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Myeloma: Can Failed Drugs Work Again?
TOPLINE:
METHODOLOGY:
- Researchers retrospectively reviewed patients with relapsed/refractory multiple myeloma who started new systemic therapy for disease progression between January 2015 and April 2022 at their institution.
- Analysis included 315 patients treated with a drug that their disease had previously been refractory to, defined as disease progression while receiving the drug or within 60 days of the last dose.
- Patient characteristics collected at diagnosis included age, sex, International Staging System stage, revised International Staging System stage, and interphase fluorescence in situ hybridization abnormalities.
- Investigators considered the first relapse after January 2015 requiring new systemic therapy as the index relapse and study start time.
TAKEAWAY:
- Analysis revealed an overall response rate of 56.2% and median progression-free survival of 11 months with retreatment.
- Patients with longer initial therapy duration with index drug (> 28.4 months) demonstrated superior progression-free survival (median, 16.9 vs 8.1 months; P < .001).
- Researchers found that patients with longer time gap between initial therapy and retreatment (> 46.1 months) showed better progression-free survival (median, 28.2 vs 8.9 months; P = .016).
- Among the 285 evaluable patients, 26% achieved partial response and 30.2% achieved very good partial response or better with retreatment.
IN PRACTICE:
“Retreatment with previously refractory drugs is a viable option for late-line [relapsed/refractory multiple myeloma]. Patients with a longer gap between initial line of therapy with index drug and retreatment had superior outcomes with retreatment,” wrote the authors of the study.
SOURCE:
The study was led by Utkarsh Goel, Division of Hematology, Mayo Clinic in Rochester, Minnesota. It was published online on December 24, 2024, in Blood Advances.
LIMITATIONS:
The retrospective nature and single-institution design of the study may introduce bias in terms of patient population and practice patterns. The favorable outcomes observed in patients with longer initial therapy duration and greater time between treatments could reflect selection bias toward more indolent disease biology. Despite adjusting for nonrefractory partner drugs during index relapse, residual bias may limit the ability to attribute outcomes solely to retreatment. The heterogeneous nature of treatments received during index relapse may limit comparisons across different groups.
DISCLOSURES:
Nelson Leung reported ties with AbbVie, Senseonics, Verrica Pharmaceuticals, and Omeros. Yi Lin disclosed relationships with multiple institutions, including Bristol Myers Squibb, Caribou Biosciences, and Janssen Oncology. Shaji Kumar reported ties with AbbVie, Bristol-Myers Squibb/Celgene, and Janssen Oncology. Additional disclosures were noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers retrospectively reviewed patients with relapsed/refractory multiple myeloma who started new systemic therapy for disease progression between January 2015 and April 2022 at their institution.
- Analysis included 315 patients treated with a drug that their disease had previously been refractory to, defined as disease progression while receiving the drug or within 60 days of the last dose.
- Patient characteristics collected at diagnosis included age, sex, International Staging System stage, revised International Staging System stage, and interphase fluorescence in situ hybridization abnormalities.
- Investigators considered the first relapse after January 2015 requiring new systemic therapy as the index relapse and study start time.
TAKEAWAY:
- Analysis revealed an overall response rate of 56.2% and median progression-free survival of 11 months with retreatment.
- Patients with longer initial therapy duration with index drug (> 28.4 months) demonstrated superior progression-free survival (median, 16.9 vs 8.1 months; P < .001).
- Researchers found that patients with longer time gap between initial therapy and retreatment (> 46.1 months) showed better progression-free survival (median, 28.2 vs 8.9 months; P = .016).
- Among the 285 evaluable patients, 26% achieved partial response and 30.2% achieved very good partial response or better with retreatment.
IN PRACTICE:
“Retreatment with previously refractory drugs is a viable option for late-line [relapsed/refractory multiple myeloma]. Patients with a longer gap between initial line of therapy with index drug and retreatment had superior outcomes with retreatment,” wrote the authors of the study.
SOURCE:
The study was led by Utkarsh Goel, Division of Hematology, Mayo Clinic in Rochester, Minnesota. It was published online on December 24, 2024, in Blood Advances.
LIMITATIONS:
The retrospective nature and single-institution design of the study may introduce bias in terms of patient population and practice patterns. The favorable outcomes observed in patients with longer initial therapy duration and greater time between treatments could reflect selection bias toward more indolent disease biology. Despite adjusting for nonrefractory partner drugs during index relapse, residual bias may limit the ability to attribute outcomes solely to retreatment. The heterogeneous nature of treatments received during index relapse may limit comparisons across different groups.
DISCLOSURES:
Nelson Leung reported ties with AbbVie, Senseonics, Verrica Pharmaceuticals, and Omeros. Yi Lin disclosed relationships with multiple institutions, including Bristol Myers Squibb, Caribou Biosciences, and Janssen Oncology. Shaji Kumar reported ties with AbbVie, Bristol-Myers Squibb/Celgene, and Janssen Oncology. Additional disclosures were noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers retrospectively reviewed patients with relapsed/refractory multiple myeloma who started new systemic therapy for disease progression between January 2015 and April 2022 at their institution.
- Analysis included 315 patients treated with a drug that their disease had previously been refractory to, defined as disease progression while receiving the drug or within 60 days of the last dose.
- Patient characteristics collected at diagnosis included age, sex, International Staging System stage, revised International Staging System stage, and interphase fluorescence in situ hybridization abnormalities.
- Investigators considered the first relapse after January 2015 requiring new systemic therapy as the index relapse and study start time.
TAKEAWAY:
- Analysis revealed an overall response rate of 56.2% and median progression-free survival of 11 months with retreatment.
- Patients with longer initial therapy duration with index drug (> 28.4 months) demonstrated superior progression-free survival (median, 16.9 vs 8.1 months; P < .001).
- Researchers found that patients with longer time gap between initial therapy and retreatment (> 46.1 months) showed better progression-free survival (median, 28.2 vs 8.9 months; P = .016).
- Among the 285 evaluable patients, 26% achieved partial response and 30.2% achieved very good partial response or better with retreatment.
IN PRACTICE:
“Retreatment with previously refractory drugs is a viable option for late-line [relapsed/refractory multiple myeloma]. Patients with a longer gap between initial line of therapy with index drug and retreatment had superior outcomes with retreatment,” wrote the authors of the study.
SOURCE:
The study was led by Utkarsh Goel, Division of Hematology, Mayo Clinic in Rochester, Minnesota. It was published online on December 24, 2024, in Blood Advances.
LIMITATIONS:
The retrospective nature and single-institution design of the study may introduce bias in terms of patient population and practice patterns. The favorable outcomes observed in patients with longer initial therapy duration and greater time between treatments could reflect selection bias toward more indolent disease biology. Despite adjusting for nonrefractory partner drugs during index relapse, residual bias may limit the ability to attribute outcomes solely to retreatment. The heterogeneous nature of treatments received during index relapse may limit comparisons across different groups.
DISCLOSURES:
Nelson Leung reported ties with AbbVie, Senseonics, Verrica Pharmaceuticals, and Omeros. Yi Lin disclosed relationships with multiple institutions, including Bristol Myers Squibb, Caribou Biosciences, and Janssen Oncology. Shaji Kumar reported ties with AbbVie, Bristol-Myers Squibb/Celgene, and Janssen Oncology. Additional disclosures were noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
VA Pays Billions for Costs Shifted From Medicare
In Fiscal Year (FY) 2023, > 40% of veterans enrolled by the US Department of Veterans Affairs (VA) received care from private practice, mainly for emergency services. Costs associated with that care have shifted from Medicare to the VA to the tune of billions of dollars, according to a recent study published in JAMA Health Forum.
The expenses are a result of the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act of 2018, which established the Veterans Community Care Program (VCCP) and allowed the VA to contract with private clinicians. This provided veterans enrolled in both the Veterans Health Administration (VHA) and Medicare to have 2 government sources of health care financing. The VHA is billed if the veteran receives care at one of its facilities or is referred to a community facility; Medicare is billed only if the veteran is treated for a service not covered by VHA.
These shifts are concerning, according to Kenneth W. Kizer, MD, MPH, and Said Ibrahim, MD, MPH. In an accompanying editorial, they outline how the changes affect whether VHA care will have adequate funding to provide care for the additional 740,000 enrollees who have entered the system in the past 2 years.
“This has created a $12 billion medical care budget shortfall for FY 2024,” Kizer and Ibrahim argue. The resulting “substantial budgetary tumult … is adversely impacting the front lines of care delivery at individual VA facilities, leading to delays in hiring caregivers and impeding access to VA care and timely care delivery, as well as greatly straining the traditional roles of VA staff and clinicians trying to manage the challenging cross-system referral processes.”
The study calculated the number of yearly emergency department (ED) visits per 1000 veterans in Medicare overall and by VA ED visits, VA-purchased community ED visits, and Medicare-purchased community ED visits. Estimated total costs shifted from Medicare to the VA after the MISSION Act between 2016 and 2021 were then calculated.
Of the 4,960,189 VA and Medicare enrollees in 2016, 37.0% presented to the ED at least once. Of the 4,837,436 dual enrollees in 2021, 37.6% presented to the ED at least once. ED visits increased 8%, from 820 per 1000 veterans in 2016, to 886 per 1000 veterans in 2019. The COVID-19 pandemic caused a dip in ED visits in 2020 by veterans (769 per 1000), but the number rose 2021 (852 per 1000 veterans).
Between 2016 and 2021, the percentage of VA-purchased community ED visits more than doubled, from 8.0% to 21.1%, while Medicare-purchased community ED visits dropped from 65.2% to 52.6%. Patterns were similar among veterans enrolled in traditional Medicare vs Medicare Advantage (MA). The study estimated that in 2021 at least $2 billion of VA community ED spending was due to payer shift from Medicare.
The shift is “particularly concerning” among veterans enrolled in MA since insurance plans receive capitated payments regardless of actual use of VA- or Medicare-covered services. However, the study’s observational design “limited our ability to infer causality between MISSION Act implementation and payer change.”
The cost shifting is “symptomatic of the fiscally undisciplined implementation of the VCCP and the lack of financially sound policy on payment for VA-Medicare dual enrollees,” according to Drs. Kizer and Ibrahim. “Addressing this matter seems especially important in light of numerous studies showing that the quality of community care often may be inferior to VA care, as well as less timely.”
Kizer and Ibrahim point out that when a veteran who is jointly enrolled in VA and MA plans receives care from the VA, the VA incurs the cost of providing those services even though the MA plan is being paid to provide them. The VA is not allowed to recoup its costs from Medicare. Thus, the government pays twice for the care of the same person.
A recent study reported > $78 billion in duplicate VA-MA spending between 2011 and 2020, with $12 billion in FY 2020. Kizer and Ibrahim suggest the current VA-MA duplicate spending is likely to be significantly more than the reported amounts.
“[No] evidence shows that this duplicate spending yields a demonstrable health benefit for veterans, although undoubtedly it benefits the financial well-being of the MA plans,” they write.
It’s a “challenging policy and programmatic conundrum,” the co-authors say, noting that eligible veterans often have military service-related conditions that the VA is uniquely experienced in treating.
“Policies and programs need to be designed and aligned to ensure that veterans have timely access to emergency and other services and that rising community care costs do not jeopardize veterans’ choice to access and use VA services, nor compromise the nationally vital roles of the VA in graduate medical education and other health professional training, research, and emergency preparedness.”
In Fiscal Year (FY) 2023, > 40% of veterans enrolled by the US Department of Veterans Affairs (VA) received care from private practice, mainly for emergency services. Costs associated with that care have shifted from Medicare to the VA to the tune of billions of dollars, according to a recent study published in JAMA Health Forum.
The expenses are a result of the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act of 2018, which established the Veterans Community Care Program (VCCP) and allowed the VA to contract with private clinicians. This provided veterans enrolled in both the Veterans Health Administration (VHA) and Medicare to have 2 government sources of health care financing. The VHA is billed if the veteran receives care at one of its facilities or is referred to a community facility; Medicare is billed only if the veteran is treated for a service not covered by VHA.
These shifts are concerning, according to Kenneth W. Kizer, MD, MPH, and Said Ibrahim, MD, MPH. In an accompanying editorial, they outline how the changes affect whether VHA care will have adequate funding to provide care for the additional 740,000 enrollees who have entered the system in the past 2 years.
“This has created a $12 billion medical care budget shortfall for FY 2024,” Kizer and Ibrahim argue. The resulting “substantial budgetary tumult … is adversely impacting the front lines of care delivery at individual VA facilities, leading to delays in hiring caregivers and impeding access to VA care and timely care delivery, as well as greatly straining the traditional roles of VA staff and clinicians trying to manage the challenging cross-system referral processes.”
The study calculated the number of yearly emergency department (ED) visits per 1000 veterans in Medicare overall and by VA ED visits, VA-purchased community ED visits, and Medicare-purchased community ED visits. Estimated total costs shifted from Medicare to the VA after the MISSION Act between 2016 and 2021 were then calculated.
Of the 4,960,189 VA and Medicare enrollees in 2016, 37.0% presented to the ED at least once. Of the 4,837,436 dual enrollees in 2021, 37.6% presented to the ED at least once. ED visits increased 8%, from 820 per 1000 veterans in 2016, to 886 per 1000 veterans in 2019. The COVID-19 pandemic caused a dip in ED visits in 2020 by veterans (769 per 1000), but the number rose 2021 (852 per 1000 veterans).
Between 2016 and 2021, the percentage of VA-purchased community ED visits more than doubled, from 8.0% to 21.1%, while Medicare-purchased community ED visits dropped from 65.2% to 52.6%. Patterns were similar among veterans enrolled in traditional Medicare vs Medicare Advantage (MA). The study estimated that in 2021 at least $2 billion of VA community ED spending was due to payer shift from Medicare.
The shift is “particularly concerning” among veterans enrolled in MA since insurance plans receive capitated payments regardless of actual use of VA- or Medicare-covered services. However, the study’s observational design “limited our ability to infer causality between MISSION Act implementation and payer change.”
The cost shifting is “symptomatic of the fiscally undisciplined implementation of the VCCP and the lack of financially sound policy on payment for VA-Medicare dual enrollees,” according to Drs. Kizer and Ibrahim. “Addressing this matter seems especially important in light of numerous studies showing that the quality of community care often may be inferior to VA care, as well as less timely.”
Kizer and Ibrahim point out that when a veteran who is jointly enrolled in VA and MA plans receives care from the VA, the VA incurs the cost of providing those services even though the MA plan is being paid to provide them. The VA is not allowed to recoup its costs from Medicare. Thus, the government pays twice for the care of the same person.
A recent study reported > $78 billion in duplicate VA-MA spending between 2011 and 2020, with $12 billion in FY 2020. Kizer and Ibrahim suggest the current VA-MA duplicate spending is likely to be significantly more than the reported amounts.
“[No] evidence shows that this duplicate spending yields a demonstrable health benefit for veterans, although undoubtedly it benefits the financial well-being of the MA plans,” they write.
It’s a “challenging policy and programmatic conundrum,” the co-authors say, noting that eligible veterans often have military service-related conditions that the VA is uniquely experienced in treating.
“Policies and programs need to be designed and aligned to ensure that veterans have timely access to emergency and other services and that rising community care costs do not jeopardize veterans’ choice to access and use VA services, nor compromise the nationally vital roles of the VA in graduate medical education and other health professional training, research, and emergency preparedness.”
In Fiscal Year (FY) 2023, > 40% of veterans enrolled by the US Department of Veterans Affairs (VA) received care from private practice, mainly for emergency services. Costs associated with that care have shifted from Medicare to the VA to the tune of billions of dollars, according to a recent study published in JAMA Health Forum.
The expenses are a result of the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act of 2018, which established the Veterans Community Care Program (VCCP) and allowed the VA to contract with private clinicians. This provided veterans enrolled in both the Veterans Health Administration (VHA) and Medicare to have 2 government sources of health care financing. The VHA is billed if the veteran receives care at one of its facilities or is referred to a community facility; Medicare is billed only if the veteran is treated for a service not covered by VHA.
These shifts are concerning, according to Kenneth W. Kizer, MD, MPH, and Said Ibrahim, MD, MPH. In an accompanying editorial, they outline how the changes affect whether VHA care will have adequate funding to provide care for the additional 740,000 enrollees who have entered the system in the past 2 years.
“This has created a $12 billion medical care budget shortfall for FY 2024,” Kizer and Ibrahim argue. The resulting “substantial budgetary tumult … is adversely impacting the front lines of care delivery at individual VA facilities, leading to delays in hiring caregivers and impeding access to VA care and timely care delivery, as well as greatly straining the traditional roles of VA staff and clinicians trying to manage the challenging cross-system referral processes.”
The study calculated the number of yearly emergency department (ED) visits per 1000 veterans in Medicare overall and by VA ED visits, VA-purchased community ED visits, and Medicare-purchased community ED visits. Estimated total costs shifted from Medicare to the VA after the MISSION Act between 2016 and 2021 were then calculated.
Of the 4,960,189 VA and Medicare enrollees in 2016, 37.0% presented to the ED at least once. Of the 4,837,436 dual enrollees in 2021, 37.6% presented to the ED at least once. ED visits increased 8%, from 820 per 1000 veterans in 2016, to 886 per 1000 veterans in 2019. The COVID-19 pandemic caused a dip in ED visits in 2020 by veterans (769 per 1000), but the number rose 2021 (852 per 1000 veterans).
Between 2016 and 2021, the percentage of VA-purchased community ED visits more than doubled, from 8.0% to 21.1%, while Medicare-purchased community ED visits dropped from 65.2% to 52.6%. Patterns were similar among veterans enrolled in traditional Medicare vs Medicare Advantage (MA). The study estimated that in 2021 at least $2 billion of VA community ED spending was due to payer shift from Medicare.
The shift is “particularly concerning” among veterans enrolled in MA since insurance plans receive capitated payments regardless of actual use of VA- or Medicare-covered services. However, the study’s observational design “limited our ability to infer causality between MISSION Act implementation and payer change.”
The cost shifting is “symptomatic of the fiscally undisciplined implementation of the VCCP and the lack of financially sound policy on payment for VA-Medicare dual enrollees,” according to Drs. Kizer and Ibrahim. “Addressing this matter seems especially important in light of numerous studies showing that the quality of community care often may be inferior to VA care, as well as less timely.”
Kizer and Ibrahim point out that when a veteran who is jointly enrolled in VA and MA plans receives care from the VA, the VA incurs the cost of providing those services even though the MA plan is being paid to provide them. The VA is not allowed to recoup its costs from Medicare. Thus, the government pays twice for the care of the same person.
A recent study reported > $78 billion in duplicate VA-MA spending between 2011 and 2020, with $12 billion in FY 2020. Kizer and Ibrahim suggest the current VA-MA duplicate spending is likely to be significantly more than the reported amounts.
“[No] evidence shows that this duplicate spending yields a demonstrable health benefit for veterans, although undoubtedly it benefits the financial well-being of the MA plans,” they write.
It’s a “challenging policy and programmatic conundrum,” the co-authors say, noting that eligible veterans often have military service-related conditions that the VA is uniquely experienced in treating.
“Policies and programs need to be designed and aligned to ensure that veterans have timely access to emergency and other services and that rising community care costs do not jeopardize veterans’ choice to access and use VA services, nor compromise the nationally vital roles of the VA in graduate medical education and other health professional training, research, and emergency preparedness.”
Updated Alzheimer’s Guidelines Chart the Full Diagnostic Journey
This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.
What’s New?
“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.
“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.
Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.
Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.
What Are the Key Recommendations?
The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations:
Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.
Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.
Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.
History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.
Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.
Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.
Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.
Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.
Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.
Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.
Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.
Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.
Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.
Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.
Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.
Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.
Future Directions?
Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.
“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.
Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.”
However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.
New Appropriate Use Guidance
A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.
They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.
“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.
The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.
Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.
“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.
“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.
The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.
In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”
This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.
A version of this article first appeared on Medscape.com.
This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.
What’s New?
“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.
“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.
Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.
Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.
What Are the Key Recommendations?
The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations:
Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.
Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.
Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.
History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.
Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.
Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.
Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.
Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.
Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.
Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.
Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.
Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.
Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.
Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.
Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.
Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.
Future Directions?
Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.
“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.
Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.”
However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.
New Appropriate Use Guidance
A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.
They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.
“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.
The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.
Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.
“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.
“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.
The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.
In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”
This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.
A version of this article first appeared on Medscape.com.
This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.
What’s New?
“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.
“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.
Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.
Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.
What Are the Key Recommendations?
The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations:
Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.
Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.
Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.
History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.
Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.
Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.
Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.
Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.
Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.
Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.
Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.
Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.
Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.
Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.
Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.
Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.
Future Directions?
Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.
“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.
Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.”
However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.
New Appropriate Use Guidance
A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.
They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.
“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.
The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.
Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.
“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.
“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.
The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.
In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”
This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.
A version of this article first appeared on Medscape.com.
FROM ALZHEIMER’S & DEMENTIA
Murthy Offers Hope as Tenure Ends
In his parting words as US Surgeon General, Vivek Murthy, MD, MBA, urges togetherness as it works through current and future issues, as opposed to continuing down the path of divisiveness.
“Today, we are faced with a profound choice: do we continue with the status quo, marked by pain, disconnection, and division? Or do we choose a different path—one of joy, health, and fulfillment where we turn toward each other instead of away from each other, where we choose love over fear; where we recognize community as the irreplaceable foundation for our well-being?” Murthy writes in his Jan. 7 valedictory essay. “As I finish my tenure as Surgeon General, this is my parting prescription, my final wish for all of us: choose community.”
Murthy based his essay on personal and professional experiences from his tenures as the 19th and 21st US Surgeon General. He outlines his individual perspective on the root causes of widespread pain and unhappiness he has seen across America and offers a prescription for how we can “cultivate health and fulfillment.”
The core pillars of community—relationships, service, and purpose—are powerful drivers of fulfillment, Murthy writes, because “community is a powerful source of life satisfaction and life expectancy.” In his essay, he describes how these elements affect our health.
Relationships can be a powerful source of joy and support. They can act as buffers to stress and break down the barriers of loneliness and improve your overall health. According to Murthy, one-third of adults and one-half of young people experience loneliness; and social disconnectedness increases the risk of heart disease, dementia, depression, anxiety, and premature death.
Service comprises the actions we take that benefit others. Research shows that sustained service efforts can reduce the risk of hypertension, stroke, early death, depression, and cognitive decline.
And purpose is the feeling of having an overarching life aim to guide our decisions and actions. Simply, it is the “why” we do something, and according to Murthy, a high sense of individual purpose may reduce the risk of early death as well as stroke, lung disease, and dementia.
Building community isn’t always easy, Murthy wrote. It requires “rethinking and, in some cases, rejecting the conventional wisdom that tells us what defines success and a good life.” At the conclusion of his essay, Murthy notes how choices we make now must be made with an eye toward the future.
“The choice we make to build community has the power to change lives and transform society,” he writes. “Let us never forget that good people with hearts full of love can change the world.”
In his parting words as US Surgeon General, Vivek Murthy, MD, MBA, urges togetherness as it works through current and future issues, as opposed to continuing down the path of divisiveness.
“Today, we are faced with a profound choice: do we continue with the status quo, marked by pain, disconnection, and division? Or do we choose a different path—one of joy, health, and fulfillment where we turn toward each other instead of away from each other, where we choose love over fear; where we recognize community as the irreplaceable foundation for our well-being?” Murthy writes in his Jan. 7 valedictory essay. “As I finish my tenure as Surgeon General, this is my parting prescription, my final wish for all of us: choose community.”
Murthy based his essay on personal and professional experiences from his tenures as the 19th and 21st US Surgeon General. He outlines his individual perspective on the root causes of widespread pain and unhappiness he has seen across America and offers a prescription for how we can “cultivate health and fulfillment.”
The core pillars of community—relationships, service, and purpose—are powerful drivers of fulfillment, Murthy writes, because “community is a powerful source of life satisfaction and life expectancy.” In his essay, he describes how these elements affect our health.
Relationships can be a powerful source of joy and support. They can act as buffers to stress and break down the barriers of loneliness and improve your overall health. According to Murthy, one-third of adults and one-half of young people experience loneliness; and social disconnectedness increases the risk of heart disease, dementia, depression, anxiety, and premature death.
Service comprises the actions we take that benefit others. Research shows that sustained service efforts can reduce the risk of hypertension, stroke, early death, depression, and cognitive decline.
And purpose is the feeling of having an overarching life aim to guide our decisions and actions. Simply, it is the “why” we do something, and according to Murthy, a high sense of individual purpose may reduce the risk of early death as well as stroke, lung disease, and dementia.
Building community isn’t always easy, Murthy wrote. It requires “rethinking and, in some cases, rejecting the conventional wisdom that tells us what defines success and a good life.” At the conclusion of his essay, Murthy notes how choices we make now must be made with an eye toward the future.
“The choice we make to build community has the power to change lives and transform society,” he writes. “Let us never forget that good people with hearts full of love can change the world.”
In his parting words as US Surgeon General, Vivek Murthy, MD, MBA, urges togetherness as it works through current and future issues, as opposed to continuing down the path of divisiveness.
“Today, we are faced with a profound choice: do we continue with the status quo, marked by pain, disconnection, and division? Or do we choose a different path—one of joy, health, and fulfillment where we turn toward each other instead of away from each other, where we choose love over fear; where we recognize community as the irreplaceable foundation for our well-being?” Murthy writes in his Jan. 7 valedictory essay. “As I finish my tenure as Surgeon General, this is my parting prescription, my final wish for all of us: choose community.”
Murthy based his essay on personal and professional experiences from his tenures as the 19th and 21st US Surgeon General. He outlines his individual perspective on the root causes of widespread pain and unhappiness he has seen across America and offers a prescription for how we can “cultivate health and fulfillment.”
The core pillars of community—relationships, service, and purpose—are powerful drivers of fulfillment, Murthy writes, because “community is a powerful source of life satisfaction and life expectancy.” In his essay, he describes how these elements affect our health.
Relationships can be a powerful source of joy and support. They can act as buffers to stress and break down the barriers of loneliness and improve your overall health. According to Murthy, one-third of adults and one-half of young people experience loneliness; and social disconnectedness increases the risk of heart disease, dementia, depression, anxiety, and premature death.
Service comprises the actions we take that benefit others. Research shows that sustained service efforts can reduce the risk of hypertension, stroke, early death, depression, and cognitive decline.
And purpose is the feeling of having an overarching life aim to guide our decisions and actions. Simply, it is the “why” we do something, and according to Murthy, a high sense of individual purpose may reduce the risk of early death as well as stroke, lung disease, and dementia.
Building community isn’t always easy, Murthy wrote. It requires “rethinking and, in some cases, rejecting the conventional wisdom that tells us what defines success and a good life.” At the conclusion of his essay, Murthy notes how choices we make now must be made with an eye toward the future.
“The choice we make to build community has the power to change lives and transform society,” he writes. “Let us never forget that good people with hearts full of love can change the world.”
Commission Issues ‘Radical Overhaul’ of Obesity Diagnosis
“We propose a radical overhaul of the actual diagnosis of obesity to improve global healthcare and practices and policies. The specific aims were to facilitate individualized assessment and care of people living with obesity while preserving resources by reducing overdiagnosis and unnecessary or inadequate interventions,” Professor Louise Baur, chair of Child & Adolescent Health at the University of Sydney, Australia, said during a UK Science Media Centre (SMC) news briefing.
The report calls first for a diagnosis of obesity via confirmation of excess adiposity using measures such as waist circumference or waist-to-hip ratio in addition to BMI. Next, a clinical assessment of signs and symptoms of organ dysfunction due to obesity and/or functional limitations determines whether the individual has the disease “clinical obesity,” or “preclinical obesity,” a condition of health risk but not an illness itself.
Published on January 14, 2025, in The Lancet Diabetes & Endocrinology, the document also provides broad guidance on management for the two obesity conditions, emphasizing a personalized and stigma-free approach. The Lancet Commission on Obesity comprised 56 experts in relevant fields including endocrinology, surgery, nutrition, and public health, along with people living with obesity.
The report has been endorsed by more than 75 medical organizations, including the Association of British Clinical Diabetologists, the American Association of Clinical Endocrinologists, the American Diabetes Association, the American Heart Association, the Obesity Society, the World Obesity Federation, and obesity and endocrinology societies from countries in Europe, Latin America, Asia, and South Africa.
In recent years, many in the field have found fault with the current BMI-based definition of obesity (> 30 for people of European descent or other cutoffs for specific ethnic groups), primarily because BMI alone doesn’t reflect a person’s fat vs lean mass, fat distribution, or overall health. The new definition aims to overcome these limitations, as well as settle the debate about whether obesity is a “disease.”
“We now have a clinical diagnosis for obesity, which has been lacking. ... The traditional classification based on BMI ... reflects simply whether or not there is excess adiposity, and sometimes not even precise in that regard, either…It has never been a classification that was meant to diagnose a specific illness with its own clinical characteristics in the same way we diagnose any other illness,” Commission Chair Francesco Rubino, MD, professor and chair of Metabolic and Bariatric Surgery at King’s College London, England, said in an interview.
He added, “The fact that now we have a clinical diagnosis allows recognition of the nuance that obesity is generally a risk and for some can be an illness. There are some who have risk but don’t have the illness here and now. And it’s crucially important for clinical decision-making, but also for policies to have a distinction between those two things because the treatment strategy for one and the other are substantially different.”
Asked to comment, obesity specialist Michael A. Weintraub, MD, clinical assistant professor of endocrinology at New York University Langone Health, said in an interview, “I wholeheartedly agree with modifying the definition of obesity in this more accurate way. ... There has already been a lot of talk about the fallibility of BMI and that BMI over 30 does not equal obesity. ... So a major Commission article like this I think can really move those discussions even more into the forefront and start changing practice.”
However, Weintraub added, “I think there needs to be another step here of more practical guidance on how to actually implement this ... including how to measure waist circumference and to put it into a patient flow.”
Asked to comment, obesity expert Luca Busetto, MD, associate professor of internal medicine at the Department of Medicine of the University of Padova, Italy, said in an interview that he agrees with the general concept of moving beyond BMI in defining obesity. That view was expressed in a proposed “framework” from the European Association for the Study of Obesity (EASO), for which Busetto was the lead author.
Busetto also agrees with the emphasis on the need for a complete clinical evaluation of patients to define their health status. “The precise definition of the symptoms defining clinical obesity in adults and children is extremely important, emphasizing the fact that obesity is a severe and disabling disease by itself, even without or before the occurrence of obesity-related complications,” he said.
However, he takes issue with the Commission’s designation that “preclinical” obesity is not a disease. “The critical point of disagreement for me is the message that obesity is a disease only if it is clinical or only if it presents functional impairment or clinical symptoms. This remains, in my opinion, an oversimplification, not taking into account the fact that the pathophysiological mechanisms that lead to fat accumulation and ‘adipose tissue-based chronic disease’ usually start well before the occurrence of symptoms.”
Busetto pointed to examples such as type 2 diabetes and chronic kidney disease, both of which can be asymptomatic in their early phases yet are still considered diseases at those points. “I have no problem in accepting a distinction between preclinical and clinical stages of the disease, and I like the definition of clinical obesity, but why should this imply the fact that obesity is NOT a disease since its beginning?”
The Commission does state that preclinical obesity should be addressed, mostly with preventive approaches but in some cases with more intensive management. “This is highly relevant, but the risk of an undertreatment of obesity in its asymptomatic state remains in place. This could delay appropriate management for a progressive disease that certainly should not be treated only when presenting symptoms. It would be too late,” Busetto said.
And EASO framework coauthor Gijs Goossens, PhD, professor of cardiometabolic physiology of obesity at Maastricht University Medical Centre, the Netherlands, added a concern that those with excess adiposity but lower BMI might be missed entirely, noting “Since abdominal fat accumulation better predicts chronic cardiometabolic diseases and can also be accompanied by clinical manifestations in individuals with overweight as a consequence of compromised adipose tissue function, the proposed model may lead to underdiagnosis or undertreatment in individuals with BMI 25-30 who have excess abdominal fat.”
Diagnosis and Management Beyond BMI
The Commission advises the use of BMI solely as a marker to screen for potential obesity. Those with a BMI > 40 can be assumed to have excess body fat. For others with a BMI at or near the threshold for obesity in a specific country or ethnic group or for whom there is the clinical judgment of the potential for clinical obesity, confirmation of excess or abnormal adiposity is needed by one of the following:
- At least one measurement of body size and BMI
- At least two measures of body size, regardless of BMI
- Direct body fat measurement, such as a dual-energy x-ray absorptiometry (DEXA) scan
Measurement of body size can be assessed in three ways:
- Waist circumference ≥ 102 cm for men and ≥ 88 cm for women
- Waist-to-hip ratio > 0.90 for men and > 0.50 for women
- Waist-to-height ratio > 0.50 for all.
Weintraub noted, “Telemedicine is a useful tool used by many patients and providers but may also make it challenging to accurately assess someone’s body size. Having technology like an iPhone app to measure body size would circumvent this challenge but this type of tool has not yet been validated.”
If the person does not have excess adiposity, they don’t have obesity. Those with excess adiposity do have obesity. Further assessment is then needed to establish whether the person has an illness, that is, clinical obesity, indicated by signs/symptoms of organ dysfunction, and/or limitations of daily activities. If not, they have “preclinical” obesity.
The document provides a list of 18 obesity-related organ, tissue, and body system criteria for diagnosing “clinical” obesity in adults, including upper airways (eg, apneas/hypopneas), respiratory (breathlessness), cardiovascular (hypertension, heart failure), liver (fatty liver disease with hepatic fibrosis), reproductive (polycystic ovary syndrome, hypogonadism), and metabolism (hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol). A list of 13 such criteria is also provided for children. “Limitations of day-to-day activities” are included on both lists.
Management Differs by Designation
For preclinical obesity, management should focus on risk reduction and prevention of progression to clinical obesity or other obesity-related diseases. Such approaches include health counseling for weight loss or prevention of weight gain, monitoring over time, and active weight loss interventions in people at higher risk of developing clinical obesity and other obesity-related diseases.
Management for clinical obesity focuses on improvements or reversal of the organ dysfunction. The type of evidence-based treatment and management should be informed by individual risk-benefit assessments and decided via “active discussion” with the patient. Success is determined by improvement in the signs and symptoms rather than measures of weight loss.
In response to a reporter’s question at the SMC briefing about the implications for the use of weight-loss medications, Rubino noted that this wasn’t the focus of the report, but nonetheless said that this new obesity definition could help with their targeted use. “The strategy and intent by which you use the drugs is different in clinical and preclinical obesity. ... Pharmacological interventions could be used for patients with high-risk preclinical obesity, with the intent of reducing risk, but we ... would use the same medication at a different intensity, dose, and maybe in combination therapies.”
As for clinical obesity, “It could be more or less severe and could affect more than one organ, and so clinical obesity might require drugs, might require surgery, or may require, in some cases, a combination of both of them, to achieve the best possible outcomes. ... We want to make sure that the person is restoring health ... with whatever it takes.”
Rubino believes this new definition will convince the remaining clinicians who haven’t yet accepted the concept of obesity as a disease. “When they see clinical obesity, I think it will be much harder to say that a biological process that is capable of causing a dysfunction in the heart or the lungs is less of a disease than another biological process that causes similar dysfunction in the heart of the lungs. ... It’s going to be objective. Obesity is a spectrum of different situations. ... When it’s an illness, clinical obesity, it’s not a matter of if or when. It’s a matter of fact.”
There were no industrial grants or other funding for this initiative. King’s Health Partners hosted the initiative and provided logistical and personnel support to facilitate administrative work and the Delphi-like consensus-development process. Rubino declared receiving research grants from Ethicon (Johnson & Johnson), Novo Nordisk, and Medtronic; consulting fees from Morphic Medical; speaking honoraria from Medtronic, Ethicon, Novo Nordisk, Eli Lilly, and Amgen. Rubino has served (unpaid) as a member of the scientific advisory board for Keyron and a member of the data safety and monitoring board for GI Metabolic Solutions; is president of the Metabolic Health Institute (non-profit); and is the sole director of Metabolic Health International and London Metabolic and Bariatric Surgery (private practice). Baur declared serving on the scientific advisory board for Novo Nordisk (for the ACTION Teens study) and Eli Lilly and receiving speaker fees (paid to the institution) from Novo Nordisk.
A version of this article first appeared on Medscape.com.
“We propose a radical overhaul of the actual diagnosis of obesity to improve global healthcare and practices and policies. The specific aims were to facilitate individualized assessment and care of people living with obesity while preserving resources by reducing overdiagnosis and unnecessary or inadequate interventions,” Professor Louise Baur, chair of Child & Adolescent Health at the University of Sydney, Australia, said during a UK Science Media Centre (SMC) news briefing.
The report calls first for a diagnosis of obesity via confirmation of excess adiposity using measures such as waist circumference or waist-to-hip ratio in addition to BMI. Next, a clinical assessment of signs and symptoms of organ dysfunction due to obesity and/or functional limitations determines whether the individual has the disease “clinical obesity,” or “preclinical obesity,” a condition of health risk but not an illness itself.
Published on January 14, 2025, in The Lancet Diabetes & Endocrinology, the document also provides broad guidance on management for the two obesity conditions, emphasizing a personalized and stigma-free approach. The Lancet Commission on Obesity comprised 56 experts in relevant fields including endocrinology, surgery, nutrition, and public health, along with people living with obesity.
The report has been endorsed by more than 75 medical organizations, including the Association of British Clinical Diabetologists, the American Association of Clinical Endocrinologists, the American Diabetes Association, the American Heart Association, the Obesity Society, the World Obesity Federation, and obesity and endocrinology societies from countries in Europe, Latin America, Asia, and South Africa.
In recent years, many in the field have found fault with the current BMI-based definition of obesity (> 30 for people of European descent or other cutoffs for specific ethnic groups), primarily because BMI alone doesn’t reflect a person’s fat vs lean mass, fat distribution, or overall health. The new definition aims to overcome these limitations, as well as settle the debate about whether obesity is a “disease.”
“We now have a clinical diagnosis for obesity, which has been lacking. ... The traditional classification based on BMI ... reflects simply whether or not there is excess adiposity, and sometimes not even precise in that regard, either…It has never been a classification that was meant to diagnose a specific illness with its own clinical characteristics in the same way we diagnose any other illness,” Commission Chair Francesco Rubino, MD, professor and chair of Metabolic and Bariatric Surgery at King’s College London, England, said in an interview.
He added, “The fact that now we have a clinical diagnosis allows recognition of the nuance that obesity is generally a risk and for some can be an illness. There are some who have risk but don’t have the illness here and now. And it’s crucially important for clinical decision-making, but also for policies to have a distinction between those two things because the treatment strategy for one and the other are substantially different.”
Asked to comment, obesity specialist Michael A. Weintraub, MD, clinical assistant professor of endocrinology at New York University Langone Health, said in an interview, “I wholeheartedly agree with modifying the definition of obesity in this more accurate way. ... There has already been a lot of talk about the fallibility of BMI and that BMI over 30 does not equal obesity. ... So a major Commission article like this I think can really move those discussions even more into the forefront and start changing practice.”
However, Weintraub added, “I think there needs to be another step here of more practical guidance on how to actually implement this ... including how to measure waist circumference and to put it into a patient flow.”
Asked to comment, obesity expert Luca Busetto, MD, associate professor of internal medicine at the Department of Medicine of the University of Padova, Italy, said in an interview that he agrees with the general concept of moving beyond BMI in defining obesity. That view was expressed in a proposed “framework” from the European Association for the Study of Obesity (EASO), for which Busetto was the lead author.
Busetto also agrees with the emphasis on the need for a complete clinical evaluation of patients to define their health status. “The precise definition of the symptoms defining clinical obesity in adults and children is extremely important, emphasizing the fact that obesity is a severe and disabling disease by itself, even without or before the occurrence of obesity-related complications,” he said.
However, he takes issue with the Commission’s designation that “preclinical” obesity is not a disease. “The critical point of disagreement for me is the message that obesity is a disease only if it is clinical or only if it presents functional impairment or clinical symptoms. This remains, in my opinion, an oversimplification, not taking into account the fact that the pathophysiological mechanisms that lead to fat accumulation and ‘adipose tissue-based chronic disease’ usually start well before the occurrence of symptoms.”
Busetto pointed to examples such as type 2 diabetes and chronic kidney disease, both of which can be asymptomatic in their early phases yet are still considered diseases at those points. “I have no problem in accepting a distinction between preclinical and clinical stages of the disease, and I like the definition of clinical obesity, but why should this imply the fact that obesity is NOT a disease since its beginning?”
The Commission does state that preclinical obesity should be addressed, mostly with preventive approaches but in some cases with more intensive management. “This is highly relevant, but the risk of an undertreatment of obesity in its asymptomatic state remains in place. This could delay appropriate management for a progressive disease that certainly should not be treated only when presenting symptoms. It would be too late,” Busetto said.
And EASO framework coauthor Gijs Goossens, PhD, professor of cardiometabolic physiology of obesity at Maastricht University Medical Centre, the Netherlands, added a concern that those with excess adiposity but lower BMI might be missed entirely, noting “Since abdominal fat accumulation better predicts chronic cardiometabolic diseases and can also be accompanied by clinical manifestations in individuals with overweight as a consequence of compromised adipose tissue function, the proposed model may lead to underdiagnosis or undertreatment in individuals with BMI 25-30 who have excess abdominal fat.”
Diagnosis and Management Beyond BMI
The Commission advises the use of BMI solely as a marker to screen for potential obesity. Those with a BMI > 40 can be assumed to have excess body fat. For others with a BMI at or near the threshold for obesity in a specific country or ethnic group or for whom there is the clinical judgment of the potential for clinical obesity, confirmation of excess or abnormal adiposity is needed by one of the following:
- At least one measurement of body size and BMI
- At least two measures of body size, regardless of BMI
- Direct body fat measurement, such as a dual-energy x-ray absorptiometry (DEXA) scan
Measurement of body size can be assessed in three ways:
- Waist circumference ≥ 102 cm for men and ≥ 88 cm for women
- Waist-to-hip ratio > 0.90 for men and > 0.50 for women
- Waist-to-height ratio > 0.50 for all.
Weintraub noted, “Telemedicine is a useful tool used by many patients and providers but may also make it challenging to accurately assess someone’s body size. Having technology like an iPhone app to measure body size would circumvent this challenge but this type of tool has not yet been validated.”
If the person does not have excess adiposity, they don’t have obesity. Those with excess adiposity do have obesity. Further assessment is then needed to establish whether the person has an illness, that is, clinical obesity, indicated by signs/symptoms of organ dysfunction, and/or limitations of daily activities. If not, they have “preclinical” obesity.
The document provides a list of 18 obesity-related organ, tissue, and body system criteria for diagnosing “clinical” obesity in adults, including upper airways (eg, apneas/hypopneas), respiratory (breathlessness), cardiovascular (hypertension, heart failure), liver (fatty liver disease with hepatic fibrosis), reproductive (polycystic ovary syndrome, hypogonadism), and metabolism (hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol). A list of 13 such criteria is also provided for children. “Limitations of day-to-day activities” are included on both lists.
Management Differs by Designation
For preclinical obesity, management should focus on risk reduction and prevention of progression to clinical obesity or other obesity-related diseases. Such approaches include health counseling for weight loss or prevention of weight gain, monitoring over time, and active weight loss interventions in people at higher risk of developing clinical obesity and other obesity-related diseases.
Management for clinical obesity focuses on improvements or reversal of the organ dysfunction. The type of evidence-based treatment and management should be informed by individual risk-benefit assessments and decided via “active discussion” with the patient. Success is determined by improvement in the signs and symptoms rather than measures of weight loss.
In response to a reporter’s question at the SMC briefing about the implications for the use of weight-loss medications, Rubino noted that this wasn’t the focus of the report, but nonetheless said that this new obesity definition could help with their targeted use. “The strategy and intent by which you use the drugs is different in clinical and preclinical obesity. ... Pharmacological interventions could be used for patients with high-risk preclinical obesity, with the intent of reducing risk, but we ... would use the same medication at a different intensity, dose, and maybe in combination therapies.”
As for clinical obesity, “It could be more or less severe and could affect more than one organ, and so clinical obesity might require drugs, might require surgery, or may require, in some cases, a combination of both of them, to achieve the best possible outcomes. ... We want to make sure that the person is restoring health ... with whatever it takes.”
Rubino believes this new definition will convince the remaining clinicians who haven’t yet accepted the concept of obesity as a disease. “When they see clinical obesity, I think it will be much harder to say that a biological process that is capable of causing a dysfunction in the heart or the lungs is less of a disease than another biological process that causes similar dysfunction in the heart of the lungs. ... It’s going to be objective. Obesity is a spectrum of different situations. ... When it’s an illness, clinical obesity, it’s not a matter of if or when. It’s a matter of fact.”
There were no industrial grants or other funding for this initiative. King’s Health Partners hosted the initiative and provided logistical and personnel support to facilitate administrative work and the Delphi-like consensus-development process. Rubino declared receiving research grants from Ethicon (Johnson & Johnson), Novo Nordisk, and Medtronic; consulting fees from Morphic Medical; speaking honoraria from Medtronic, Ethicon, Novo Nordisk, Eli Lilly, and Amgen. Rubino has served (unpaid) as a member of the scientific advisory board for Keyron and a member of the data safety and monitoring board for GI Metabolic Solutions; is president of the Metabolic Health Institute (non-profit); and is the sole director of Metabolic Health International and London Metabolic and Bariatric Surgery (private practice). Baur declared serving on the scientific advisory board for Novo Nordisk (for the ACTION Teens study) and Eli Lilly and receiving speaker fees (paid to the institution) from Novo Nordisk.
A version of this article first appeared on Medscape.com.
“We propose a radical overhaul of the actual diagnosis of obesity to improve global healthcare and practices and policies. The specific aims were to facilitate individualized assessment and care of people living with obesity while preserving resources by reducing overdiagnosis and unnecessary or inadequate interventions,” Professor Louise Baur, chair of Child & Adolescent Health at the University of Sydney, Australia, said during a UK Science Media Centre (SMC) news briefing.
The report calls first for a diagnosis of obesity via confirmation of excess adiposity using measures such as waist circumference or waist-to-hip ratio in addition to BMI. Next, a clinical assessment of signs and symptoms of organ dysfunction due to obesity and/or functional limitations determines whether the individual has the disease “clinical obesity,” or “preclinical obesity,” a condition of health risk but not an illness itself.
Published on January 14, 2025, in The Lancet Diabetes & Endocrinology, the document also provides broad guidance on management for the two obesity conditions, emphasizing a personalized and stigma-free approach. The Lancet Commission on Obesity comprised 56 experts in relevant fields including endocrinology, surgery, nutrition, and public health, along with people living with obesity.
The report has been endorsed by more than 75 medical organizations, including the Association of British Clinical Diabetologists, the American Association of Clinical Endocrinologists, the American Diabetes Association, the American Heart Association, the Obesity Society, the World Obesity Federation, and obesity and endocrinology societies from countries in Europe, Latin America, Asia, and South Africa.
In recent years, many in the field have found fault with the current BMI-based definition of obesity (> 30 for people of European descent or other cutoffs for specific ethnic groups), primarily because BMI alone doesn’t reflect a person’s fat vs lean mass, fat distribution, or overall health. The new definition aims to overcome these limitations, as well as settle the debate about whether obesity is a “disease.”
“We now have a clinical diagnosis for obesity, which has been lacking. ... The traditional classification based on BMI ... reflects simply whether or not there is excess adiposity, and sometimes not even precise in that regard, either…It has never been a classification that was meant to diagnose a specific illness with its own clinical characteristics in the same way we diagnose any other illness,” Commission Chair Francesco Rubino, MD, professor and chair of Metabolic and Bariatric Surgery at King’s College London, England, said in an interview.
He added, “The fact that now we have a clinical diagnosis allows recognition of the nuance that obesity is generally a risk and for some can be an illness. There are some who have risk but don’t have the illness here and now. And it’s crucially important for clinical decision-making, but also for policies to have a distinction between those two things because the treatment strategy for one and the other are substantially different.”
Asked to comment, obesity specialist Michael A. Weintraub, MD, clinical assistant professor of endocrinology at New York University Langone Health, said in an interview, “I wholeheartedly agree with modifying the definition of obesity in this more accurate way. ... There has already been a lot of talk about the fallibility of BMI and that BMI over 30 does not equal obesity. ... So a major Commission article like this I think can really move those discussions even more into the forefront and start changing practice.”
However, Weintraub added, “I think there needs to be another step here of more practical guidance on how to actually implement this ... including how to measure waist circumference and to put it into a patient flow.”
Asked to comment, obesity expert Luca Busetto, MD, associate professor of internal medicine at the Department of Medicine of the University of Padova, Italy, said in an interview that he agrees with the general concept of moving beyond BMI in defining obesity. That view was expressed in a proposed “framework” from the European Association for the Study of Obesity (EASO), for which Busetto was the lead author.
Busetto also agrees with the emphasis on the need for a complete clinical evaluation of patients to define their health status. “The precise definition of the symptoms defining clinical obesity in adults and children is extremely important, emphasizing the fact that obesity is a severe and disabling disease by itself, even without or before the occurrence of obesity-related complications,” he said.
However, he takes issue with the Commission’s designation that “preclinical” obesity is not a disease. “The critical point of disagreement for me is the message that obesity is a disease only if it is clinical or only if it presents functional impairment or clinical symptoms. This remains, in my opinion, an oversimplification, not taking into account the fact that the pathophysiological mechanisms that lead to fat accumulation and ‘adipose tissue-based chronic disease’ usually start well before the occurrence of symptoms.”
Busetto pointed to examples such as type 2 diabetes and chronic kidney disease, both of which can be asymptomatic in their early phases yet are still considered diseases at those points. “I have no problem in accepting a distinction between preclinical and clinical stages of the disease, and I like the definition of clinical obesity, but why should this imply the fact that obesity is NOT a disease since its beginning?”
The Commission does state that preclinical obesity should be addressed, mostly with preventive approaches but in some cases with more intensive management. “This is highly relevant, but the risk of an undertreatment of obesity in its asymptomatic state remains in place. This could delay appropriate management for a progressive disease that certainly should not be treated only when presenting symptoms. It would be too late,” Busetto said.
And EASO framework coauthor Gijs Goossens, PhD, professor of cardiometabolic physiology of obesity at Maastricht University Medical Centre, the Netherlands, added a concern that those with excess adiposity but lower BMI might be missed entirely, noting “Since abdominal fat accumulation better predicts chronic cardiometabolic diseases and can also be accompanied by clinical manifestations in individuals with overweight as a consequence of compromised adipose tissue function, the proposed model may lead to underdiagnosis or undertreatment in individuals with BMI 25-30 who have excess abdominal fat.”
Diagnosis and Management Beyond BMI
The Commission advises the use of BMI solely as a marker to screen for potential obesity. Those with a BMI > 40 can be assumed to have excess body fat. For others with a BMI at or near the threshold for obesity in a specific country or ethnic group or for whom there is the clinical judgment of the potential for clinical obesity, confirmation of excess or abnormal adiposity is needed by one of the following:
- At least one measurement of body size and BMI
- At least two measures of body size, regardless of BMI
- Direct body fat measurement, such as a dual-energy x-ray absorptiometry (DEXA) scan
Measurement of body size can be assessed in three ways:
- Waist circumference ≥ 102 cm for men and ≥ 88 cm for women
- Waist-to-hip ratio > 0.90 for men and > 0.50 for women
- Waist-to-height ratio > 0.50 for all.
Weintraub noted, “Telemedicine is a useful tool used by many patients and providers but may also make it challenging to accurately assess someone’s body size. Having technology like an iPhone app to measure body size would circumvent this challenge but this type of tool has not yet been validated.”
If the person does not have excess adiposity, they don’t have obesity. Those with excess adiposity do have obesity. Further assessment is then needed to establish whether the person has an illness, that is, clinical obesity, indicated by signs/symptoms of organ dysfunction, and/or limitations of daily activities. If not, they have “preclinical” obesity.
The document provides a list of 18 obesity-related organ, tissue, and body system criteria for diagnosing “clinical” obesity in adults, including upper airways (eg, apneas/hypopneas), respiratory (breathlessness), cardiovascular (hypertension, heart failure), liver (fatty liver disease with hepatic fibrosis), reproductive (polycystic ovary syndrome, hypogonadism), and metabolism (hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol). A list of 13 such criteria is also provided for children. “Limitations of day-to-day activities” are included on both lists.
Management Differs by Designation
For preclinical obesity, management should focus on risk reduction and prevention of progression to clinical obesity or other obesity-related diseases. Such approaches include health counseling for weight loss or prevention of weight gain, monitoring over time, and active weight loss interventions in people at higher risk of developing clinical obesity and other obesity-related diseases.
Management for clinical obesity focuses on improvements or reversal of the organ dysfunction. The type of evidence-based treatment and management should be informed by individual risk-benefit assessments and decided via “active discussion” with the patient. Success is determined by improvement in the signs and symptoms rather than measures of weight loss.
In response to a reporter’s question at the SMC briefing about the implications for the use of weight-loss medications, Rubino noted that this wasn’t the focus of the report, but nonetheless said that this new obesity definition could help with their targeted use. “The strategy and intent by which you use the drugs is different in clinical and preclinical obesity. ... Pharmacological interventions could be used for patients with high-risk preclinical obesity, with the intent of reducing risk, but we ... would use the same medication at a different intensity, dose, and maybe in combination therapies.”
As for clinical obesity, “It could be more or less severe and could affect more than one organ, and so clinical obesity might require drugs, might require surgery, or may require, in some cases, a combination of both of them, to achieve the best possible outcomes. ... We want to make sure that the person is restoring health ... with whatever it takes.”
Rubino believes this new definition will convince the remaining clinicians who haven’t yet accepted the concept of obesity as a disease. “When they see clinical obesity, I think it will be much harder to say that a biological process that is capable of causing a dysfunction in the heart or the lungs is less of a disease than another biological process that causes similar dysfunction in the heart of the lungs. ... It’s going to be objective. Obesity is a spectrum of different situations. ... When it’s an illness, clinical obesity, it’s not a matter of if or when. It’s a matter of fact.”
There were no industrial grants or other funding for this initiative. King’s Health Partners hosted the initiative and provided logistical and personnel support to facilitate administrative work and the Delphi-like consensus-development process. Rubino declared receiving research grants from Ethicon (Johnson & Johnson), Novo Nordisk, and Medtronic; consulting fees from Morphic Medical; speaking honoraria from Medtronic, Ethicon, Novo Nordisk, Eli Lilly, and Amgen. Rubino has served (unpaid) as a member of the scientific advisory board for Keyron and a member of the data safety and monitoring board for GI Metabolic Solutions; is president of the Metabolic Health Institute (non-profit); and is the sole director of Metabolic Health International and London Metabolic and Bariatric Surgery (private practice). Baur declared serving on the scientific advisory board for Novo Nordisk (for the ACTION Teens study) and Eli Lilly and receiving speaker fees (paid to the institution) from Novo Nordisk.
A version of this article first appeared on Medscape.com.
FROM THE LANCET DIABETES & ENDOCRINOLOGY
Losing Your Mind Trying to Understand the BP-Dementia Link
You could be forgiven if you are confused about how blood pressure (BP) affects dementia. First, you read an article extolling the benefits of BP lowering, then a study about how stopping antihypertensives slows cognitive decline in nursing home residents. It’s enough to make you lose your mind.
The Brain Benefits of BP Lowering
It should be stated unequivocally that you should absolutely treat high BP. It may have once been acceptable to state, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.” But those dark days are long behind us.
In these divided times, at least we can agree that we should treat high BP. The cardiovascular (CV) benefits, in and of themselves, justify the decision. But BP’s relationship with dementia is more complex. There are different types of dementia even though we tend to lump them all into one category. Vascular dementia is driven by the same pathophysiology and risk factors as cardiac disease. It’s intuitive that treating hypertension, diabetes, hypercholesterolemia, and smoking will decrease the risk for stroke and limit the damage to the brain that we see with repeated vascular insults. For Alzheimer’s disease, high BP and other CV risk factors seem to increase the risk even if the mechanism is not fully elucidated.
Estimates suggest that if we could lower the prevalence of hypertension by 25%, there would be 160,000 fewer cases of Alzheimer’s disease. But the data are not as robust as one might hope. A 2021 Cochrane review found that hypertension treatment slowed cognitive decline, but the quality of the evidence was low. Short duration of follow-up, dropouts, crossovers, and other problems with the data precluded any certainty. What’s more, hypertension in midlife is associated with cognitive decline and dementia, but its impact in those over age 70 is less clear. Later in life, or once cognitive impairment has already developed, it may be too late for BP lowering to have any impact.
Potential Harms of Lowering BP
All this needs to be weighed against the potential harms of treating hypertension. I will reiterate that hypertension should be treated and treated aggressively for the prevention of CV events. But overtreatment, especially in older patients, is associated with hypotension, falls, and syncope. Older patients are also at risk for polypharmacy and drug-drug interactions.
A Korean nationwide survey showed a U-shaped association between BP and Alzheimer’s disease risk in adults (mean age, 67 years), with both high and low BPs associated with a higher risk for Alzheimer’s disease. Though not all studies agree. A post hoc analysis of SPRINT MIND did not find any negative impact of intensive BP lowering on cognitive outcomes or cerebral perfusion in older adults (mean age, 68 years). But it didn’t do much good either. Given the heterogeneity of the data, doubts remain on whether aggressive BP lowering might be detrimental in older patients with comorbidities and preexisting dementia. The obvious corollary then is whether deprescribing hypertensive medications could be beneficial.
A recent publication in JAMA Internal Medicine attempted to address this very question. The cohort study used data from Veterans Affairs nursing home residents (mean age, 78 years) to emulate a randomized trial on deprescribing antihypertensives and cognitive decline. Many of the residents’ cognitive scores worsened over the course of follow-up; however, the decline was less pronounced in the deprescribing group (10% vs 12%). The same group did a similar analysis looking at CV outcomes and found no increased risk for heart attack or stroke with deprescribing BP medications. Taken together, these nursing home data suggest that deprescribing may help slow cognitive decline without the expected trade-off of increased CV events.
Deprescribing, Yes or No?
However, randomized data would obviously be preferable, and these are in short supply. One such trial, the DANTE study, found no benefit to deprescribing in terms of cognition in adults aged 75 years or older with mild cognitive impairment. The study follow-up was only 16 weeks, however, which is hardly enough time to demonstrate any effect, positive or negative. The most that can be said is that it didn’t cause many short-term adverse events.
Perhaps the best conclusion to draw from this somewhat underwhelming collection of data is that lowering high BP is important, but less important the closer we get to the end of life. Hypotension is obviously bad, and overly aggressive BP lowering is going to lead to negative outcomes in older adults because gravity is an unforgiving mistress.
Deprescribing antihypertensives in older adults is probably not going to cause major negative outcomes, but whether it will do much good in nonhypotensive patients is debatable. The bigger problem is the millions of people with undiagnosed or undertreated hypertension. We would probably have less dementia if we treated hypertension when it does the most good: as a primary-prevention strategy in midlife.
Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, Quebec, Canada. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
You could be forgiven if you are confused about how blood pressure (BP) affects dementia. First, you read an article extolling the benefits of BP lowering, then a study about how stopping antihypertensives slows cognitive decline in nursing home residents. It’s enough to make you lose your mind.
The Brain Benefits of BP Lowering
It should be stated unequivocally that you should absolutely treat high BP. It may have once been acceptable to state, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.” But those dark days are long behind us.
In these divided times, at least we can agree that we should treat high BP. The cardiovascular (CV) benefits, in and of themselves, justify the decision. But BP’s relationship with dementia is more complex. There are different types of dementia even though we tend to lump them all into one category. Vascular dementia is driven by the same pathophysiology and risk factors as cardiac disease. It’s intuitive that treating hypertension, diabetes, hypercholesterolemia, and smoking will decrease the risk for stroke and limit the damage to the brain that we see with repeated vascular insults. For Alzheimer’s disease, high BP and other CV risk factors seem to increase the risk even if the mechanism is not fully elucidated.
Estimates suggest that if we could lower the prevalence of hypertension by 25%, there would be 160,000 fewer cases of Alzheimer’s disease. But the data are not as robust as one might hope. A 2021 Cochrane review found that hypertension treatment slowed cognitive decline, but the quality of the evidence was low. Short duration of follow-up, dropouts, crossovers, and other problems with the data precluded any certainty. What’s more, hypertension in midlife is associated with cognitive decline and dementia, but its impact in those over age 70 is less clear. Later in life, or once cognitive impairment has already developed, it may be too late for BP lowering to have any impact.
Potential Harms of Lowering BP
All this needs to be weighed against the potential harms of treating hypertension. I will reiterate that hypertension should be treated and treated aggressively for the prevention of CV events. But overtreatment, especially in older patients, is associated with hypotension, falls, and syncope. Older patients are also at risk for polypharmacy and drug-drug interactions.
A Korean nationwide survey showed a U-shaped association between BP and Alzheimer’s disease risk in adults (mean age, 67 years), with both high and low BPs associated with a higher risk for Alzheimer’s disease. Though not all studies agree. A post hoc analysis of SPRINT MIND did not find any negative impact of intensive BP lowering on cognitive outcomes or cerebral perfusion in older adults (mean age, 68 years). But it didn’t do much good either. Given the heterogeneity of the data, doubts remain on whether aggressive BP lowering might be detrimental in older patients with comorbidities and preexisting dementia. The obvious corollary then is whether deprescribing hypertensive medications could be beneficial.
A recent publication in JAMA Internal Medicine attempted to address this very question. The cohort study used data from Veterans Affairs nursing home residents (mean age, 78 years) to emulate a randomized trial on deprescribing antihypertensives and cognitive decline. Many of the residents’ cognitive scores worsened over the course of follow-up; however, the decline was less pronounced in the deprescribing group (10% vs 12%). The same group did a similar analysis looking at CV outcomes and found no increased risk for heart attack or stroke with deprescribing BP medications. Taken together, these nursing home data suggest that deprescribing may help slow cognitive decline without the expected trade-off of increased CV events.
Deprescribing, Yes or No?
However, randomized data would obviously be preferable, and these are in short supply. One such trial, the DANTE study, found no benefit to deprescribing in terms of cognition in adults aged 75 years or older with mild cognitive impairment. The study follow-up was only 16 weeks, however, which is hardly enough time to demonstrate any effect, positive or negative. The most that can be said is that it didn’t cause many short-term adverse events.
Perhaps the best conclusion to draw from this somewhat underwhelming collection of data is that lowering high BP is important, but less important the closer we get to the end of life. Hypotension is obviously bad, and overly aggressive BP lowering is going to lead to negative outcomes in older adults because gravity is an unforgiving mistress.
Deprescribing antihypertensives in older adults is probably not going to cause major negative outcomes, but whether it will do much good in nonhypotensive patients is debatable. The bigger problem is the millions of people with undiagnosed or undertreated hypertension. We would probably have less dementia if we treated hypertension when it does the most good: as a primary-prevention strategy in midlife.
Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, Quebec, Canada. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
You could be forgiven if you are confused about how blood pressure (BP) affects dementia. First, you read an article extolling the benefits of BP lowering, then a study about how stopping antihypertensives slows cognitive decline in nursing home residents. It’s enough to make you lose your mind.
The Brain Benefits of BP Lowering
It should be stated unequivocally that you should absolutely treat high BP. It may have once been acceptable to state, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.” But those dark days are long behind us.
In these divided times, at least we can agree that we should treat high BP. The cardiovascular (CV) benefits, in and of themselves, justify the decision. But BP’s relationship with dementia is more complex. There are different types of dementia even though we tend to lump them all into one category. Vascular dementia is driven by the same pathophysiology and risk factors as cardiac disease. It’s intuitive that treating hypertension, diabetes, hypercholesterolemia, and smoking will decrease the risk for stroke and limit the damage to the brain that we see with repeated vascular insults. For Alzheimer’s disease, high BP and other CV risk factors seem to increase the risk even if the mechanism is not fully elucidated.
Estimates suggest that if we could lower the prevalence of hypertension by 25%, there would be 160,000 fewer cases of Alzheimer’s disease. But the data are not as robust as one might hope. A 2021 Cochrane review found that hypertension treatment slowed cognitive decline, but the quality of the evidence was low. Short duration of follow-up, dropouts, crossovers, and other problems with the data precluded any certainty. What’s more, hypertension in midlife is associated with cognitive decline and dementia, but its impact in those over age 70 is less clear. Later in life, or once cognitive impairment has already developed, it may be too late for BP lowering to have any impact.
Potential Harms of Lowering BP
All this needs to be weighed against the potential harms of treating hypertension. I will reiterate that hypertension should be treated and treated aggressively for the prevention of CV events. But overtreatment, especially in older patients, is associated with hypotension, falls, and syncope. Older patients are also at risk for polypharmacy and drug-drug interactions.
A Korean nationwide survey showed a U-shaped association between BP and Alzheimer’s disease risk in adults (mean age, 67 years), with both high and low BPs associated with a higher risk for Alzheimer’s disease. Though not all studies agree. A post hoc analysis of SPRINT MIND did not find any negative impact of intensive BP lowering on cognitive outcomes or cerebral perfusion in older adults (mean age, 68 years). But it didn’t do much good either. Given the heterogeneity of the data, doubts remain on whether aggressive BP lowering might be detrimental in older patients with comorbidities and preexisting dementia. The obvious corollary then is whether deprescribing hypertensive medications could be beneficial.
A recent publication in JAMA Internal Medicine attempted to address this very question. The cohort study used data from Veterans Affairs nursing home residents (mean age, 78 years) to emulate a randomized trial on deprescribing antihypertensives and cognitive decline. Many of the residents’ cognitive scores worsened over the course of follow-up; however, the decline was less pronounced in the deprescribing group (10% vs 12%). The same group did a similar analysis looking at CV outcomes and found no increased risk for heart attack or stroke with deprescribing BP medications. Taken together, these nursing home data suggest that deprescribing may help slow cognitive decline without the expected trade-off of increased CV events.
Deprescribing, Yes or No?
However, randomized data would obviously be preferable, and these are in short supply. One such trial, the DANTE study, found no benefit to deprescribing in terms of cognition in adults aged 75 years or older with mild cognitive impairment. The study follow-up was only 16 weeks, however, which is hardly enough time to demonstrate any effect, positive or negative. The most that can be said is that it didn’t cause many short-term adverse events.
Perhaps the best conclusion to draw from this somewhat underwhelming collection of data is that lowering high BP is important, but less important the closer we get to the end of life. Hypotension is obviously bad, and overly aggressive BP lowering is going to lead to negative outcomes in older adults because gravity is an unforgiving mistress.
Deprescribing antihypertensives in older adults is probably not going to cause major negative outcomes, but whether it will do much good in nonhypotensive patients is debatable. The bigger problem is the millions of people with undiagnosed or undertreated hypertension. We would probably have less dementia if we treated hypertension when it does the most good: as a primary-prevention strategy in midlife.
Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, Quebec, Canada. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
How Long Does It Take to See a Neurologist?
a cross-sectional analysis of Medicare data showed.
Wait times were not affected by the number of available neurologists. However, those with multiple sclerosis (MS), epilepsy, Parkinson’s disease, dementia, and sleep disorders had the longest wait times.
“In general, early referral to specialists has been shown to improve outcomes and increase patient satisfaction,” study author Chun Chieh Lin, PhD, MBA, of Ohio State University, Columbus, said in a press release. “Our findings underscore the need to develop new strategies to help people with neurological conditions see neurologists faster.”
The findings were published online in Neurology.
No National Benchmark for Wait Times
For this study, researchers analyzed a large sample of fee-for-service Medicare data from 2018 to 2019. Researchers identified patients with a year or less between their last referring physician visit and a new neurologist visit.
Exclusion criteria included enrollment in health maintenance organization plans without continuous enrollment in Medicare Part A and Part B for 2 years before the index neurologist visit, missing patient data, no physician referral at all, or referral by a different neurologist.
In addition to assessing wait times, investigators examined the availability of neurologists who provided medical services to Medicare beneficiaries in the 2018 dataset across 306 hospital referral regions in the United States, based on zip codes.
Results showed that 163,313 patients (average age, 74 years; 58% women; 85% White) were referred by 84,975 physicians to 10,250 neurologists across the United States.
Overall, the average wait time from physician referral to index neurologist visit was 34 days (range, 1-365 days), with longer wait times for White patients, women, and those aged 65-69 years. Overall, 18% waited longer than 90 days for an appointment.
The most common conditions diagnosed at the index neurologist visit were chronic pain/abnormality of gait (13%), sleep disorders (11%), and peripheral neuropathy (10%).
Using a linear mixed-effects statistical model, investigators found that patients with back pain waited an average of 30 days to see a neurologist, with longer waits for other conditions. Those with MS had an average wait that was 29 days longer, patients with epilepsy waited an average of 10 days longer, and those with Parkinson’s disease waited 9 days longer (P < .0001).
The number of available neurologists (range, 10-50 neurologists per 100,000 Medicare patients) did not affect wait times. However, there were differences in wait times across states because of different policies or regulations regarding healthcare access, with wait times ranging from a median high of 49 days in Idaho to a low of 24 days in Wyoming.
Notably, when patients saw a neurologist outside of their physician’s referral area, wait times were longer by an average of 11 days.
More than 40% of patients with new neurology referrals had prior office-based visits for the same neurologic diagnosis. For these patients, the median time between diagnosis and index neurologist visit was 342 days (range, 66-753 days).
Female patients in this category waited slightly longer (median, 353 days) than male patients (median, 328 days), and Black and Hispanic patients had longer median waits than White patients (389.5 days and 397 days respectively, vs 337 days; P = .0003).
“It is important to note that there is no national benchmark for determining appropriate wait times for specialist care, making it difficult to standardize expectations for timely access to specialists,” the authors noted.
The investigators suggested that a direct communication channel between primary care physicians and neurologists such as an eConsult service may hasten access to neurology consultation without the need for a formal appointment. Telemedicine in rural areas could also shorten wait times, they added.
Study limitations included the inability to determine if patients followed through with their index neurology visits or whether the last visit with the physician was the time of referral, as this could not be determined through the claims data.
This study was funded by the American Academy of Neurology. Lin reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a cross-sectional analysis of Medicare data showed.
Wait times were not affected by the number of available neurologists. However, those with multiple sclerosis (MS), epilepsy, Parkinson’s disease, dementia, and sleep disorders had the longest wait times.
“In general, early referral to specialists has been shown to improve outcomes and increase patient satisfaction,” study author Chun Chieh Lin, PhD, MBA, of Ohio State University, Columbus, said in a press release. “Our findings underscore the need to develop new strategies to help people with neurological conditions see neurologists faster.”
The findings were published online in Neurology.
No National Benchmark for Wait Times
For this study, researchers analyzed a large sample of fee-for-service Medicare data from 2018 to 2019. Researchers identified patients with a year or less between their last referring physician visit and a new neurologist visit.
Exclusion criteria included enrollment in health maintenance organization plans without continuous enrollment in Medicare Part A and Part B for 2 years before the index neurologist visit, missing patient data, no physician referral at all, or referral by a different neurologist.
In addition to assessing wait times, investigators examined the availability of neurologists who provided medical services to Medicare beneficiaries in the 2018 dataset across 306 hospital referral regions in the United States, based on zip codes.
Results showed that 163,313 patients (average age, 74 years; 58% women; 85% White) were referred by 84,975 physicians to 10,250 neurologists across the United States.
Overall, the average wait time from physician referral to index neurologist visit was 34 days (range, 1-365 days), with longer wait times for White patients, women, and those aged 65-69 years. Overall, 18% waited longer than 90 days for an appointment.
The most common conditions diagnosed at the index neurologist visit were chronic pain/abnormality of gait (13%), sleep disorders (11%), and peripheral neuropathy (10%).
Using a linear mixed-effects statistical model, investigators found that patients with back pain waited an average of 30 days to see a neurologist, with longer waits for other conditions. Those with MS had an average wait that was 29 days longer, patients with epilepsy waited an average of 10 days longer, and those with Parkinson’s disease waited 9 days longer (P < .0001).
The number of available neurologists (range, 10-50 neurologists per 100,000 Medicare patients) did not affect wait times. However, there were differences in wait times across states because of different policies or regulations regarding healthcare access, with wait times ranging from a median high of 49 days in Idaho to a low of 24 days in Wyoming.
Notably, when patients saw a neurologist outside of their physician’s referral area, wait times were longer by an average of 11 days.
More than 40% of patients with new neurology referrals had prior office-based visits for the same neurologic diagnosis. For these patients, the median time between diagnosis and index neurologist visit was 342 days (range, 66-753 days).
Female patients in this category waited slightly longer (median, 353 days) than male patients (median, 328 days), and Black and Hispanic patients had longer median waits than White patients (389.5 days and 397 days respectively, vs 337 days; P = .0003).
“It is important to note that there is no national benchmark for determining appropriate wait times for specialist care, making it difficult to standardize expectations for timely access to specialists,” the authors noted.
The investigators suggested that a direct communication channel between primary care physicians and neurologists such as an eConsult service may hasten access to neurology consultation without the need for a formal appointment. Telemedicine in rural areas could also shorten wait times, they added.
Study limitations included the inability to determine if patients followed through with their index neurology visits or whether the last visit with the physician was the time of referral, as this could not be determined through the claims data.
This study was funded by the American Academy of Neurology. Lin reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a cross-sectional analysis of Medicare data showed.
Wait times were not affected by the number of available neurologists. However, those with multiple sclerosis (MS), epilepsy, Parkinson’s disease, dementia, and sleep disorders had the longest wait times.
“In general, early referral to specialists has been shown to improve outcomes and increase patient satisfaction,” study author Chun Chieh Lin, PhD, MBA, of Ohio State University, Columbus, said in a press release. “Our findings underscore the need to develop new strategies to help people with neurological conditions see neurologists faster.”
The findings were published online in Neurology.
No National Benchmark for Wait Times
For this study, researchers analyzed a large sample of fee-for-service Medicare data from 2018 to 2019. Researchers identified patients with a year or less between their last referring physician visit and a new neurologist visit.
Exclusion criteria included enrollment in health maintenance organization plans without continuous enrollment in Medicare Part A and Part B for 2 years before the index neurologist visit, missing patient data, no physician referral at all, or referral by a different neurologist.
In addition to assessing wait times, investigators examined the availability of neurologists who provided medical services to Medicare beneficiaries in the 2018 dataset across 306 hospital referral regions in the United States, based on zip codes.
Results showed that 163,313 patients (average age, 74 years; 58% women; 85% White) were referred by 84,975 physicians to 10,250 neurologists across the United States.
Overall, the average wait time from physician referral to index neurologist visit was 34 days (range, 1-365 days), with longer wait times for White patients, women, and those aged 65-69 years. Overall, 18% waited longer than 90 days for an appointment.
The most common conditions diagnosed at the index neurologist visit were chronic pain/abnormality of gait (13%), sleep disorders (11%), and peripheral neuropathy (10%).
Using a linear mixed-effects statistical model, investigators found that patients with back pain waited an average of 30 days to see a neurologist, with longer waits for other conditions. Those with MS had an average wait that was 29 days longer, patients with epilepsy waited an average of 10 days longer, and those with Parkinson’s disease waited 9 days longer (P < .0001).
The number of available neurologists (range, 10-50 neurologists per 100,000 Medicare patients) did not affect wait times. However, there were differences in wait times across states because of different policies or regulations regarding healthcare access, with wait times ranging from a median high of 49 days in Idaho to a low of 24 days in Wyoming.
Notably, when patients saw a neurologist outside of their physician’s referral area, wait times were longer by an average of 11 days.
More than 40% of patients with new neurology referrals had prior office-based visits for the same neurologic diagnosis. For these patients, the median time between diagnosis and index neurologist visit was 342 days (range, 66-753 days).
Female patients in this category waited slightly longer (median, 353 days) than male patients (median, 328 days), and Black and Hispanic patients had longer median waits than White patients (389.5 days and 397 days respectively, vs 337 days; P = .0003).
“It is important to note that there is no national benchmark for determining appropriate wait times for specialist care, making it difficult to standardize expectations for timely access to specialists,” the authors noted.
The investigators suggested that a direct communication channel between primary care physicians and neurologists such as an eConsult service may hasten access to neurology consultation without the need for a formal appointment. Telemedicine in rural areas could also shorten wait times, they added.
Study limitations included the inability to determine if patients followed through with their index neurology visits or whether the last visit with the physician was the time of referral, as this could not be determined through the claims data.
This study was funded by the American Academy of Neurology. Lin reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Can Sea Lions Expand Our Knowledge of Epilepsy?
In 2022, the Journal of Neurosurgery took the unusual step of publishing a case report of a nonhuman subject, in this case an 8-year-old male sea lion named Cronutt, who had severe epilepsy that in many ways mirrored the common form seen in humans.
A 2020 xenotransplantation of interneuron progenitor cells in the sea lion’s hippocampus may have cured him. “He’s doing fantastic,” said Scott Baraban, PhD, a professor of neurological surgery at the University of California San Francisco Weill Institute for Neurosciences. The procedure offered a confirmation of success stories in mice and could serve as a bridge to human studies, although the science remains murky.
Cronutt’s story began the first time he was found stranded along the California coast in San Luis Obispo County, in November 2017, lethargic and disoriented. Nevertheless, he improved quickly under the care of the Marine Mammal Rescue Center in Sausalito, California, and they released him back into the wild 2 weeks later. Unfortunately, his troubles weren’t over. In the next 2 months, he came to the attention of the rehabilitation center two more times, and the resulting habituation to humans meant that he could not be re-released to the wild.
Things only got worse from there. He experienced a convulsive seizure and loss of consciousness in early 2018 and another seizure a year later. Despite anti-seizure medication, the episodes continued, and eventually, he stopped eating for long periods and lost a quarter of his body weight. It looked like euthanasia was the only alternative.
Neurosurgeons Take Notice
Baraban has devoted his career to animal models of epilepsy, focusing mainly on mice. He developed a method to transplant GABAergic interneurons from pigs, which can pick up the inhibitory role of endogenous neurons. In epileptic mice, mouse-derived progenitor cells mature into inhibitory synapses and dampen seizures, and even reverse behavioral problems.
Baraban was intrigued by the potential of the procedure to help sea lions and potentially bridge the gap between murine and human studies, and he was eager to try the approach after he learned of Cronutt’s case through his colleague Paul Buckmaster at Stanford University, California, who had collaborated with the Marine Mammal Rescue Center to demonstrate that sea lions suffer hippocampal damage that is very similar to human temporal lobe epilepsy.
It turns out that surgery on a sea lion is more complicated than on a mouse. The surgeon needs to conduct an MRI scan to locate the lesion and guide the placement of transplanted cells, and the big animals need to be sedated and intubated. Their caretakers are not enthusiastic about invasive procedures, but Cronutt had already been imaged as part of an earlier study of the effects of exposure to domoic acid on the sea lion brain, giving neurosurgeons at UCSF the information they needed.
In 2020, they transplanted GABAergic interneurons into Cronutt’s hippocampus in a last-ditch effort to save his life. He improved rapidly, and his caregivers eventually tapered off his anti-seizure medications. Today, Cronutt is living seizure-free at the Six Flags Discovery Kingdom in Vallejo, California. He even began participating in shows at Six Flags. “He is able to learn things and do things cognitively that he couldn’t do before,” said Baraban.
The researchers have not followed up with more imaging. “We just haven’t had any reason to bother him. It’s very invasive to get him to an MRI center,” said Baraban.
There haven’t been any more procedures on sea lions, in part because sea lions at rescue centers must be returned to the wild within 6-8 months, and animals with pig-based progenitor cells can’t be released. Any sea lion that would undergo such a procedure would have to live permanently in captivity, potentially for 20-30 years. “It’s a huge undertaking and expense,” said Baraban. There are also logistical challenges with the need to have MRI and other facilities close at hand to where the sea lion is kept.
Human Connections
As a veterinarian interested in human epilepsy, Buckmaster sought to find additional animal models for human temporal lobe epilepsy. He later met a veterinarian who worked with the Marine Mammal Center, who told him about temporal lobe epilepsy in sea lions.
Cronutt was just one of hundreds of California sea lions and other mammals rendered helpless by epileptic seizures induced by exposure to domoic acid, a chemical released by toxic algal blooms. Sea otters, whales, and even birds can likewise be affected. Humans, too, though it is rare: A domoic acid poisoning event in mussels from Prince Edward Island led to convulsions and an eventual diagnosis of temporal lobe epilepsy in an 84-year-old Canadian man, and three others died.
Most of Buckmaster’s work had been done in rats, but seizures are different than what are seen in humans. The damage isn’t unilateral, as in human epilepsy. The damage is unilateral in sea lions, and they suffer damage to similar neurons to those injured in humans. “In rats, you don’t see much loss of granule cells, which are the main neuron in the dentate gyrus, a region that’s really affected in temporal lobe epilepsy. In people, there’s a lot of variation, but [on average] you lose about half your granule cells, and that’s similar to sea lions. In rats, they just don’t lose them,” said Buckmaster.
That makes sea lions a useful model, but they hardly crack the case of human epilepsy. “To be humble about it, we don’t really know what’s causing the seizures. We have an idea of what region of the brain the seizures are coming from, but in terms of the cellular mechanisms, it’s still not clear,” said Buckmaster.
He also noted that, unlike sea lions, the vast majority of patients with human epilepsy have no exposure to domoic acid. That said, the case of sea lions and other marine animals makes researchers wonder. “This is speculative, but a lot of people with temporal epilepsy will have a history of some kind of precipitating event. Typically, it’s earlier in life, and a common one is prolonged febrile seizures. That could be a link to the domoic acid exposure in sea lions because the domoic acid exposure in sea lions frequently causes prolonged seizures. If the seizures are severe enough and long enough, they cause permanent brain damage, and that can cause temporal lobe epilepsy. That’s what we strongly believe is causing the temporal lobe epilepsy in sea lions. Prolonged, severe seizures can be caused by many things other than domoic acid, and that could be what causes it in many cases of human temporal lobe epilepsy,” said Buckmaster.
The approach taken with Cronutt makes sense to Buckmaster, who was not directly involved in the procedure. “The ideal treatment would be something that you would administer once, and it would cause cessation of seizures without any side effects. The transplantation of inhibitory cells is a treatment that would last and hopefully wouldn’t have any side effects and hopefully would provide complete control of seizures. It’s unlikely to reach all those goals, but it’s a step in the right direction, hopefully,” said Buckmaster.
He noted that Cronutt is only a single case and not proof that the procedure will work more generally. It’s possible the sea lion would have improved on his own without treatment, and the procedure itself could have influenced the brain. “That’s been the case with other neurological conditions that have attempted to be treated with cell transplantation,” said Buckmaster.
A phase 1/2 clinical trial, sponsored by Neurona Therapeutics, is currently recruiting patients to test transplant of human interneurons created from pluripotent stem cells into both temporal lobes of patients with drug-resistant bilateral mesial temporal lobe epilepsy.
Cronutt’s Course
Although he has improved dramatically, it’s possible that Cronutt continues to experience nonconvulsive seizures, which would not be easy to detect in an animal. “You don’t know if Cronutt’s seizures are controlled or not unless you can look at the electrical activity in Cronutt’s brain, and to my knowledge that has not been done,” said Buckmaster.
Previous studies in rats did repeatedly demonstrate the potential of the treatment approach. Despite the feel-good story of Cronutt, “that’s probably the most compelling evidence in support of that arm of treatment,” said Buckmaster.
Buckmaster and Barbaran had no relevant financial disclosures.
A version of this article appeared on Medscape.com.
In 2022, the Journal of Neurosurgery took the unusual step of publishing a case report of a nonhuman subject, in this case an 8-year-old male sea lion named Cronutt, who had severe epilepsy that in many ways mirrored the common form seen in humans.
A 2020 xenotransplantation of interneuron progenitor cells in the sea lion’s hippocampus may have cured him. “He’s doing fantastic,” said Scott Baraban, PhD, a professor of neurological surgery at the University of California San Francisco Weill Institute for Neurosciences. The procedure offered a confirmation of success stories in mice and could serve as a bridge to human studies, although the science remains murky.
Cronutt’s story began the first time he was found stranded along the California coast in San Luis Obispo County, in November 2017, lethargic and disoriented. Nevertheless, he improved quickly under the care of the Marine Mammal Rescue Center in Sausalito, California, and they released him back into the wild 2 weeks later. Unfortunately, his troubles weren’t over. In the next 2 months, he came to the attention of the rehabilitation center two more times, and the resulting habituation to humans meant that he could not be re-released to the wild.
Things only got worse from there. He experienced a convulsive seizure and loss of consciousness in early 2018 and another seizure a year later. Despite anti-seizure medication, the episodes continued, and eventually, he stopped eating for long periods and lost a quarter of his body weight. It looked like euthanasia was the only alternative.
Neurosurgeons Take Notice
Baraban has devoted his career to animal models of epilepsy, focusing mainly on mice. He developed a method to transplant GABAergic interneurons from pigs, which can pick up the inhibitory role of endogenous neurons. In epileptic mice, mouse-derived progenitor cells mature into inhibitory synapses and dampen seizures, and even reverse behavioral problems.
Baraban was intrigued by the potential of the procedure to help sea lions and potentially bridge the gap between murine and human studies, and he was eager to try the approach after he learned of Cronutt’s case through his colleague Paul Buckmaster at Stanford University, California, who had collaborated with the Marine Mammal Rescue Center to demonstrate that sea lions suffer hippocampal damage that is very similar to human temporal lobe epilepsy.
It turns out that surgery on a sea lion is more complicated than on a mouse. The surgeon needs to conduct an MRI scan to locate the lesion and guide the placement of transplanted cells, and the big animals need to be sedated and intubated. Their caretakers are not enthusiastic about invasive procedures, but Cronutt had already been imaged as part of an earlier study of the effects of exposure to domoic acid on the sea lion brain, giving neurosurgeons at UCSF the information they needed.
In 2020, they transplanted GABAergic interneurons into Cronutt’s hippocampus in a last-ditch effort to save his life. He improved rapidly, and his caregivers eventually tapered off his anti-seizure medications. Today, Cronutt is living seizure-free at the Six Flags Discovery Kingdom in Vallejo, California. He even began participating in shows at Six Flags. “He is able to learn things and do things cognitively that he couldn’t do before,” said Baraban.
The researchers have not followed up with more imaging. “We just haven’t had any reason to bother him. It’s very invasive to get him to an MRI center,” said Baraban.
There haven’t been any more procedures on sea lions, in part because sea lions at rescue centers must be returned to the wild within 6-8 months, and animals with pig-based progenitor cells can’t be released. Any sea lion that would undergo such a procedure would have to live permanently in captivity, potentially for 20-30 years. “It’s a huge undertaking and expense,” said Baraban. There are also logistical challenges with the need to have MRI and other facilities close at hand to where the sea lion is kept.
Human Connections
As a veterinarian interested in human epilepsy, Buckmaster sought to find additional animal models for human temporal lobe epilepsy. He later met a veterinarian who worked with the Marine Mammal Center, who told him about temporal lobe epilepsy in sea lions.
Cronutt was just one of hundreds of California sea lions and other mammals rendered helpless by epileptic seizures induced by exposure to domoic acid, a chemical released by toxic algal blooms. Sea otters, whales, and even birds can likewise be affected. Humans, too, though it is rare: A domoic acid poisoning event in mussels from Prince Edward Island led to convulsions and an eventual diagnosis of temporal lobe epilepsy in an 84-year-old Canadian man, and three others died.
Most of Buckmaster’s work had been done in rats, but seizures are different than what are seen in humans. The damage isn’t unilateral, as in human epilepsy. The damage is unilateral in sea lions, and they suffer damage to similar neurons to those injured in humans. “In rats, you don’t see much loss of granule cells, which are the main neuron in the dentate gyrus, a region that’s really affected in temporal lobe epilepsy. In people, there’s a lot of variation, but [on average] you lose about half your granule cells, and that’s similar to sea lions. In rats, they just don’t lose them,” said Buckmaster.
That makes sea lions a useful model, but they hardly crack the case of human epilepsy. “To be humble about it, we don’t really know what’s causing the seizures. We have an idea of what region of the brain the seizures are coming from, but in terms of the cellular mechanisms, it’s still not clear,” said Buckmaster.
He also noted that, unlike sea lions, the vast majority of patients with human epilepsy have no exposure to domoic acid. That said, the case of sea lions and other marine animals makes researchers wonder. “This is speculative, but a lot of people with temporal epilepsy will have a history of some kind of precipitating event. Typically, it’s earlier in life, and a common one is prolonged febrile seizures. That could be a link to the domoic acid exposure in sea lions because the domoic acid exposure in sea lions frequently causes prolonged seizures. If the seizures are severe enough and long enough, they cause permanent brain damage, and that can cause temporal lobe epilepsy. That’s what we strongly believe is causing the temporal lobe epilepsy in sea lions. Prolonged, severe seizures can be caused by many things other than domoic acid, and that could be what causes it in many cases of human temporal lobe epilepsy,” said Buckmaster.
The approach taken with Cronutt makes sense to Buckmaster, who was not directly involved in the procedure. “The ideal treatment would be something that you would administer once, and it would cause cessation of seizures without any side effects. The transplantation of inhibitory cells is a treatment that would last and hopefully wouldn’t have any side effects and hopefully would provide complete control of seizures. It’s unlikely to reach all those goals, but it’s a step in the right direction, hopefully,” said Buckmaster.
He noted that Cronutt is only a single case and not proof that the procedure will work more generally. It’s possible the sea lion would have improved on his own without treatment, and the procedure itself could have influenced the brain. “That’s been the case with other neurological conditions that have attempted to be treated with cell transplantation,” said Buckmaster.
A phase 1/2 clinical trial, sponsored by Neurona Therapeutics, is currently recruiting patients to test transplant of human interneurons created from pluripotent stem cells into both temporal lobes of patients with drug-resistant bilateral mesial temporal lobe epilepsy.
Cronutt’s Course
Although he has improved dramatically, it’s possible that Cronutt continues to experience nonconvulsive seizures, which would not be easy to detect in an animal. “You don’t know if Cronutt’s seizures are controlled or not unless you can look at the electrical activity in Cronutt’s brain, and to my knowledge that has not been done,” said Buckmaster.
Previous studies in rats did repeatedly demonstrate the potential of the treatment approach. Despite the feel-good story of Cronutt, “that’s probably the most compelling evidence in support of that arm of treatment,” said Buckmaster.
Buckmaster and Barbaran had no relevant financial disclosures.
A version of this article appeared on Medscape.com.
In 2022, the Journal of Neurosurgery took the unusual step of publishing a case report of a nonhuman subject, in this case an 8-year-old male sea lion named Cronutt, who had severe epilepsy that in many ways mirrored the common form seen in humans.
A 2020 xenotransplantation of interneuron progenitor cells in the sea lion’s hippocampus may have cured him. “He’s doing fantastic,” said Scott Baraban, PhD, a professor of neurological surgery at the University of California San Francisco Weill Institute for Neurosciences. The procedure offered a confirmation of success stories in mice and could serve as a bridge to human studies, although the science remains murky.
Cronutt’s story began the first time he was found stranded along the California coast in San Luis Obispo County, in November 2017, lethargic and disoriented. Nevertheless, he improved quickly under the care of the Marine Mammal Rescue Center in Sausalito, California, and they released him back into the wild 2 weeks later. Unfortunately, his troubles weren’t over. In the next 2 months, he came to the attention of the rehabilitation center two more times, and the resulting habituation to humans meant that he could not be re-released to the wild.
Things only got worse from there. He experienced a convulsive seizure and loss of consciousness in early 2018 and another seizure a year later. Despite anti-seizure medication, the episodes continued, and eventually, he stopped eating for long periods and lost a quarter of his body weight. It looked like euthanasia was the only alternative.
Neurosurgeons Take Notice
Baraban has devoted his career to animal models of epilepsy, focusing mainly on mice. He developed a method to transplant GABAergic interneurons from pigs, which can pick up the inhibitory role of endogenous neurons. In epileptic mice, mouse-derived progenitor cells mature into inhibitory synapses and dampen seizures, and even reverse behavioral problems.
Baraban was intrigued by the potential of the procedure to help sea lions and potentially bridge the gap between murine and human studies, and he was eager to try the approach after he learned of Cronutt’s case through his colleague Paul Buckmaster at Stanford University, California, who had collaborated with the Marine Mammal Rescue Center to demonstrate that sea lions suffer hippocampal damage that is very similar to human temporal lobe epilepsy.
It turns out that surgery on a sea lion is more complicated than on a mouse. The surgeon needs to conduct an MRI scan to locate the lesion and guide the placement of transplanted cells, and the big animals need to be sedated and intubated. Their caretakers are not enthusiastic about invasive procedures, but Cronutt had already been imaged as part of an earlier study of the effects of exposure to domoic acid on the sea lion brain, giving neurosurgeons at UCSF the information they needed.
In 2020, they transplanted GABAergic interneurons into Cronutt’s hippocampus in a last-ditch effort to save his life. He improved rapidly, and his caregivers eventually tapered off his anti-seizure medications. Today, Cronutt is living seizure-free at the Six Flags Discovery Kingdom in Vallejo, California. He even began participating in shows at Six Flags. “He is able to learn things and do things cognitively that he couldn’t do before,” said Baraban.
The researchers have not followed up with more imaging. “We just haven’t had any reason to bother him. It’s very invasive to get him to an MRI center,” said Baraban.
There haven’t been any more procedures on sea lions, in part because sea lions at rescue centers must be returned to the wild within 6-8 months, and animals with pig-based progenitor cells can’t be released. Any sea lion that would undergo such a procedure would have to live permanently in captivity, potentially for 20-30 years. “It’s a huge undertaking and expense,” said Baraban. There are also logistical challenges with the need to have MRI and other facilities close at hand to where the sea lion is kept.
Human Connections
As a veterinarian interested in human epilepsy, Buckmaster sought to find additional animal models for human temporal lobe epilepsy. He later met a veterinarian who worked with the Marine Mammal Center, who told him about temporal lobe epilepsy in sea lions.
Cronutt was just one of hundreds of California sea lions and other mammals rendered helpless by epileptic seizures induced by exposure to domoic acid, a chemical released by toxic algal blooms. Sea otters, whales, and even birds can likewise be affected. Humans, too, though it is rare: A domoic acid poisoning event in mussels from Prince Edward Island led to convulsions and an eventual diagnosis of temporal lobe epilepsy in an 84-year-old Canadian man, and three others died.
Most of Buckmaster’s work had been done in rats, but seizures are different than what are seen in humans. The damage isn’t unilateral, as in human epilepsy. The damage is unilateral in sea lions, and they suffer damage to similar neurons to those injured in humans. “In rats, you don’t see much loss of granule cells, which are the main neuron in the dentate gyrus, a region that’s really affected in temporal lobe epilepsy. In people, there’s a lot of variation, but [on average] you lose about half your granule cells, and that’s similar to sea lions. In rats, they just don’t lose them,” said Buckmaster.
That makes sea lions a useful model, but they hardly crack the case of human epilepsy. “To be humble about it, we don’t really know what’s causing the seizures. We have an idea of what region of the brain the seizures are coming from, but in terms of the cellular mechanisms, it’s still not clear,” said Buckmaster.
He also noted that, unlike sea lions, the vast majority of patients with human epilepsy have no exposure to domoic acid. That said, the case of sea lions and other marine animals makes researchers wonder. “This is speculative, but a lot of people with temporal epilepsy will have a history of some kind of precipitating event. Typically, it’s earlier in life, and a common one is prolonged febrile seizures. That could be a link to the domoic acid exposure in sea lions because the domoic acid exposure in sea lions frequently causes prolonged seizures. If the seizures are severe enough and long enough, they cause permanent brain damage, and that can cause temporal lobe epilepsy. That’s what we strongly believe is causing the temporal lobe epilepsy in sea lions. Prolonged, severe seizures can be caused by many things other than domoic acid, and that could be what causes it in many cases of human temporal lobe epilepsy,” said Buckmaster.
The approach taken with Cronutt makes sense to Buckmaster, who was not directly involved in the procedure. “The ideal treatment would be something that you would administer once, and it would cause cessation of seizures without any side effects. The transplantation of inhibitory cells is a treatment that would last and hopefully wouldn’t have any side effects and hopefully would provide complete control of seizures. It’s unlikely to reach all those goals, but it’s a step in the right direction, hopefully,” said Buckmaster.
He noted that Cronutt is only a single case and not proof that the procedure will work more generally. It’s possible the sea lion would have improved on his own without treatment, and the procedure itself could have influenced the brain. “That’s been the case with other neurological conditions that have attempted to be treated with cell transplantation,” said Buckmaster.
A phase 1/2 clinical trial, sponsored by Neurona Therapeutics, is currently recruiting patients to test transplant of human interneurons created from pluripotent stem cells into both temporal lobes of patients with drug-resistant bilateral mesial temporal lobe epilepsy.
Cronutt’s Course
Although he has improved dramatically, it’s possible that Cronutt continues to experience nonconvulsive seizures, which would not be easy to detect in an animal. “You don’t know if Cronutt’s seizures are controlled or not unless you can look at the electrical activity in Cronutt’s brain, and to my knowledge that has not been done,” said Buckmaster.
Previous studies in rats did repeatedly demonstrate the potential of the treatment approach. Despite the feel-good story of Cronutt, “that’s probably the most compelling evidence in support of that arm of treatment,” said Buckmaster.
Buckmaster and Barbaran had no relevant financial disclosures.
A version of this article appeared on Medscape.com.
Hispanic Patients Face Disparities in MASLD
according to a new systematic review and meta-analysis.
These findings underscore worsening health disparities in MASLD management and outcomes in this patient population, Kaleb Tesfai, BS, of the University of California, San Diego, and colleagues reported.
Previously, a 2018 meta-analysis found that Hispanic individuals had a higher MASLD prevalence than non-Hispanic White and Black individuals, along with an elevated relative risk of MASH.
“In the setting of the evolving obesity epidemic, prevalence of MASLD has increased and characteristics of patient populations of interest have changed since the time of this prior meta-analysis,” Mr. Tesfai and colleagues wrote in Clinical Gastroenterology and Hepatology. “Importantly, MASH has become a leading indication for liver transplant, thereby impacting long-term clinical outcomes. As such, accurate, updated prevalence rates and relative risk estimates of MASLD, MASH, advanced fibrosis/cirrhosis, and clinical outcomes for Hispanic adults in the US remain poorly characterized.”
The present meta-analysis focused specifically on Hispanic adults in the United States; it compared their disease prevalence, severity, and risk to non-Hispanic adults. Twenty-two studies, conducted between January 1, 2010, and December 31, 2023, were included, comprising 756,088 participants, of whom 62,072 were Hispanic.
Study eligibility required reported data on the prevalence of MASLD, MASH, or advanced fibrosis, as well as racial or ethnic subgroup analyses. Studies were excluded if they did not use validated diagnostic methods, such as liver biopsy or imaging, or if they lacked stratification by Hispanic ethnicity. Prevalence estimates and relative risks were calculated using random-effects models. The analysis also accounted for potential confounding factors, including demographic characteristics, metabolic comorbidities, and social determinants of health (SDOH).
The pooled prevalence of MASLD among Hispanic adults was 41% (95% CI, 30%-52%), compared with 27% in non-Hispanic populations, reflecting a relative risk (RR) of 1.50 (95% CI, 1.32-1.69). For MASH, the pooled prevalence among Hispanic adults with MASLD was 61% (95% CI, 39%-82%), with an RR of 1.42 (95% CI, 1.04-1.93), compared with non-Hispanic adults.
“Our systematic review and meta-analysis highlights the worsening health disparities experienced by Hispanic adults in the US, with significant increase in the relative risk of MASLD and MASH in contemporary cohorts compared with prior estimates,” the investigators wrote.
Despite these elevated risks for MASLD and MASH, advanced fibrosis and cirrhosis did not show statistically significant differences between Hispanic and non-Hispanic populations.
The study also characterized the relationship between SDOH and detected health disparities. Adjustments for factors such as income, education, and health care access eliminated the independent association between Hispanic and MASLD risk, suggesting that these structural inequities play a meaningful role in disease disparities.
Still, genetic factors, including PNPLA3 and TM6SF2 risk alleles, were identified as contributors to the higher disease burden in Hispanic populations.
Mr. Tesfai and colleagues called for prospective studies with standardized outcome definitions to better understand risks of advanced fibrosis and cirrhosis, as well as long-term clinical outcomes. In addition, they recommended further investigation of SDOH to determine optimal intervention targets.
“Public health initiatives focused on increasing screening for MASLD and MASH and enhancing health care delivery for this high-risk group are critically needed to optimize health outcomes for Hispanic adults in the US,” they concluded.This study was supported by various institutes at the National Institutes of Health, Gilead Sciences, and the SDSU-UCSD CREATE Partnership. The investigators disclosed additional relationships with Eli Lilly, Galmed, Pfizer, and others.
according to a new systematic review and meta-analysis.
These findings underscore worsening health disparities in MASLD management and outcomes in this patient population, Kaleb Tesfai, BS, of the University of California, San Diego, and colleagues reported.
Previously, a 2018 meta-analysis found that Hispanic individuals had a higher MASLD prevalence than non-Hispanic White and Black individuals, along with an elevated relative risk of MASH.
“In the setting of the evolving obesity epidemic, prevalence of MASLD has increased and characteristics of patient populations of interest have changed since the time of this prior meta-analysis,” Mr. Tesfai and colleagues wrote in Clinical Gastroenterology and Hepatology. “Importantly, MASH has become a leading indication for liver transplant, thereby impacting long-term clinical outcomes. As such, accurate, updated prevalence rates and relative risk estimates of MASLD, MASH, advanced fibrosis/cirrhosis, and clinical outcomes for Hispanic adults in the US remain poorly characterized.”
The present meta-analysis focused specifically on Hispanic adults in the United States; it compared their disease prevalence, severity, and risk to non-Hispanic adults. Twenty-two studies, conducted between January 1, 2010, and December 31, 2023, were included, comprising 756,088 participants, of whom 62,072 were Hispanic.
Study eligibility required reported data on the prevalence of MASLD, MASH, or advanced fibrosis, as well as racial or ethnic subgroup analyses. Studies were excluded if they did not use validated diagnostic methods, such as liver biopsy or imaging, or if they lacked stratification by Hispanic ethnicity. Prevalence estimates and relative risks were calculated using random-effects models. The analysis also accounted for potential confounding factors, including demographic characteristics, metabolic comorbidities, and social determinants of health (SDOH).
The pooled prevalence of MASLD among Hispanic adults was 41% (95% CI, 30%-52%), compared with 27% in non-Hispanic populations, reflecting a relative risk (RR) of 1.50 (95% CI, 1.32-1.69). For MASH, the pooled prevalence among Hispanic adults with MASLD was 61% (95% CI, 39%-82%), with an RR of 1.42 (95% CI, 1.04-1.93), compared with non-Hispanic adults.
“Our systematic review and meta-analysis highlights the worsening health disparities experienced by Hispanic adults in the US, with significant increase in the relative risk of MASLD and MASH in contemporary cohorts compared with prior estimates,” the investigators wrote.
Despite these elevated risks for MASLD and MASH, advanced fibrosis and cirrhosis did not show statistically significant differences between Hispanic and non-Hispanic populations.
The study also characterized the relationship between SDOH and detected health disparities. Adjustments for factors such as income, education, and health care access eliminated the independent association between Hispanic and MASLD risk, suggesting that these structural inequities play a meaningful role in disease disparities.
Still, genetic factors, including PNPLA3 and TM6SF2 risk alleles, were identified as contributors to the higher disease burden in Hispanic populations.
Mr. Tesfai and colleagues called for prospective studies with standardized outcome definitions to better understand risks of advanced fibrosis and cirrhosis, as well as long-term clinical outcomes. In addition, they recommended further investigation of SDOH to determine optimal intervention targets.
“Public health initiatives focused on increasing screening for MASLD and MASH and enhancing health care delivery for this high-risk group are critically needed to optimize health outcomes for Hispanic adults in the US,” they concluded.This study was supported by various institutes at the National Institutes of Health, Gilead Sciences, and the SDSU-UCSD CREATE Partnership. The investigators disclosed additional relationships with Eli Lilly, Galmed, Pfizer, and others.
according to a new systematic review and meta-analysis.
These findings underscore worsening health disparities in MASLD management and outcomes in this patient population, Kaleb Tesfai, BS, of the University of California, San Diego, and colleagues reported.
Previously, a 2018 meta-analysis found that Hispanic individuals had a higher MASLD prevalence than non-Hispanic White and Black individuals, along with an elevated relative risk of MASH.
“In the setting of the evolving obesity epidemic, prevalence of MASLD has increased and characteristics of patient populations of interest have changed since the time of this prior meta-analysis,” Mr. Tesfai and colleagues wrote in Clinical Gastroenterology and Hepatology. “Importantly, MASH has become a leading indication for liver transplant, thereby impacting long-term clinical outcomes. As such, accurate, updated prevalence rates and relative risk estimates of MASLD, MASH, advanced fibrosis/cirrhosis, and clinical outcomes for Hispanic adults in the US remain poorly characterized.”
The present meta-analysis focused specifically on Hispanic adults in the United States; it compared their disease prevalence, severity, and risk to non-Hispanic adults. Twenty-two studies, conducted between January 1, 2010, and December 31, 2023, were included, comprising 756,088 participants, of whom 62,072 were Hispanic.
Study eligibility required reported data on the prevalence of MASLD, MASH, or advanced fibrosis, as well as racial or ethnic subgroup analyses. Studies were excluded if they did not use validated diagnostic methods, such as liver biopsy or imaging, or if they lacked stratification by Hispanic ethnicity. Prevalence estimates and relative risks were calculated using random-effects models. The analysis also accounted for potential confounding factors, including demographic characteristics, metabolic comorbidities, and social determinants of health (SDOH).
The pooled prevalence of MASLD among Hispanic adults was 41% (95% CI, 30%-52%), compared with 27% in non-Hispanic populations, reflecting a relative risk (RR) of 1.50 (95% CI, 1.32-1.69). For MASH, the pooled prevalence among Hispanic adults with MASLD was 61% (95% CI, 39%-82%), with an RR of 1.42 (95% CI, 1.04-1.93), compared with non-Hispanic adults.
“Our systematic review and meta-analysis highlights the worsening health disparities experienced by Hispanic adults in the US, with significant increase in the relative risk of MASLD and MASH in contemporary cohorts compared with prior estimates,” the investigators wrote.
Despite these elevated risks for MASLD and MASH, advanced fibrosis and cirrhosis did not show statistically significant differences between Hispanic and non-Hispanic populations.
The study also characterized the relationship between SDOH and detected health disparities. Adjustments for factors such as income, education, and health care access eliminated the independent association between Hispanic and MASLD risk, suggesting that these structural inequities play a meaningful role in disease disparities.
Still, genetic factors, including PNPLA3 and TM6SF2 risk alleles, were identified as contributors to the higher disease burden in Hispanic populations.
Mr. Tesfai and colleagues called for prospective studies with standardized outcome definitions to better understand risks of advanced fibrosis and cirrhosis, as well as long-term clinical outcomes. In addition, they recommended further investigation of SDOH to determine optimal intervention targets.
“Public health initiatives focused on increasing screening for MASLD and MASH and enhancing health care delivery for this high-risk group are critically needed to optimize health outcomes for Hispanic adults in the US,” they concluded.This study was supported by various institutes at the National Institutes of Health, Gilead Sciences, and the SDSU-UCSD CREATE Partnership. The investigators disclosed additional relationships with Eli Lilly, Galmed, Pfizer, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Sexual Assaults in Military Down, Benefits Claims Up
The number of sexual assaults in the US military dropped for the first time in a decade, according an annual report from the Pentagon, while benefits claims for assault survivors are on the rise.
Records show that 29,000 active-duty members reported being sexually assaulted in 2023, or 7000 fewer than in 2021. A confidential survey also found the number of service members who experienced some type of unwanted sexual contact dropped nearly 20%, leaving the Pentagon “cautiously optimistic“ its investments in preventing sexual assault and building a healthy climate are having an impact.
Despite these investments, issues persist. An Army anesthesiologist recently pleaded guilty to 41 charges of sexual misconduct involving 21 victims at Madigan Army Medical Center at Joint Base Lewis-McChord in Washington. The alleged incidents occurred between 2019 and 2022 and involved the doctor unnecessarily focusing on the genital area of patients during what he described as routine examinations. Maj. Michael Stockin faces nearly 14 years in prison, should the judge accept the plea agreement Stockin and his attorneys made with government prosecutors.
Additionally, a report from the Watson Institute of International and Public Affairs at Brown University indicated that 24% of active-duty women and 1.9% of active-duty men experienced sexual assault from 2001 to 2021.During post-9/11 wars, “the prioritization of force readiness above all else allowed the problem of sexual assault to fester, papering over internal violence and gender inequalities within military institutions,” the report said. There was also a slight uptick in reports of military sexual assaults in 2020, when troops were largely on lockdown as a result of the COVID-19 pandemic.
Efforts to address sexual assault in the military have increased in the past 10 years to the tune of 10 Department of Defense Inspector General engagements, 60 Government Accountability Office recommendations, > 200 government panel and task force recommendations, > 150 Congressional provisions, and > 50 Secretary of Defense initiatives. Additionally, the 2022 National Defense Authorization gave authority in sexual assault cases to independent prosecutors rather than commanders. Other reforms have included incorporating trauma-informed practices in the claims process.
Meanwhile, the US Department of Veterans Affairs (VA) has also been attempting to convince more sexual assault survivors to file claims for benefits. Assistant Deputy Under Secretary for Field Operations Kenesha Britton said in December that the VA has held 3500 events in the past 14 months focused on benefits for victims of military sexual assault and harassment. It appears to be working, as the VA received 57,400 claims for military sexual trauma in fiscal year 2024 (an 18% increase from 2023), and approved > 63% of them, compared to 40% more than a decade ago. Prior to Oct. 1, VA staffers processed > 11,000 cases in a single day twice. Since that date, they have processed that amount on 9 separate occasions.
“We recognize the remarkable courage it takes for survivors of military sexual trauma to seek the benefits and support they’ve earned,” Britton said. “Our mission is driven by a commitment to ensure survivors are met with care, dignity and sensitivity throughout the claims process.”
The increase in trust is a byproduct of the outreach campaigns, VA Under Secretary for Benefits Josh Jacobs said: “[M]ore veterans are coming in to apply for benefits and I think that has to do with building trust because we are actively trying to reach veterans telling them we want to connect them with their earned benefits.”
The number of sexual assaults in the US military dropped for the first time in a decade, according an annual report from the Pentagon, while benefits claims for assault survivors are on the rise.
Records show that 29,000 active-duty members reported being sexually assaulted in 2023, or 7000 fewer than in 2021. A confidential survey also found the number of service members who experienced some type of unwanted sexual contact dropped nearly 20%, leaving the Pentagon “cautiously optimistic“ its investments in preventing sexual assault and building a healthy climate are having an impact.
Despite these investments, issues persist. An Army anesthesiologist recently pleaded guilty to 41 charges of sexual misconduct involving 21 victims at Madigan Army Medical Center at Joint Base Lewis-McChord in Washington. The alleged incidents occurred between 2019 and 2022 and involved the doctor unnecessarily focusing on the genital area of patients during what he described as routine examinations. Maj. Michael Stockin faces nearly 14 years in prison, should the judge accept the plea agreement Stockin and his attorneys made with government prosecutors.
Additionally, a report from the Watson Institute of International and Public Affairs at Brown University indicated that 24% of active-duty women and 1.9% of active-duty men experienced sexual assault from 2001 to 2021.During post-9/11 wars, “the prioritization of force readiness above all else allowed the problem of sexual assault to fester, papering over internal violence and gender inequalities within military institutions,” the report said. There was also a slight uptick in reports of military sexual assaults in 2020, when troops were largely on lockdown as a result of the COVID-19 pandemic.
Efforts to address sexual assault in the military have increased in the past 10 years to the tune of 10 Department of Defense Inspector General engagements, 60 Government Accountability Office recommendations, > 200 government panel and task force recommendations, > 150 Congressional provisions, and > 50 Secretary of Defense initiatives. Additionally, the 2022 National Defense Authorization gave authority in sexual assault cases to independent prosecutors rather than commanders. Other reforms have included incorporating trauma-informed practices in the claims process.
Meanwhile, the US Department of Veterans Affairs (VA) has also been attempting to convince more sexual assault survivors to file claims for benefits. Assistant Deputy Under Secretary for Field Operations Kenesha Britton said in December that the VA has held 3500 events in the past 14 months focused on benefits for victims of military sexual assault and harassment. It appears to be working, as the VA received 57,400 claims for military sexual trauma in fiscal year 2024 (an 18% increase from 2023), and approved > 63% of them, compared to 40% more than a decade ago. Prior to Oct. 1, VA staffers processed > 11,000 cases in a single day twice. Since that date, they have processed that amount on 9 separate occasions.
“We recognize the remarkable courage it takes for survivors of military sexual trauma to seek the benefits and support they’ve earned,” Britton said. “Our mission is driven by a commitment to ensure survivors are met with care, dignity and sensitivity throughout the claims process.”
The increase in trust is a byproduct of the outreach campaigns, VA Under Secretary for Benefits Josh Jacobs said: “[M]ore veterans are coming in to apply for benefits and I think that has to do with building trust because we are actively trying to reach veterans telling them we want to connect them with their earned benefits.”
The number of sexual assaults in the US military dropped for the first time in a decade, according an annual report from the Pentagon, while benefits claims for assault survivors are on the rise.
Records show that 29,000 active-duty members reported being sexually assaulted in 2023, or 7000 fewer than in 2021. A confidential survey also found the number of service members who experienced some type of unwanted sexual contact dropped nearly 20%, leaving the Pentagon “cautiously optimistic“ its investments in preventing sexual assault and building a healthy climate are having an impact.
Despite these investments, issues persist. An Army anesthesiologist recently pleaded guilty to 41 charges of sexual misconduct involving 21 victims at Madigan Army Medical Center at Joint Base Lewis-McChord in Washington. The alleged incidents occurred between 2019 and 2022 and involved the doctor unnecessarily focusing on the genital area of patients during what he described as routine examinations. Maj. Michael Stockin faces nearly 14 years in prison, should the judge accept the plea agreement Stockin and his attorneys made with government prosecutors.
Additionally, a report from the Watson Institute of International and Public Affairs at Brown University indicated that 24% of active-duty women and 1.9% of active-duty men experienced sexual assault from 2001 to 2021.During post-9/11 wars, “the prioritization of force readiness above all else allowed the problem of sexual assault to fester, papering over internal violence and gender inequalities within military institutions,” the report said. There was also a slight uptick in reports of military sexual assaults in 2020, when troops were largely on lockdown as a result of the COVID-19 pandemic.
Efforts to address sexual assault in the military have increased in the past 10 years to the tune of 10 Department of Defense Inspector General engagements, 60 Government Accountability Office recommendations, > 200 government panel and task force recommendations, > 150 Congressional provisions, and > 50 Secretary of Defense initiatives. Additionally, the 2022 National Defense Authorization gave authority in sexual assault cases to independent prosecutors rather than commanders. Other reforms have included incorporating trauma-informed practices in the claims process.
Meanwhile, the US Department of Veterans Affairs (VA) has also been attempting to convince more sexual assault survivors to file claims for benefits. Assistant Deputy Under Secretary for Field Operations Kenesha Britton said in December that the VA has held 3500 events in the past 14 months focused on benefits for victims of military sexual assault and harassment. It appears to be working, as the VA received 57,400 claims for military sexual trauma in fiscal year 2024 (an 18% increase from 2023), and approved > 63% of them, compared to 40% more than a decade ago. Prior to Oct. 1, VA staffers processed > 11,000 cases in a single day twice. Since that date, they have processed that amount on 9 separate occasions.
“We recognize the remarkable courage it takes for survivors of military sexual trauma to seek the benefits and support they’ve earned,” Britton said. “Our mission is driven by a commitment to ensure survivors are met with care, dignity and sensitivity throughout the claims process.”
The increase in trust is a byproduct of the outreach campaigns, VA Under Secretary for Benefits Josh Jacobs said: “[M]ore veterans are coming in to apply for benefits and I think that has to do with building trust because we are actively trying to reach veterans telling them we want to connect them with their earned benefits.”