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Managing Atopic Dermatitis in Older Adults: A Common, Unique Challenge
WASHINGTON, DC — Jonathan I. Silverberg, MD, PhD, MPH, said at the ElderDerm Conference on dermatology in the older patient hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC.
“I walked out of residency under the impression that if it didn’t start in the first year or two of life, it’s not AD,” said Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University. “The numbers tell us a very different story.” 
The prevalence of AD in the United States fluctuates between 6% and 8% through adulthood, including age categories up to 81-85 years, according to 2012 National Health Interview Survey data. And while persistence of childhood-onset AD is common, a systematic review and meta-analysis published in 2018 concluded that one in four adults with AD report adult-onset disease.
The investigators, including Dr. Silverberg, identified 25 observational studies — studies conducted across 16 countries and published during 1956-2017 — that included an analysis of age of onset beyond 10 years of age, and other inclusion criteria. Of the 25 studies, 17 reported age of onset after 16 years of age and had sufficient data for the meta-analysis. Using random-effects weighting, the investigators found a pooled proportion of adult-onset AD of 26.1% (95% CI, 16.5%-37.2%).
The research demonstrates that “the age of onset is distributed well throughout the lifespan,” Dr. Silverberg said, with the data “indicating there are many elderly-onset cases of true AD as well.” (Thirteen of the studies analyzed an age of onset from age ≥ 65, and several looked beyond age 80).
A 2021 study of a primary care database in the United Kingdom of 3.85 million children and adults found a “fascinating” bimodal distribution of incidence across the lifespan, with peaks in both infancy and older adulthood, he said. Incidence in adulthood was relatively stable from ages 18-49 years, after which, “into the 50s, 60s and beyond, you started to see a steady climb again.”
Also intriguing, Dr. Silverberg continued, are findings from a study of outpatient healthcare utilization for AD in which he and his coinvestigator analyzed data from the National Ambulatory Medical Care Survey (NAMCS). In the article, published in 2023 covering data from the 1993-2015 NAMCS, they reported that AD visits were more common among children aged 0-4 years (32.0%) and 5-9 years of age (10.6%), then decreased in adolescents aged 10-19 years (11.6%), remained fairly steady in patients aged 20-89 years (1.0%-4.7%), and increased in patients aged > 90 years (20.7%).
“The peak usage for dermatologists, primary care physicians, etc., is happening in the first few years of life, partially because that’s when the disease is more common and more severe but also partially because that’s when parents and caregivers are first learning [about] the disease and trying to understand how to gain control,” Dr. Silverberg said at the meeting, presenting data from an expanded, unpublished analysis of NAMCS data showing these same outpatient utilization patterns.
“It’s fascinating — there’s a much greater utilization in the elderly population. Why? The short answer is, we don’t know,” he said.
Risk Factors, Immune Differences
People with adult-onset AD were more likely to be women, smokers in adulthood, and have a lower childhood socioeconomic status than those whose AD started in childhood in a longitudinal study of two large birth cohorts from the United Kingdom , Dr. Silverberg pointed out.
Patients with childhood-onset AD, meanwhile, were more likely to have asthma, allergen-specific immunoglobulin E (IgE), and known genetic polymorphisms previously associated with AD. (Each cohort — the 1958 British Cohort Study and the 1970 British Cohort Study — had more than 17,000 participants who were followed from birth through middle age.)
Data is limited, but “mechanistically,” AD in much older adults appears to have a unique serum cytokine pattern, Dr. Silverberg said. He pointed to a cross-sectional study in China of 1312 children and adults with AD in which researchers analyzed clinical features, serum samples, and skin biopsy samples.
Adults aged > 60 years showed more lesions on the trunk and extensor sites of the extremities and lower levels of serum IgE and peripheral eosinophil counts than those in younger age groups. And “interestingly,” compared with healthy controls, older patients with AD had “higher levels of serum expression of a variety of cytokines, including IL [interleukin]-4 but also high TARC levels ... and a variety of cytokines related to the Th17, TH1 axes, etc.,” he said.
“So, we’re seeing a fascinating new profile that may be a little different than younger-onset cases,” he said, noting that TARC (thymus and activation-regulated chemokine) is regarded as a “decent biomarker” for AD.
In addition to higher levels of IL-4 and TARC, the study investigators reported significantly higher levels of IL-17A, IL-6, IL-22, IL-33, and thymic stromal lymphopoietin in older patients, compared with healthy controls.
Research also suggests that air pollution may play a role in the onset of AD in older age, Dr. Silverberg said, referencing a 2023 study that explored the association of air pollution and genetic risk with the onset of AD after age 50. The study analyzed 337,910 participants from the UK Biobank, with a median 12-year follow-up. Genetic risks were assessed as low, intermediate, and high, based on tertiles of polygenic risk scores. Exposure to various air pollutants was assessed using weighted quantile sum and also categorized into tertiles.
The incidence of older adult-onset AD was associated with medium and high air pollution compared with low air pollution, with hazard ratios (HRs) of 1.182 (P = .003) and 1.359 (P < .001), respectively. And “to a lesser extent,” Dr. Silverberg said, incidence was associated with medium and high genetic susceptibility, with HRs of 1.065 (P = .249) and 1.153 (P = .008).
The researchers calculated a greater population-attributable fraction of air pollution (15.5%) than genetic risk (6.4%). “This means that yes, genetics can contribute even to later-onset disease ... but environment may play an even more important role,” Dr. Silverberg said.
In the Clinic
In all patients, and especially in older adults, sleep disturbance associated with AD is a consideration for care. Data collected at the eczema clinic of Northwestern University, Chicago, Illinois, between 2014 and 2019 through previsit, self-administered questionnaires show that patients ≥ 65 years of age have more profound sleep disturbance (especially trouble staying asleep) than patients aged 18-64 years, despite having similar AD severity, said Dr. Silverberg, a coinvestigator of the study.
Older age was associated with having an increased number of nights of sleep disturbance (3-7 nights in the previous week) because of eczema (adjusted odds ratio [aOR], 2.14; 95% CI, 1.16-3.92). It was also associated with itching-attributed delays in falling asleep and nighttime awakenings in the prior 2 weeks (aOR, 1.88; 95% CI, 1.05-3.39).
“The aging population has dysregulated sleep patterns and altered circadian rhythms, so some of this is just natural predisposition,” Dr. Silverberg said. “But it’s amplified [with AD and itching], and it becomes a big clinical problem when we get into treatment because it’s our natural inclination to prescribe antihistamines for their sedative properties.”
Antihistamines can cause more profound sedation, more forgetfulness, and more anticholinergic side effects, he said, noting that “there’s some evidence that high-dose antihistamines may exacerbate dementia.”
Medication side effects and medication interactions, comorbidities, and decreased renal and hepatic clearance all can complicate treatment of AD in older adults. So can mobility, the extent of social/caregiving support, and other aspects of aging. For example, “I’m a big fan of ‘soak and smears’ ... but you have to ask, can you get out of a bathtub safely?” Dr. Silverberg said. “And you have to ask, can you reach the areas you need to [in order] to apply topicals?”
With oral Janus kinase inhibitors and other systemic medications, as with other drugs, “our older population is the most vulnerable from a safety perspective,” he said. A recently published post hoc analysis of four randomized trials of dupilumab in adults ≥ 60 years of age with moderate to severe AD demonstrated efficacy comparable with that in younger patients and “a really clean safety profile,” said Dr. Silverberg, the lead author. “We really need more of these types of post hocs to have some relative contextualization” for older adults.
Dr. Silverberg reported being a speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; a consultant and/or advisory board member for Regeneron, Sanofi-Genzyme, and other companies; and an investigator for several companies.
A version of this article first appeared on Medscape.com.
WASHINGTON, DC — Jonathan I. Silverberg, MD, PhD, MPH, said at the ElderDerm Conference on dermatology in the older patient hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC.
“I walked out of residency under the impression that if it didn’t start in the first year or two of life, it’s not AD,” said Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University. “The numbers tell us a very different story.”
The prevalence of AD in the United States fluctuates between 6% and 8% through adulthood, including age categories up to 81-85 years, according to 2012 National Health Interview Survey data. And while persistence of childhood-onset AD is common, a systematic review and meta-analysis published in 2018 concluded that one in four adults with AD report adult-onset disease.
The investigators, including Dr. Silverberg, identified 25 observational studies — studies conducted across 16 countries and published during 1956-2017 — that included an analysis of age of onset beyond 10 years of age, and other inclusion criteria. Of the 25 studies, 17 reported age of onset after 16 years of age and had sufficient data for the meta-analysis. Using random-effects weighting, the investigators found a pooled proportion of adult-onset AD of 26.1% (95% CI, 16.5%-37.2%).
The research demonstrates that “the age of onset is distributed well throughout the lifespan,” Dr. Silverberg said, with the data “indicating there are many elderly-onset cases of true AD as well.” (Thirteen of the studies analyzed an age of onset from age ≥ 65, and several looked beyond age 80).
A 2021 study of a primary care database in the United Kingdom of 3.85 million children and adults found a “fascinating” bimodal distribution of incidence across the lifespan, with peaks in both infancy and older adulthood, he said. Incidence in adulthood was relatively stable from ages 18-49 years, after which, “into the 50s, 60s and beyond, you started to see a steady climb again.”
Also intriguing, Dr. Silverberg continued, are findings from a study of outpatient healthcare utilization for AD in which he and his coinvestigator analyzed data from the National Ambulatory Medical Care Survey (NAMCS). In the article, published in 2023 covering data from the 1993-2015 NAMCS, they reported that AD visits were more common among children aged 0-4 years (32.0%) and 5-9 years of age (10.6%), then decreased in adolescents aged 10-19 years (11.6%), remained fairly steady in patients aged 20-89 years (1.0%-4.7%), and increased in patients aged > 90 years (20.7%).
“The peak usage for dermatologists, primary care physicians, etc., is happening in the first few years of life, partially because that’s when the disease is more common and more severe but also partially because that’s when parents and caregivers are first learning [about] the disease and trying to understand how to gain control,” Dr. Silverberg said at the meeting, presenting data from an expanded, unpublished analysis of NAMCS data showing these same outpatient utilization patterns.
“It’s fascinating — there’s a much greater utilization in the elderly population. Why? The short answer is, we don’t know,” he said.
Risk Factors, Immune Differences
People with adult-onset AD were more likely to be women, smokers in adulthood, and have a lower childhood socioeconomic status than those whose AD started in childhood in a longitudinal study of two large birth cohorts from the United Kingdom , Dr. Silverberg pointed out.
Patients with childhood-onset AD, meanwhile, were more likely to have asthma, allergen-specific immunoglobulin E (IgE), and known genetic polymorphisms previously associated with AD. (Each cohort — the 1958 British Cohort Study and the 1970 British Cohort Study — had more than 17,000 participants who were followed from birth through middle age.)
Data is limited, but “mechanistically,” AD in much older adults appears to have a unique serum cytokine pattern, Dr. Silverberg said. He pointed to a cross-sectional study in China of 1312 children and adults with AD in which researchers analyzed clinical features, serum samples, and skin biopsy samples.
Adults aged > 60 years showed more lesions on the trunk and extensor sites of the extremities and lower levels of serum IgE and peripheral eosinophil counts than those in younger age groups. And “interestingly,” compared with healthy controls, older patients with AD had “higher levels of serum expression of a variety of cytokines, including IL [interleukin]-4 but also high TARC levels ... and a variety of cytokines related to the Th17, TH1 axes, etc.,” he said.
“So, we’re seeing a fascinating new profile that may be a little different than younger-onset cases,” he said, noting that TARC (thymus and activation-regulated chemokine) is regarded as a “decent biomarker” for AD.
In addition to higher levels of IL-4 and TARC, the study investigators reported significantly higher levels of IL-17A, IL-6, IL-22, IL-33, and thymic stromal lymphopoietin in older patients, compared with healthy controls.
Research also suggests that air pollution may play a role in the onset of AD in older age, Dr. Silverberg said, referencing a 2023 study that explored the association of air pollution and genetic risk with the onset of AD after age 50. The study analyzed 337,910 participants from the UK Biobank, with a median 12-year follow-up. Genetic risks were assessed as low, intermediate, and high, based on tertiles of polygenic risk scores. Exposure to various air pollutants was assessed using weighted quantile sum and also categorized into tertiles.
The incidence of older adult-onset AD was associated with medium and high air pollution compared with low air pollution, with hazard ratios (HRs) of 1.182 (P = .003) and 1.359 (P < .001), respectively. And “to a lesser extent,” Dr. Silverberg said, incidence was associated with medium and high genetic susceptibility, with HRs of 1.065 (P = .249) and 1.153 (P = .008).
The researchers calculated a greater population-attributable fraction of air pollution (15.5%) than genetic risk (6.4%). “This means that yes, genetics can contribute even to later-onset disease ... but environment may play an even more important role,” Dr. Silverberg said.
In the Clinic
In all patients, and especially in older adults, sleep disturbance associated with AD is a consideration for care. Data collected at the eczema clinic of Northwestern University, Chicago, Illinois, between 2014 and 2019 through previsit, self-administered questionnaires show that patients ≥ 65 years of age have more profound sleep disturbance (especially trouble staying asleep) than patients aged 18-64 years, despite having similar AD severity, said Dr. Silverberg, a coinvestigator of the study.
Older age was associated with having an increased number of nights of sleep disturbance (3-7 nights in the previous week) because of eczema (adjusted odds ratio [aOR], 2.14; 95% CI, 1.16-3.92). It was also associated with itching-attributed delays in falling asleep and nighttime awakenings in the prior 2 weeks (aOR, 1.88; 95% CI, 1.05-3.39).
“The aging population has dysregulated sleep patterns and altered circadian rhythms, so some of this is just natural predisposition,” Dr. Silverberg said. “But it’s amplified [with AD and itching], and it becomes a big clinical problem when we get into treatment because it’s our natural inclination to prescribe antihistamines for their sedative properties.”
Antihistamines can cause more profound sedation, more forgetfulness, and more anticholinergic side effects, he said, noting that “there’s some evidence that high-dose antihistamines may exacerbate dementia.”
Medication side effects and medication interactions, comorbidities, and decreased renal and hepatic clearance all can complicate treatment of AD in older adults. So can mobility, the extent of social/caregiving support, and other aspects of aging. For example, “I’m a big fan of ‘soak and smears’ ... but you have to ask, can you get out of a bathtub safely?” Dr. Silverberg said. “And you have to ask, can you reach the areas you need to [in order] to apply topicals?”
With oral Janus kinase inhibitors and other systemic medications, as with other drugs, “our older population is the most vulnerable from a safety perspective,” he said. A recently published post hoc analysis of four randomized trials of dupilumab in adults ≥ 60 years of age with moderate to severe AD demonstrated efficacy comparable with that in younger patients and “a really clean safety profile,” said Dr. Silverberg, the lead author. “We really need more of these types of post hocs to have some relative contextualization” for older adults.
Dr. Silverberg reported being a speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; a consultant and/or advisory board member for Regeneron, Sanofi-Genzyme, and other companies; and an investigator for several companies.
A version of this article first appeared on Medscape.com.
WASHINGTON, DC — Jonathan I. Silverberg, MD, PhD, MPH, said at the ElderDerm Conference on dermatology in the older patient hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC.
“I walked out of residency under the impression that if it didn’t start in the first year or two of life, it’s not AD,” said Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University. “The numbers tell us a very different story.”
The prevalence of AD in the United States fluctuates between 6% and 8% through adulthood, including age categories up to 81-85 years, according to 2012 National Health Interview Survey data. And while persistence of childhood-onset AD is common, a systematic review and meta-analysis published in 2018 concluded that one in four adults with AD report adult-onset disease.
The investigators, including Dr. Silverberg, identified 25 observational studies — studies conducted across 16 countries and published during 1956-2017 — that included an analysis of age of onset beyond 10 years of age, and other inclusion criteria. Of the 25 studies, 17 reported age of onset after 16 years of age and had sufficient data for the meta-analysis. Using random-effects weighting, the investigators found a pooled proportion of adult-onset AD of 26.1% (95% CI, 16.5%-37.2%).
The research demonstrates that “the age of onset is distributed well throughout the lifespan,” Dr. Silverberg said, with the data “indicating there are many elderly-onset cases of true AD as well.” (Thirteen of the studies analyzed an age of onset from age ≥ 65, and several looked beyond age 80).
A 2021 study of a primary care database in the United Kingdom of 3.85 million children and adults found a “fascinating” bimodal distribution of incidence across the lifespan, with peaks in both infancy and older adulthood, he said. Incidence in adulthood was relatively stable from ages 18-49 years, after which, “into the 50s, 60s and beyond, you started to see a steady climb again.”
Also intriguing, Dr. Silverberg continued, are findings from a study of outpatient healthcare utilization for AD in which he and his coinvestigator analyzed data from the National Ambulatory Medical Care Survey (NAMCS). In the article, published in 2023 covering data from the 1993-2015 NAMCS, they reported that AD visits were more common among children aged 0-4 years (32.0%) and 5-9 years of age (10.6%), then decreased in adolescents aged 10-19 years (11.6%), remained fairly steady in patients aged 20-89 years (1.0%-4.7%), and increased in patients aged > 90 years (20.7%).
“The peak usage for dermatologists, primary care physicians, etc., is happening in the first few years of life, partially because that’s when the disease is more common and more severe but also partially because that’s when parents and caregivers are first learning [about] the disease and trying to understand how to gain control,” Dr. Silverberg said at the meeting, presenting data from an expanded, unpublished analysis of NAMCS data showing these same outpatient utilization patterns.
“It’s fascinating — there’s a much greater utilization in the elderly population. Why? The short answer is, we don’t know,” he said.
Risk Factors, Immune Differences
People with adult-onset AD were more likely to be women, smokers in adulthood, and have a lower childhood socioeconomic status than those whose AD started in childhood in a longitudinal study of two large birth cohorts from the United Kingdom , Dr. Silverberg pointed out.
Patients with childhood-onset AD, meanwhile, were more likely to have asthma, allergen-specific immunoglobulin E (IgE), and known genetic polymorphisms previously associated with AD. (Each cohort — the 1958 British Cohort Study and the 1970 British Cohort Study — had more than 17,000 participants who were followed from birth through middle age.)
Data is limited, but “mechanistically,” AD in much older adults appears to have a unique serum cytokine pattern, Dr. Silverberg said. He pointed to a cross-sectional study in China of 1312 children and adults with AD in which researchers analyzed clinical features, serum samples, and skin biopsy samples.
Adults aged > 60 years showed more lesions on the trunk and extensor sites of the extremities and lower levels of serum IgE and peripheral eosinophil counts than those in younger age groups. And “interestingly,” compared with healthy controls, older patients with AD had “higher levels of serum expression of a variety of cytokines, including IL [interleukin]-4 but also high TARC levels ... and a variety of cytokines related to the Th17, TH1 axes, etc.,” he said.
“So, we’re seeing a fascinating new profile that may be a little different than younger-onset cases,” he said, noting that TARC (thymus and activation-regulated chemokine) is regarded as a “decent biomarker” for AD.
In addition to higher levels of IL-4 and TARC, the study investigators reported significantly higher levels of IL-17A, IL-6, IL-22, IL-33, and thymic stromal lymphopoietin in older patients, compared with healthy controls.
Research also suggests that air pollution may play a role in the onset of AD in older age, Dr. Silverberg said, referencing a 2023 study that explored the association of air pollution and genetic risk with the onset of AD after age 50. The study analyzed 337,910 participants from the UK Biobank, with a median 12-year follow-up. Genetic risks were assessed as low, intermediate, and high, based on tertiles of polygenic risk scores. Exposure to various air pollutants was assessed using weighted quantile sum and also categorized into tertiles.
The incidence of older adult-onset AD was associated with medium and high air pollution compared with low air pollution, with hazard ratios (HRs) of 1.182 (P = .003) and 1.359 (P < .001), respectively. And “to a lesser extent,” Dr. Silverberg said, incidence was associated with medium and high genetic susceptibility, with HRs of 1.065 (P = .249) and 1.153 (P = .008).
The researchers calculated a greater population-attributable fraction of air pollution (15.5%) than genetic risk (6.4%). “This means that yes, genetics can contribute even to later-onset disease ... but environment may play an even more important role,” Dr. Silverberg said.
In the Clinic
In all patients, and especially in older adults, sleep disturbance associated with AD is a consideration for care. Data collected at the eczema clinic of Northwestern University, Chicago, Illinois, between 2014 and 2019 through previsit, self-administered questionnaires show that patients ≥ 65 years of age have more profound sleep disturbance (especially trouble staying asleep) than patients aged 18-64 years, despite having similar AD severity, said Dr. Silverberg, a coinvestigator of the study.
Older age was associated with having an increased number of nights of sleep disturbance (3-7 nights in the previous week) because of eczema (adjusted odds ratio [aOR], 2.14; 95% CI, 1.16-3.92). It was also associated with itching-attributed delays in falling asleep and nighttime awakenings in the prior 2 weeks (aOR, 1.88; 95% CI, 1.05-3.39).
“The aging population has dysregulated sleep patterns and altered circadian rhythms, so some of this is just natural predisposition,” Dr. Silverberg said. “But it’s amplified [with AD and itching], and it becomes a big clinical problem when we get into treatment because it’s our natural inclination to prescribe antihistamines for their sedative properties.”
Antihistamines can cause more profound sedation, more forgetfulness, and more anticholinergic side effects, he said, noting that “there’s some evidence that high-dose antihistamines may exacerbate dementia.”
Medication side effects and medication interactions, comorbidities, and decreased renal and hepatic clearance all can complicate treatment of AD in older adults. So can mobility, the extent of social/caregiving support, and other aspects of aging. For example, “I’m a big fan of ‘soak and smears’ ... but you have to ask, can you get out of a bathtub safely?” Dr. Silverberg said. “And you have to ask, can you reach the areas you need to [in order] to apply topicals?”
With oral Janus kinase inhibitors and other systemic medications, as with other drugs, “our older population is the most vulnerable from a safety perspective,” he said. A recently published post hoc analysis of four randomized trials of dupilumab in adults ≥ 60 years of age with moderate to severe AD demonstrated efficacy comparable with that in younger patients and “a really clean safety profile,” said Dr. Silverberg, the lead author. “We really need more of these types of post hocs to have some relative contextualization” for older adults.
Dr. Silverberg reported being a speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; a consultant and/or advisory board member for Regeneron, Sanofi-Genzyme, and other companies; and an investigator for several companies.
A version of this article first appeared on Medscape.com.
FROM ELDERDERM 2024
Treatable Condition Misdiagnosed as Dementia in Almost 13% of Cases
, one of the main causes of the condition, new research suggests.
The study of more than 68,000 individuals in the general population diagnosed with dementia between 2009 and 2019 found that almost 13% had FIB-4 scores indicative of cirrhosis and potential hepatic encephalopathy.
The findings, recently published online in The American Journal of Medicine, corroborate and extend the researchers’ previous work, which showed that about 10% of US veterans with a dementia diagnosis may in fact have hepatic encephalopathy.
“We need to increase awareness that cirrhosis and related brain complications are common, silent, but treatable when found,” said corresponding author Jasmohan Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia. “Moreover, these are being increasingly diagnosed in older individuals.”
“Cirrhosis can also predispose patients to liver cancer and other complications, so diagnosing it in all patients is important, regardless of the hepatic encephalopathy-dementia connection,” he said.
FIB-4 Is Key
Dr. Bajaj and colleagues analyzed data from 72 healthcare centers on 68,807 nonveteran patients diagnosed with dementia at two or more physician visits between 2009 and 2019. Patients had no prior cirrhosis diagnosis, the mean age was 73 years, 44.7% were men, and 78% were White.
The team measured the prevalence of two high FIB-4 scores (> 2.67 and > 3.25), selected for their strong predictive value for advanced cirrhosis. Researchers also examined associations between high scores and multiple comorbidities and demographic factors.
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet labs were collected up to 2 years after the index dementia diagnosis because they are used to calculate FIB-4.
The mean FIB-4 score was 1.78, mean ALT was 23.72 U/L, mean AST was 27.42 U/L, and mean platelets were 243.51 × 109/µL.
A total of 8683 participants (12.8%) had a FIB-4 score greater than 2.67 and 5185 (7.6%) had a score greater than 3.25.
In multivariable logistic regression models, FIB-4 greater than 3.25 was associated with viral hepatitis (odds ratio [OR], 2.23), congestive heart failure (OR,1.73), HIV (OR, 1.72), male gender (OR, 1.42), alcohol use disorder (OR, 1.39), and chronic kidney disease (OR, 1.38).
FIB-4 greater than 3.25 was inversely associated with White race (OR, 0.76) and diabetes (OR, 0.82).
The associations were similar when using a threshold score of greater than 2.67.
“With the aging population, including those with cirrhosis, the potential for overlap between hepatic encephalopathy and dementia has risen and should be considered in the differential diagnosis,” the authors wrote. “Undiagnosed cirrhosis and potential hepatic encephalopathy can be a treatable cause of or contributor towards cognitive impairment in patients diagnosed with dementia.”
Providers should use the FIB-4 index as a screening tool to detect cirrhosis in patients with dementia, they concluded.
The team’s next steps will include investigating barriers to the use of FIB-4 among practitioners, Dr. Bajaj said.
Incorporating use of the FIB-4 index into screening guidelines “with input from all stakeholders, including geriatricians, primary care providers, and neurologists … would greatly expand the diagnosis of cirrhosis and potentially hepatic encephalopathy in dementia patients,” Dr. Bajaj said.
The study had a few limitations, including the selected centers in the cohort database, lack of chart review to confirm diagnoses in individual cases, and the use of a modified FIB-4, with age capped at 65 years.
‘Easy to Miss’
Commenting on the research, Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago, said that it is easy for physicians to miss asymptomatic liver disease that could progress and lead to cognitive decline.
“Most of my patients are already labeled with liver disease; however, it is not uncommon to receive a patient from another specialist who felt their presentation was more consistent with liver disease than the issue they were referred for,” she said.
Still, even in metabolic dysfunction–associated steatotic liver disease, which affects nearly one third of the population, the condition isn’t advanced enough in most patients to cause symptoms similar to those of dementia, said Dr. Reau, who was not associated with the study.
“It is more important for specialists in neurology to exclude liver disease and for hepatologists or gastroenterologists to be equipped with tools to exclude alternative explanations for neurocognitive presentations,” she said. “It is important to not label a patient as having HE and then miss alternative explanations.”
“Every presentation has a differential diagnosis. Using easy tools like FIB-4 can make sure you don’t miss liver disease as a contributing factor in a patient that presents with neurocognitive symptoms,” Dr. Reau said.
This work was partly supported by grants from Department of Veterans Affairs merit review program and the National Institutes of Health’s National Center for Advancing Translational Science. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
A version of this article appeared on Medscape.com.
, one of the main causes of the condition, new research suggests.
The study of more than 68,000 individuals in the general population diagnosed with dementia between 2009 and 2019 found that almost 13% had FIB-4 scores indicative of cirrhosis and potential hepatic encephalopathy.
The findings, recently published online in The American Journal of Medicine, corroborate and extend the researchers’ previous work, which showed that about 10% of US veterans with a dementia diagnosis may in fact have hepatic encephalopathy.
“We need to increase awareness that cirrhosis and related brain complications are common, silent, but treatable when found,” said corresponding author Jasmohan Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia. “Moreover, these are being increasingly diagnosed in older individuals.”
“Cirrhosis can also predispose patients to liver cancer and other complications, so diagnosing it in all patients is important, regardless of the hepatic encephalopathy-dementia connection,” he said.
FIB-4 Is Key
Dr. Bajaj and colleagues analyzed data from 72 healthcare centers on 68,807 nonveteran patients diagnosed with dementia at two or more physician visits between 2009 and 2019. Patients had no prior cirrhosis diagnosis, the mean age was 73 years, 44.7% were men, and 78% were White.
The team measured the prevalence of two high FIB-4 scores (> 2.67 and > 3.25), selected for their strong predictive value for advanced cirrhosis. Researchers also examined associations between high scores and multiple comorbidities and demographic factors.
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet labs were collected up to 2 years after the index dementia diagnosis because they are used to calculate FIB-4.
The mean FIB-4 score was 1.78, mean ALT was 23.72 U/L, mean AST was 27.42 U/L, and mean platelets were 243.51 × 109/µL.
A total of 8683 participants (12.8%) had a FIB-4 score greater than 2.67 and 5185 (7.6%) had a score greater than 3.25.
In multivariable logistic regression models, FIB-4 greater than 3.25 was associated with viral hepatitis (odds ratio [OR], 2.23), congestive heart failure (OR,1.73), HIV (OR, 1.72), male gender (OR, 1.42), alcohol use disorder (OR, 1.39), and chronic kidney disease (OR, 1.38).
FIB-4 greater than 3.25 was inversely associated with White race (OR, 0.76) and diabetes (OR, 0.82).
The associations were similar when using a threshold score of greater than 2.67.
“With the aging population, including those with cirrhosis, the potential for overlap between hepatic encephalopathy and dementia has risen and should be considered in the differential diagnosis,” the authors wrote. “Undiagnosed cirrhosis and potential hepatic encephalopathy can be a treatable cause of or contributor towards cognitive impairment in patients diagnosed with dementia.”
Providers should use the FIB-4 index as a screening tool to detect cirrhosis in patients with dementia, they concluded.
The team’s next steps will include investigating barriers to the use of FIB-4 among practitioners, Dr. Bajaj said.
Incorporating use of the FIB-4 index into screening guidelines “with input from all stakeholders, including geriatricians, primary care providers, and neurologists … would greatly expand the diagnosis of cirrhosis and potentially hepatic encephalopathy in dementia patients,” Dr. Bajaj said.
The study had a few limitations, including the selected centers in the cohort database, lack of chart review to confirm diagnoses in individual cases, and the use of a modified FIB-4, with age capped at 65 years.
‘Easy to Miss’
Commenting on the research, Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago, said that it is easy for physicians to miss asymptomatic liver disease that could progress and lead to cognitive decline.
“Most of my patients are already labeled with liver disease; however, it is not uncommon to receive a patient from another specialist who felt their presentation was more consistent with liver disease than the issue they were referred for,” she said.
Still, even in metabolic dysfunction–associated steatotic liver disease, which affects nearly one third of the population, the condition isn’t advanced enough in most patients to cause symptoms similar to those of dementia, said Dr. Reau, who was not associated with the study.
“It is more important for specialists in neurology to exclude liver disease and for hepatologists or gastroenterologists to be equipped with tools to exclude alternative explanations for neurocognitive presentations,” she said. “It is important to not label a patient as having HE and then miss alternative explanations.”
“Every presentation has a differential diagnosis. Using easy tools like FIB-4 can make sure you don’t miss liver disease as a contributing factor in a patient that presents with neurocognitive symptoms,” Dr. Reau said.
This work was partly supported by grants from Department of Veterans Affairs merit review program and the National Institutes of Health’s National Center for Advancing Translational Science. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
A version of this article appeared on Medscape.com.
, one of the main causes of the condition, new research suggests.
The study of more than 68,000 individuals in the general population diagnosed with dementia between 2009 and 2019 found that almost 13% had FIB-4 scores indicative of cirrhosis and potential hepatic encephalopathy.
The findings, recently published online in The American Journal of Medicine, corroborate and extend the researchers’ previous work, which showed that about 10% of US veterans with a dementia diagnosis may in fact have hepatic encephalopathy.
“We need to increase awareness that cirrhosis and related brain complications are common, silent, but treatable when found,” said corresponding author Jasmohan Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia. “Moreover, these are being increasingly diagnosed in older individuals.”
“Cirrhosis can also predispose patients to liver cancer and other complications, so diagnosing it in all patients is important, regardless of the hepatic encephalopathy-dementia connection,” he said.
FIB-4 Is Key
Dr. Bajaj and colleagues analyzed data from 72 healthcare centers on 68,807 nonveteran patients diagnosed with dementia at two or more physician visits between 2009 and 2019. Patients had no prior cirrhosis diagnosis, the mean age was 73 years, 44.7% were men, and 78% were White.
The team measured the prevalence of two high FIB-4 scores (> 2.67 and > 3.25), selected for their strong predictive value for advanced cirrhosis. Researchers also examined associations between high scores and multiple comorbidities and demographic factors.
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet labs were collected up to 2 years after the index dementia diagnosis because they are used to calculate FIB-4.
The mean FIB-4 score was 1.78, mean ALT was 23.72 U/L, mean AST was 27.42 U/L, and mean platelets were 243.51 × 109/µL.
A total of 8683 participants (12.8%) had a FIB-4 score greater than 2.67 and 5185 (7.6%) had a score greater than 3.25.
In multivariable logistic regression models, FIB-4 greater than 3.25 was associated with viral hepatitis (odds ratio [OR], 2.23), congestive heart failure (OR,1.73), HIV (OR, 1.72), male gender (OR, 1.42), alcohol use disorder (OR, 1.39), and chronic kidney disease (OR, 1.38).
FIB-4 greater than 3.25 was inversely associated with White race (OR, 0.76) and diabetes (OR, 0.82).
The associations were similar when using a threshold score of greater than 2.67.
“With the aging population, including those with cirrhosis, the potential for overlap between hepatic encephalopathy and dementia has risen and should be considered in the differential diagnosis,” the authors wrote. “Undiagnosed cirrhosis and potential hepatic encephalopathy can be a treatable cause of or contributor towards cognitive impairment in patients diagnosed with dementia.”
Providers should use the FIB-4 index as a screening tool to detect cirrhosis in patients with dementia, they concluded.
The team’s next steps will include investigating barriers to the use of FIB-4 among practitioners, Dr. Bajaj said.
Incorporating use of the FIB-4 index into screening guidelines “with input from all stakeholders, including geriatricians, primary care providers, and neurologists … would greatly expand the diagnosis of cirrhosis and potentially hepatic encephalopathy in dementia patients,” Dr. Bajaj said.
The study had a few limitations, including the selected centers in the cohort database, lack of chart review to confirm diagnoses in individual cases, and the use of a modified FIB-4, with age capped at 65 years.
‘Easy to Miss’
Commenting on the research, Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago, said that it is easy for physicians to miss asymptomatic liver disease that could progress and lead to cognitive decline.
“Most of my patients are already labeled with liver disease; however, it is not uncommon to receive a patient from another specialist who felt their presentation was more consistent with liver disease than the issue they were referred for,” she said.
Still, even in metabolic dysfunction–associated steatotic liver disease, which affects nearly one third of the population, the condition isn’t advanced enough in most patients to cause symptoms similar to those of dementia, said Dr. Reau, who was not associated with the study.
“It is more important for specialists in neurology to exclude liver disease and for hepatologists or gastroenterologists to be equipped with tools to exclude alternative explanations for neurocognitive presentations,” she said. “It is important to not label a patient as having HE and then miss alternative explanations.”
“Every presentation has a differential diagnosis. Using easy tools like FIB-4 can make sure you don’t miss liver disease as a contributing factor in a patient that presents with neurocognitive symptoms,” Dr. Reau said.
This work was partly supported by grants from Department of Veterans Affairs merit review program and the National Institutes of Health’s National Center for Advancing Translational Science. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
A version of this article appeared on Medscape.com.
From the American Journal of Medicine
Debate: Should Dermatologists or Rheumatologists Manage Musculoskeletal Symptoms in Patients With Psoriasis?
SEATTLE — That was the subject of a debate between a dermatologist and a rheumatologist at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
Fabian Proft, MD, the rheumatologist, spoke first and emphasized the potential that MSK symptoms are a sign of psoriatic arthritis (PsA) and therefore should be managed by a rheumatologist.
“Obviously, the rheumatologist perspective [is that] I should be in the driver’s seat when taking care of patient with psoriasis and MSK symptoms, but I will still need to have a copilot there: [The dermatologist] will have a slot,” said Dr. Proft, who is a rheumatologist at Charité — Universitätsmedizin Berlin.
“It’s so important that we make the correct and early diagnosis of [psoriatic arthritis and psoriasis] symptoms,” said Dr. Proft. He specifically called out cases where patients have symptoms that are difficult to determine, whether the cause is inflammatory, and when experience with imaging can be a key factor in the diagnosis.
It’s important not to overdiagnose or overtreat patients, he said, providing an example of a patient with psoriasis who had been training for a marathon. The MRI image suggested that his Achilles tendonitis pain was related to his athletic training, not PsA-associated inflammation. “So I think this is very important that you have the knowledge to read MRIs, and especially also carefully assessing them so as not to overdiagnose patients,” said Dr. Proft.
Dermatologist Rebuttal
In her rebuttal, Laura Savage, MD, PhD, emphasized the need for more of a coequal partnership between the two specialties because of the ability of dermatologists to intervene early in the treatment and prevention of PsA.
“Traditionally, I agree rheumatologists would solely be responsible for the assessment and the management of psoriatic arthritis, but I think that paradigm has shifted in part due to the increased recognition of the need for earlier intervention to limit disease progression and to reduce or even prevent functional limitation,” said Dr. Savage, who is a consultant dermatologist at Leeds Teaching Hospitals NHS Trust and a senior lecturer at the University of Leeds, Leeds, England.
Ideally, molecular biomarkers would be available to predict the development of PsA, but there aren’t any. Still, “we have a huge biomarker in the form of the skin, and it’s recognized that the majority of patients who will develop psoriatic arthritis will have antecedent psoriasis in about 70% of cases,” Dr. Savage said. “There’s a typical time delay of around 7-12 years between the onset of the skin [disease] and the patients developing psoriatic arthritis, and so many of them are going to be into the care of other healthcare practitioners, and particularly the care of dermatologists.”
Dermatologists may also be able to play a role in the prevention of PsA, according to Dr. Savage. In one retrospective study, treatment of skin lesions with biologics was associated with a reduced frequency of progression to PsA (11.1% vs 16.4%) over 10 years (P = .0006). Studies with tumor necrosis factor inhibitors and other interventions have shown similar results.
Such findings have led to the treat intercept strategy, which targets patients with psoriasis who have risk factors for transition to PsA — such as nail pitting, gluteal cleft disease, scalp disease, type 2 diabetes, obesity, and a first-degree relative with PsA — as well as symptoms of prodromal PSA, such as arthralgia and fatigue.
“I think dermatologists are aware of the need to not leave our patients languishing on these therapies and actually escalating them onto effective treatments that may also be able to treat early psoriatic arthritis. We could be more mindful about our choice of treatments for these patients, going on to thinking about their increased risk of PSA and trying to intercept,” Dr. Savage said. “What we don’t want is our patients to be developing these musculoskeletal symptoms of pain and stiffness and functional limitation and disability. We want to be treating the patients with musculoskeletal symptoms of that earlier prodromal phase when they’re developing arthralgia and fatigue.”
She conceded that more complicated patients are good candidates for care by the rheumatologist. “You can do your fancy imaging, and we’ll leave that to you, and the difficult-to-treat patients to [the rheumatologist], but actually we need to just get on and treat them,” she said. “One could argue as well that as a dermatologist, I’m likely to broaden my horizons in terms of choice of therapy and treat all of the domains of the patient. So I would argue that actually it should be the dermatologist who is in that driving seat, particularly when it comes to the management of early psoriatic arthritis, and actually what we should be doing is driving our patients and steering them to earlier intervention and better control for all domains of disease.”
Collaborative Care
During the follow-up discussion, both Dr. Proft and Dr. Savage agreed that dermatologists and rheumatologists should be working together in managing patients. “What we need to do is steer our patients toward collaborative care with our rheumatologists by trying to minimize delays to treatment, by working together in parallel clinics, combined clinics, and on virtual [multidisciplinary teams],” said Dr. Savage.
Dr. Proft agreed. “We should join forces and make decisions together.”
Dr. Savage and Dr. Proft did not provide any financial disclosures.
A version of this article appeared on Medscape.com.
SEATTLE — That was the subject of a debate between a dermatologist and a rheumatologist at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
Fabian Proft, MD, the rheumatologist, spoke first and emphasized the potential that MSK symptoms are a sign of psoriatic arthritis (PsA) and therefore should be managed by a rheumatologist.
“Obviously, the rheumatologist perspective [is that] I should be in the driver’s seat when taking care of patient with psoriasis and MSK symptoms, but I will still need to have a copilot there: [The dermatologist] will have a slot,” said Dr. Proft, who is a rheumatologist at Charité — Universitätsmedizin Berlin.
“It’s so important that we make the correct and early diagnosis of [psoriatic arthritis and psoriasis] symptoms,” said Dr. Proft. He specifically called out cases where patients have symptoms that are difficult to determine, whether the cause is inflammatory, and when experience with imaging can be a key factor in the diagnosis.
It’s important not to overdiagnose or overtreat patients, he said, providing an example of a patient with psoriasis who had been training for a marathon. The MRI image suggested that his Achilles tendonitis pain was related to his athletic training, not PsA-associated inflammation. “So I think this is very important that you have the knowledge to read MRIs, and especially also carefully assessing them so as not to overdiagnose patients,” said Dr. Proft.
Dermatologist Rebuttal
In her rebuttal, Laura Savage, MD, PhD, emphasized the need for more of a coequal partnership between the two specialties because of the ability of dermatologists to intervene early in the treatment and prevention of PsA.
“Traditionally, I agree rheumatologists would solely be responsible for the assessment and the management of psoriatic arthritis, but I think that paradigm has shifted in part due to the increased recognition of the need for earlier intervention to limit disease progression and to reduce or even prevent functional limitation,” said Dr. Savage, who is a consultant dermatologist at Leeds Teaching Hospitals NHS Trust and a senior lecturer at the University of Leeds, Leeds, England.
Ideally, molecular biomarkers would be available to predict the development of PsA, but there aren’t any. Still, “we have a huge biomarker in the form of the skin, and it’s recognized that the majority of patients who will develop psoriatic arthritis will have antecedent psoriasis in about 70% of cases,” Dr. Savage said. “There’s a typical time delay of around 7-12 years between the onset of the skin [disease] and the patients developing psoriatic arthritis, and so many of them are going to be into the care of other healthcare practitioners, and particularly the care of dermatologists.”
Dermatologists may also be able to play a role in the prevention of PsA, according to Dr. Savage. In one retrospective study, treatment of skin lesions with biologics was associated with a reduced frequency of progression to PsA (11.1% vs 16.4%) over 10 years (P = .0006). Studies with tumor necrosis factor inhibitors and other interventions have shown similar results.
Such findings have led to the treat intercept strategy, which targets patients with psoriasis who have risk factors for transition to PsA — such as nail pitting, gluteal cleft disease, scalp disease, type 2 diabetes, obesity, and a first-degree relative with PsA — as well as symptoms of prodromal PSA, such as arthralgia and fatigue.
“I think dermatologists are aware of the need to not leave our patients languishing on these therapies and actually escalating them onto effective treatments that may also be able to treat early psoriatic arthritis. We could be more mindful about our choice of treatments for these patients, going on to thinking about their increased risk of PSA and trying to intercept,” Dr. Savage said. “What we don’t want is our patients to be developing these musculoskeletal symptoms of pain and stiffness and functional limitation and disability. We want to be treating the patients with musculoskeletal symptoms of that earlier prodromal phase when they’re developing arthralgia and fatigue.”
She conceded that more complicated patients are good candidates for care by the rheumatologist. “You can do your fancy imaging, and we’ll leave that to you, and the difficult-to-treat patients to [the rheumatologist], but actually we need to just get on and treat them,” she said. “One could argue as well that as a dermatologist, I’m likely to broaden my horizons in terms of choice of therapy and treat all of the domains of the patient. So I would argue that actually it should be the dermatologist who is in that driving seat, particularly when it comes to the management of early psoriatic arthritis, and actually what we should be doing is driving our patients and steering them to earlier intervention and better control for all domains of disease.”
Collaborative Care
During the follow-up discussion, both Dr. Proft and Dr. Savage agreed that dermatologists and rheumatologists should be working together in managing patients. “What we need to do is steer our patients toward collaborative care with our rheumatologists by trying to minimize delays to treatment, by working together in parallel clinics, combined clinics, and on virtual [multidisciplinary teams],” said Dr. Savage.
Dr. Proft agreed. “We should join forces and make decisions together.”
Dr. Savage and Dr. Proft did not provide any financial disclosures.
A version of this article appeared on Medscape.com.
SEATTLE — That was the subject of a debate between a dermatologist and a rheumatologist at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
Fabian Proft, MD, the rheumatologist, spoke first and emphasized the potential that MSK symptoms are a sign of psoriatic arthritis (PsA) and therefore should be managed by a rheumatologist.
“Obviously, the rheumatologist perspective [is that] I should be in the driver’s seat when taking care of patient with psoriasis and MSK symptoms, but I will still need to have a copilot there: [The dermatologist] will have a slot,” said Dr. Proft, who is a rheumatologist at Charité — Universitätsmedizin Berlin.
“It’s so important that we make the correct and early diagnosis of [psoriatic arthritis and psoriasis] symptoms,” said Dr. Proft. He specifically called out cases where patients have symptoms that are difficult to determine, whether the cause is inflammatory, and when experience with imaging can be a key factor in the diagnosis.
It’s important not to overdiagnose or overtreat patients, he said, providing an example of a patient with psoriasis who had been training for a marathon. The MRI image suggested that his Achilles tendonitis pain was related to his athletic training, not PsA-associated inflammation. “So I think this is very important that you have the knowledge to read MRIs, and especially also carefully assessing them so as not to overdiagnose patients,” said Dr. Proft.
Dermatologist Rebuttal
In her rebuttal, Laura Savage, MD, PhD, emphasized the need for more of a coequal partnership between the two specialties because of the ability of dermatologists to intervene early in the treatment and prevention of PsA.
“Traditionally, I agree rheumatologists would solely be responsible for the assessment and the management of psoriatic arthritis, but I think that paradigm has shifted in part due to the increased recognition of the need for earlier intervention to limit disease progression and to reduce or even prevent functional limitation,” said Dr. Savage, who is a consultant dermatologist at Leeds Teaching Hospitals NHS Trust and a senior lecturer at the University of Leeds, Leeds, England.
Ideally, molecular biomarkers would be available to predict the development of PsA, but there aren’t any. Still, “we have a huge biomarker in the form of the skin, and it’s recognized that the majority of patients who will develop psoriatic arthritis will have antecedent psoriasis in about 70% of cases,” Dr. Savage said. “There’s a typical time delay of around 7-12 years between the onset of the skin [disease] and the patients developing psoriatic arthritis, and so many of them are going to be into the care of other healthcare practitioners, and particularly the care of dermatologists.”
Dermatologists may also be able to play a role in the prevention of PsA, according to Dr. Savage. In one retrospective study, treatment of skin lesions with biologics was associated with a reduced frequency of progression to PsA (11.1% vs 16.4%) over 10 years (P = .0006). Studies with tumor necrosis factor inhibitors and other interventions have shown similar results.
Such findings have led to the treat intercept strategy, which targets patients with psoriasis who have risk factors for transition to PsA — such as nail pitting, gluteal cleft disease, scalp disease, type 2 diabetes, obesity, and a first-degree relative with PsA — as well as symptoms of prodromal PSA, such as arthralgia and fatigue.
“I think dermatologists are aware of the need to not leave our patients languishing on these therapies and actually escalating them onto effective treatments that may also be able to treat early psoriatic arthritis. We could be more mindful about our choice of treatments for these patients, going on to thinking about their increased risk of PSA and trying to intercept,” Dr. Savage said. “What we don’t want is our patients to be developing these musculoskeletal symptoms of pain and stiffness and functional limitation and disability. We want to be treating the patients with musculoskeletal symptoms of that earlier prodromal phase when they’re developing arthralgia and fatigue.”
She conceded that more complicated patients are good candidates for care by the rheumatologist. “You can do your fancy imaging, and we’ll leave that to you, and the difficult-to-treat patients to [the rheumatologist], but actually we need to just get on and treat them,” she said. “One could argue as well that as a dermatologist, I’m likely to broaden my horizons in terms of choice of therapy and treat all of the domains of the patient. So I would argue that actually it should be the dermatologist who is in that driving seat, particularly when it comes to the management of early psoriatic arthritis, and actually what we should be doing is driving our patients and steering them to earlier intervention and better control for all domains of disease.”
Collaborative Care
During the follow-up discussion, both Dr. Proft and Dr. Savage agreed that dermatologists and rheumatologists should be working together in managing patients. “What we need to do is steer our patients toward collaborative care with our rheumatologists by trying to minimize delays to treatment, by working together in parallel clinics, combined clinics, and on virtual [multidisciplinary teams],” said Dr. Savage.
Dr. Proft agreed. “We should join forces and make decisions together.”
Dr. Savage and Dr. Proft did not provide any financial disclosures.
A version of this article appeared on Medscape.com.
FROM GRAPPA 2024
Two New Studies on Benzoyl Peroxide Provide Reassuring Data on Safety
Two .
Earlier this year, controversy erupted after an independent lab Valisure petitioned the US Food and Drug Administration (FDA) to recall acne products with BP because it found extremely high levels of the carcinogen benzene. In the research, the lab directors contended that the products can form over 800 times the “conditionally restricted” FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter (OTC) products affected. The issue, according to the lab’s report, is one of degradation, not contamination; BP can decompose into benzene. Exposures to benzene have been linked with a higher risk for leukemia and other blood cancers.
(“Conditionally restricted” means that the maximum of 2 ppm only applies to a drug product in which the use of benzene is unavoidable in order to produce a drug product with a significant therapeutic advance, according to FDA guidance.)
Critics of the report questioned the method used to test the products, calling for more “real-world” use data, and said the temperature used may not be what is expected with everyday use.
Now, both new studies are reassuring about the safety of the products, John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a telephone interview. He was a coauthor of both studies. A leading dermatologist not involved in the new research reviewed the findings and agreed.
One study using data from the National Health and Nutrition Examination Survey compared blood levels of benzene between 14 people who had used BP products and 65 people without a history of BP product use, finding no difference between the groups .
The other, much larger study analyzed electronic health records of more than 27,000 patients with acne using BP products, comparing them with more than 27,000 controls who did not use the products. The patients were followed for 10 years after the use of BP products began, and no increased risk for cancer, either blood cancers or solid tumors, was found.
The studies were recently published in the Journal of the American Academy of Dermatology.
“Both studies are well done,” said Henry W. Lim, MD, former chair of the Department of Dermatology and senior vice president for academic affairs at Henry Ford Health, Detroit. Dr. Lim, a former president of the American Academy of Dermatology, reviewed the results of both studies.
“These studies indicate that [a] report of detection of benzene in [BP] products exposed to high temperature does not have any relevant clinical significance, both in terms of blood levels and in terms of internal cancer,” Dr. Lim said. “This is consistent with the clinical experience of practicing dermatologists; no internal side effects have been observed in patients using [BP products].”
Further Details
Under high temperatures, or over a long period, BP can decompose to benzene, a colorless, flammable liquid with a sweet odor. Benzene is formed from natural processes such as forest fires and volcanoes, according to the American Cancer Society, and is found in the air, cigarette smoke, some foods (at low levels), and contaminated drinking water. It’s one of the 20 widely used chemicals involved in making plastics, resins, detergents, and pesticides, among other products.
In the study evaluating blood levels, the researchers matched 14 people who used BP products currently with 65 controls who did not. Five (36%) of those using the products had detectable blood levels; 21 (32%) of those who did not use them did. There was no association between BP exposure and detectable blood benzene levels (odds ratio, 1.12; P = .80).
In the larger study, the researchers used the TriNetX US Collaborative Network database, comparing more than 27,000 patients treated with BP products for acne with more than 27,000 patients aged 12-40 years who had a diagnosis of nevus or seborrheic keratosis with no exposure to prescribed BP or any diagnosis of acne, hidradenitis suppurativa, or rosacea. The researchers looked at the database over the subsequent 10 years to determine the risk for either blood cancers or internal malignancies.
Compared with patients diagnosed with nevus or seborrheic keratosis, those with acne treated with BP had no significant difference in the risk for lymphoma (hazard ratio [HR], 1.00), leukemia (HR, 0.91), any lymphoma or leukemia (HR, 1.04), and internal malignancies (HR, 0.93).
The findings suggest no increased risk for malignancy, the researchers said, although they acknowledged study limitations, such as possible misclassification of BP exposure due to OTC availability and other issues.
Value of BP Treatments
BP is the “go-to” acne treatment, as Dr. Barbieri pointed out. “It’s probably the number one treatment for acne,” and there’s no substitute for it and it’s one of the most effective topical acne treatments, he noted.
Despite the reassuring findings, Dr. Barbieri repeated advice he gave soon after the Valisure report was released. Use common sense and don’t store BP-containing products in hot cars or other hot environments. In warmer climates, refrigeration could be considered, he said. Discard old products. Manufacturers should use cold-chain storage from the manufacturing site to retail or pharmacy sale sites, he added.
FDA and Citizen Petition Status
Asked about the status of the petition from Valisure, an FDA spokesperson said: “The FDA does not comment on the status of pending petitions.”
Dr. Barbieri and Dr. Lim had no relevant disclosures. There were no funding sources for either of the two studies.
A version of this article first appeared on Medscape.com.
Two .
Earlier this year, controversy erupted after an independent lab Valisure petitioned the US Food and Drug Administration (FDA) to recall acne products with BP because it found extremely high levels of the carcinogen benzene. In the research, the lab directors contended that the products can form over 800 times the “conditionally restricted” FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter (OTC) products affected. The issue, according to the lab’s report, is one of degradation, not contamination; BP can decompose into benzene. Exposures to benzene have been linked with a higher risk for leukemia and other blood cancers.
(“Conditionally restricted” means that the maximum of 2 ppm only applies to a drug product in which the use of benzene is unavoidable in order to produce a drug product with a significant therapeutic advance, according to FDA guidance.)
Critics of the report questioned the method used to test the products, calling for more “real-world” use data, and said the temperature used may not be what is expected with everyday use.
Now, both new studies are reassuring about the safety of the products, John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a telephone interview. He was a coauthor of both studies. A leading dermatologist not involved in the new research reviewed the findings and agreed.
One study using data from the National Health and Nutrition Examination Survey compared blood levels of benzene between 14 people who had used BP products and 65 people without a history of BP product use, finding no difference between the groups .
The other, much larger study analyzed electronic health records of more than 27,000 patients with acne using BP products, comparing them with more than 27,000 controls who did not use the products. The patients were followed for 10 years after the use of BP products began, and no increased risk for cancer, either blood cancers or solid tumors, was found.
The studies were recently published in the Journal of the American Academy of Dermatology.
“Both studies are well done,” said Henry W. Lim, MD, former chair of the Department of Dermatology and senior vice president for academic affairs at Henry Ford Health, Detroit. Dr. Lim, a former president of the American Academy of Dermatology, reviewed the results of both studies.
“These studies indicate that [a] report of detection of benzene in [BP] products exposed to high temperature does not have any relevant clinical significance, both in terms of blood levels and in terms of internal cancer,” Dr. Lim said. “This is consistent with the clinical experience of practicing dermatologists; no internal side effects have been observed in patients using [BP products].”
Further Details
Under high temperatures, or over a long period, BP can decompose to benzene, a colorless, flammable liquid with a sweet odor. Benzene is formed from natural processes such as forest fires and volcanoes, according to the American Cancer Society, and is found in the air, cigarette smoke, some foods (at low levels), and contaminated drinking water. It’s one of the 20 widely used chemicals involved in making plastics, resins, detergents, and pesticides, among other products.
In the study evaluating blood levels, the researchers matched 14 people who used BP products currently with 65 controls who did not. Five (36%) of those using the products had detectable blood levels; 21 (32%) of those who did not use them did. There was no association between BP exposure and detectable blood benzene levels (odds ratio, 1.12; P = .80).
In the larger study, the researchers used the TriNetX US Collaborative Network database, comparing more than 27,000 patients treated with BP products for acne with more than 27,000 patients aged 12-40 years who had a diagnosis of nevus or seborrheic keratosis with no exposure to prescribed BP or any diagnosis of acne, hidradenitis suppurativa, or rosacea. The researchers looked at the database over the subsequent 10 years to determine the risk for either blood cancers or internal malignancies.
Compared with patients diagnosed with nevus or seborrheic keratosis, those with acne treated with BP had no significant difference in the risk for lymphoma (hazard ratio [HR], 1.00), leukemia (HR, 0.91), any lymphoma or leukemia (HR, 1.04), and internal malignancies (HR, 0.93).
The findings suggest no increased risk for malignancy, the researchers said, although they acknowledged study limitations, such as possible misclassification of BP exposure due to OTC availability and other issues.
Value of BP Treatments
BP is the “go-to” acne treatment, as Dr. Barbieri pointed out. “It’s probably the number one treatment for acne,” and there’s no substitute for it and it’s one of the most effective topical acne treatments, he noted.
Despite the reassuring findings, Dr. Barbieri repeated advice he gave soon after the Valisure report was released. Use common sense and don’t store BP-containing products in hot cars or other hot environments. In warmer climates, refrigeration could be considered, he said. Discard old products. Manufacturers should use cold-chain storage from the manufacturing site to retail or pharmacy sale sites, he added.
FDA and Citizen Petition Status
Asked about the status of the petition from Valisure, an FDA spokesperson said: “The FDA does not comment on the status of pending petitions.”
Dr. Barbieri and Dr. Lim had no relevant disclosures. There were no funding sources for either of the two studies.
A version of this article first appeared on Medscape.com.
Two .
Earlier this year, controversy erupted after an independent lab Valisure petitioned the US Food and Drug Administration (FDA) to recall acne products with BP because it found extremely high levels of the carcinogen benzene. In the research, the lab directors contended that the products can form over 800 times the “conditionally restricted” FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter (OTC) products affected. The issue, according to the lab’s report, is one of degradation, not contamination; BP can decompose into benzene. Exposures to benzene have been linked with a higher risk for leukemia and other blood cancers.
(“Conditionally restricted” means that the maximum of 2 ppm only applies to a drug product in which the use of benzene is unavoidable in order to produce a drug product with a significant therapeutic advance, according to FDA guidance.)
Critics of the report questioned the method used to test the products, calling for more “real-world” use data, and said the temperature used may not be what is expected with everyday use.
Now, both new studies are reassuring about the safety of the products, John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a telephone interview. He was a coauthor of both studies. A leading dermatologist not involved in the new research reviewed the findings and agreed.
One study using data from the National Health and Nutrition Examination Survey compared blood levels of benzene between 14 people who had used BP products and 65 people without a history of BP product use, finding no difference between the groups .
The other, much larger study analyzed electronic health records of more than 27,000 patients with acne using BP products, comparing them with more than 27,000 controls who did not use the products. The patients were followed for 10 years after the use of BP products began, and no increased risk for cancer, either blood cancers or solid tumors, was found.
The studies were recently published in the Journal of the American Academy of Dermatology.
“Both studies are well done,” said Henry W. Lim, MD, former chair of the Department of Dermatology and senior vice president for academic affairs at Henry Ford Health, Detroit. Dr. Lim, a former president of the American Academy of Dermatology, reviewed the results of both studies.
“These studies indicate that [a] report of detection of benzene in [BP] products exposed to high temperature does not have any relevant clinical significance, both in terms of blood levels and in terms of internal cancer,” Dr. Lim said. “This is consistent with the clinical experience of practicing dermatologists; no internal side effects have been observed in patients using [BP products].”
Further Details
Under high temperatures, or over a long period, BP can decompose to benzene, a colorless, flammable liquid with a sweet odor. Benzene is formed from natural processes such as forest fires and volcanoes, according to the American Cancer Society, and is found in the air, cigarette smoke, some foods (at low levels), and contaminated drinking water. It’s one of the 20 widely used chemicals involved in making plastics, resins, detergents, and pesticides, among other products.
In the study evaluating blood levels, the researchers matched 14 people who used BP products currently with 65 controls who did not. Five (36%) of those using the products had detectable blood levels; 21 (32%) of those who did not use them did. There was no association between BP exposure and detectable blood benzene levels (odds ratio, 1.12; P = .80).
In the larger study, the researchers used the TriNetX US Collaborative Network database, comparing more than 27,000 patients treated with BP products for acne with more than 27,000 patients aged 12-40 years who had a diagnosis of nevus or seborrheic keratosis with no exposure to prescribed BP or any diagnosis of acne, hidradenitis suppurativa, or rosacea. The researchers looked at the database over the subsequent 10 years to determine the risk for either blood cancers or internal malignancies.
Compared with patients diagnosed with nevus or seborrheic keratosis, those with acne treated with BP had no significant difference in the risk for lymphoma (hazard ratio [HR], 1.00), leukemia (HR, 0.91), any lymphoma or leukemia (HR, 1.04), and internal malignancies (HR, 0.93).
The findings suggest no increased risk for malignancy, the researchers said, although they acknowledged study limitations, such as possible misclassification of BP exposure due to OTC availability and other issues.
Value of BP Treatments
BP is the “go-to” acne treatment, as Dr. Barbieri pointed out. “It’s probably the number one treatment for acne,” and there’s no substitute for it and it’s one of the most effective topical acne treatments, he noted.
Despite the reassuring findings, Dr. Barbieri repeated advice he gave soon after the Valisure report was released. Use common sense and don’t store BP-containing products in hot cars or other hot environments. In warmer climates, refrigeration could be considered, he said. Discard old products. Manufacturers should use cold-chain storage from the manufacturing site to retail or pharmacy sale sites, he added.
FDA and Citizen Petition Status
Asked about the status of the petition from Valisure, an FDA spokesperson said: “The FDA does not comment on the status of pending petitions.”
Dr. Barbieri and Dr. Lim had no relevant disclosures. There were no funding sources for either of the two studies.
A version of this article first appeared on Medscape.com.
Hemophilia: Novel Tx Also Cuts Bleeding in Kids
“In this study, once-weekly efanesoctocog alfa provided high sustained factor VIII activity and highly efficacious protection against bleeding episodes in children with severe hemophilia A, a population in which this goal has been difficult to achieve without burdensome treatment regimens,” report the authors in the study, published in The New England Journal of Medicine.
The results are from the phase 3, open-label XTEND-Kids study, in which first author Lynn Malec, MD, medical director of the Comprehensive Center for Bleeding Disorders and associate professor of medicine and pediatrics at The Medical College of Wisconsin, in Milwaukee, and colleagues enrolled 74 male pediatric patients with hemophilia A, including 38 under the age of 6 and 36 ages 6-12.
The participants received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kg of body weight), for 52 weeks.
Prior to the treatment period, all patients had received factor VIII replacement therapy, with the exception of one who received the therapy on demand. Most (70%) received extended half-life products, such as doses twice a week or every 3 days, and the remaining 30% received standard half-life products, with dose regimens ranging from every 2 days to twice a week.
Over the course of the year-long study, none of the patients developed factor VIII inhibitors, neutralizing antibodies, a common complication in hemophilia A that prevents factor VIII replacement treatment from working to form clots.
In addition, no serious adverse events occurred that were determined to be related to efanesoctocog alfa.
“No inhibitors to factor VIII developed, most adverse events were not serious, and no adverse events led to discontinuation of efanesoctocog alfa,” the authors report.
In terms of efficacy, among 73 patients who were treated according to the protocol, the median annualized bleeding rate was 0.00 and the model-based mean rate was 0.61.
Overall, 47 patients (64%) experienced no treated bleeding episodes during the study, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints.
Of 43 bleeding episodes, most (41; 95%) resolved with a single injection of efanesoctocog alfa.
Of note, “shortening the weekly administration interval was not deemed to be necessary in any patient during this study,” the authors add.
In comparison, other studies of children receiving other factor VIII products, including damoctocog alfa pegol, rurioctocog alfa pegol, and efmoroctocog alfa, show higher annualized bleeding rates of 2.9, 2.0, and 1.96, respectively, and studies showed the percentages of patients with no bleeding with those products were 23%, 38%, and 46%, respectively, compared with the 64% in the current study of efanesoctocog alfa.
“Although these clinical study results cannot be directly compared because of the differences in patient populations and study designs, the XTEND-Kids study showed favorable bleeding protection with efanesoctocog alfa prophylaxis as compared with these extended half-life factor VIII products,” the authors report.
Data on the once-weekly monoclonal antibody emicizumab, which has the important benefit of being administered subcutaneously instead of intravenously, is limited in children under age 12 with severe hemophilia A and without factor VIII inhibitors, the authors note.
However, the mean annualized bleeding rate with efanesoctocog alfa appears improved compared with that observed in a small Japanese study of 13 children who received emicizumab prophylaxis every 2 weeks or every 4 weeks, which showed annualized rates of treated bleeding episodes of 1.3 and 0.7 with the respective emicizumab regimens.
Results Compare With Findings in Adults
The results are similar to those reported among adults in the previous XTEND-1 phase 3 study, which was the basis for US Food and Drug Administration (FDA) approval of the drug in 2023 for routine prevention and on-demand treatment for the control of bleeding episodes, in addition to perioperative surgery for adults.
That approval was extended to children as well at the time, based on earlier interim results from the XTEND-Kids trial.
The annualized bleeding rate among adult patients treated with efanesoctocog alfa decreased from 2.96 to 0.69 over the 52 weeks, which was a significantly greater improvement compared with prestudy prophylaxis with conventional factor VIII prophylaxis (P < .001).
In children and adults alike, the decreased bleeding events were accompanied by improvements in physical health, pain, and joint health.
“Weekly prophylaxis with efanesoctocog alfa has the potential to provide long-term preservation of joint health,” the authors conclude.
Commenting in an editorial published concurrently with the study, Pratima Chowdary, MD, of the Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, England, underscored the need for a longer duration of prophylaxis, particularly in children.
“In children, the factor VIII protein has a shorter half-life than in adults, and intravenous administration of coagulation factors is particularly challenging, owing to poor venous access,” she explains.
“In this context, a notable outcome in [the study] is the achievement of once-weekly prophylaxis in children with sustained factor VIII levels through the week, which augurs well for protection in the context of delayed or missed doses.”
Dr. Chowdary adds that limitations include that “the study participants had pre-existing tolerance of factor VIII, because only those with previous exposure to factor VIII and without inhibitors were eligible for enrollment.”
“As such, immunogenicity needs to be assessed in other patients, especially those with no previous treatment with factor VIII.”
Further commenting to this news organization, Dr. Chowdary emphasized “the key takeaway for patients with hemophilia is that the notion of a single, lifelong treatment is outdated.”
“Regular reviews and adjustments to prophylaxis are necessary to ensure optimal control of hemophilia, aiming for zero bleeds each year,” Dr. Chowdary noted.
Furthermore, “the treatment regimen to achieve this must also align with the life goals of both patients and their parents,” she said.
The study was supported by Sanofi and Sobi. The authors’ and Dr. Chowdary’s disclosures are published with the study and editorial, respectively.
“In this study, once-weekly efanesoctocog alfa provided high sustained factor VIII activity and highly efficacious protection against bleeding episodes in children with severe hemophilia A, a population in which this goal has been difficult to achieve without burdensome treatment regimens,” report the authors in the study, published in The New England Journal of Medicine.
The results are from the phase 3, open-label XTEND-Kids study, in which first author Lynn Malec, MD, medical director of the Comprehensive Center for Bleeding Disorders and associate professor of medicine and pediatrics at The Medical College of Wisconsin, in Milwaukee, and colleagues enrolled 74 male pediatric patients with hemophilia A, including 38 under the age of 6 and 36 ages 6-12.
The participants received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kg of body weight), for 52 weeks.
Prior to the treatment period, all patients had received factor VIII replacement therapy, with the exception of one who received the therapy on demand. Most (70%) received extended half-life products, such as doses twice a week or every 3 days, and the remaining 30% received standard half-life products, with dose regimens ranging from every 2 days to twice a week.
Over the course of the year-long study, none of the patients developed factor VIII inhibitors, neutralizing antibodies, a common complication in hemophilia A that prevents factor VIII replacement treatment from working to form clots.
In addition, no serious adverse events occurred that were determined to be related to efanesoctocog alfa.
“No inhibitors to factor VIII developed, most adverse events were not serious, and no adverse events led to discontinuation of efanesoctocog alfa,” the authors report.
In terms of efficacy, among 73 patients who were treated according to the protocol, the median annualized bleeding rate was 0.00 and the model-based mean rate was 0.61.
Overall, 47 patients (64%) experienced no treated bleeding episodes during the study, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints.
Of 43 bleeding episodes, most (41; 95%) resolved with a single injection of efanesoctocog alfa.
Of note, “shortening the weekly administration interval was not deemed to be necessary in any patient during this study,” the authors add.
In comparison, other studies of children receiving other factor VIII products, including damoctocog alfa pegol, rurioctocog alfa pegol, and efmoroctocog alfa, show higher annualized bleeding rates of 2.9, 2.0, and 1.96, respectively, and studies showed the percentages of patients with no bleeding with those products were 23%, 38%, and 46%, respectively, compared with the 64% in the current study of efanesoctocog alfa.
“Although these clinical study results cannot be directly compared because of the differences in patient populations and study designs, the XTEND-Kids study showed favorable bleeding protection with efanesoctocog alfa prophylaxis as compared with these extended half-life factor VIII products,” the authors report.
Data on the once-weekly monoclonal antibody emicizumab, which has the important benefit of being administered subcutaneously instead of intravenously, is limited in children under age 12 with severe hemophilia A and without factor VIII inhibitors, the authors note.
However, the mean annualized bleeding rate with efanesoctocog alfa appears improved compared with that observed in a small Japanese study of 13 children who received emicizumab prophylaxis every 2 weeks or every 4 weeks, which showed annualized rates of treated bleeding episodes of 1.3 and 0.7 with the respective emicizumab regimens.
Results Compare With Findings in Adults
The results are similar to those reported among adults in the previous XTEND-1 phase 3 study, which was the basis for US Food and Drug Administration (FDA) approval of the drug in 2023 for routine prevention and on-demand treatment for the control of bleeding episodes, in addition to perioperative surgery for adults.
That approval was extended to children as well at the time, based on earlier interim results from the XTEND-Kids trial.
The annualized bleeding rate among adult patients treated with efanesoctocog alfa decreased from 2.96 to 0.69 over the 52 weeks, which was a significantly greater improvement compared with prestudy prophylaxis with conventional factor VIII prophylaxis (P < .001).
In children and adults alike, the decreased bleeding events were accompanied by improvements in physical health, pain, and joint health.
“Weekly prophylaxis with efanesoctocog alfa has the potential to provide long-term preservation of joint health,” the authors conclude.
Commenting in an editorial published concurrently with the study, Pratima Chowdary, MD, of the Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, England, underscored the need for a longer duration of prophylaxis, particularly in children.
“In children, the factor VIII protein has a shorter half-life than in adults, and intravenous administration of coagulation factors is particularly challenging, owing to poor venous access,” she explains.
“In this context, a notable outcome in [the study] is the achievement of once-weekly prophylaxis in children with sustained factor VIII levels through the week, which augurs well for protection in the context of delayed or missed doses.”
Dr. Chowdary adds that limitations include that “the study participants had pre-existing tolerance of factor VIII, because only those with previous exposure to factor VIII and without inhibitors were eligible for enrollment.”
“As such, immunogenicity needs to be assessed in other patients, especially those with no previous treatment with factor VIII.”
Further commenting to this news organization, Dr. Chowdary emphasized “the key takeaway for patients with hemophilia is that the notion of a single, lifelong treatment is outdated.”
“Regular reviews and adjustments to prophylaxis are necessary to ensure optimal control of hemophilia, aiming for zero bleeds each year,” Dr. Chowdary noted.
Furthermore, “the treatment regimen to achieve this must also align with the life goals of both patients and their parents,” she said.
The study was supported by Sanofi and Sobi. The authors’ and Dr. Chowdary’s disclosures are published with the study and editorial, respectively.
“In this study, once-weekly efanesoctocog alfa provided high sustained factor VIII activity and highly efficacious protection against bleeding episodes in children with severe hemophilia A, a population in which this goal has been difficult to achieve without burdensome treatment regimens,” report the authors in the study, published in The New England Journal of Medicine.
The results are from the phase 3, open-label XTEND-Kids study, in which first author Lynn Malec, MD, medical director of the Comprehensive Center for Bleeding Disorders and associate professor of medicine and pediatrics at The Medical College of Wisconsin, in Milwaukee, and colleagues enrolled 74 male pediatric patients with hemophilia A, including 38 under the age of 6 and 36 ages 6-12.
The participants received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kg of body weight), for 52 weeks.
Prior to the treatment period, all patients had received factor VIII replacement therapy, with the exception of one who received the therapy on demand. Most (70%) received extended half-life products, such as doses twice a week or every 3 days, and the remaining 30% received standard half-life products, with dose regimens ranging from every 2 days to twice a week.
Over the course of the year-long study, none of the patients developed factor VIII inhibitors, neutralizing antibodies, a common complication in hemophilia A that prevents factor VIII replacement treatment from working to form clots.
In addition, no serious adverse events occurred that were determined to be related to efanesoctocog alfa.
“No inhibitors to factor VIII developed, most adverse events were not serious, and no adverse events led to discontinuation of efanesoctocog alfa,” the authors report.
In terms of efficacy, among 73 patients who were treated according to the protocol, the median annualized bleeding rate was 0.00 and the model-based mean rate was 0.61.
Overall, 47 patients (64%) experienced no treated bleeding episodes during the study, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints.
Of 43 bleeding episodes, most (41; 95%) resolved with a single injection of efanesoctocog alfa.
Of note, “shortening the weekly administration interval was not deemed to be necessary in any patient during this study,” the authors add.
In comparison, other studies of children receiving other factor VIII products, including damoctocog alfa pegol, rurioctocog alfa pegol, and efmoroctocog alfa, show higher annualized bleeding rates of 2.9, 2.0, and 1.96, respectively, and studies showed the percentages of patients with no bleeding with those products were 23%, 38%, and 46%, respectively, compared with the 64% in the current study of efanesoctocog alfa.
“Although these clinical study results cannot be directly compared because of the differences in patient populations and study designs, the XTEND-Kids study showed favorable bleeding protection with efanesoctocog alfa prophylaxis as compared with these extended half-life factor VIII products,” the authors report.
Data on the once-weekly monoclonal antibody emicizumab, which has the important benefit of being administered subcutaneously instead of intravenously, is limited in children under age 12 with severe hemophilia A and without factor VIII inhibitors, the authors note.
However, the mean annualized bleeding rate with efanesoctocog alfa appears improved compared with that observed in a small Japanese study of 13 children who received emicizumab prophylaxis every 2 weeks or every 4 weeks, which showed annualized rates of treated bleeding episodes of 1.3 and 0.7 with the respective emicizumab regimens.
Results Compare With Findings in Adults
The results are similar to those reported among adults in the previous XTEND-1 phase 3 study, which was the basis for US Food and Drug Administration (FDA) approval of the drug in 2023 for routine prevention and on-demand treatment for the control of bleeding episodes, in addition to perioperative surgery for adults.
That approval was extended to children as well at the time, based on earlier interim results from the XTEND-Kids trial.
The annualized bleeding rate among adult patients treated with efanesoctocog alfa decreased from 2.96 to 0.69 over the 52 weeks, which was a significantly greater improvement compared with prestudy prophylaxis with conventional factor VIII prophylaxis (P < .001).
In children and adults alike, the decreased bleeding events were accompanied by improvements in physical health, pain, and joint health.
“Weekly prophylaxis with efanesoctocog alfa has the potential to provide long-term preservation of joint health,” the authors conclude.
Commenting in an editorial published concurrently with the study, Pratima Chowdary, MD, of the Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, England, underscored the need for a longer duration of prophylaxis, particularly in children.
“In children, the factor VIII protein has a shorter half-life than in adults, and intravenous administration of coagulation factors is particularly challenging, owing to poor venous access,” she explains.
“In this context, a notable outcome in [the study] is the achievement of once-weekly prophylaxis in children with sustained factor VIII levels through the week, which augurs well for protection in the context of delayed or missed doses.”
Dr. Chowdary adds that limitations include that “the study participants had pre-existing tolerance of factor VIII, because only those with previous exposure to factor VIII and without inhibitors were eligible for enrollment.”
“As such, immunogenicity needs to be assessed in other patients, especially those with no previous treatment with factor VIII.”
Further commenting to this news organization, Dr. Chowdary emphasized “the key takeaway for patients with hemophilia is that the notion of a single, lifelong treatment is outdated.”
“Regular reviews and adjustments to prophylaxis are necessary to ensure optimal control of hemophilia, aiming for zero bleeds each year,” Dr. Chowdary noted.
Furthermore, “the treatment regimen to achieve this must also align with the life goals of both patients and their parents,” she said.
The study was supported by Sanofi and Sobi. The authors’ and Dr. Chowdary’s disclosures are published with the study and editorial, respectively.
Vitamin B1 May Reduce Constipation in Adults
TOPLINE:
Increased dietary intake of vitamin B1 is associated with a lower prevalence of constipation, particularly among men and individuals without hypertension or diabetes.
METHODOLOGY:
- Researchers conducted a cross-sectional study using National Health and Nutrition Examination Survey data from 2005-2010 involving 10,371 adults aged ≥ 20 years.
- Participants provided information on fecal characteristics and bowel movement frequency, which was documented for 30 days prior to data collection.
- Constipation was established by either frequency of bowel movements (fewer than three per week) or stool consistency (Bristol Stool Scale type 1 or 2).
- Data on vitamin B1 intake were collected through 24-hour total nutritional intake recall interviews. Patients were divided into three groups based on their level of B1 intake: 0.064-1.21 mg, 1.21-1.76 mg, and 1.76-12.61 mg.
TAKEAWAY:
- Overall, 10.8% of participants were identified as having constipation.
- Greater dietary vitamin B1 intake was associated with a 23% reduction in constipation risk (P = .034).
- Additionally, a subgroup analysis found that higher B1 intake was associated with a reduction in constipation risk of 20% in men, 16% in people without hypertension, and 14% in those without diabetes.
IN PRACTICE:
“This association suggests that enhanced intake of vitamin B1 through diet may facilitate softer stools and heightened intestinal motility, thereby potentially alleviating constipation symptoms. Consequently, healthcare professionals are advised to prioritize the promotion of a well-balanced diet as an initial therapeutic approach, preceding medical interventions,” the authors wrote.
SOURCE:
The study, led by Wenyi Du, the Affiliated Stomatological Hospital of Soochow University, Suzhou Stomatological Hospital, Suzhou, China, and Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Wuxi, China, was published online in BMC Gastroenterology.
LIMITATIONS:
A causal relationship could not be established between vitamin B1 intake and constipation owing to the cross-sectional nature of the study. The study relied on patient interviews and patient self-reported data. Additionally, 24-hour dietary recalls may not have accurately reflected the long-term eating habits of the participants.
DISCLOSURES:
The study had no specific funding source. The authors declared no competing interests.
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:
Increased dietary intake of vitamin B1 is associated with a lower prevalence of constipation, particularly among men and individuals without hypertension or diabetes.
METHODOLOGY:
- Researchers conducted a cross-sectional study using National Health and Nutrition Examination Survey data from 2005-2010 involving 10,371 adults aged ≥ 20 years.
- Participants provided information on fecal characteristics and bowel movement frequency, which was documented for 30 days prior to data collection.
- Constipation was established by either frequency of bowel movements (fewer than three per week) or stool consistency (Bristol Stool Scale type 1 or 2).
- Data on vitamin B1 intake were collected through 24-hour total nutritional intake recall interviews. Patients were divided into three groups based on their level of B1 intake: 0.064-1.21 mg, 1.21-1.76 mg, and 1.76-12.61 mg.
TAKEAWAY:
- Overall, 10.8% of participants were identified as having constipation.
- Greater dietary vitamin B1 intake was associated with a 23% reduction in constipation risk (P = .034).
- Additionally, a subgroup analysis found that higher B1 intake was associated with a reduction in constipation risk of 20% in men, 16% in people without hypertension, and 14% in those without diabetes.
IN PRACTICE:
“This association suggests that enhanced intake of vitamin B1 through diet may facilitate softer stools and heightened intestinal motility, thereby potentially alleviating constipation symptoms. Consequently, healthcare professionals are advised to prioritize the promotion of a well-balanced diet as an initial therapeutic approach, preceding medical interventions,” the authors wrote.
SOURCE:
The study, led by Wenyi Du, the Affiliated Stomatological Hospital of Soochow University, Suzhou Stomatological Hospital, Suzhou, China, and Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Wuxi, China, was published online in BMC Gastroenterology.
LIMITATIONS:
A causal relationship could not be established between vitamin B1 intake and constipation owing to the cross-sectional nature of the study. The study relied on patient interviews and patient self-reported data. Additionally, 24-hour dietary recalls may not have accurately reflected the long-term eating habits of the participants.
DISCLOSURES:
The study had no specific funding source. The authors declared no competing interests.
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:
Increased dietary intake of vitamin B1 is associated with a lower prevalence of constipation, particularly among men and individuals without hypertension or diabetes.
METHODOLOGY:
- Researchers conducted a cross-sectional study using National Health and Nutrition Examination Survey data from 2005-2010 involving 10,371 adults aged ≥ 20 years.
- Participants provided information on fecal characteristics and bowel movement frequency, which was documented for 30 days prior to data collection.
- Constipation was established by either frequency of bowel movements (fewer than three per week) or stool consistency (Bristol Stool Scale type 1 or 2).
- Data on vitamin B1 intake were collected through 24-hour total nutritional intake recall interviews. Patients were divided into three groups based on their level of B1 intake: 0.064-1.21 mg, 1.21-1.76 mg, and 1.76-12.61 mg.
TAKEAWAY:
- Overall, 10.8% of participants were identified as having constipation.
- Greater dietary vitamin B1 intake was associated with a 23% reduction in constipation risk (P = .034).
- Additionally, a subgroup analysis found that higher B1 intake was associated with a reduction in constipation risk of 20% in men, 16% in people without hypertension, and 14% in those without diabetes.
IN PRACTICE:
“This association suggests that enhanced intake of vitamin B1 through diet may facilitate softer stools and heightened intestinal motility, thereby potentially alleviating constipation symptoms. Consequently, healthcare professionals are advised to prioritize the promotion of a well-balanced diet as an initial therapeutic approach, preceding medical interventions,” the authors wrote.
SOURCE:
The study, led by Wenyi Du, the Affiliated Stomatological Hospital of Soochow University, Suzhou Stomatological Hospital, Suzhou, China, and Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Wuxi, China, was published online in BMC Gastroenterology.
LIMITATIONS:
A causal relationship could not be established between vitamin B1 intake and constipation owing to the cross-sectional nature of the study. The study relied on patient interviews and patient self-reported data. Additionally, 24-hour dietary recalls may not have accurately reflected the long-term eating habits of the participants.
DISCLOSURES:
The study had no specific funding source. The authors declared no competing interests.
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.
Ask Teenage Boys If They Use Muscle-Building Supplements
such as protein or creatine, according to a new commentary in the Journal of Adolescent Health.
Muscle-building supplements are not tested before going to market, as are pharmaceutical drugs, and they are associated with greater rates of death and disability in adolescents than are vitamin supplements such as A, C, and folate. Even if protein shakes or creatine gummies do not seem to negatively affect a teen, in many cases the needed nutrients are obtained from food intake, and supplements are not necessary.
“For many young people, particularly boys, use of these supplements is pretty ubiquitous,” said Kyle T. Ganson, PhD, MSW, assistant professor of social work at the University of Toronto, and author of the commentary.
Other research has shown that males are more likely to have eating disorders linked to muscle-building, in addition to being the largest number of consumers of muscle-building supplements.
Dr. Ganson’s research has shown that more than 80% of adolescent boys and young men take a protein supplement, and 50% or less take a creatine boost. But health clinicians may not know about use because they do not ask, Dr. Ganson added.
After clinicians ask about use and learn that a teenager or young adult is taking a dietary supplement, they should use a harm reduction approach that encourages curtailing or modifying supplement use rather than insisting on total abstinence, Dr. Ganson and coauthors wrote.
For example, a clinician can assess the patient’s dietary intake of carbohydrates, proteins, fats, calories, vitamins, and minerals, and, if appropriate, advise the teen that he or she can get all the necessary nutrients at mealtime. Michele LaBotz, MD, medical director of the Master of Science in Athletic Training program at the University of New England in Biddeford, Maine, said most teen boys and young adults will not listen to a clinician telling them about the potential harms from supplements.
However, counseling these patients that the supplements are probably a waste of money — muscles will develop just fine with a healthy diet and regular exercise — is more effective at reducing use, according to Dr. LaBotz, who was a sports medicine physician for nearly 20 years.
Keeping open lines of communication about supplements may open the door for teens to share that they are also using muscle-building steroids. Dr. Ganson said the step to a more dangerous product sometimes occurs after teens no longer perceive they are benefiting from supplements.
“It’s not one conversation and you’re done: It’s about providing support and medical monitoring,” Dr. Ganson said.
Dr. Ganson said his colleagues hope professional societies develop formal clinical practice guidelines about muscle-building supplements in teens and young adults.
Contaminated and Dangerous Supplements
Although any teenage boy may want to build muscles, athletes are of particular concern. Dr. LaBotz authored an American Academy of Pediatrics recommendation that young athletes adhere to appropriate nutrition and training programs rather than turning to supplements.
Adverse outcomes from muscle-building supplements can occur when the products are labeled deceptively. For example, what is sold as creatine sometimes contains other ingredients that may be harmful, such as deterenol or oxilofrine, which are not approved for use in the United States.
Words like “proprietary,” “blend,” or “complex” on a supplement label should raise red flags, according to Pieter Cohen, MD, associate professor at Harvard Medical School, Boston, and an internist at the Cambridge Health Alliance who advises clinicians and patients about the safe use of dietary supplements.
Unlike for pharmaceuticals, the US Food and Drug Administration (FDA) is not authorized to assess the safety of dietary supplements before they are sold to consumers. Supplement manufacturers are not required to disclose the quantity of each ingredient in a proprietary blend on product labels. By one estimate, 23,000 emergency department visits annually in the United States are due to adverse effects from dietary supplements, ranging from cardiac trouble to swallowing difficulties.
In general, Dr. Cohen said, supplements with fewer than six ingredients that have been certified by a third party are more likely than others to be safe. The Department of Defense provides a scorecard for consumers to help decipher which supplements are safer to use.
“American consumers are the lab rats for these products,” said Bryn Austin, ScD, SM, professor of social sciences at the Harvard T.H. Chan School of Public Health, Boston, and director of a program that trains health professionals how to intervene to prevent eating disorders. “This industry invests a lot of money to invent a health halo for themselves. Muscle-building supplements can be downright dangerous and will not turn anyone into the elite athlete of their dreams.”
The commentary authors reported no financial disclosures.
A version of this article first appeared on Medscape.com.
such as protein or creatine, according to a new commentary in the Journal of Adolescent Health.
Muscle-building supplements are not tested before going to market, as are pharmaceutical drugs, and they are associated with greater rates of death and disability in adolescents than are vitamin supplements such as A, C, and folate. Even if protein shakes or creatine gummies do not seem to negatively affect a teen, in many cases the needed nutrients are obtained from food intake, and supplements are not necessary.
“For many young people, particularly boys, use of these supplements is pretty ubiquitous,” said Kyle T. Ganson, PhD, MSW, assistant professor of social work at the University of Toronto, and author of the commentary.
Other research has shown that males are more likely to have eating disorders linked to muscle-building, in addition to being the largest number of consumers of muscle-building supplements.
Dr. Ganson’s research has shown that more than 80% of adolescent boys and young men take a protein supplement, and 50% or less take a creatine boost. But health clinicians may not know about use because they do not ask, Dr. Ganson added.
After clinicians ask about use and learn that a teenager or young adult is taking a dietary supplement, they should use a harm reduction approach that encourages curtailing or modifying supplement use rather than insisting on total abstinence, Dr. Ganson and coauthors wrote.
For example, a clinician can assess the patient’s dietary intake of carbohydrates, proteins, fats, calories, vitamins, and minerals, and, if appropriate, advise the teen that he or she can get all the necessary nutrients at mealtime. Michele LaBotz, MD, medical director of the Master of Science in Athletic Training program at the University of New England in Biddeford, Maine, said most teen boys and young adults will not listen to a clinician telling them about the potential harms from supplements.
However, counseling these patients that the supplements are probably a waste of money — muscles will develop just fine with a healthy diet and regular exercise — is more effective at reducing use, according to Dr. LaBotz, who was a sports medicine physician for nearly 20 years.
Keeping open lines of communication about supplements may open the door for teens to share that they are also using muscle-building steroids. Dr. Ganson said the step to a more dangerous product sometimes occurs after teens no longer perceive they are benefiting from supplements.
“It’s not one conversation and you’re done: It’s about providing support and medical monitoring,” Dr. Ganson said.
Dr. Ganson said his colleagues hope professional societies develop formal clinical practice guidelines about muscle-building supplements in teens and young adults.
Contaminated and Dangerous Supplements
Although any teenage boy may want to build muscles, athletes are of particular concern. Dr. LaBotz authored an American Academy of Pediatrics recommendation that young athletes adhere to appropriate nutrition and training programs rather than turning to supplements.
Adverse outcomes from muscle-building supplements can occur when the products are labeled deceptively. For example, what is sold as creatine sometimes contains other ingredients that may be harmful, such as deterenol or oxilofrine, which are not approved for use in the United States.
Words like “proprietary,” “blend,” or “complex” on a supplement label should raise red flags, according to Pieter Cohen, MD, associate professor at Harvard Medical School, Boston, and an internist at the Cambridge Health Alliance who advises clinicians and patients about the safe use of dietary supplements.
Unlike for pharmaceuticals, the US Food and Drug Administration (FDA) is not authorized to assess the safety of dietary supplements before they are sold to consumers. Supplement manufacturers are not required to disclose the quantity of each ingredient in a proprietary blend on product labels. By one estimate, 23,000 emergency department visits annually in the United States are due to adverse effects from dietary supplements, ranging from cardiac trouble to swallowing difficulties.
In general, Dr. Cohen said, supplements with fewer than six ingredients that have been certified by a third party are more likely than others to be safe. The Department of Defense provides a scorecard for consumers to help decipher which supplements are safer to use.
“American consumers are the lab rats for these products,” said Bryn Austin, ScD, SM, professor of social sciences at the Harvard T.H. Chan School of Public Health, Boston, and director of a program that trains health professionals how to intervene to prevent eating disorders. “This industry invests a lot of money to invent a health halo for themselves. Muscle-building supplements can be downright dangerous and will not turn anyone into the elite athlete of their dreams.”
The commentary authors reported no financial disclosures.
A version of this article first appeared on Medscape.com.
such as protein or creatine, according to a new commentary in the Journal of Adolescent Health.
Muscle-building supplements are not tested before going to market, as are pharmaceutical drugs, and they are associated with greater rates of death and disability in adolescents than are vitamin supplements such as A, C, and folate. Even if protein shakes or creatine gummies do not seem to negatively affect a teen, in many cases the needed nutrients are obtained from food intake, and supplements are not necessary.
“For many young people, particularly boys, use of these supplements is pretty ubiquitous,” said Kyle T. Ganson, PhD, MSW, assistant professor of social work at the University of Toronto, and author of the commentary.
Other research has shown that males are more likely to have eating disorders linked to muscle-building, in addition to being the largest number of consumers of muscle-building supplements.
Dr. Ganson’s research has shown that more than 80% of adolescent boys and young men take a protein supplement, and 50% or less take a creatine boost. But health clinicians may not know about use because they do not ask, Dr. Ganson added.
After clinicians ask about use and learn that a teenager or young adult is taking a dietary supplement, they should use a harm reduction approach that encourages curtailing or modifying supplement use rather than insisting on total abstinence, Dr. Ganson and coauthors wrote.
For example, a clinician can assess the patient’s dietary intake of carbohydrates, proteins, fats, calories, vitamins, and minerals, and, if appropriate, advise the teen that he or she can get all the necessary nutrients at mealtime. Michele LaBotz, MD, medical director of the Master of Science in Athletic Training program at the University of New England in Biddeford, Maine, said most teen boys and young adults will not listen to a clinician telling them about the potential harms from supplements.
However, counseling these patients that the supplements are probably a waste of money — muscles will develop just fine with a healthy diet and regular exercise — is more effective at reducing use, according to Dr. LaBotz, who was a sports medicine physician for nearly 20 years.
Keeping open lines of communication about supplements may open the door for teens to share that they are also using muscle-building steroids. Dr. Ganson said the step to a more dangerous product sometimes occurs after teens no longer perceive they are benefiting from supplements.
“It’s not one conversation and you’re done: It’s about providing support and medical monitoring,” Dr. Ganson said.
Dr. Ganson said his colleagues hope professional societies develop formal clinical practice guidelines about muscle-building supplements in teens and young adults.
Contaminated and Dangerous Supplements
Although any teenage boy may want to build muscles, athletes are of particular concern. Dr. LaBotz authored an American Academy of Pediatrics recommendation that young athletes adhere to appropriate nutrition and training programs rather than turning to supplements.
Adverse outcomes from muscle-building supplements can occur when the products are labeled deceptively. For example, what is sold as creatine sometimes contains other ingredients that may be harmful, such as deterenol or oxilofrine, which are not approved for use in the United States.
Words like “proprietary,” “blend,” or “complex” on a supplement label should raise red flags, according to Pieter Cohen, MD, associate professor at Harvard Medical School, Boston, and an internist at the Cambridge Health Alliance who advises clinicians and patients about the safe use of dietary supplements.
Unlike for pharmaceuticals, the US Food and Drug Administration (FDA) is not authorized to assess the safety of dietary supplements before they are sold to consumers. Supplement manufacturers are not required to disclose the quantity of each ingredient in a proprietary blend on product labels. By one estimate, 23,000 emergency department visits annually in the United States are due to adverse effects from dietary supplements, ranging from cardiac trouble to swallowing difficulties.
In general, Dr. Cohen said, supplements with fewer than six ingredients that have been certified by a third party are more likely than others to be safe. The Department of Defense provides a scorecard for consumers to help decipher which supplements are safer to use.
“American consumers are the lab rats for these products,” said Bryn Austin, ScD, SM, professor of social sciences at the Harvard T.H. Chan School of Public Health, Boston, and director of a program that trains health professionals how to intervene to prevent eating disorders. “This industry invests a lot of money to invent a health halo for themselves. Muscle-building supplements can be downright dangerous and will not turn anyone into the elite athlete of their dreams.”
The commentary authors reported no financial disclosures.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF ADOLESCENT HEALTH
Diabetes-Related Outcomes and Costs Have Mostly Improved
TOPLINE:
Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.
METHODOLOGY:
- Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
- Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.
TAKEAWAY:
- The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
- After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
- The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
- Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
- Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
- For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
- Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
- Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
- However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
- In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.
IN PRACTICE:
“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.
“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
SOURCE:
This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.
LIMITATIONS:
Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.
DISCLOSURES:
The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.
A version of this article first appeared on Medscape.com.
TOPLINE:
Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.
METHODOLOGY:
- Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
- Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.
TAKEAWAY:
- The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
- After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
- The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
- Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
- Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
- For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
- Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
- Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
- However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
- In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.
IN PRACTICE:
“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.
“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
SOURCE:
This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.
LIMITATIONS:
Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.
DISCLOSURES:
The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.
A version of this article first appeared on Medscape.com.
TOPLINE:
Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.
METHODOLOGY:
- Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
- Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.
TAKEAWAY:
- The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
- After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
- The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
- Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
- Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
- For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
- Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
- Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
- However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
- In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.
IN PRACTICE:
“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.
“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
SOURCE:
This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.
LIMITATIONS:
Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.
DISCLOSURES:
The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.
A version of this article first appeared on Medscape.com.
Transvaginal Ultrasound Often Misses Endometrial Cancer in Black Women
TOPLINE:
The transvaginal ultrasonography triage strategy is unreliable for diagnosing endometrial cancer in high-risk Black women, with a significant risk for false-negative results at different endometrial thickness thresholds.
METHODOLOGY:
- Poor performance of transvaginal ultrasonography-measured endometrial thickness as a diagnostic triage strategy for endometrial cancer may contribute to racial disparity in stage at diagnosis between Black and White women.
- Researchers assessed the false-negative probability using transvaginal ultrasonography-measured endometrial thickness thresholds as triage for endometrial cancer in 1494 Black women (median age, 46 years) who underwent hysterectomy.
- The researchers focused on endometrial thickness measurements recorded within 24 months before hysterectomy, as well as demographic and clinical data.
- The endometrial thickness thresholds were defined as < 3 mm, < 4 mm, and < 5 mm, with the rest grouped as ≥ 5 mm, consistent with guidelines.
- A total of 210 women had endometrial cancer. The most common presenting symptoms were fibroids (78%), vaginal bleeding (71%), and pelvic pain (57%).
TAKEAWAY:
- Twenty-four cases of endometrial cancer were below the 5-mm endometrial thickness threshold that would trigger biopsy, resulting overall in 11.4% of endometrial cancer cases potentially missed.
- The false-negative probability was 9.5% (20 cases) at the < 4-mm threshold and 3.8% (8 cases) at the < 3-mm threshold.
- Classic risk factors for endometrial cancer (postmenopausal bleeding, age ≥ 50 years, and BMI > 40) did not result in improved performance of the endometrial thickness triage strategy.
- False-negative probability was also similar among those with fibroids (12%) but higher in the setting of partial endometrial thickness visibility (26%) and pelvic pain (15%).
IN PRACTICE:
This study reveals a “concerning error rate for a triage strategy that would terminate further workup and provide false reassurance to both patients and physicians.” The results contribute to “an increasing body of work questioning the wisdom of the (transvaginal ultrasonography) triage strategy. It may be the case that the (transvaginal ultrasonography) triage for endometrial biopsy is no longer a preferred strategy in the setting of increasing endometrial cancer rates for all. For Black patients with concerning symptoms, tissue biopsy is recommended to avoid misdiagnosis of endometrial cancer,” the researchers concluded.
SOURCE:
The study, with first author Kemi M. Doll, MD, Fred Hutchinson Cancer Center, University of Washington, Seattle, was published online in JAMA Oncology.
LIMITATIONS:
The study did not include cases where transvaginal ultrasonography reports omitted endometrial thickness measurements or reported nonvisible endometrial thickness, possibly underestimating the failure rate of the transvaginal ultrasonography triage strategy.
The sample did not include endometrial cancer cases that were not treated with hysterectomy, which may occur in young women with grade 1 endometrial cancer, those medically incapable of undergoing surgery, and those with disease so advanced that surgery is no longer an option.
DISCLOSURES:
Funding was provided by Kuni Discovery Grants for Cancer Research: Advancing Innovation and by a grant from the National Institutes of Health. Dr. Doll reported receiving investigator-initiated research grants from the Patient Centered Outcomes Research Institute, American Association of Cancer Research, and Merck.
A version of this article first appeared on Medscape.com.
TOPLINE:
The transvaginal ultrasonography triage strategy is unreliable for diagnosing endometrial cancer in high-risk Black women, with a significant risk for false-negative results at different endometrial thickness thresholds.
METHODOLOGY:
- Poor performance of transvaginal ultrasonography-measured endometrial thickness as a diagnostic triage strategy for endometrial cancer may contribute to racial disparity in stage at diagnosis between Black and White women.
- Researchers assessed the false-negative probability using transvaginal ultrasonography-measured endometrial thickness thresholds as triage for endometrial cancer in 1494 Black women (median age, 46 years) who underwent hysterectomy.
- The researchers focused on endometrial thickness measurements recorded within 24 months before hysterectomy, as well as demographic and clinical data.
- The endometrial thickness thresholds were defined as < 3 mm, < 4 mm, and < 5 mm, with the rest grouped as ≥ 5 mm, consistent with guidelines.
- A total of 210 women had endometrial cancer. The most common presenting symptoms were fibroids (78%), vaginal bleeding (71%), and pelvic pain (57%).
TAKEAWAY:
- Twenty-four cases of endometrial cancer were below the 5-mm endometrial thickness threshold that would trigger biopsy, resulting overall in 11.4% of endometrial cancer cases potentially missed.
- The false-negative probability was 9.5% (20 cases) at the < 4-mm threshold and 3.8% (8 cases) at the < 3-mm threshold.
- Classic risk factors for endometrial cancer (postmenopausal bleeding, age ≥ 50 years, and BMI > 40) did not result in improved performance of the endometrial thickness triage strategy.
- False-negative probability was also similar among those with fibroids (12%) but higher in the setting of partial endometrial thickness visibility (26%) and pelvic pain (15%).
IN PRACTICE:
This study reveals a “concerning error rate for a triage strategy that would terminate further workup and provide false reassurance to both patients and physicians.” The results contribute to “an increasing body of work questioning the wisdom of the (transvaginal ultrasonography) triage strategy. It may be the case that the (transvaginal ultrasonography) triage for endometrial biopsy is no longer a preferred strategy in the setting of increasing endometrial cancer rates for all. For Black patients with concerning symptoms, tissue biopsy is recommended to avoid misdiagnosis of endometrial cancer,” the researchers concluded.
SOURCE:
The study, with first author Kemi M. Doll, MD, Fred Hutchinson Cancer Center, University of Washington, Seattle, was published online in JAMA Oncology.
LIMITATIONS:
The study did not include cases where transvaginal ultrasonography reports omitted endometrial thickness measurements or reported nonvisible endometrial thickness, possibly underestimating the failure rate of the transvaginal ultrasonography triage strategy.
The sample did not include endometrial cancer cases that were not treated with hysterectomy, which may occur in young women with grade 1 endometrial cancer, those medically incapable of undergoing surgery, and those with disease so advanced that surgery is no longer an option.
DISCLOSURES:
Funding was provided by Kuni Discovery Grants for Cancer Research: Advancing Innovation and by a grant from the National Institutes of Health. Dr. Doll reported receiving investigator-initiated research grants from the Patient Centered Outcomes Research Institute, American Association of Cancer Research, and Merck.
A version of this article first appeared on Medscape.com.
TOPLINE:
The transvaginal ultrasonography triage strategy is unreliable for diagnosing endometrial cancer in high-risk Black women, with a significant risk for false-negative results at different endometrial thickness thresholds.
METHODOLOGY:
- Poor performance of transvaginal ultrasonography-measured endometrial thickness as a diagnostic triage strategy for endometrial cancer may contribute to racial disparity in stage at diagnosis between Black and White women.
- Researchers assessed the false-negative probability using transvaginal ultrasonography-measured endometrial thickness thresholds as triage for endometrial cancer in 1494 Black women (median age, 46 years) who underwent hysterectomy.
- The researchers focused on endometrial thickness measurements recorded within 24 months before hysterectomy, as well as demographic and clinical data.
- The endometrial thickness thresholds were defined as < 3 mm, < 4 mm, and < 5 mm, with the rest grouped as ≥ 5 mm, consistent with guidelines.
- A total of 210 women had endometrial cancer. The most common presenting symptoms were fibroids (78%), vaginal bleeding (71%), and pelvic pain (57%).
TAKEAWAY:
- Twenty-four cases of endometrial cancer were below the 5-mm endometrial thickness threshold that would trigger biopsy, resulting overall in 11.4% of endometrial cancer cases potentially missed.
- The false-negative probability was 9.5% (20 cases) at the < 4-mm threshold and 3.8% (8 cases) at the < 3-mm threshold.
- Classic risk factors for endometrial cancer (postmenopausal bleeding, age ≥ 50 years, and BMI > 40) did not result in improved performance of the endometrial thickness triage strategy.
- False-negative probability was also similar among those with fibroids (12%) but higher in the setting of partial endometrial thickness visibility (26%) and pelvic pain (15%).
IN PRACTICE:
This study reveals a “concerning error rate for a triage strategy that would terminate further workup and provide false reassurance to both patients and physicians.” The results contribute to “an increasing body of work questioning the wisdom of the (transvaginal ultrasonography) triage strategy. It may be the case that the (transvaginal ultrasonography) triage for endometrial biopsy is no longer a preferred strategy in the setting of increasing endometrial cancer rates for all. For Black patients with concerning symptoms, tissue biopsy is recommended to avoid misdiagnosis of endometrial cancer,” the researchers concluded.
SOURCE:
The study, with first author Kemi M. Doll, MD, Fred Hutchinson Cancer Center, University of Washington, Seattle, was published online in JAMA Oncology.
LIMITATIONS:
The study did not include cases where transvaginal ultrasonography reports omitted endometrial thickness measurements or reported nonvisible endometrial thickness, possibly underestimating the failure rate of the transvaginal ultrasonography triage strategy.
The sample did not include endometrial cancer cases that were not treated with hysterectomy, which may occur in young women with grade 1 endometrial cancer, those medically incapable of undergoing surgery, and those with disease so advanced that surgery is no longer an option.
DISCLOSURES:
Funding was provided by Kuni Discovery Grants for Cancer Research: Advancing Innovation and by a grant from the National Institutes of Health. Dr. Doll reported receiving investigator-initiated research grants from the Patient Centered Outcomes Research Institute, American Association of Cancer Research, and Merck.
A version of this article first appeared on Medscape.com.
Accelerated Brain Stimulation Rapidly Curbs Resistant Bipolar Depression
the results of a small randomized controlled trial showed.
Investigators found those who received active aiTBS had a substantial decrease in depressive symptoms compared with those who received sham stimulation.
“aiTBS offers a new potential therapy for depressed patients with bipolar disorder who may not respond well to drugs or cannot tolerate their side effects while also significantly shortening the treatment window,” lead researcher Yvette Sheline, MD, director of the Center for Neuromodulation in Depression and Stress at the University of Pennsylvania, Philadelphia, said in a news release.
The study was published online in JAMA Psychiatry.
Remission After 5 Days
The Food and Drug Administration (FDA) cleared aiTBS to treat major depressive disorder. However, the treatment is not yet approved for bipolar depression.
The investigators assessed the effectiveness of aiTBS in 12 men and 12 women (mean age, 43 years) with treatment-resistant bipolar disorder. All participants were on mood stabilizers for at least 4 weeks and had Montgomery-Åsberg Depression Rating Scale (MADRS) scores of 20 or greater.
Of the 24 participants, 22 had a diagnosis of bipolar II disorder. Over 5 days, participants were randomized to receive, on a 1:1 basis, 10 sessions per day of imaging-guided active aiTBS or sham aiTBS over the left dorsolateral prefrontal cortex. Each session lasted for 1 hour. All 24 participants completed the assigned treatment and 1-month follow-up.
Active aiTBS was significantly more effective than sham stimulation in relieving depressive symptoms.
In the active treatment group, MADRS scores dropped from a mean of 30.4 at baseline to 10.5 after treatment. In contrast, the sham group experienced a minor change in MADRS scores, which decreased from a mean of 28.0 at baseline to 25.3 posttreatment.
After 5 days of treatment, half of the participants in the active aiTBS group were in remission, compared with none in the sham group.
The results demonstrate the “clinical efficacy and a short time to achieve improvement in this difficult-to-treat condition. The effect was seen even though the participant sample had high depression severity and treatment resistance, both associated with poor response,” the investigators noted.
Dr. Sheline said there were no differences between active and sham stimulation in the “expected adverse events of headache and dizziness. There were no incidences of manic “flip,” and the Young Mania Rating Scale scores were stable in both active and sham groups with no difference between them.”
The researchers noted that the “large effect size” of active aiTBS could be caused by several factors, including optimized stimulation targeting, accelerated time course, and high pulse number (18,000 per day, 90,000 total).
Future studies are needed to examine the relative contributions of the different protocol components to optimize and personalize treatment and evaluate the durability of the antidepressant effects of aiTBS, they added.
A Revolutionary Approach
For comment on the study, we reached out to Nolan Williams, MD, associate professor of psychiatry and behavioral sciences at Stanford University and director of the Stanford Brain Stimulation Lab, Stanford, California.
His laboratory pioneered the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), which was cleared by the FDA in 2022 for treatment-resistant depression.
Dr. Williams noted that the stimulation and targeting approach used in the current study “mirrors most aspects of the SAINT protocol with very similar results.”
“It’s exciting that we see this kind of pseudo-replication essentially of our work and is supportive of the general view that this approach is revolutionary in its ability to treat people quickly and have such a dramatic clinical effect,” said Dr. Williams.
In March 2024, Dr. Williams and colleagues reported the results of a pilot study of SAINT for bipolar depression, which demonstrated antidepressant efficacy akin to what was observed in the unipolar depression population.
Dr. Williams said, in his experience, the accelerated treatment protocol is convenient and well-liked by patients and, in general, is where the field of psychiatric treatment is headed.
“A general theme that we see in depression and psychiatry is that patients no longer accept long time frames for treatment as being the norm. Whether it be ketamine or this or the upcoming psychedelics, rapid-acting treatments that match the level of acuity will be the norm,” Dr. Williams said.
The study was funded by the Milken Institute and the Baszucki Brain Research Fund. The authors have disclosed no conflicts of interest. Dr. Williams is a named inventor on Stanford-owned intellectual property relating to accelerated TMS pulse pattern sequences and neuroimaging-based TMS targeting. He disclosed ties with Otsuka, NeuraWell, Magnus Medical, and Nooma.
A version of this article first appeared on Medscape.com.
the results of a small randomized controlled trial showed.
Investigators found those who received active aiTBS had a substantial decrease in depressive symptoms compared with those who received sham stimulation.
“aiTBS offers a new potential therapy for depressed patients with bipolar disorder who may not respond well to drugs or cannot tolerate their side effects while also significantly shortening the treatment window,” lead researcher Yvette Sheline, MD, director of the Center for Neuromodulation in Depression and Stress at the University of Pennsylvania, Philadelphia, said in a news release.
The study was published online in JAMA Psychiatry.
Remission After 5 Days
The Food and Drug Administration (FDA) cleared aiTBS to treat major depressive disorder. However, the treatment is not yet approved for bipolar depression.
The investigators assessed the effectiveness of aiTBS in 12 men and 12 women (mean age, 43 years) with treatment-resistant bipolar disorder. All participants were on mood stabilizers for at least 4 weeks and had Montgomery-Åsberg Depression Rating Scale (MADRS) scores of 20 or greater.
Of the 24 participants, 22 had a diagnosis of bipolar II disorder. Over 5 days, participants were randomized to receive, on a 1:1 basis, 10 sessions per day of imaging-guided active aiTBS or sham aiTBS over the left dorsolateral prefrontal cortex. Each session lasted for 1 hour. All 24 participants completed the assigned treatment and 1-month follow-up.
Active aiTBS was significantly more effective than sham stimulation in relieving depressive symptoms.
In the active treatment group, MADRS scores dropped from a mean of 30.4 at baseline to 10.5 after treatment. In contrast, the sham group experienced a minor change in MADRS scores, which decreased from a mean of 28.0 at baseline to 25.3 posttreatment.
After 5 days of treatment, half of the participants in the active aiTBS group were in remission, compared with none in the sham group.
The results demonstrate the “clinical efficacy and a short time to achieve improvement in this difficult-to-treat condition. The effect was seen even though the participant sample had high depression severity and treatment resistance, both associated with poor response,” the investigators noted.
Dr. Sheline said there were no differences between active and sham stimulation in the “expected adverse events of headache and dizziness. There were no incidences of manic “flip,” and the Young Mania Rating Scale scores were stable in both active and sham groups with no difference between them.”
The researchers noted that the “large effect size” of active aiTBS could be caused by several factors, including optimized stimulation targeting, accelerated time course, and high pulse number (18,000 per day, 90,000 total).
Future studies are needed to examine the relative contributions of the different protocol components to optimize and personalize treatment and evaluate the durability of the antidepressant effects of aiTBS, they added.
A Revolutionary Approach
For comment on the study, we reached out to Nolan Williams, MD, associate professor of psychiatry and behavioral sciences at Stanford University and director of the Stanford Brain Stimulation Lab, Stanford, California.
His laboratory pioneered the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), which was cleared by the FDA in 2022 for treatment-resistant depression.
Dr. Williams noted that the stimulation and targeting approach used in the current study “mirrors most aspects of the SAINT protocol with very similar results.”
“It’s exciting that we see this kind of pseudo-replication essentially of our work and is supportive of the general view that this approach is revolutionary in its ability to treat people quickly and have such a dramatic clinical effect,” said Dr. Williams.
In March 2024, Dr. Williams and colleagues reported the results of a pilot study of SAINT for bipolar depression, which demonstrated antidepressant efficacy akin to what was observed in the unipolar depression population.
Dr. Williams said, in his experience, the accelerated treatment protocol is convenient and well-liked by patients and, in general, is where the field of psychiatric treatment is headed.
“A general theme that we see in depression and psychiatry is that patients no longer accept long time frames for treatment as being the norm. Whether it be ketamine or this or the upcoming psychedelics, rapid-acting treatments that match the level of acuity will be the norm,” Dr. Williams said.
The study was funded by the Milken Institute and the Baszucki Brain Research Fund. The authors have disclosed no conflicts of interest. Dr. Williams is a named inventor on Stanford-owned intellectual property relating to accelerated TMS pulse pattern sequences and neuroimaging-based TMS targeting. He disclosed ties with Otsuka, NeuraWell, Magnus Medical, and Nooma.
A version of this article first appeared on Medscape.com.
the results of a small randomized controlled trial showed.
Investigators found those who received active aiTBS had a substantial decrease in depressive symptoms compared with those who received sham stimulation.
“aiTBS offers a new potential therapy for depressed patients with bipolar disorder who may not respond well to drugs or cannot tolerate their side effects while also significantly shortening the treatment window,” lead researcher Yvette Sheline, MD, director of the Center for Neuromodulation in Depression and Stress at the University of Pennsylvania, Philadelphia, said in a news release.
The study was published online in JAMA Psychiatry.
Remission After 5 Days
The Food and Drug Administration (FDA) cleared aiTBS to treat major depressive disorder. However, the treatment is not yet approved for bipolar depression.
The investigators assessed the effectiveness of aiTBS in 12 men and 12 women (mean age, 43 years) with treatment-resistant bipolar disorder. All participants were on mood stabilizers for at least 4 weeks and had Montgomery-Åsberg Depression Rating Scale (MADRS) scores of 20 or greater.
Of the 24 participants, 22 had a diagnosis of bipolar II disorder. Over 5 days, participants were randomized to receive, on a 1:1 basis, 10 sessions per day of imaging-guided active aiTBS or sham aiTBS over the left dorsolateral prefrontal cortex. Each session lasted for 1 hour. All 24 participants completed the assigned treatment and 1-month follow-up.
Active aiTBS was significantly more effective than sham stimulation in relieving depressive symptoms.
In the active treatment group, MADRS scores dropped from a mean of 30.4 at baseline to 10.5 after treatment. In contrast, the sham group experienced a minor change in MADRS scores, which decreased from a mean of 28.0 at baseline to 25.3 posttreatment.
After 5 days of treatment, half of the participants in the active aiTBS group were in remission, compared with none in the sham group.
The results demonstrate the “clinical efficacy and a short time to achieve improvement in this difficult-to-treat condition. The effect was seen even though the participant sample had high depression severity and treatment resistance, both associated with poor response,” the investigators noted.
Dr. Sheline said there were no differences between active and sham stimulation in the “expected adverse events of headache and dizziness. There were no incidences of manic “flip,” and the Young Mania Rating Scale scores were stable in both active and sham groups with no difference between them.”
The researchers noted that the “large effect size” of active aiTBS could be caused by several factors, including optimized stimulation targeting, accelerated time course, and high pulse number (18,000 per day, 90,000 total).
Future studies are needed to examine the relative contributions of the different protocol components to optimize and personalize treatment and evaluate the durability of the antidepressant effects of aiTBS, they added.
A Revolutionary Approach
For comment on the study, we reached out to Nolan Williams, MD, associate professor of psychiatry and behavioral sciences at Stanford University and director of the Stanford Brain Stimulation Lab, Stanford, California.
His laboratory pioneered the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), which was cleared by the FDA in 2022 for treatment-resistant depression.
Dr. Williams noted that the stimulation and targeting approach used in the current study “mirrors most aspects of the SAINT protocol with very similar results.”
“It’s exciting that we see this kind of pseudo-replication essentially of our work and is supportive of the general view that this approach is revolutionary in its ability to treat people quickly and have such a dramatic clinical effect,” said Dr. Williams.
In March 2024, Dr. Williams and colleagues reported the results of a pilot study of SAINT for bipolar depression, which demonstrated antidepressant efficacy akin to what was observed in the unipolar depression population.
Dr. Williams said, in his experience, the accelerated treatment protocol is convenient and well-liked by patients and, in general, is where the field of psychiatric treatment is headed.
“A general theme that we see in depression and psychiatry is that patients no longer accept long time frames for treatment as being the norm. Whether it be ketamine or this or the upcoming psychedelics, rapid-acting treatments that match the level of acuity will be the norm,” Dr. Williams said.
The study was funded by the Milken Institute and the Baszucki Brain Research Fund. The authors have disclosed no conflicts of interest. Dr. Williams is a named inventor on Stanford-owned intellectual property relating to accelerated TMS pulse pattern sequences and neuroimaging-based TMS targeting. He disclosed ties with Otsuka, NeuraWell, Magnus Medical, and Nooma.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY