normal ratio. Therefore, they should not be grouped together based solely on a single measure of obesity. In addition, this combination can help identify more individuals at high risk for POP, compared with using either alone,” the study authors wrote.
 

SOURCE:

This study was led by Keyi Si, PhD, of Tongji University in Shanghai, China, and was published online in Obstetrics & Gynecology.

LIMITATIONS:

Differences in healthcare-seeking behavior could have biased the association between obesity and risk for POP, as individuals with obesity may have been less likely to notice or report symptoms of POP. The diagnosis of POP was according to ICD-10 codes rather than physical examination, which may have affected accuracy. Other limitations included missing data on delivery mode and history of constipation.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, the Shanghai Hospital Development Center, and the Shanghai First Maternity and Infant Hospital. The authors reported no conflicts of interest.

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

TOPLINE:

People with central obesity (CO), characterized by excess fat around the abdomen, are at a greater risk for pelvic organ prolapse (POP), particularly those who are younger than 60 years or without a history of hysterectomy. Also, women who have overweight but do not have CO are at greater risk.

METHODOLOGY:

• Researchers conducted a prospective cohort study to estimate the association between CO and general obesity and the risk for POP in individuals using the UK Biobank.
• A total of 251,143 participants (median age, 57 years) without preexisting POP were included, of whom 60.9% were postmenopausal and 17.2% had undergone hysterectomy before enrollment.
• Participants were followed for a median duration of 13.8 years, and POP cases were identified using International Classification of Diseases, 10th Revision (ICD-10) codes.
• Waist circumference, height, and body weight were measured at enrollment for the calculation of waist/height ratio and body mass index (BMI); CO was defined as a waist/height ratio ≥ 0.5.
• The relative risk of POP for the various combinations of waist/height ratio and BMI was evaluated against the reference group (waist/height ratio < 0.5; BMI < 25) using Cox proportional hazards models.

TAKEAWAY:

• During the follow-up period, 9781 cases of POP were identified, of which 71.2% occurred in a single pelvic compartment.
• Around 21.7% of all POP cases were attributable to CO; 2% were attributable to being overweight without CO.
• The risk for POP was 48% higher in individuals with CO regardless of BMI (hazard ratio [HR], 1.48; 95% CI, 1.41-1.56) and 23% higher in those who had overweight without CO (HR, 1.23; 95% CI, 1.14-1.34).
• The association between POP and CO was further strengthened in individuals who were younger than 60 years and those without a history of hysterectomy.

IN PRACTICE:

“We found that waist/height ratio combined with BMI could help differentiate individuals with varying risks of prolapse more accurately. Among individuals within the same BMI category, waist/height ratio can vary, with those having a higher ratio generally facing a greater risk of POP, compared with those with a normal ratio. Therefore, they should not be grouped together based solely on a single measure of obesity. In addition, this combination can help identify more individuals at high risk for POP, compared with using either alone,” the study authors wrote.
 

SOURCE:

This study was led by Keyi Si, PhD, of Tongji University in Shanghai, China, and was published online in Obstetrics & Gynecology.

LIMITATIONS:

Differences in healthcare-seeking behavior could have biased the association between obesity and risk for POP, as individuals with obesity may have been less likely to notice or report symptoms of POP. The diagnosis of POP was according to ICD-10 codes rather than physical examination, which may have affected accuracy. Other limitations included missing data on delivery mode and history of constipation.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, the Shanghai Hospital Development Center, and the Shanghai First Maternity and Infant Hospital. The authors reported no conflicts of interest.

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

TOPLINE:

People with central obesity (CO), characterized by excess fat around the abdomen, are at a greater risk for pelvic organ prolapse (POP), particularly those who are younger than 60 years or without a history of hysterectomy. Also, women who have overweight but do not have CO are at greater risk.

METHODOLOGY:

• Researchers conducted a prospective cohort study to estimate the association between CO and general obesity and the risk for POP in individuals using the UK Biobank.
• A total of 251,143 participants (median age, 57 years) without preexisting POP were included, of whom 60.9% were postmenopausal and 17.2% had undergone hysterectomy before enrollment.
• Participants were followed for a median duration of 13.8 years, and POP cases were identified using International Classification of Diseases, 10th Revision (ICD-10) codes.
• Waist circumference, height, and body weight were measured at enrollment for the calculation of waist/height ratio and body mass index (BMI); CO was defined as a waist/height ratio ≥ 0.5.
• The relative risk of POP for the various combinations of waist/height ratio and BMI was evaluated against the reference group (waist/height ratio < 0.5; BMI < 25) using Cox proportional hazards models.

TAKEAWAY:

• During the follow-up period, 9781 cases of POP were identified, of which 71.2% occurred in a single pelvic compartment.
• Around 21.7% of all POP cases were attributable to CO; 2% were attributable to being overweight without CO.
• The risk for POP was 48% higher in individuals with CO regardless of BMI (hazard ratio [HR], 1.48; 95% CI, 1.41-1.56) and 23% higher in those who had overweight without CO (HR, 1.23; 95% CI, 1.14-1.34).
• The association between POP and CO was further strengthened in individuals who were younger than 60 years and those without a history of hysterectomy.

IN PRACTICE:

“We found that waist/height ratio combined with BMI could help differentiate individuals with varying risks of prolapse more accurately. Among individuals within the same BMI category, waist/height ratio can vary, with those having a higher ratio generally facing a greater risk of POP, compared with those with a normal ratio. Therefore, they should not be grouped together based solely on a single measure of obesity. In addition, this combination can help identify more individuals at high risk for POP, compared with using either alone,” the study authors wrote.
 

SOURCE:

This study was led by Keyi Si, PhD, of Tongji University in Shanghai, China, and was published online in Obstetrics & Gynecology.

LIMITATIONS:

Differences in healthcare-seeking behavior could have biased the association between obesity and risk for POP, as individuals with obesity may have been less likely to notice or report symptoms of POP. The diagnosis of POP was according to ICD-10 codes rather than physical examination, which may have affected accuracy. Other limitations included missing data on delivery mode and history of constipation.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, the Shanghai Hospital Development Center, and the Shanghai First Maternity and Infant Hospital. The authors reported no conflicts of interest.

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

A group of international experts is challenging revised diagnostic criteria for Alzheimer’s disease as laid out by the Alzheimer’s Association earlier in 2024.

In a paper published online in JAMA Neurology, the International Working Group (IWG), which includes 46 experts from 17 countries, is recommending that the diagnosis of Alzheimer’s disease be limited to individuals with mild cognitive impairment or dementia and not be applied to cognitively normal individuals with Alzheimer’s disease biomarkers such as amyloid-beta 42/40 or p-tau.

Clinicians should be “very careful” about using the “A” word (Alzheimer’s) for cognitively unimpaired people with Alzheimer’s disease biomarkers, said the paper’s first author Bruno Dubois, MD, professor of neurology, Sorbonne University and Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France.

Providing an Alzheimer’s disease diagnosis to those who have a high chance of never developing cognitive impairment can be psychologically harmful, said Dubois.

“It’s not something small like telling someone they have a fever. Just imagine you’re 65 years old and are amyloid positive, and you’re told you have Alzheimer’s disease. It affects the decisions you make for the rest of your life and changes your vision of your future, even though you may never develop the disease,” he added.
 

Divergent View

The IWG’s perspective on Alzheimer’s disease contrasts with a recent proposal from the Alzheimer’s Association. The Alzheimer’s Association criteria suggest that Alzheimer’s disease should be regarded solely as a biological entity, which could include cognitively normal individuals with one core Alzheimer’s disease biomarker.

The IWG noted that its concerns regarding the application of a purely biological definition of Alzheimer’s disease in clinical practice prompted the group to consider updating its guidelines, potentially offering “an alternative definitional view of Alzheimer’s disease as a clinical-biological construct for clinical use.”

The group conducted a PubMed search for relevant Alzheimer’s disease articles, and included references, published between July 2020 and March 2024. The research showed the majority of biomarker-positive, cognitively normal individuals will not become symptomatic during their lifetime.

The risk of a 55-year-old who is amyloid positive developing Alzheimer’s disease is not that much higher than that for an individual of a similar age who is amyloid negative, Dubois noted. “There’s an 83% chance that person will never develop Alzheimer’s disease.”

Disclosing a diagnosis of Alzheimer’s disease to cognitively normal people with only one core Alzheimer’s disease biomarker represents “the most problematic implication of a purely biological definition of the disease,” the authors noted.

“A biomarker is a marker of pathology, not a biomarker of disease,” said Dubois, adding that a person may have markers for several different brain diseases.

The IWG recommends the following nomenclature: At risk for Alzheimer’s disease for those with Alzheimer’s disease biomarkers but low lifetime risk and presymptomatic Alzheimer’s disease for those with Alzheimer’s disease biomarkers with a very high lifetime risk for progression such as individuals with autosomal dominant genetic mutations and other distinct biomarker profiles that put them at extremely high lifetime risk of developing the disease.

Dubois emphasized the difference between those showing typical Alzheimer’s disease symptoms with positive biomarkers who should be considered to have the disease and those with positive biomarkers but no typical Alzheimer’s disease symptoms who should be considered at risk.

This is an important distinction as it affects research approaches and assessment of risks, he said.

For low-risk asymptomatic individuals, the IWG does not recommend routine diagnostic testing outside of the research setting. “There’s no reason to send a 65-year-old cognitively normal subject off to collect biomarker information,” said Dubois.

He reiterated the importance of clinicians using appropriate and sensitive language surrounding Alzheimer’s disease when face to face with patients. This issue “is not purely semantic; this is real life.”

For these patients in the clinical setting, “we have to be very careful about proposing treatments that may have side effects,” he said.

However, this does not mean asymptomatic at-risk people should not be studied to determine what pharmacological interventions might prevent or delay the onset of clinical disease, he noted.

Presymptomatic individuals who are at a high risk of developing Alzheimer’s disease “should be the target for clinical trials in the future” to determine best ways to delay the conversion to Alzheimer’s disease, he said.

The main focus of such research should be to better understand the “biomarker pattern profile” that is associated with a high risk of developing Alzheimer’s disease, said Dubois.
 

Plea for Unity

In an accompanying editorial, Ronald C. Petersen, PhD, MD, director, Mayo Clinic Alzheimer’s Disease Research Center and Mayo Clinic Study of Aging, Rochester, Minnesota, and colleagues outline the difference between the IWG and Alzheimer’s Association positions.

As the IWG uses Alzheimer’s disease to define those with cognitive impairment and the Alzheimer’s Association group uses Alzheimer’s disease to define those with the pathology of the disease, the field is now at a crossroads. “Do we name the disease before clinical symptoms?” they asked.

They note that Alzheimer’s Association criteria distinguish between a disease and an illness, whereas the IWG does not. “As such, although the primary disagreement between the groups is semantic, the ramifications of the labeling can be significant.”

It is “incumbent” that the field “come together” on an Alzheimer’s disease definition, the editorial concluded. “Neither the Alzheimer’s Association or IWG documents are appropriate to serve as a guide for how to apply biomarkers in a clinical setting. Appropriate-use criteria are needed to form a bridge between biological frameworks and real-world clinical practice so we can all maximally help all of our patients with this disorder.”

In a comment, Reisa Sperling, MD, professor of neurology, Harvard Medical School, and director, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital and Massachusetts General Hospital, all in Boston, who is part of the Alzheimer’s Association work group that published the revised criteria for diagnosis and staging of Alzheimer’s disease, likened Alzheimer’s disease, which begins in the brain many years before dementia onset, to cardiovascular disease in that it involves multiple processes. She noted the World Health Organization classifies cardiovascular disease as a “disease” prior to clinical manifestations such as stroke and myocardial infarction.

“If someone has Alzheimer’s disease pathology in their brain, they are at risk for dementia or clinical manifestations of the disease — just like vascular disease quantifies the risk of stroke or heart attack, not risk of developing ‘vascular disease’ if the underlying vascular disease is already present,” said Sperling.

A large part of the controversy is related to terminology and the “stigma” of the “A” word in the same way there used to be fear around using the “C” word — cancer, said Sperling.

“Once people began talking about cancer publicly as a potentially treatable disease and began getting screened and diagnosed before symptoms of cancer were manifest, this has had a tremendous impact on public health.”

She clarified that her work group does not recommend screening asymptomatic people with Alzheimer’s disease biomarkers. “We actually need to prove that treating at the preclinical stage of the disease is able to prevent clinical impairment and dementia,” she said, adding “hopefully, we are getting closer to this.”

Dubois reported no relevant disclosures. Petersen reported receiving personal fees from Roche, Genentech, Eli Lilly and Company, Eisai, and Novo Nordisk outside the submitted work and royalties from Oxford University Press, UpToDate, and Medscape educational activities.

A version of this article appeared on Medscape.com.

A group of international experts is challenging revised diagnostic criteria for Alzheimer’s disease as laid out by the Alzheimer’s Association earlier in 2024.

In a paper published online in JAMA Neurology, the International Working Group (IWG), which includes 46 experts from 17 countries, is recommending that the diagnosis of Alzheimer’s disease be limited to individuals with mild cognitive impairment or dementia and not be applied to cognitively normal individuals with Alzheimer’s disease biomarkers such as amyloid-beta 42/40 or p-tau.

Clinicians should be “very careful” about using the “A” word (Alzheimer’s) for cognitively unimpaired people with Alzheimer’s disease biomarkers, said the paper’s first author Bruno Dubois, MD, professor of neurology, Sorbonne University and Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France.

Providing an Alzheimer’s disease diagnosis to those who have a high chance of never developing cognitive impairment can be psychologically harmful, said Dubois.

“It’s not something small like telling someone they have a fever. Just imagine you’re 65 years old and are amyloid positive, and you’re told you have Alzheimer’s disease. It affects the decisions you make for the rest of your life and changes your vision of your future, even though you may never develop the disease,” he added.
 

Divergent View

The IWG’s perspective on Alzheimer’s disease contrasts with a recent proposal from the Alzheimer’s Association. The Alzheimer’s Association criteria suggest that Alzheimer’s disease should be regarded solely as a biological entity, which could include cognitively normal individuals with one core Alzheimer’s disease biomarker.

The IWG noted that its concerns regarding the application of a purely biological definition of Alzheimer’s disease in clinical practice prompted the group to consider updating its guidelines, potentially offering “an alternative definitional view of Alzheimer’s disease as a clinical-biological construct for clinical use.”

The group conducted a PubMed search for relevant Alzheimer’s disease articles, and included references, published between July 2020 and March 2024. The research showed the majority of biomarker-positive, cognitively normal individuals will not become symptomatic during their lifetime.

The risk of a 55-year-old who is amyloid positive developing Alzheimer’s disease is not that much higher than that for an individual of a similar age who is amyloid negative, Dubois noted. “There’s an 83% chance that person will never develop Alzheimer’s disease.”

Disclosing a diagnosis of Alzheimer’s disease to cognitively normal people with only one core Alzheimer’s disease biomarker represents “the most problematic implication of a purely biological definition of the disease,” the authors noted.

“A biomarker is a marker of pathology, not a biomarker of disease,” said Dubois, adding that a person may have markers for several different brain diseases.

The IWG recommends the following nomenclature: At risk for Alzheimer’s disease for those with Alzheimer’s disease biomarkers but low lifetime risk and presymptomatic Alzheimer’s disease for those with Alzheimer’s disease biomarkers with a very high lifetime risk for progression such as individuals with autosomal dominant genetic mutations and other distinct biomarker profiles that put them at extremely high lifetime risk of developing the disease.

Dubois emphasized the difference between those showing typical Alzheimer’s disease symptoms with positive biomarkers who should be considered to have the disease and those with positive biomarkers but no typical Alzheimer’s disease symptoms who should be considered at risk.

This is an important distinction as it affects research approaches and assessment of risks, he said.

For low-risk asymptomatic individuals, the IWG does not recommend routine diagnostic testing outside of the research setting. “There’s no reason to send a 65-year-old cognitively normal subject off to collect biomarker information,” said Dubois.

He reiterated the importance of clinicians using appropriate and sensitive language surrounding Alzheimer’s disease when face to face with patients. This issue “is not purely semantic; this is real life.”

For these patients in the clinical setting, “we have to be very careful about proposing treatments that may have side effects,” he said.

However, this does not mean asymptomatic at-risk people should not be studied to determine what pharmacological interventions might prevent or delay the onset of clinical disease, he noted.

Presymptomatic individuals who are at a high risk of developing Alzheimer’s disease “should be the target for clinical trials in the future” to determine best ways to delay the conversion to Alzheimer’s disease, he said.

The main focus of such research should be to better understand the “biomarker pattern profile” that is associated with a high risk of developing Alzheimer’s disease, said Dubois.
 

Plea for Unity

In an accompanying editorial, Ronald C. Petersen, PhD, MD, director, Mayo Clinic Alzheimer’s Disease Research Center and Mayo Clinic Study of Aging, Rochester, Minnesota, and colleagues outline the difference between the IWG and Alzheimer’s Association positions.

As the IWG uses Alzheimer’s disease to define those with cognitive impairment and the Alzheimer’s Association group uses Alzheimer’s disease to define those with the pathology of the disease, the field is now at a crossroads. “Do we name the disease before clinical symptoms?” they asked.

They note that Alzheimer’s Association criteria distinguish between a disease and an illness, whereas the IWG does not. “As such, although the primary disagreement between the groups is semantic, the ramifications of the labeling can be significant.”

It is “incumbent” that the field “come together” on an Alzheimer’s disease definition, the editorial concluded. “Neither the Alzheimer’s Association or IWG documents are appropriate to serve as a guide for how to apply biomarkers in a clinical setting. Appropriate-use criteria are needed to form a bridge between biological frameworks and real-world clinical practice so we can all maximally help all of our patients with this disorder.”

In a comment, Reisa Sperling, MD, professor of neurology, Harvard Medical School, and director, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital and Massachusetts General Hospital, all in Boston, who is part of the Alzheimer’s Association work group that published the revised criteria for diagnosis and staging of Alzheimer’s disease, likened Alzheimer’s disease, which begins in the brain many years before dementia onset, to cardiovascular disease in that it involves multiple processes. She noted the World Health Organization classifies cardiovascular disease as a “disease” prior to clinical manifestations such as stroke and myocardial infarction.

“If someone has Alzheimer’s disease pathology in their brain, they are at risk for dementia or clinical manifestations of the disease — just like vascular disease quantifies the risk of stroke or heart attack, not risk of developing ‘vascular disease’ if the underlying vascular disease is already present,” said Sperling.

A large part of the controversy is related to terminology and the “stigma” of the “A” word in the same way there used to be fear around using the “C” word — cancer, said Sperling.

“Once people began talking about cancer publicly as a potentially treatable disease and began getting screened and diagnosed before symptoms of cancer were manifest, this has had a tremendous impact on public health.”

She clarified that her work group does not recommend screening asymptomatic people with Alzheimer’s disease biomarkers. “We actually need to prove that treating at the preclinical stage of the disease is able to prevent clinical impairment and dementia,” she said, adding “hopefully, we are getting closer to this.”

Dubois reported no relevant disclosures. Petersen reported receiving personal fees from Roche, Genentech, Eli Lilly and Company, Eisai, and Novo Nordisk outside the submitted work and royalties from Oxford University Press, UpToDate, and Medscape educational activities.

A version of this article appeared on Medscape.com.

A group of international experts is challenging revised diagnostic criteria for Alzheimer’s disease as laid out by the Alzheimer’s Association earlier in 2024.

In a paper published online in JAMA Neurology, the International Working Group (IWG), which includes 46 experts from 17 countries, is recommending that the diagnosis of Alzheimer’s disease be limited to individuals with mild cognitive impairment or dementia and not be applied to cognitively normal individuals with Alzheimer’s disease biomarkers such as amyloid-beta 42/40 or p-tau.

Clinicians should be “very careful” about using the “A” word (Alzheimer’s) for cognitively unimpaired people with Alzheimer’s disease biomarkers, said the paper’s first author Bruno Dubois, MD, professor of neurology, Sorbonne University and Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France.

Providing an Alzheimer’s disease diagnosis to those who have a high chance of never developing cognitive impairment can be psychologically harmful, said Dubois.

“It’s not something small like telling someone they have a fever. Just imagine you’re 65 years old and are amyloid positive, and you’re told you have Alzheimer’s disease. It affects the decisions you make for the rest of your life and changes your vision of your future, even though you may never develop the disease,” he added.
 

Divergent View

The IWG’s perspective on Alzheimer’s disease contrasts with a recent proposal from the Alzheimer’s Association. The Alzheimer’s Association criteria suggest that Alzheimer’s disease should be regarded solely as a biological entity, which could include cognitively normal individuals with one core Alzheimer’s disease biomarker.

The IWG noted that its concerns regarding the application of a purely biological definition of Alzheimer’s disease in clinical practice prompted the group to consider updating its guidelines, potentially offering “an alternative definitional view of Alzheimer’s disease as a clinical-biological construct for clinical use.”

The group conducted a PubMed search for relevant Alzheimer’s disease articles, and included references, published between July 2020 and March 2024. The research showed the majority of biomarker-positive, cognitively normal individuals will not become symptomatic during their lifetime.

The risk of a 55-year-old who is amyloid positive developing Alzheimer’s disease is not that much higher than that for an individual of a similar age who is amyloid negative, Dubois noted. “There’s an 83% chance that person will never develop Alzheimer’s disease.”

Disclosing a diagnosis of Alzheimer’s disease to cognitively normal people with only one core Alzheimer’s disease biomarker represents “the most problematic implication of a purely biological definition of the disease,” the authors noted.

“A biomarker is a marker of pathology, not a biomarker of disease,” said Dubois, adding that a person may have markers for several different brain diseases.

The IWG recommends the following nomenclature: At risk for Alzheimer’s disease for those with Alzheimer’s disease biomarkers but low lifetime risk and presymptomatic Alzheimer’s disease for those with Alzheimer’s disease biomarkers with a very high lifetime risk for progression such as individuals with autosomal dominant genetic mutations and other distinct biomarker profiles that put them at extremely high lifetime risk of developing the disease.

Dubois emphasized the difference between those showing typical Alzheimer’s disease symptoms with positive biomarkers who should be considered to have the disease and those with positive biomarkers but no typical Alzheimer’s disease symptoms who should be considered at risk.

This is an important distinction as it affects research approaches and assessment of risks, he said.

For low-risk asymptomatic individuals, the IWG does not recommend routine diagnostic testing outside of the research setting. “There’s no reason to send a 65-year-old cognitively normal subject off to collect biomarker information,” said Dubois.

He reiterated the importance of clinicians using appropriate and sensitive language surrounding Alzheimer’s disease when face to face with patients. This issue “is not purely semantic; this is real life.”

For these patients in the clinical setting, “we have to be very careful about proposing treatments that may have side effects,” he said.

However, this does not mean asymptomatic at-risk people should not be studied to determine what pharmacological interventions might prevent or delay the onset of clinical disease, he noted.

Presymptomatic individuals who are at a high risk of developing Alzheimer’s disease “should be the target for clinical trials in the future” to determine best ways to delay the conversion to Alzheimer’s disease, he said.

The main focus of such research should be to better understand the “biomarker pattern profile” that is associated with a high risk of developing Alzheimer’s disease, said Dubois.
 

Plea for Unity

In an accompanying editorial, Ronald C. Petersen, PhD, MD, director, Mayo Clinic Alzheimer’s Disease Research Center and Mayo Clinic Study of Aging, Rochester, Minnesota, and colleagues outline the difference between the IWG and Alzheimer’s Association positions.

As the IWG uses Alzheimer’s disease to define those with cognitive impairment and the Alzheimer’s Association group uses Alzheimer’s disease to define those with the pathology of the disease, the field is now at a crossroads. “Do we name the disease before clinical symptoms?” they asked.

They note that Alzheimer’s Association criteria distinguish between a disease and an illness, whereas the IWG does not. “As such, although the primary disagreement between the groups is semantic, the ramifications of the labeling can be significant.”

It is “incumbent” that the field “come together” on an Alzheimer’s disease definition, the editorial concluded. “Neither the Alzheimer’s Association or IWG documents are appropriate to serve as a guide for how to apply biomarkers in a clinical setting. Appropriate-use criteria are needed to form a bridge between biological frameworks and real-world clinical practice so we can all maximally help all of our patients with this disorder.”

In a comment, Reisa Sperling, MD, professor of neurology, Harvard Medical School, and director, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital and Massachusetts General Hospital, all in Boston, who is part of the Alzheimer’s Association work group that published the revised criteria for diagnosis and staging of Alzheimer’s disease, likened Alzheimer’s disease, which begins in the brain many years before dementia onset, to cardiovascular disease in that it involves multiple processes. She noted the World Health Organization classifies cardiovascular disease as a “disease” prior to clinical manifestations such as stroke and myocardial infarction.

“If someone has Alzheimer’s disease pathology in their brain, they are at risk for dementia or clinical manifestations of the disease — just like vascular disease quantifies the risk of stroke or heart attack, not risk of developing ‘vascular disease’ if the underlying vascular disease is already present,” said Sperling.

A large part of the controversy is related to terminology and the “stigma” of the “A” word in the same way there used to be fear around using the “C” word — cancer, said Sperling.

“Once people began talking about cancer publicly as a potentially treatable disease and began getting screened and diagnosed before symptoms of cancer were manifest, this has had a tremendous impact on public health.”

She clarified that her work group does not recommend screening asymptomatic people with Alzheimer’s disease biomarkers. “We actually need to prove that treating at the preclinical stage of the disease is able to prevent clinical impairment and dementia,” she said, adding “hopefully, we are getting closer to this.”

Dubois reported no relevant disclosures. Petersen reported receiving personal fees from Roche, Genentech, Eli Lilly and Company, Eisai, and Novo Nordisk outside the submitted work and royalties from Oxford University Press, UpToDate, and Medscape educational activities.

A version of this article appeared on Medscape.com.

TOPLINE:

Weight loss interventions using medication or behavioral changes can improve insulin resistance, hormonal markers, and menstrual frequency in women with polycystic ovary syndrome (PCOS), according to a new meta-analysis. Losing weight may not significantly reduce hirsutism or improve quality of life in women with the condition, however.

METHODOLOGY:

• Researchers systematically reviewed randomized controlled trials comparing weight loss interventions to usual care in women with PCOS.
• They focused on 12 studies with behavioral interventions (mainly diets with modest energy deficits), nine trials that used glucagon-like peptide 1 (GLP-1) receptor agonists, and eight studies using other weight loss medications.
• A total of 1529 participants were included in the analysis.
• The investigators synthesized the data using a random-effects meta-analysis with Knapp-Hartung adjustment to examine pooled mean differences.

TAKEAWAY:

• Menstrual frequency increased by 2.64 menses per year (95% CI, 0.65-4.63) with weight loss interventions.
• “To our knowledge, this is the first review to show a clinically significant association in improvement in menstrual frequency with weight loss interventions, an important indicator of subsequent fertility and an important outcome for women,” the researchers wrote.
• Glycemic control also improved, with a mean reduction in homeostatic model assessment of insulin resistance of 0.45 (95% CI, –0.75 to –0.15).
• Free androgen index decreased by an average of 2.03 (95% CI, –3.0 to –1.07).

IN PRACTICE:

“Clinicians may use these findings to counsel women with PCOS on the expected improvements in PCOS markers after weight loss and direct patients toward interventions,” the authors of the study wrote. “Because weight loss programs are cost-effective interventions to improve cardiometabolic risk, they may be particularly valuable for this population at elevated risk.”

SOURCE:

The study was led by Jadine Scragg, PhD, with the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England. It was published online in Annals of Internal Medicine.

LIMITATIONS:

Interventions using GLP-1 agonists were dosed for glycemic control rather than weight management. The studies in the meta-analysis were relatively few and heterogeneous. Data were insufficient to assess ovulation and acne.

DISCLOSURES:

The meta-analysis was supported by grants from the National Institute for Health and Care Research School for Primary Care Research. Authors disclosed ties to Nestlé Health Science and Second Nature.

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

TOPLINE:

Weight loss interventions using medication or behavioral changes can improve insulin resistance, hormonal markers, and menstrual frequency in women with polycystic ovary syndrome (PCOS), according to a new meta-analysis. Losing weight may not significantly reduce hirsutism or improve quality of life in women with the condition, however.

METHODOLOGY:

• Researchers systematically reviewed randomized controlled trials comparing weight loss interventions to usual care in women with PCOS.
• They focused on 12 studies with behavioral interventions (mainly diets with modest energy deficits), nine trials that used glucagon-like peptide 1 (GLP-1) receptor agonists, and eight studies using other weight loss medications.
• A total of 1529 participants were included in the analysis.
• The investigators synthesized the data using a random-effects meta-analysis with Knapp-Hartung adjustment to examine pooled mean differences.

TAKEAWAY:

• Menstrual frequency increased by 2.64 menses per year (95% CI, 0.65-4.63) with weight loss interventions.
• “To our knowledge, this is the first review to show a clinically significant association in improvement in menstrual frequency with weight loss interventions, an important indicator of subsequent fertility and an important outcome for women,” the researchers wrote.
• Glycemic control also improved, with a mean reduction in homeostatic model assessment of insulin resistance of 0.45 (95% CI, –0.75 to –0.15).
• Free androgen index decreased by an average of 2.03 (95% CI, –3.0 to –1.07).

IN PRACTICE:

“Clinicians may use these findings to counsel women with PCOS on the expected improvements in PCOS markers after weight loss and direct patients toward interventions,” the authors of the study wrote. “Because weight loss programs are cost-effective interventions to improve cardiometabolic risk, they may be particularly valuable for this population at elevated risk.”

SOURCE:

The study was led by Jadine Scragg, PhD, with the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England. It was published online in Annals of Internal Medicine.

LIMITATIONS:

Interventions using GLP-1 agonists were dosed for glycemic control rather than weight management. The studies in the meta-analysis were relatively few and heterogeneous. Data were insufficient to assess ovulation and acne.

DISCLOSURES:

The meta-analysis was supported by grants from the National Institute for Health and Care Research School for Primary Care Research. Authors disclosed ties to Nestlé Health Science and Second Nature.

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

TOPLINE:

Weight loss interventions using medication or behavioral changes can improve insulin resistance, hormonal markers, and menstrual frequency in women with polycystic ovary syndrome (PCOS), according to a new meta-analysis. Losing weight may not significantly reduce hirsutism or improve quality of life in women with the condition, however.

METHODOLOGY:

• Researchers systematically reviewed randomized controlled trials comparing weight loss interventions to usual care in women with PCOS.
• They focused on 12 studies with behavioral interventions (mainly diets with modest energy deficits), nine trials that used glucagon-like peptide 1 (GLP-1) receptor agonists, and eight studies using other weight loss medications.
• A total of 1529 participants were included in the analysis.
• The investigators synthesized the data using a random-effects meta-analysis with Knapp-Hartung adjustment to examine pooled mean differences.

TAKEAWAY:

• Menstrual frequency increased by 2.64 menses per year (95% CI, 0.65-4.63) with weight loss interventions.
• “To our knowledge, this is the first review to show a clinically significant association in improvement in menstrual frequency with weight loss interventions, an important indicator of subsequent fertility and an important outcome for women,” the researchers wrote.
• Glycemic control also improved, with a mean reduction in homeostatic model assessment of insulin resistance of 0.45 (95% CI, –0.75 to –0.15).
• Free androgen index decreased by an average of 2.03 (95% CI, –3.0 to –1.07).

IN PRACTICE:

“Clinicians may use these findings to counsel women with PCOS on the expected improvements in PCOS markers after weight loss and direct patients toward interventions,” the authors of the study wrote. “Because weight loss programs are cost-effective interventions to improve cardiometabolic risk, they may be particularly valuable for this population at elevated risk.”

SOURCE:

The study was led by Jadine Scragg, PhD, with the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England. It was published online in Annals of Internal Medicine.

LIMITATIONS:

Interventions using GLP-1 agonists were dosed for glycemic control rather than weight management. The studies in the meta-analysis were relatively few and heterogeneous. Data were insufficient to assess ovulation and acne.

DISCLOSURES:

The meta-analysis was supported by grants from the National Institute for Health and Care Research School for Primary Care Research. Authors disclosed ties to Nestlé Health Science and Second Nature.

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

TOPLINE:

In women with polycystic ovary syndrome (PCOS) and with obesity or overweight, the combination of topiramate and metformin along with a low-calorie diet can result in effective weight loss and improve androgen levels, lipid levels, and psychosocial scores, without any serious adverse events.

METHODOLOGY:

• Topiramate is often used off-label for weight loss and may be a promising option added to a metformin regimen to improve cardiometabolic and reproductive health in women with PCOS and obesity or overweight when lifestyle changes alone fall short.
• This double-blind trial conducted at Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil, evaluated the effects of adding topiramate to metformin in 61 women aged 14-40 years with PCOS and body mass index (BMI) ≥ 30 or BMI ≥ 27 with concurrent hypertension, type 2 diabetes, or dyslipidemia.
• All participants were prescribed a 20 kcal/kg diet, as well as desogestrel for contraception during the study, and either started on 850 mg metformin or continued with their existing metformin regimen.
• They were randomly assigned to receive either topiramate or placebo (25 mg for 15 days and then 50 mg at night) along with metformin, with dose adjustments based on weight loss at 3 months.
• The primary outcome was the percent change in body weight from baseline, and the secondary outcomes included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features at 3 and 6 months.

TAKEAWAY:

• Topiramate combined with metformin resulted in greater mean weight loss at 3 months (−3.4% vs −1.6%; P = .03) and 6 months (−4.5% vs −1.4%; P = .03) than placebo plus metformin.
• Both treatment groups showed improvements in androgen and lipid levels and psychosocial scores, while the levels of C-reactive protein decreased only in the topiramate plus metformin group.
• Women who experienced ≥ 3% weight loss at 6 months showed a significant improvement in hirsutism scores (change in modified Ferriman-Gallwey scores, 8.4-6.5), unlike those who experienced < 3% weight loss (change in modified Ferriman-Gallwey scores, 8.02-8.78).
• Paresthesia was more common in the topiramate plus metformin group than in the metformin plus placebo group (23.3% vs 3.2%), but no serious adverse events were reported.

IN PRACTICE:

“In the era of new effective drugs for treating obesity, topiramate with metformin can be an option for women with obesity and PCOS, considering its low cost, reports of long-term experience with this medication, and ease to use,” the authors wrote.

SOURCE:

The study was led by Lucas Bandeira Marchesan, Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The small sample size and high attrition rates were major limitations of this study. Increasing the topiramate dose at 3 months in those with < 3% weight loss did not provide additional benefit, and this study did not test for a higher topiramate dose response from the beginning, which could have potentially provided a better response to the medication. The small sample size of the study also prevented the authors from conducting a subgroup analysis.

DISCLOSURES:

The study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil. The authors declared no conflicts of interest.

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

TOPLINE:

In women with polycystic ovary syndrome (PCOS) and with obesity or overweight, the combination of topiramate and metformin along with a low-calorie diet can result in effective weight loss and improve androgen levels, lipid levels, and psychosocial scores, without any serious adverse events.

METHODOLOGY:

• Topiramate is often used off-label for weight loss and may be a promising option added to a metformin regimen to improve cardiometabolic and reproductive health in women with PCOS and obesity or overweight when lifestyle changes alone fall short.
• This double-blind trial conducted at Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil, evaluated the effects of adding topiramate to metformin in 61 women aged 14-40 years with PCOS and body mass index (BMI) ≥ 30 or BMI ≥ 27 with concurrent hypertension, type 2 diabetes, or dyslipidemia.
• All participants were prescribed a 20 kcal/kg diet, as well as desogestrel for contraception during the study, and either started on 850 mg metformin or continued with their existing metformin regimen.
• They were randomly assigned to receive either topiramate or placebo (25 mg for 15 days and then 50 mg at night) along with metformin, with dose adjustments based on weight loss at 3 months.
• The primary outcome was the percent change in body weight from baseline, and the secondary outcomes included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features at 3 and 6 months.

TAKEAWAY:

• Topiramate combined with metformin resulted in greater mean weight loss at 3 months (−3.4% vs −1.6%; P = .03) and 6 months (−4.5% vs −1.4%; P = .03) than placebo plus metformin.
• Both treatment groups showed improvements in androgen and lipid levels and psychosocial scores, while the levels of C-reactive protein decreased only in the topiramate plus metformin group.
• Women who experienced ≥ 3% weight loss at 6 months showed a significant improvement in hirsutism scores (change in modified Ferriman-Gallwey scores, 8.4-6.5), unlike those who experienced < 3% weight loss (change in modified Ferriman-Gallwey scores, 8.02-8.78).
• Paresthesia was more common in the topiramate plus metformin group than in the metformin plus placebo group (23.3% vs 3.2%), but no serious adverse events were reported.

IN PRACTICE:

“In the era of new effective drugs for treating obesity, topiramate with metformin can be an option for women with obesity and PCOS, considering its low cost, reports of long-term experience with this medication, and ease to use,” the authors wrote.

SOURCE:

The study was led by Lucas Bandeira Marchesan, Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The small sample size and high attrition rates were major limitations of this study. Increasing the topiramate dose at 3 months in those with < 3% weight loss did not provide additional benefit, and this study did not test for a higher topiramate dose response from the beginning, which could have potentially provided a better response to the medication. The small sample size of the study also prevented the authors from conducting a subgroup analysis.

DISCLOSURES:

The study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil. The authors declared no conflicts of interest.

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

TOPLINE:

In women with polycystic ovary syndrome (PCOS) and with obesity or overweight, the combination of topiramate and metformin along with a low-calorie diet can result in effective weight loss and improve androgen levels, lipid levels, and psychosocial scores, without any serious adverse events.

METHODOLOGY:

• Topiramate is often used off-label for weight loss and may be a promising option added to a metformin regimen to improve cardiometabolic and reproductive health in women with PCOS and obesity or overweight when lifestyle changes alone fall short.
• This double-blind trial conducted at Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil, evaluated the effects of adding topiramate to metformin in 61 women aged 14-40 years with PCOS and body mass index (BMI) ≥ 30 or BMI ≥ 27 with concurrent hypertension, type 2 diabetes, or dyslipidemia.
• All participants were prescribed a 20 kcal/kg diet, as well as desogestrel for contraception during the study, and either started on 850 mg metformin or continued with their existing metformin regimen.
• They were randomly assigned to receive either topiramate or placebo (25 mg for 15 days and then 50 mg at night) along with metformin, with dose adjustments based on weight loss at 3 months.
• The primary outcome was the percent change in body weight from baseline, and the secondary outcomes included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features at 3 and 6 months.

TAKEAWAY:

• Topiramate combined with metformin resulted in greater mean weight loss at 3 months (−3.4% vs −1.6%; P = .03) and 6 months (−4.5% vs −1.4%; P = .03) than placebo plus metformin.
• Both treatment groups showed improvements in androgen and lipid levels and psychosocial scores, while the levels of C-reactive protein decreased only in the topiramate plus metformin group.
• Women who experienced ≥ 3% weight loss at 6 months showed a significant improvement in hirsutism scores (change in modified Ferriman-Gallwey scores, 8.4-6.5), unlike those who experienced < 3% weight loss (change in modified Ferriman-Gallwey scores, 8.02-8.78).
• Paresthesia was more common in the topiramate plus metformin group than in the metformin plus placebo group (23.3% vs 3.2%), but no serious adverse events were reported.

IN PRACTICE:

“In the era of new effective drugs for treating obesity, topiramate with metformin can be an option for women with obesity and PCOS, considering its low cost, reports of long-term experience with this medication, and ease to use,” the authors wrote.

SOURCE:

The study was led by Lucas Bandeira Marchesan, Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The small sample size and high attrition rates were major limitations of this study. Increasing the topiramate dose at 3 months in those with < 3% weight loss did not provide additional benefit, and this study did not test for a higher topiramate dose response from the beginning, which could have potentially provided a better response to the medication. The small sample size of the study also prevented the authors from conducting a subgroup analysis.

DISCLOSURES:

The study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil. The authors declared no conflicts of interest.

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

TOPLINE:

An estimated 72 million ambulatory visits for superficial cutaneous fungal infections (SCFIs) in the United States were recorded during 2005-2016, with an increasing trend over the years. Tinea unguium, tinea pedis, and tinea corporis were among the most common infections.

METHODOLOGY:

• Researchers analyzed data from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey from 2005 to 2016, to evaluate trends in the prevalence of SCFIs during this period.
• The analysis included over 13 billion ambulatory visits to nonfederally funded community, office-based physician practices, and emergency or outpatient departments in the United States, with an estimated 1,104,258,333 annual average.
• The Jonckheere-Terpstra nonparametric test for trend was used to determine the pattern of SCFI prevalence over the 12-year period.

TAKEAWAY:

• SCFIs constituted approximately 0.54% of all annual ambulatory visits, with an estimated 6,001,852 visits for SCFIs per year and over 72 million total visits for the infections during the study period.
• Tinea unguium, tinea pedis, and tinea corporis were the most common infections, comprising 20.5%, 12.2%, and 12.0% of the total visits, respectively.
• Researchers noted an increasing trend in annual SCFIs (P = .03).

IN PRACTICE:

“We observed a high burden of SCFIs among outpatient visits in the United States and an increasing trend in their prevalence,” the authors wrote. These results, they added, “highlight the importance of healthcare providers being able to identify, treat, and, when necessary, refer patients with SCFIs, as a high burden of disease is associated with a significant negative impact on the individual and population levels.”

SOURCE:

The study was co-led by Sarah L. Spaulding, BS, and A. Mitchel Wride, BA, from the Yale School of Medicine, New Haven, Connecticut, and was published online October 30 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The authors did not list any study limitations.

DISCLOSURES:

The lead authors were supported by Yale School of Medicine Medical Student Research Fellowships. Two other authors declared receiving consulting fees, research funding, and licensing fees outside the submitted work and also served on a data and safety monitoring board for Advarra Inc.
 

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

TOPLINE:

An estimated 72 million ambulatory visits for superficial cutaneous fungal infections (SCFIs) in the United States were recorded during 2005-2016, with an increasing trend over the years. Tinea unguium, tinea pedis, and tinea corporis were among the most common infections.

METHODOLOGY:

• Researchers analyzed data from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey from 2005 to 2016, to evaluate trends in the prevalence of SCFIs during this period.
• The analysis included over 13 billion ambulatory visits to nonfederally funded community, office-based physician practices, and emergency or outpatient departments in the United States, with an estimated 1,104,258,333 annual average.
• The Jonckheere-Terpstra nonparametric test for trend was used to determine the pattern of SCFI prevalence over the 12-year period.

TAKEAWAY:

• SCFIs constituted approximately 0.54% of all annual ambulatory visits, with an estimated 6,001,852 visits for SCFIs per year and over 72 million total visits for the infections during the study period.
• Tinea unguium, tinea pedis, and tinea corporis were the most common infections, comprising 20.5%, 12.2%, and 12.0% of the total visits, respectively.
• Researchers noted an increasing trend in annual SCFIs (P = .03).

IN PRACTICE:

“We observed a high burden of SCFIs among outpatient visits in the United States and an increasing trend in their prevalence,” the authors wrote. These results, they added, “highlight the importance of healthcare providers being able to identify, treat, and, when necessary, refer patients with SCFIs, as a high burden of disease is associated with a significant negative impact on the individual and population levels.”

SOURCE:

The study was co-led by Sarah L. Spaulding, BS, and A. Mitchel Wride, BA, from the Yale School of Medicine, New Haven, Connecticut, and was published online October 30 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The authors did not list any study limitations.

DISCLOSURES:

The lead authors were supported by Yale School of Medicine Medical Student Research Fellowships. Two other authors declared receiving consulting fees, research funding, and licensing fees outside the submitted work and also served on a data and safety monitoring board for Advarra Inc.
 

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

TOPLINE:

An estimated 72 million ambulatory visits for superficial cutaneous fungal infections (SCFIs) in the United States were recorded during 2005-2016, with an increasing trend over the years. Tinea unguium, tinea pedis, and tinea corporis were among the most common infections.

METHODOLOGY:

• Researchers analyzed data from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey from 2005 to 2016, to evaluate trends in the prevalence of SCFIs during this period.
• The analysis included over 13 billion ambulatory visits to nonfederally funded community, office-based physician practices, and emergency or outpatient departments in the United States, with an estimated 1,104,258,333 annual average.
• The Jonckheere-Terpstra nonparametric test for trend was used to determine the pattern of SCFI prevalence over the 12-year period.

TAKEAWAY:

• SCFIs constituted approximately 0.54% of all annual ambulatory visits, with an estimated 6,001,852 visits for SCFIs per year and over 72 million total visits for the infections during the study period.
• Tinea unguium, tinea pedis, and tinea corporis were the most common infections, comprising 20.5%, 12.2%, and 12.0% of the total visits, respectively.
• Researchers noted an increasing trend in annual SCFIs (P = .03).

IN PRACTICE:

“We observed a high burden of SCFIs among outpatient visits in the United States and an increasing trend in their prevalence,” the authors wrote. These results, they added, “highlight the importance of healthcare providers being able to identify, treat, and, when necessary, refer patients with SCFIs, as a high burden of disease is associated with a significant negative impact on the individual and population levels.”

SOURCE:

The study was co-led by Sarah L. Spaulding, BS, and A. Mitchel Wride, BA, from the Yale School of Medicine, New Haven, Connecticut, and was published online October 30 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The authors did not list any study limitations.

DISCLOSURES:

The lead authors were supported by Yale School of Medicine Medical Student Research Fellowships. Two other authors declared receiving consulting fees, research funding, and licensing fees outside the submitted work and also served on a data and safety monitoring board for Advarra Inc.
 

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

TOPLINE:

Weekend exercise, involving one or two sessions per week, is associated with a similar reduction in risk for mild dementia as that reported with more frequent exercise, a new study shows. Investigators say the findings suggest even limited physical activity may offer protective cognitive benefits.

METHODOLOGY:

• Researchers analyzed the data of 10,033 participants in the Mexico City Prospective Study who were aged 35 years or older.
• Physical activity patterns were categorized into four groups: No exercise, weekend warriors (one or two sessions per week), regularly active (three or more sessions per week), and a combined group.
• Cognitive function was assessed using the Mini-Mental State Examination (MMSE).
• The analysis adjusted for confounders such as age, sex, education, income, blood pressure, smoking status, body mass index, civil status, sleep duration, diet, and alcohol intake.
• The mean follow-up duration was 16 years.

TAKEAWAY:

• When mild dementia was defined as an MMSE score ≤ 22, dementia prevalence was 26% in those who did not exercise, 14% in weekend warriors, and 18.5% in the regularly active group.
• When mild dementia was defined as an MMSE score ≤ 23, dementia prevalence was 30% in those who did not exercise, 20% in weekend warriors, and 22% in the regularly active group.
• Compared with people who did not exercise and after adjusting for confounding factors, risk for mild dementia was 13%-25% lower in weekend warriors, 11%-12% lower in the regular activity group, and 12%-16% lower in the two groups combined.
• The findings were consistent in men and women.

IN PRACTICE:

“To the best of our knowledge, this is the first prospective cohort study to show that the weekend warrior physical activity pattern and the regularly active physical activity pattern are associated with similar reductions in the risk of mild dementia. This study has important implications for policy and practice because the weekend warrior physical activity pattern may be a more convenient option for busy people around the world,” the authors wrote.

SOURCE:

The study was led by Gary O’Donovan, Faculty of Medicine, University of the Andes, Bogotá, Colombia. It was published online in the British Journal of Sports Medicine.

LIMITATIONS:

The survey respondents may not have been truly representative of middle-aged adults. Further, there were no objective measures of physical activity. The observational nature of the study does not provide insights into causality.

DISCLOSURES:

The study was funded by the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Wellcome, and the UK Medical Research Council. No conflicts of interest were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Weekend exercise, involving one or two sessions per week, is associated with a similar reduction in risk for mild dementia as that reported with more frequent exercise, a new study shows. Investigators say the findings suggest even limited physical activity may offer protective cognitive benefits.

METHODOLOGY:

• Researchers analyzed the data of 10,033 participants in the Mexico City Prospective Study who were aged 35 years or older.
• Physical activity patterns were categorized into four groups: No exercise, weekend warriors (one or two sessions per week), regularly active (three or more sessions per week), and a combined group.
• Cognitive function was assessed using the Mini-Mental State Examination (MMSE).
• The analysis adjusted for confounders such as age, sex, education, income, blood pressure, smoking status, body mass index, civil status, sleep duration, diet, and alcohol intake.
• The mean follow-up duration was 16 years.

TAKEAWAY:

• When mild dementia was defined as an MMSE score ≤ 22, dementia prevalence was 26% in those who did not exercise, 14% in weekend warriors, and 18.5% in the regularly active group.
• When mild dementia was defined as an MMSE score ≤ 23, dementia prevalence was 30% in those who did not exercise, 20% in weekend warriors, and 22% in the regularly active group.
• Compared with people who did not exercise and after adjusting for confounding factors, risk for mild dementia was 13%-25% lower in weekend warriors, 11%-12% lower in the regular activity group, and 12%-16% lower in the two groups combined.
• The findings were consistent in men and women.

IN PRACTICE:

“To the best of our knowledge, this is the first prospective cohort study to show that the weekend warrior physical activity pattern and the regularly active physical activity pattern are associated with similar reductions in the risk of mild dementia. This study has important implications for policy and practice because the weekend warrior physical activity pattern may be a more convenient option for busy people around the world,” the authors wrote.

SOURCE:

The study was led by Gary O’Donovan, Faculty of Medicine, University of the Andes, Bogotá, Colombia. It was published online in the British Journal of Sports Medicine.

LIMITATIONS:

The survey respondents may not have been truly representative of middle-aged adults. Further, there were no objective measures of physical activity. The observational nature of the study does not provide insights into causality.

DISCLOSURES:

The study was funded by the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Wellcome, and the UK Medical Research Council. No conflicts of interest were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Weekend exercise, involving one or two sessions per week, is associated with a similar reduction in risk for mild dementia as that reported with more frequent exercise, a new study shows. Investigators say the findings suggest even limited physical activity may offer protective cognitive benefits.

METHODOLOGY:

• Researchers analyzed the data of 10,033 participants in the Mexico City Prospective Study who were aged 35 years or older.
• Physical activity patterns were categorized into four groups: No exercise, weekend warriors (one or two sessions per week), regularly active (three or more sessions per week), and a combined group.
• Cognitive function was assessed using the Mini-Mental State Examination (MMSE).
• The analysis adjusted for confounders such as age, sex, education, income, blood pressure, smoking status, body mass index, civil status, sleep duration, diet, and alcohol intake.
• The mean follow-up duration was 16 years.

TAKEAWAY:

• When mild dementia was defined as an MMSE score ≤ 22, dementia prevalence was 26% in those who did not exercise, 14% in weekend warriors, and 18.5% in the regularly active group.
• When mild dementia was defined as an MMSE score ≤ 23, dementia prevalence was 30% in those who did not exercise, 20% in weekend warriors, and 22% in the regularly active group.
• Compared with people who did not exercise and after adjusting for confounding factors, risk for mild dementia was 13%-25% lower in weekend warriors, 11%-12% lower in the regular activity group, and 12%-16% lower in the two groups combined.
• The findings were consistent in men and women.

IN PRACTICE:

“To the best of our knowledge, this is the first prospective cohort study to show that the weekend warrior physical activity pattern and the regularly active physical activity pattern are associated with similar reductions in the risk of mild dementia. This study has important implications for policy and practice because the weekend warrior physical activity pattern may be a more convenient option for busy people around the world,” the authors wrote.

SOURCE:

The study was led by Gary O’Donovan, Faculty of Medicine, University of the Andes, Bogotá, Colombia. It was published online in the British Journal of Sports Medicine.

LIMITATIONS:

The survey respondents may not have been truly representative of middle-aged adults. Further, there were no objective measures of physical activity. The observational nature of the study does not provide insights into causality.

DISCLOSURES:

The study was funded by the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Wellcome, and the UK Medical Research Council. No conflicts of interest were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 

A version of this article appeared on Medscape.com.

An expert panel has published noninvasive test (NIT) cutoffs to identify patients with metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis who may benefit from resmetirom therapy.

This guidance document allows clinicians to use a variety of NITs to start and monitor resmetirom therapy, precluding the need for a biopsy, lead author Mazen Noureddin, MD, of Houston Research Institute, Houston Methodist Hospital in Texas, and colleagues reported.

Houston Methodist Hospital

“The recent conditional approval by the [Food and Drug Administration] of resmetirom ... presents a much-anticipated therapeutic option for patients with noncirrhotic advanced MASH,” the investigators wrote in Clinical Gastroenterology and Hepatology.

However, the approval also “presents important challenges,” they noted, “including how to noninvasively identify patients with fibrosis stages 2-3, and how to exclude patients with more advanced disease who should not be treated until further data emerge on the use of resmetirom in this population.”

To help identify which patients should get this new intervention, Noureddin and colleagues considered benchmarks from published literature, and conducted a post hoc analysis of phase 3 MASTERO-NASH trial data. Trial enrollment required at least three cardiometabolic risk factors and a vibration-controlled transient elastography (VCTE) prescreening within the past 3 months. The population included 888 patients with F2 or F3 disease.

Recommendations were split into three categories: treat with resmetirom, consider treating with resmetirom, and do not treat with resmetirom.

The recommendation to treat calls for a VCTE of 10-15 kPa, a magnetic resonance elastography (MRE) of 3.3-4.2 kPa, or an Enhanced Liver Fibrosis (ELF) score of 9.2-10.4, with the caveat that an ELF score below 9.8 requires a second NIT for confirmation. Alternatively, a positive composite score such as FibroScan–aspartate aminotransferase (FAST), MRI–AST (MAST), or MRE + Fibrosis-4 (MEFIB) may serve as grounds for treatment. For any of the previous, platelets must concurrently be at least 140 with no evidence of portal hypertension.

The recommendation to consider treatment depends upon a VCTE of 15.1-19.9 kPa, an MRE of 4.3-4.9 kPa, an ELF score of 10.5-11.3, or positive FAST, MAST, or MEFIB. Again, these require a concurrent platelet count of 140 and no portal hypertension.

Finally, patients should not be treated with resmetirom if they have a VCTE of 20 kPa or greater, an MRE of 5 kPa or greater, and an ELF score greater than 11.3.

Noureddin and colleagues also offered guidance on monitoring strategies, including follow-up at 3, 6, and 12 months.

At 3 months, the focus should be safety, including screening for drug-related liver injury and other adverse events that warrant cessation.

At 6 months, alanine aminotransferase (ALT) levels, VCTE, or MRI–proton density fat fraction (PDFF) tests can indicate early response, but treatment should generally continue regardless of results.

At 12 months, efficacy can be fully evaluated. ALT normalization, or improvement of more than 17 IU/L or more than 20%, along with a 30% or greater drop in VCTE, or at least 30% drop in liver fat on MRI-PDFF, serve as grounds for continuation.

Noureddin and colleagues noted that ALT improvement should be paired with corresponding improvements in imaging, such as a 30% reduction in MRI-PDFF. Even if ALT levels do not improve, a 30% or greater reduction in MRI-PDFF can still indicate a positive response; however, VCTE alone may not be sufficient to fully assess treatment response.

“Emerging data, particularly regarding the noninvasive assessment of treatment response, are likely to further modify patient selection, safety signals, and efficacy algorithms,” they concluded.This study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, the John C. Martin Foundation, and the National Institute on Alcohol Abuse and Alcoholism. The investigators disclosed additional relationships with Novo Nordisk, Pfizer, Shire, and others.

An expert panel has published noninvasive test (NIT) cutoffs to identify patients with metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis who may benefit from resmetirom therapy.

This guidance document allows clinicians to use a variety of NITs to start and monitor resmetirom therapy, precluding the need for a biopsy, lead author Mazen Noureddin, MD, of Houston Research Institute, Houston Methodist Hospital in Texas, and colleagues reported.

Houston Methodist Hospital

“The recent conditional approval by the [Food and Drug Administration] of resmetirom ... presents a much-anticipated therapeutic option for patients with noncirrhotic advanced MASH,” the investigators wrote in Clinical Gastroenterology and Hepatology.

However, the approval also “presents important challenges,” they noted, “including how to noninvasively identify patients with fibrosis stages 2-3, and how to exclude patients with more advanced disease who should not be treated until further data emerge on the use of resmetirom in this population.”

To help identify which patients should get this new intervention, Noureddin and colleagues considered benchmarks from published literature, and conducted a post hoc analysis of phase 3 MASTERO-NASH trial data. Trial enrollment required at least three cardiometabolic risk factors and a vibration-controlled transient elastography (VCTE) prescreening within the past 3 months. The population included 888 patients with F2 or F3 disease.

Recommendations were split into three categories: treat with resmetirom, consider treating with resmetirom, and do not treat with resmetirom.

The recommendation to treat calls for a VCTE of 10-15 kPa, a magnetic resonance elastography (MRE) of 3.3-4.2 kPa, or an Enhanced Liver Fibrosis (ELF) score of 9.2-10.4, with the caveat that an ELF score below 9.8 requires a second NIT for confirmation. Alternatively, a positive composite score such as FibroScan–aspartate aminotransferase (FAST), MRI–AST (MAST), or MRE + Fibrosis-4 (MEFIB) may serve as grounds for treatment. For any of the previous, platelets must concurrently be at least 140 with no evidence of portal hypertension.

The recommendation to consider treatment depends upon a VCTE of 15.1-19.9 kPa, an MRE of 4.3-4.9 kPa, an ELF score of 10.5-11.3, or positive FAST, MAST, or MEFIB. Again, these require a concurrent platelet count of 140 and no portal hypertension.

Finally, patients should not be treated with resmetirom if they have a VCTE of 20 kPa or greater, an MRE of 5 kPa or greater, and an ELF score greater than 11.3.

Noureddin and colleagues also offered guidance on monitoring strategies, including follow-up at 3, 6, and 12 months.

At 3 months, the focus should be safety, including screening for drug-related liver injury and other adverse events that warrant cessation.

At 6 months, alanine aminotransferase (ALT) levels, VCTE, or MRI–proton density fat fraction (PDFF) tests can indicate early response, but treatment should generally continue regardless of results.

At 12 months, efficacy can be fully evaluated. ALT normalization, or improvement of more than 17 IU/L or more than 20%, along with a 30% or greater drop in VCTE, or at least 30% drop in liver fat on MRI-PDFF, serve as grounds for continuation.

Noureddin and colleagues noted that ALT improvement should be paired with corresponding improvements in imaging, such as a 30% reduction in MRI-PDFF. Even if ALT levels do not improve, a 30% or greater reduction in MRI-PDFF can still indicate a positive response; however, VCTE alone may not be sufficient to fully assess treatment response.

“Emerging data, particularly regarding the noninvasive assessment of treatment response, are likely to further modify patient selection, safety signals, and efficacy algorithms,” they concluded.This study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, the John C. Martin Foundation, and the National Institute on Alcohol Abuse and Alcoholism. The investigators disclosed additional relationships with Novo Nordisk, Pfizer, Shire, and others.

An expert panel has published noninvasive test (NIT) cutoffs to identify patients with metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis who may benefit from resmetirom therapy.

This guidance document allows clinicians to use a variety of NITs to start and monitor resmetirom therapy, precluding the need for a biopsy, lead author Mazen Noureddin, MD, of Houston Research Institute, Houston Methodist Hospital in Texas, and colleagues reported.

Houston Methodist Hospital

“The recent conditional approval by the [Food and Drug Administration] of resmetirom ... presents a much-anticipated therapeutic option for patients with noncirrhotic advanced MASH,” the investigators wrote in Clinical Gastroenterology and Hepatology.

However, the approval also “presents important challenges,” they noted, “including how to noninvasively identify patients with fibrosis stages 2-3, and how to exclude patients with more advanced disease who should not be treated until further data emerge on the use of resmetirom in this population.”

To help identify which patients should get this new intervention, Noureddin and colleagues considered benchmarks from published literature, and conducted a post hoc analysis of phase 3 MASTERO-NASH trial data. Trial enrollment required at least three cardiometabolic risk factors and a vibration-controlled transient elastography (VCTE) prescreening within the past 3 months. The population included 888 patients with F2 or F3 disease.

Recommendations were split into three categories: treat with resmetirom, consider treating with resmetirom, and do not treat with resmetirom.

The recommendation to treat calls for a VCTE of 10-15 kPa, a magnetic resonance elastography (MRE) of 3.3-4.2 kPa, or an Enhanced Liver Fibrosis (ELF) score of 9.2-10.4, with the caveat that an ELF score below 9.8 requires a second NIT for confirmation. Alternatively, a positive composite score such as FibroScan–aspartate aminotransferase (FAST), MRI–AST (MAST), or MRE + Fibrosis-4 (MEFIB) may serve as grounds for treatment. For any of the previous, platelets must concurrently be at least 140 with no evidence of portal hypertension.

The recommendation to consider treatment depends upon a VCTE of 15.1-19.9 kPa, an MRE of 4.3-4.9 kPa, an ELF score of 10.5-11.3, or positive FAST, MAST, or MEFIB. Again, these require a concurrent platelet count of 140 and no portal hypertension.

Finally, patients should not be treated with resmetirom if they have a VCTE of 20 kPa or greater, an MRE of 5 kPa or greater, and an ELF score greater than 11.3.

Noureddin and colleagues also offered guidance on monitoring strategies, including follow-up at 3, 6, and 12 months.

At 3 months, the focus should be safety, including screening for drug-related liver injury and other adverse events that warrant cessation.

At 6 months, alanine aminotransferase (ALT) levels, VCTE, or MRI–proton density fat fraction (PDFF) tests can indicate early response, but treatment should generally continue regardless of results.

At 12 months, efficacy can be fully evaluated. ALT normalization, or improvement of more than 17 IU/L or more than 20%, along with a 30% or greater drop in VCTE, or at least 30% drop in liver fat on MRI-PDFF, serve as grounds for continuation.

Noureddin and colleagues noted that ALT improvement should be paired with corresponding improvements in imaging, such as a 30% reduction in MRI-PDFF. Even if ALT levels do not improve, a 30% or greater reduction in MRI-PDFF can still indicate a positive response; however, VCTE alone may not be sufficient to fully assess treatment response.

“Emerging data, particularly regarding the noninvasive assessment of treatment response, are likely to further modify patient selection, safety signals, and efficacy algorithms,” they concluded.This study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, the John C. Martin Foundation, and the National Institute on Alcohol Abuse and Alcoholism. The investigators disclosed additional relationships with Novo Nordisk, Pfizer, Shire, and others.

Cannabis use may lead to thinning of the cerebral cortex in adolescents, research in mice and humans suggested.

The multilevel study demonstrated that tetrahydrocannabinol (THC), an active substance in cannabis, causes shrinkage of dendritic arborization — the neurons’ network of antennae that play a critical role in communication between brain cells.

The connection between dendritic arborization and cortical thickness was hinted at in an earlier study by Tomáš Paus, MD, PhD, professor of psychiatry and addictology at the University of Montreal, Quebec, Canada, and colleagues, who found that cannabis use in early adolescence was associated with lower cortical thickness in boys with a high genetic risk for schizophrenia.

“We speculated at that time that the differences in cortical thickness might be related to differences in dendritic arborization, and our current study confirmed it,” Paus said.

That confirmation came in the mouse part of the study, when coauthor Graciela Piñeyro, MD, PhD, also of the University of Montreal, counted the dendritic branches of mice exposed to THC and compared the total with the number of dendritic branches in unexposed mice. “What surprised me was finding that THC in the mice was targeting the same type of cells and structures that Dr. Paus had predicted would be affected from the human studies,” she said. “Structurally, they were mostly the neurons that contribute to synapses in the cortex, and their branching was reduced.”

Paus explained that in humans, a decrease in input from the affected dendrites “makes it harder for the brain to learn new things, interact with people, cope with new situations, et cetera. In other words, it makes the brain more vulnerable to everything that can happen in a young person’s life.”

The study was published online on October 9 in the Journal of Neuroscience.
 

Of Mice, Men, and Cannabis

Although associations between cannabis use by teenagers and variations in brain maturation have been well studied, the cellular and molecular underpinnings of these associations were unclear, according to the authors.

To investigate further, they conducted this three-step study. First, they exposed adolescent male mice to THC or a synthetic cannabinoid (WIN 55,212-2) and assessed differentially expressed genes, spine numbers, and the extent of dendritic complexity in the frontal cortex of each mouse.

Next, using MRI, they examined differences in cortical thickness in 34 brain regions in 140 male adolescents who experimented with cannabis before age 16 years and 327 who did not.

Then, they again conducted experiments in mice and found that 13 THC-related genes correlated with variations in cortical thickness. Virtual histology revealed that these 13 genes were coexpressed with cell markers of astrocytes, microglia, and a type of pyramidal cell enriched in genes that regulate dendritic expression.

Similarly, the WIN-related genes correlated with differences in cortical thickness and showed coexpression patterns with the same three cell types.

Furthermore, the affected genes were also found in humans, particularly in the thinner cortical regions of the adolescents who experimented with cannabis.

By acting on microglia, THC seems to promote the removal of synapses and, eventually, the reduction of the dendritic tree in mice, Piñeyro explained. That’s important not only because a similar mechanism may be at work in humans but also because “we now might have a model to test different types of cannabis products to see which ones are producing the greatest effect on neurons and therefore greater removal of synapses through the microglia. This could be a way of testing drugs that are out in the street to see which would be the most or least dangerous to the synapses in the brain.”
 

‘Significant Implications’

Commenting on the study, Yasmin Hurd, PhD, Ward-Coleman chair of translational neuroscience at the Icahn School of Medicine at Mount Sinai and director of the Addiction Institute of Mount Sinai in New York City, said, “These findings are in line with previous results, so they are feasible. This study adds more depth by showing that cortical genes that were differentially altered by adolescent THC correlated with cannabis-related changes in cortical thickness based on human neuroimaging data.” Hurd did not participate in the research.

“The results emphasize that consumption of potent cannabis products during adolescence can impact cortical function, which has significant implications for decision-making and risky behavior as well. It also can increase vulnerability to psychiatric disorders such as schizophrenia.”

Although a mouse model is “not truly the same as the human condition, the fact that the animal model also showed evidence of the morphological changes indicative of reduced cortical thickness, [like] the humans, is strong,” she said.

Additional research could include women and assess potential sex differences, she added.

Ronald Ellis, MD, PhD, an investigator in the Center for Medicinal Cannabis Research at the University of California, San Diego School of Medicine, said, “The findings are plausible and extend prior work showing evidence of increased risk for psychotic disorders later in life in adolescents who use cannabis.” Ellis did not participate in the research.

“Future studies should explore how these findings might vary across different demographic groups, which could provide a more inclusive understanding of how cannabis impacts the brain,” he said. “Additionally, longitudinal studies to track changes in the brain over time could help to establish causal relationships more robustly.

“The take-home message to clinicians at this point is to discuss cannabis use history carefully and confidentially with adolescent patients to better provide advice on its potential risks,” he concluded.

Paus added that he would tell patients, “If you’re going to use cannabis, don’t start early. If you have to, then do so in moderation. And if you have family history of mental illness, be very careful.”

No funding for the study was reported. Paus, Piñeyro, Hurd, and Ellis declared having no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Cannabis use may lead to thinning of the cerebral cortex in adolescents, research in mice and humans suggested.

The multilevel study demonstrated that tetrahydrocannabinol (THC), an active substance in cannabis, causes shrinkage of dendritic arborization — the neurons’ network of antennae that play a critical role in communication between brain cells.

The connection between dendritic arborization and cortical thickness was hinted at in an earlier study by Tomáš Paus, MD, PhD, professor of psychiatry and addictology at the University of Montreal, Quebec, Canada, and colleagues, who found that cannabis use in early adolescence was associated with lower cortical thickness in boys with a high genetic risk for schizophrenia.

“We speculated at that time that the differences in cortical thickness might be related to differences in dendritic arborization, and our current study confirmed it,” Paus said.

That confirmation came in the mouse part of the study, when coauthor Graciela Piñeyro, MD, PhD, also of the University of Montreal, counted the dendritic branches of mice exposed to THC and compared the total with the number of dendritic branches in unexposed mice. “What surprised me was finding that THC in the mice was targeting the same type of cells and structures that Dr. Paus had predicted would be affected from the human studies,” she said. “Structurally, they were mostly the neurons that contribute to synapses in the cortex, and their branching was reduced.”

Paus explained that in humans, a decrease in input from the affected dendrites “makes it harder for the brain to learn new things, interact with people, cope with new situations, et cetera. In other words, it makes the brain more vulnerable to everything that can happen in a young person’s life.”

The study was published online on October 9 in the Journal of Neuroscience.
 

Of Mice, Men, and Cannabis

Although associations between cannabis use by teenagers and variations in brain maturation have been well studied, the cellular and molecular underpinnings of these associations were unclear, according to the authors.

To investigate further, they conducted this three-step study. First, they exposed adolescent male mice to THC or a synthetic cannabinoid (WIN 55,212-2) and assessed differentially expressed genes, spine numbers, and the extent of dendritic complexity in the frontal cortex of each mouse.

Next, using MRI, they examined differences in cortical thickness in 34 brain regions in 140 male adolescents who experimented with cannabis before age 16 years and 327 who did not.

Then, they again conducted experiments in mice and found that 13 THC-related genes correlated with variations in cortical thickness. Virtual histology revealed that these 13 genes were coexpressed with cell markers of astrocytes, microglia, and a type of pyramidal cell enriched in genes that regulate dendritic expression.

Similarly, the WIN-related genes correlated with differences in cortical thickness and showed coexpression patterns with the same three cell types.

Furthermore, the affected genes were also found in humans, particularly in the thinner cortical regions of the adolescents who experimented with cannabis.

By acting on microglia, THC seems to promote the removal of synapses and, eventually, the reduction of the dendritic tree in mice, Piñeyro explained. That’s important not only because a similar mechanism may be at work in humans but also because “we now might have a model to test different types of cannabis products to see which ones are producing the greatest effect on neurons and therefore greater removal of synapses through the microglia. This could be a way of testing drugs that are out in the street to see which would be the most or least dangerous to the synapses in the brain.”
 

‘Significant Implications’

Commenting on the study, Yasmin Hurd, PhD, Ward-Coleman chair of translational neuroscience at the Icahn School of Medicine at Mount Sinai and director of the Addiction Institute of Mount Sinai in New York City, said, “These findings are in line with previous results, so they are feasible. This study adds more depth by showing that cortical genes that were differentially altered by adolescent THC correlated with cannabis-related changes in cortical thickness based on human neuroimaging data.” Hurd did not participate in the research.

“The results emphasize that consumption of potent cannabis products during adolescence can impact cortical function, which has significant implications for decision-making and risky behavior as well. It also can increase vulnerability to psychiatric disorders such as schizophrenia.”

Although a mouse model is “not truly the same as the human condition, the fact that the animal model also showed evidence of the morphological changes indicative of reduced cortical thickness, [like] the humans, is strong,” she said.

Additional research could include women and assess potential sex differences, she added.

Ronald Ellis, MD, PhD, an investigator in the Center for Medicinal Cannabis Research at the University of California, San Diego School of Medicine, said, “The findings are plausible and extend prior work showing evidence of increased risk for psychotic disorders later in life in adolescents who use cannabis.” Ellis did not participate in the research.

“Future studies should explore how these findings might vary across different demographic groups, which could provide a more inclusive understanding of how cannabis impacts the brain,” he said. “Additionally, longitudinal studies to track changes in the brain over time could help to establish causal relationships more robustly.

“The take-home message to clinicians at this point is to discuss cannabis use history carefully and confidentially with adolescent patients to better provide advice on its potential risks,” he concluded.

Paus added that he would tell patients, “If you’re going to use cannabis, don’t start early. If you have to, then do so in moderation. And if you have family history of mental illness, be very careful.”

No funding for the study was reported. Paus, Piñeyro, Hurd, and Ellis declared having no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Cannabis use may lead to thinning of the cerebral cortex in adolescents, research in mice and humans suggested.

The multilevel study demonstrated that tetrahydrocannabinol (THC), an active substance in cannabis, causes shrinkage of dendritic arborization — the neurons’ network of antennae that play a critical role in communication between brain cells.

The connection between dendritic arborization and cortical thickness was hinted at in an earlier study by Tomáš Paus, MD, PhD, professor of psychiatry and addictology at the University of Montreal, Quebec, Canada, and colleagues, who found that cannabis use in early adolescence was associated with lower cortical thickness in boys with a high genetic risk for schizophrenia.

“We speculated at that time that the differences in cortical thickness might be related to differences in dendritic arborization, and our current study confirmed it,” Paus said.

That confirmation came in the mouse part of the study, when coauthor Graciela Piñeyro, MD, PhD, also of the University of Montreal, counted the dendritic branches of mice exposed to THC and compared the total with the number of dendritic branches in unexposed mice. “What surprised me was finding that THC in the mice was targeting the same type of cells and structures that Dr. Paus had predicted would be affected from the human studies,” she said. “Structurally, they were mostly the neurons that contribute to synapses in the cortex, and their branching was reduced.”

Paus explained that in humans, a decrease in input from the affected dendrites “makes it harder for the brain to learn new things, interact with people, cope with new situations, et cetera. In other words, it makes the brain more vulnerable to everything that can happen in a young person’s life.”

The study was published online on October 9 in the Journal of Neuroscience.
 

Of Mice, Men, and Cannabis

Although associations between cannabis use by teenagers and variations in brain maturation have been well studied, the cellular and molecular underpinnings of these associations were unclear, according to the authors.

To investigate further, they conducted this three-step study. First, they exposed adolescent male mice to THC or a synthetic cannabinoid (WIN 55,212-2) and assessed differentially expressed genes, spine numbers, and the extent of dendritic complexity in the frontal cortex of each mouse.

Next, using MRI, they examined differences in cortical thickness in 34 brain regions in 140 male adolescents who experimented with cannabis before age 16 years and 327 who did not.

Then, they again conducted experiments in mice and found that 13 THC-related genes correlated with variations in cortical thickness. Virtual histology revealed that these 13 genes were coexpressed with cell markers of astrocytes, microglia, and a type of pyramidal cell enriched in genes that regulate dendritic expression.

Similarly, the WIN-related genes correlated with differences in cortical thickness and showed coexpression patterns with the same three cell types.

Furthermore, the affected genes were also found in humans, particularly in the thinner cortical regions of the adolescents who experimented with cannabis.

By acting on microglia, THC seems to promote the removal of synapses and, eventually, the reduction of the dendritic tree in mice, Piñeyro explained. That’s important not only because a similar mechanism may be at work in humans but also because “we now might have a model to test different types of cannabis products to see which ones are producing the greatest effect on neurons and therefore greater removal of synapses through the microglia. This could be a way of testing drugs that are out in the street to see which would be the most or least dangerous to the synapses in the brain.”
 

‘Significant Implications’

Commenting on the study, Yasmin Hurd, PhD, Ward-Coleman chair of translational neuroscience at the Icahn School of Medicine at Mount Sinai and director of the Addiction Institute of Mount Sinai in New York City, said, “These findings are in line with previous results, so they are feasible. This study adds more depth by showing that cortical genes that were differentially altered by adolescent THC correlated with cannabis-related changes in cortical thickness based on human neuroimaging data.” Hurd did not participate in the research.

“The results emphasize that consumption of potent cannabis products during adolescence can impact cortical function, which has significant implications for decision-making and risky behavior as well. It also can increase vulnerability to psychiatric disorders such as schizophrenia.”

Although a mouse model is “not truly the same as the human condition, the fact that the animal model also showed evidence of the morphological changes indicative of reduced cortical thickness, [like] the humans, is strong,” she said.

Additional research could include women and assess potential sex differences, she added.

Ronald Ellis, MD, PhD, an investigator in the Center for Medicinal Cannabis Research at the University of California, San Diego School of Medicine, said, “The findings are plausible and extend prior work showing evidence of increased risk for psychotic disorders later in life in adolescents who use cannabis.” Ellis did not participate in the research.

“Future studies should explore how these findings might vary across different demographic groups, which could provide a more inclusive understanding of how cannabis impacts the brain,” he said. “Additionally, longitudinal studies to track changes in the brain over time could help to establish causal relationships more robustly.

“The take-home message to clinicians at this point is to discuss cannabis use history carefully and confidentially with adolescent patients to better provide advice on its potential risks,” he concluded.

Paus added that he would tell patients, “If you’re going to use cannabis, don’t start early. If you have to, then do so in moderation. And if you have family history of mental illness, be very careful.”

No funding for the study was reported. Paus, Piñeyro, Hurd, and Ellis declared having no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Between 2011 and 2023, the US Food and Drug Administration (FDA) reported recalls of 334 cosmetic dermatology products in the United States, affecting over 77 million units, predominantly due to bacterial contamination.

METHODOLOGY:

• Researchers conducted a cross-sectional analysis of the FDA Enforcement Report database for cosmetic dermatology products from 2011 to 2023.
• Cosmetic products are any article “intended for body cleaning or beauty enhancement,” as defined by the FDA.
• Recalls were categorized by product type, reason for the recall, microbial contaminant, inorganic contaminant, distribution, and risk classification.

TAKEAWAY:

• During the study period, 334 voluntary and manufacturer-initiated recalls of cosmetic products were reported, affecting 77,135,700 units.
• A total of 297 recalls (88.9%) were categorized as Class II, indicating that they caused “medically reversible health consequences.” The median recall duration was 307 days.
• Hygiene and cleaning products accounted for most of the recalls (51.5%). Makeup gels, soaps, shampoos, tattoo ink, wipes, and lotions were the most recalled product categories. Nearly 51% of the products were distributed internationally.
• Microbial and inorganic contamination accounted for 76.8% and 10.2% of the recalls (the two most common reasons for the recall), respectively, with bacteria (80%) the most common contaminating pathogen (primarily Pseudomonas and Burkholderia species).

IN PRACTICE:

With 77 million units recalled by the FDA over 12 years, cosmetic recalls have remained common, the authors concluded, adding that “dermatologists should be key voices in pharmacovigilance given scientific expertise and frontline experience managing products and associated concerns.” Dermatologists, they added, “should also be aware of FDA enforcement reports for recall updates given that average recall termination took approximately 1 year.”

SOURCE:

The study was led by Kaushik P. Venkatesh, MBA, MPH, Harvard Medical School, Boston, and was published online on October 29 in the Journal of the American Academy of Dermatology.

LIMITATIONS: 

The study’s limitations include the potential underreporting of Class III recalls (products that are unlikely to cause any adverse health reaction but violate FDA labeling or manufacturing laws) and lack of complete information on contaminants.

DISCLOSURES:

No information on funding was provided in the study. No conflicts of interest were reported.

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

TOPLINE:

Between 2011 and 2023, the US Food and Drug Administration (FDA) reported recalls of 334 cosmetic dermatology products in the United States, affecting over 77 million units, predominantly due to bacterial contamination.

METHODOLOGY:

• Researchers conducted a cross-sectional analysis of the FDA Enforcement Report database for cosmetic dermatology products from 2011 to 2023.
• Cosmetic products are any article “intended for body cleaning or beauty enhancement,” as defined by the FDA.
• Recalls were categorized by product type, reason for the recall, microbial contaminant, inorganic contaminant, distribution, and risk classification.

TAKEAWAY:

• During the study period, 334 voluntary and manufacturer-initiated recalls of cosmetic products were reported, affecting 77,135,700 units.
• A total of 297 recalls (88.9%) were categorized as Class II, indicating that they caused “medically reversible health consequences.” The median recall duration was 307 days.
• Hygiene and cleaning products accounted for most of the recalls (51.5%). Makeup gels, soaps, shampoos, tattoo ink, wipes, and lotions were the most recalled product categories. Nearly 51% of the products were distributed internationally.
• Microbial and inorganic contamination accounted for 76.8% and 10.2% of the recalls (the two most common reasons for the recall), respectively, with bacteria (80%) the most common contaminating pathogen (primarily Pseudomonas and Burkholderia species).

IN PRACTICE:

With 77 million units recalled by the FDA over 12 years, cosmetic recalls have remained common, the authors concluded, adding that “dermatologists should be key voices in pharmacovigilance given scientific expertise and frontline experience managing products and associated concerns.” Dermatologists, they added, “should also be aware of FDA enforcement reports for recall updates given that average recall termination took approximately 1 year.”

SOURCE:

The study was led by Kaushik P. Venkatesh, MBA, MPH, Harvard Medical School, Boston, and was published online on October 29 in the Journal of the American Academy of Dermatology.

LIMITATIONS: 

The study’s limitations include the potential underreporting of Class III recalls (products that are unlikely to cause any adverse health reaction but violate FDA labeling or manufacturing laws) and lack of complete information on contaminants.

DISCLOSURES:

No information on funding was provided in the study. No conflicts of interest were reported.

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

TOPLINE:

Between 2011 and 2023, the US Food and Drug Administration (FDA) reported recalls of 334 cosmetic dermatology products in the United States, affecting over 77 million units, predominantly due to bacterial contamination.

METHODOLOGY:

• Researchers conducted a cross-sectional analysis of the FDA Enforcement Report database for cosmetic dermatology products from 2011 to 2023.
• Cosmetic products are any article “intended for body cleaning or beauty enhancement,” as defined by the FDA.
• Recalls were categorized by product type, reason for the recall, microbial contaminant, inorganic contaminant, distribution, and risk classification.

TAKEAWAY:

• During the study period, 334 voluntary and manufacturer-initiated recalls of cosmetic products were reported, affecting 77,135,700 units.
• A total of 297 recalls (88.9%) were categorized as Class II, indicating that they caused “medically reversible health consequences.” The median recall duration was 307 days.
• Hygiene and cleaning products accounted for most of the recalls (51.5%). Makeup gels, soaps, shampoos, tattoo ink, wipes, and lotions were the most recalled product categories. Nearly 51% of the products were distributed internationally.
• Microbial and inorganic contamination accounted for 76.8% and 10.2% of the recalls (the two most common reasons for the recall), respectively, with bacteria (80%) the most common contaminating pathogen (primarily Pseudomonas and Burkholderia species).

IN PRACTICE:

With 77 million units recalled by the FDA over 12 years, cosmetic recalls have remained common, the authors concluded, adding that “dermatologists should be key voices in pharmacovigilance given scientific expertise and frontline experience managing products and associated concerns.” Dermatologists, they added, “should also be aware of FDA enforcement reports for recall updates given that average recall termination took approximately 1 year.”

SOURCE:

The study was led by Kaushik P. Venkatesh, MBA, MPH, Harvard Medical School, Boston, and was published online on October 29 in the Journal of the American Academy of Dermatology.

LIMITATIONS: 

The study’s limitations include the potential underreporting of Class III recalls (products that are unlikely to cause any adverse health reaction but violate FDA labeling or manufacturing laws) and lack of complete information on contaminants.

DISCLOSURES:

No information on funding was provided in the study. No conflicts of interest were reported.

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

TOPLINE:

Patients with cutaneous lupus erythematosus (CLE) experienced improved symptoms with iberdomide, a cereblon modulator, added to standard lupus medications, particularly in subacute and chronic cases.

METHODOLOGY:

• Researchers conducted a randomized phase 2 trial to evaluate the efficacy and safety of iberdomide in 288 patients with CLE (mean age, 45 years; 97% women). Iberdomide is a cereblon modulator, which results in degradation of two transcription factors of immune cell development and homeostasis — Ikaros and Aiolos — that have been implicated in the genetic predisposition of systemic lupus.
• CLE Disease Area and Severity Index Activity (CLASI-A) endpoints included mean percent change from baseline and ≥ 50% reduction from baseline (CLASI-50), which were evaluated in all patients with baseline CLASI-A scores ≥ 8 and by CLE subtypes (acute, subacute, and chronic).
• At baseline, 56% of patients had acute CLE, 29% had chronic CLE, and 16% had subacute CLE; 28% of patients had a baseline CLASI-A score ≥ 8.
• Patients were randomly assigned to receive oral iberdomide (0.45 mg, 0.30 mg, 0.15 mg, or placebo daily) for 24 weeks while continuing standard lupus medications. At week 24, patients on placebo were rerandomized to iberdomide 0.45 mg or 0.30 mg once a day, while those on iberdomide continued their assigned dose through week 52.

TAKEAWAY:

• Among patients with baseline CLASI-A ≥ 8, the mean change in CLASI-A score from baseline at week 24 was −66.7% for those on iberdomide 0.45 mg vs −54.2% for placebo (P = .295).
• At week 24, patients with subacute CLE showed a significantly greater mean percent change from baseline in CLASI-A with iberdomide 0.45 mg vs placebo (−90.5% vs −51.2%; P = .007), while no significant differences were observed with the 0.45-mg dose vs placebo in patients with chronic or acute CLE.
• Overall, CLASI-50 responses were not significantly different among those on 0.45 mg vs placebo (55.6% vs 44.6%). The proportions of patients achieving CLASI-50 at week 24 were significantly greater for iberdomide 0.45 mg vs placebo for those with subacute CLE (91.7% vs 52.9%; P = .035) and chronic CLE (62.1% vs 27.8%; P = .029), but not for those with baseline CLASI-A ≥ 8 (66.7% vs 50%).
• More than 80% of patients had treatment-emergent adverse events (TEAEs), which were mostly mild to moderate. Over 2 years, the most common were urinary tract infections, upper respiratory tract infections, neutropenia, and nasopharyngitis. TEAEs leading to iberdomide discontinuation in one or more patients were neutropenia (n = 7), rash (n = 7), increased hepatic enzymes (n = 4), and deep vein thrombosis (n = 3).

IN PRACTICE:

“Data from this phase 2 trial of iberdomide in patients with SLE suggest that a greater proportion of patients with subacute or chronic CLE who received the higher dose of 0.45 mg iberdomide achieved CLASI-50 vs placebo. For the overall population, CLASI-50 response was not significantly different between treatment groups at week 24, partly due to a high placebo response that may have been driven by patients with acute CLE,” the authors wrote.

SOURCE:

The study was led by Victoria P. Werth, MD, of the University of Pennsylvania and the Veteran’s Administration Medical Center, both in Philadelphia, and was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study included small patient subgroups for different CLE subtypes, which may affect the generalizability of the findings. CLE subtype was determined by the investigator without additional photographic adjudication. Additionally, the use of background lupus medications could have influenced the placebo group’s response, limiting the ability to observe the treatment effect of iberdomide monotherapy.

DISCLOSURES:

The study was funded by Bristol-Myers Squibb. Six authors reported being employed by Bristol-Myers Squibb, and several others reported consultancy and research support from various sources including Bristol-Myers Squibb.

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

TOPLINE:

Patients with cutaneous lupus erythematosus (CLE) experienced improved symptoms with iberdomide, a cereblon modulator, added to standard lupus medications, particularly in subacute and chronic cases.

METHODOLOGY:

• Researchers conducted a randomized phase 2 trial to evaluate the efficacy and safety of iberdomide in 288 patients with CLE (mean age, 45 years; 97% women). Iberdomide is a cereblon modulator, which results in degradation of two transcription factors of immune cell development and homeostasis — Ikaros and Aiolos — that have been implicated in the genetic predisposition of systemic lupus.
• CLE Disease Area and Severity Index Activity (CLASI-A) endpoints included mean percent change from baseline and ≥ 50% reduction from baseline (CLASI-50), which were evaluated in all patients with baseline CLASI-A scores ≥ 8 and by CLE subtypes (acute, subacute, and chronic).
• At baseline, 56% of patients had acute CLE, 29% had chronic CLE, and 16% had subacute CLE; 28% of patients had a baseline CLASI-A score ≥ 8.
• Patients were randomly assigned to receive oral iberdomide (0.45 mg, 0.30 mg, 0.15 mg, or placebo daily) for 24 weeks while continuing standard lupus medications. At week 24, patients on placebo were rerandomized to iberdomide 0.45 mg or 0.30 mg once a day, while those on iberdomide continued their assigned dose through week 52.

TAKEAWAY:

• Among patients with baseline CLASI-A ≥ 8, the mean change in CLASI-A score from baseline at week 24 was −66.7% for those on iberdomide 0.45 mg vs −54.2% for placebo (P = .295).
• At week 24, patients with subacute CLE showed a significantly greater mean percent change from baseline in CLASI-A with iberdomide 0.45 mg vs placebo (−90.5% vs −51.2%; P = .007), while no significant differences were observed with the 0.45-mg dose vs placebo in patients with chronic or acute CLE.
• Overall, CLASI-50 responses were not significantly different among those on 0.45 mg vs placebo (55.6% vs 44.6%). The proportions of patients achieving CLASI-50 at week 24 were significantly greater for iberdomide 0.45 mg vs placebo for those with subacute CLE (91.7% vs 52.9%; P = .035) and chronic CLE (62.1% vs 27.8%; P = .029), but not for those with baseline CLASI-A ≥ 8 (66.7% vs 50%).
• More than 80% of patients had treatment-emergent adverse events (TEAEs), which were mostly mild to moderate. Over 2 years, the most common were urinary tract infections, upper respiratory tract infections, neutropenia, and nasopharyngitis. TEAEs leading to iberdomide discontinuation in one or more patients were neutropenia (n = 7), rash (n = 7), increased hepatic enzymes (n = 4), and deep vein thrombosis (n = 3).

IN PRACTICE:

“Data from this phase 2 trial of iberdomide in patients with SLE suggest that a greater proportion of patients with subacute or chronic CLE who received the higher dose of 0.45 mg iberdomide achieved CLASI-50 vs placebo. For the overall population, CLASI-50 response was not significantly different between treatment groups at week 24, partly due to a high placebo response that may have been driven by patients with acute CLE,” the authors wrote.

SOURCE:

The study was led by Victoria P. Werth, MD, of the University of Pennsylvania and the Veteran’s Administration Medical Center, both in Philadelphia, and was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study included small patient subgroups for different CLE subtypes, which may affect the generalizability of the findings. CLE subtype was determined by the investigator without additional photographic adjudication. Additionally, the use of background lupus medications could have influenced the placebo group’s response, limiting the ability to observe the treatment effect of iberdomide monotherapy.

DISCLOSURES:

The study was funded by Bristol-Myers Squibb. Six authors reported being employed by Bristol-Myers Squibb, and several others reported consultancy and research support from various sources including Bristol-Myers Squibb.

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

TOPLINE:

Patients with cutaneous lupus erythematosus (CLE) experienced improved symptoms with iberdomide, a cereblon modulator, added to standard lupus medications, particularly in subacute and chronic cases.

METHODOLOGY:

• Researchers conducted a randomized phase 2 trial to evaluate the efficacy and safety of iberdomide in 288 patients with CLE (mean age, 45 years; 97% women). Iberdomide is a cereblon modulator, which results in degradation of two transcription factors of immune cell development and homeostasis — Ikaros and Aiolos — that have been implicated in the genetic predisposition of systemic lupus.
• CLE Disease Area and Severity Index Activity (CLASI-A) endpoints included mean percent change from baseline and ≥ 50% reduction from baseline (CLASI-50), which were evaluated in all patients with baseline CLASI-A scores ≥ 8 and by CLE subtypes (acute, subacute, and chronic).
• At baseline, 56% of patients had acute CLE, 29% had chronic CLE, and 16% had subacute CLE; 28% of patients had a baseline CLASI-A score ≥ 8.
• Patients were randomly assigned to receive oral iberdomide (0.45 mg, 0.30 mg, 0.15 mg, or placebo daily) for 24 weeks while continuing standard lupus medications. At week 24, patients on placebo were rerandomized to iberdomide 0.45 mg or 0.30 mg once a day, while those on iberdomide continued their assigned dose through week 52.

TAKEAWAY:

• Among patients with baseline CLASI-A ≥ 8, the mean change in CLASI-A score from baseline at week 24 was −66.7% for those on iberdomide 0.45 mg vs −54.2% for placebo (P = .295).
• At week 24, patients with subacute CLE showed a significantly greater mean percent change from baseline in CLASI-A with iberdomide 0.45 mg vs placebo (−90.5% vs −51.2%; P = .007), while no significant differences were observed with the 0.45-mg dose vs placebo in patients with chronic or acute CLE.
• Overall, CLASI-50 responses were not significantly different among those on 0.45 mg vs placebo (55.6% vs 44.6%). The proportions of patients achieving CLASI-50 at week 24 were significantly greater for iberdomide 0.45 mg vs placebo for those with subacute CLE (91.7% vs 52.9%; P = .035) and chronic CLE (62.1% vs 27.8%; P = .029), but not for those with baseline CLASI-A ≥ 8 (66.7% vs 50%).
• More than 80% of patients had treatment-emergent adverse events (TEAEs), which were mostly mild to moderate. Over 2 years, the most common were urinary tract infections, upper respiratory tract infections, neutropenia, and nasopharyngitis. TEAEs leading to iberdomide discontinuation in one or more patients were neutropenia (n = 7), rash (n = 7), increased hepatic enzymes (n = 4), and deep vein thrombosis (n = 3).

IN PRACTICE:

“Data from this phase 2 trial of iberdomide in patients with SLE suggest that a greater proportion of patients with subacute or chronic CLE who received the higher dose of 0.45 mg iberdomide achieved CLASI-50 vs placebo. For the overall population, CLASI-50 response was not significantly different between treatment groups at week 24, partly due to a high placebo response that may have been driven by patients with acute CLE,” the authors wrote.

SOURCE:

The study was led by Victoria P. Werth, MD, of the University of Pennsylvania and the Veteran’s Administration Medical Center, both in Philadelphia, and was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study included small patient subgroups for different CLE subtypes, which may affect the generalizability of the findings. CLE subtype was determined by the investigator without additional photographic adjudication. Additionally, the use of background lupus medications could have influenced the placebo group’s response, limiting the ability to observe the treatment effect of iberdomide monotherapy.

DISCLOSURES:

The study was funded by Bristol-Myers Squibb. Six authors reported being employed by Bristol-Myers Squibb, and several others reported consultancy and research support from various sources including Bristol-Myers Squibb.

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