A blood test that measures elevations in neurofilament light chain (NfL) levels in patients with multiple sclerosis (MS) could warn of worsening disability up to 2 years before it occurs, a new study suggests.

Rising NfL levels are a known indicator of neuroaxonal injury and correlate with MS disease activity. Levels rise in the presence of an MS relapse or MRI activity and fall following treatment with disease-modifying therapies. But the link between NfL levels and worsening disability was less understood.

This new analysis of NfL in two large MS cohorts found that elevated levels of the neuronal protein at baseline were associated with large increases in future disability risk, even in patients with no clinical relapse.

“This rising of NfL up to 2 years before signs of disability worsening represents the window when interventions may prevent worsening,” lead investigator Ahmed Abdelhak, MD, department of neurology, University of California, San Francisco, said in a press release.

The findings were published online in JAMA Neurology.
 

Early warning system?

The study included data on 1,899 patients with nearly 13,000 patient visits from two observational, long-term, real-world cohorts: the U.S.-based Expression, Proteomics, Imaging, Clinical (EPIC) study (n = 609 patients), and the Swiss Multiple Sclerosis Cohort trial (SMSC; n = 1,290 patients).

Investigators analyzed longitudinal serum NfL measurements in conjunction with clinical disability worsening, defined as 6 months or more of increased impairment as measured by the Expanded Disability Status Scale.

Researchers also assessed the temporal association between NfL measurements and the risk of increased disability and distinguished between disability with and without relapse.

Worsening disability was reported in 227 patients in the EPIC group and 435 in the SMSC trial.

Elevated NfL at baseline was associated with a 70% higher risk for worsening disability with relapse about 11 months later in the SMSC study (hazard ratio, 1.70; P = .02). In the EPIC trial, there was trend toward a 91% higher risk for worsening disability with relapse at 12.6 months, although the findings did not meet statistical significance (HR, 1.91; P = .07).

The risk of future disability progression independent of clinical relapse was 40% higher in those with high NfL at baseline in the EPIC study 12 months after baseline (HR, 1.40; P = .02) and 49% higher in the SMSC trial 21 months later (HR, 1.49; P < .001).

The early elevation of NfL levels suggests a slower degradation of nerve cells and could be a possible early warning system of future progression of disability, allowing time for interventions that could slow or even halt further disability.

“Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging,” senior author Jens Kuhle, MD, PhD, leader of the Swiss cohort and head of the Multiple Sclerosis Center at University Hospital and University of Basel, said in a statement.
 

Challenges for clinicians

Commenting on the findings, Robert Fox, MD, staff neurologist at the Mellen Center for MS and vice chair for research, Neurological Institute, Cleveland Clinic, said that, while there is a clinical test to measure NfL levels, incorporating that test into standard of care isn’t straightforward.

“The challenge for the practicing clinician is to translate these population-level studies to individual patient management decisions,” said Dr. Fox, who was not a part of the study.

“The published prediction curves corrected for age, sex, disease course, disease-modifying treatment, relapse within the past 90 days, and current disability status, the combination of which makes it rather challenging to calculate and interpret adjusted z score NfL levels in routine practice and then use it in clinical decision-making.”

The investigators said the study underscores the importance of NfL as an MS biomarker and “points to the existence of different windows of dynamic central nervous system pathology” that precedes worsening disability with or without relapse. But there may be a simpler explanation, Dr. Fox suggested.

“We know MRI activity occurs 5-10 times more frequently than relapses, and we know that MRI activity is associated with both NfL increases and future disability progression,” Dr. Fox said. “It is quite likely that the elevations in NfL seen here are reflective of new MRI disease activity, which frequently is seen without symptoms of an MS relapse,” he said

The study was funded by the Westridge Foundation, F. Hoffmann–La Roche, the Fishman Family, the Swiss National Research Foundation, the National Institutes of Health/National Institute of Neurological Disorders and Stroke, and the Valhalla Foundation. Dr. Abdelhak reported receiving grants from the German Multiple Sclerosis Society and the Weill Institute for Neurosciences outside the submitted work. Dr. Kuhle has received grants from Swiss MS Society, the Swiss National Research Foundation, the Progressive MS Alliance, Biogen, Merck, Celgene, Bristol-Myers Squibb, Novartis, Octave Bioscience, Roche, Sanofi, Alnylam, Bayer, Immunic, Quanterix, Neurogenesis, Stata DX, and the University of Basel outside the submitted work. Dr. Fox reported receiving consulting fees from Siemens and Roche.

A version of this article appeared on Medscape.com.

A blood test that measures elevations in neurofilament light chain (NfL) levels in patients with multiple sclerosis (MS) could warn of worsening disability up to 2 years before it occurs, a new study suggests.

Rising NfL levels are a known indicator of neuroaxonal injury and correlate with MS disease activity. Levels rise in the presence of an MS relapse or MRI activity and fall following treatment with disease-modifying therapies. But the link between NfL levels and worsening disability was less understood.

This new analysis of NfL in two large MS cohorts found that elevated levels of the neuronal protein at baseline were associated with large increases in future disability risk, even in patients with no clinical relapse.

“This rising of NfL up to 2 years before signs of disability worsening represents the window when interventions may prevent worsening,” lead investigator Ahmed Abdelhak, MD, department of neurology, University of California, San Francisco, said in a press release.

The findings were published online in JAMA Neurology.
 

Early warning system?

The study included data on 1,899 patients with nearly 13,000 patient visits from two observational, long-term, real-world cohorts: the U.S.-based Expression, Proteomics, Imaging, Clinical (EPIC) study (n = 609 patients), and the Swiss Multiple Sclerosis Cohort trial (SMSC; n = 1,290 patients).

Investigators analyzed longitudinal serum NfL measurements in conjunction with clinical disability worsening, defined as 6 months or more of increased impairment as measured by the Expanded Disability Status Scale.

Researchers also assessed the temporal association between NfL measurements and the risk of increased disability and distinguished between disability with and without relapse.

Worsening disability was reported in 227 patients in the EPIC group and 435 in the SMSC trial.

Elevated NfL at baseline was associated with a 70% higher risk for worsening disability with relapse about 11 months later in the SMSC study (hazard ratio, 1.70; P = .02). In the EPIC trial, there was trend toward a 91% higher risk for worsening disability with relapse at 12.6 months, although the findings did not meet statistical significance (HR, 1.91; P = .07).

The risk of future disability progression independent of clinical relapse was 40% higher in those with high NfL at baseline in the EPIC study 12 months after baseline (HR, 1.40; P = .02) and 49% higher in the SMSC trial 21 months later (HR, 1.49; P < .001).

The early elevation of NfL levels suggests a slower degradation of nerve cells and could be a possible early warning system of future progression of disability, allowing time for interventions that could slow or even halt further disability.

“Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging,” senior author Jens Kuhle, MD, PhD, leader of the Swiss cohort and head of the Multiple Sclerosis Center at University Hospital and University of Basel, said in a statement.
 

Challenges for clinicians

Commenting on the findings, Robert Fox, MD, staff neurologist at the Mellen Center for MS and vice chair for research, Neurological Institute, Cleveland Clinic, said that, while there is a clinical test to measure NfL levels, incorporating that test into standard of care isn’t straightforward.

“The challenge for the practicing clinician is to translate these population-level studies to individual patient management decisions,” said Dr. Fox, who was not a part of the study.

“The published prediction curves corrected for age, sex, disease course, disease-modifying treatment, relapse within the past 90 days, and current disability status, the combination of which makes it rather challenging to calculate and interpret adjusted z score NfL levels in routine practice and then use it in clinical decision-making.”

The investigators said the study underscores the importance of NfL as an MS biomarker and “points to the existence of different windows of dynamic central nervous system pathology” that precedes worsening disability with or without relapse. But there may be a simpler explanation, Dr. Fox suggested.

“We know MRI activity occurs 5-10 times more frequently than relapses, and we know that MRI activity is associated with both NfL increases and future disability progression,” Dr. Fox said. “It is quite likely that the elevations in NfL seen here are reflective of new MRI disease activity, which frequently is seen without symptoms of an MS relapse,” he said

The study was funded by the Westridge Foundation, F. Hoffmann–La Roche, the Fishman Family, the Swiss National Research Foundation, the National Institutes of Health/National Institute of Neurological Disorders and Stroke, and the Valhalla Foundation. Dr. Abdelhak reported receiving grants from the German Multiple Sclerosis Society and the Weill Institute for Neurosciences outside the submitted work. Dr. Kuhle has received grants from Swiss MS Society, the Swiss National Research Foundation, the Progressive MS Alliance, Biogen, Merck, Celgene, Bristol-Myers Squibb, Novartis, Octave Bioscience, Roche, Sanofi, Alnylam, Bayer, Immunic, Quanterix, Neurogenesis, Stata DX, and the University of Basel outside the submitted work. Dr. Fox reported receiving consulting fees from Siemens and Roche.

A version of this article appeared on Medscape.com.

A blood test that measures elevations in neurofilament light chain (NfL) levels in patients with multiple sclerosis (MS) could warn of worsening disability up to 2 years before it occurs, a new study suggests.

Rising NfL levels are a known indicator of neuroaxonal injury and correlate with MS disease activity. Levels rise in the presence of an MS relapse or MRI activity and fall following treatment with disease-modifying therapies. But the link between NfL levels and worsening disability was less understood.

This new analysis of NfL in two large MS cohorts found that elevated levels of the neuronal protein at baseline were associated with large increases in future disability risk, even in patients with no clinical relapse.

“This rising of NfL up to 2 years before signs of disability worsening represents the window when interventions may prevent worsening,” lead investigator Ahmed Abdelhak, MD, department of neurology, University of California, San Francisco, said in a press release.

The findings were published online in JAMA Neurology.
 

Early warning system?

The study included data on 1,899 patients with nearly 13,000 patient visits from two observational, long-term, real-world cohorts: the U.S.-based Expression, Proteomics, Imaging, Clinical (EPIC) study (n = 609 patients), and the Swiss Multiple Sclerosis Cohort trial (SMSC; n = 1,290 patients).

Investigators analyzed longitudinal serum NfL measurements in conjunction with clinical disability worsening, defined as 6 months or more of increased impairment as measured by the Expanded Disability Status Scale.

Researchers also assessed the temporal association between NfL measurements and the risk of increased disability and distinguished between disability with and without relapse.

Worsening disability was reported in 227 patients in the EPIC group and 435 in the SMSC trial.

Elevated NfL at baseline was associated with a 70% higher risk for worsening disability with relapse about 11 months later in the SMSC study (hazard ratio, 1.70; P = .02). In the EPIC trial, there was trend toward a 91% higher risk for worsening disability with relapse at 12.6 months, although the findings did not meet statistical significance (HR, 1.91; P = .07).

The risk of future disability progression independent of clinical relapse was 40% higher in those with high NfL at baseline in the EPIC study 12 months after baseline (HR, 1.40; P = .02) and 49% higher in the SMSC trial 21 months later (HR, 1.49; P < .001).

The early elevation of NfL levels suggests a slower degradation of nerve cells and could be a possible early warning system of future progression of disability, allowing time for interventions that could slow or even halt further disability.

“Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging,” senior author Jens Kuhle, MD, PhD, leader of the Swiss cohort and head of the Multiple Sclerosis Center at University Hospital and University of Basel, said in a statement.
 

Challenges for clinicians

Commenting on the findings, Robert Fox, MD, staff neurologist at the Mellen Center for MS and vice chair for research, Neurological Institute, Cleveland Clinic, said that, while there is a clinical test to measure NfL levels, incorporating that test into standard of care isn’t straightforward.

“The challenge for the practicing clinician is to translate these population-level studies to individual patient management decisions,” said Dr. Fox, who was not a part of the study.

“The published prediction curves corrected for age, sex, disease course, disease-modifying treatment, relapse within the past 90 days, and current disability status, the combination of which makes it rather challenging to calculate and interpret adjusted z score NfL levels in routine practice and then use it in clinical decision-making.”

The investigators said the study underscores the importance of NfL as an MS biomarker and “points to the existence of different windows of dynamic central nervous system pathology” that precedes worsening disability with or without relapse. But there may be a simpler explanation, Dr. Fox suggested.

“We know MRI activity occurs 5-10 times more frequently than relapses, and we know that MRI activity is associated with both NfL increases and future disability progression,” Dr. Fox said. “It is quite likely that the elevations in NfL seen here are reflective of new MRI disease activity, which frequently is seen without symptoms of an MS relapse,” he said

The study was funded by the Westridge Foundation, F. Hoffmann–La Roche, the Fishman Family, the Swiss National Research Foundation, the National Institutes of Health/National Institute of Neurological Disorders and Stroke, and the Valhalla Foundation. Dr. Abdelhak reported receiving grants from the German Multiple Sclerosis Society and the Weill Institute for Neurosciences outside the submitted work. Dr. Kuhle has received grants from Swiss MS Society, the Swiss National Research Foundation, the Progressive MS Alliance, Biogen, Merck, Celgene, Bristol-Myers Squibb, Novartis, Octave Bioscience, Roche, Sanofi, Alnylam, Bayer, Immunic, Quanterix, Neurogenesis, Stata DX, and the University of Basel outside the submitted work. Dr. Fox reported receiving consulting fees from Siemens and Roche.

A version of this article appeared on Medscape.com.

PHILADELPHIA – The 2021 Chronic Kidney Disease Epidemiology Collaboration race-free equation for calculating estimated glomerular filtration rate showed the least bias and most consistent performance, compared with two alternative methods for calculating eGFR, in a study of 1,491 young adults aged 18-40 years.

The two alternative formulas for calculating eGFR, the CKiD U25 (Chronic Kidney Disease in Children under 25) and the European Kidney Function Consortium equations, showed higher levels of bias that resulted in underestimates of kidney function, particularly in younger adults 18-25 years old and in those with higher eGFR values, Leslie A. Inker, MD, said at Kidney Week 2023, organized by the American Society of Nephrology.

Mitchel L. Zoler/MDedge News

However, for young adults with a history of childhood CKD and especially for those who continue under the care of pediatric clinicians even after they become young adults, use of the CKiD U25 equation, remains a reasonable option, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston. The CKiD U25 equation is intended for people aged 1-25 years and came out in late 2020.

Pediatric nephrologists use the CKiD U25 but the results of the 2021 CKD-EPI race-free equation is what U.S. clinical labs routinely report for people aged 18 or older. “Our findings support the current practice of pediatric nephrologists” who may opt to use the CKiD U25 even when a patient turns 18 years or older, Dr. Inker said in an interview.

But the new results also support the current practice of U.S. labs, which is to focus on calculating eGFR in anyone at least 18 years old using the 2021 equation developed by the CKD-EPI, work led by Dr. Inker. The new findings confirm routine use of the 2021 CKD-EPI equation in adults as young as 18 years old, especially when they’re having their eGFR calculated for the first time, she said.
 

Discontinuity changing from CKiD U25 to CKD-EPI is ‘not huge’

“It’s important to understand that the 2021 CKD-EPI equation works in young adults,” noted Josef Coresh, MD, PhD, professor of clinical epidemiology at Johns Hopkins University, Baltimore, who collaborated on both the current study and on developing the 2021 CKD-EPI equation.

Mitchel L. Zoler/MDedge News

The new data show that the discontinuity in eGFR produced by switching from the CKiD U25 formula to the 2021 CKD-EPI formula “is not huge, maybe about 5 mL/min per 1.73 m² higher. People should focus on the new baseline and subsequent trends, not the modest difference between equations,” Dr. Coresh advised in an interview.

The study run by Dr. Inker and her associates used 1,491 people aged 18-40 years and enrolled in a cohort created by the CKD-EPI. They compared measured GFR levels in each subject with the estimates generated by the 2021 race-free CKD-EPI equation, the CKiD U25 equation, and a third equation developed by the EKFC and introduced in 2021.
 

Less bias with the 2021 CKD-EPI equation

The researchers compared the three eGFR equations with their respective measured GFR values by two metrics: bias, defined as the median difference between measured and estimated GFR; and the percentage of eGFR values that fell within 30% of the corresponding measured GFR value.

The results showed that bias was lowest using the 2021 CKD-EPI equation, with an overall median difference of 0.5 mL/min per 1.73 m². This compared with median differences of 7.2 with the CKiD U25 equation and 4.9 mL/min per 1.73 m² with the EKFC equation. The disparity in bias was greatest among those with eGFR values in the range of 60-90 mL/min per 1.73 m² and was also greatest for those 18-25 years old.

The CKD-EPI equation results also showed the greatest consistency of bias across the entire 18- to 40-year-old range. Between-group differences were small for the percentage of eGFR values that fell within 30% of measured GFR, with all three equations scoring in the range of 88%-90%.

The study received no commercial funding. Dr. Inker is a consultant to Diamtrix and her department receives research funding from Chinook, Omeros, Reata, and Tricida. Dr. Coresh is a consultant to Healthy.io and SomaLogic and he has an ownership interest in Healthy.io.

PHILADELPHIA – The 2021 Chronic Kidney Disease Epidemiology Collaboration race-free equation for calculating estimated glomerular filtration rate showed the least bias and most consistent performance, compared with two alternative methods for calculating eGFR, in a study of 1,491 young adults aged 18-40 years.

The two alternative formulas for calculating eGFR, the CKiD U25 (Chronic Kidney Disease in Children under 25) and the European Kidney Function Consortium equations, showed higher levels of bias that resulted in underestimates of kidney function, particularly in younger adults 18-25 years old and in those with higher eGFR values, Leslie A. Inker, MD, said at Kidney Week 2023, organized by the American Society of Nephrology.

Mitchel L. Zoler/MDedge News

However, for young adults with a history of childhood CKD and especially for those who continue under the care of pediatric clinicians even after they become young adults, use of the CKiD U25 equation, remains a reasonable option, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston. The CKiD U25 equation is intended for people aged 1-25 years and came out in late 2020.

Pediatric nephrologists use the CKiD U25 but the results of the 2021 CKD-EPI race-free equation is what U.S. clinical labs routinely report for people aged 18 or older. “Our findings support the current practice of pediatric nephrologists” who may opt to use the CKiD U25 even when a patient turns 18 years or older, Dr. Inker said in an interview.

But the new results also support the current practice of U.S. labs, which is to focus on calculating eGFR in anyone at least 18 years old using the 2021 equation developed by the CKD-EPI, work led by Dr. Inker. The new findings confirm routine use of the 2021 CKD-EPI equation in adults as young as 18 years old, especially when they’re having their eGFR calculated for the first time, she said.
 

Discontinuity changing from CKiD U25 to CKD-EPI is ‘not huge’

“It’s important to understand that the 2021 CKD-EPI equation works in young adults,” noted Josef Coresh, MD, PhD, professor of clinical epidemiology at Johns Hopkins University, Baltimore, who collaborated on both the current study and on developing the 2021 CKD-EPI equation.

Mitchel L. Zoler/MDedge News

The new data show that the discontinuity in eGFR produced by switching from the CKiD U25 formula to the 2021 CKD-EPI formula “is not huge, maybe about 5 mL/min per 1.73 m² higher. People should focus on the new baseline and subsequent trends, not the modest difference between equations,” Dr. Coresh advised in an interview.

The study run by Dr. Inker and her associates used 1,491 people aged 18-40 years and enrolled in a cohort created by the CKD-EPI. They compared measured GFR levels in each subject with the estimates generated by the 2021 race-free CKD-EPI equation, the CKiD U25 equation, and a third equation developed by the EKFC and introduced in 2021.
 

Less bias with the 2021 CKD-EPI equation

The researchers compared the three eGFR equations with their respective measured GFR values by two metrics: bias, defined as the median difference between measured and estimated GFR; and the percentage of eGFR values that fell within 30% of the corresponding measured GFR value.

The results showed that bias was lowest using the 2021 CKD-EPI equation, with an overall median difference of 0.5 mL/min per 1.73 m². This compared with median differences of 7.2 with the CKiD U25 equation and 4.9 mL/min per 1.73 m² with the EKFC equation. The disparity in bias was greatest among those with eGFR values in the range of 60-90 mL/min per 1.73 m² and was also greatest for those 18-25 years old.

The CKD-EPI equation results also showed the greatest consistency of bias across the entire 18- to 40-year-old range. Between-group differences were small for the percentage of eGFR values that fell within 30% of measured GFR, with all three equations scoring in the range of 88%-90%.

The study received no commercial funding. Dr. Inker is a consultant to Diamtrix and her department receives research funding from Chinook, Omeros, Reata, and Tricida. Dr. Coresh is a consultant to Healthy.io and SomaLogic and he has an ownership interest in Healthy.io.

PHILADELPHIA – The 2021 Chronic Kidney Disease Epidemiology Collaboration race-free equation for calculating estimated glomerular filtration rate showed the least bias and most consistent performance, compared with two alternative methods for calculating eGFR, in a study of 1,491 young adults aged 18-40 years.

The two alternative formulas for calculating eGFR, the CKiD U25 (Chronic Kidney Disease in Children under 25) and the European Kidney Function Consortium equations, showed higher levels of bias that resulted in underestimates of kidney function, particularly in younger adults 18-25 years old and in those with higher eGFR values, Leslie A. Inker, MD, said at Kidney Week 2023, organized by the American Society of Nephrology.

Mitchel L. Zoler/MDedge News

However, for young adults with a history of childhood CKD and especially for those who continue under the care of pediatric clinicians even after they become young adults, use of the CKiD U25 equation, remains a reasonable option, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston. The CKiD U25 equation is intended for people aged 1-25 years and came out in late 2020.

Pediatric nephrologists use the CKiD U25 but the results of the 2021 CKD-EPI race-free equation is what U.S. clinical labs routinely report for people aged 18 or older. “Our findings support the current practice of pediatric nephrologists” who may opt to use the CKiD U25 even when a patient turns 18 years or older, Dr. Inker said in an interview.

But the new results also support the current practice of U.S. labs, which is to focus on calculating eGFR in anyone at least 18 years old using the 2021 equation developed by the CKD-EPI, work led by Dr. Inker. The new findings confirm routine use of the 2021 CKD-EPI equation in adults as young as 18 years old, especially when they’re having their eGFR calculated for the first time, she said.
 

Discontinuity changing from CKiD U25 to CKD-EPI is ‘not huge’

“It’s important to understand that the 2021 CKD-EPI equation works in young adults,” noted Josef Coresh, MD, PhD, professor of clinical epidemiology at Johns Hopkins University, Baltimore, who collaborated on both the current study and on developing the 2021 CKD-EPI equation.

Mitchel L. Zoler/MDedge News

The new data show that the discontinuity in eGFR produced by switching from the CKiD U25 formula to the 2021 CKD-EPI formula “is not huge, maybe about 5 mL/min per 1.73 m² higher. People should focus on the new baseline and subsequent trends, not the modest difference between equations,” Dr. Coresh advised in an interview.

The study run by Dr. Inker and her associates used 1,491 people aged 18-40 years and enrolled in a cohort created by the CKD-EPI. They compared measured GFR levels in each subject with the estimates generated by the 2021 race-free CKD-EPI equation, the CKiD U25 equation, and a third equation developed by the EKFC and introduced in 2021.
 

Less bias with the 2021 CKD-EPI equation

The researchers compared the three eGFR equations with their respective measured GFR values by two metrics: bias, defined as the median difference between measured and estimated GFR; and the percentage of eGFR values that fell within 30% of the corresponding measured GFR value.

The results showed that bias was lowest using the 2021 CKD-EPI equation, with an overall median difference of 0.5 mL/min per 1.73 m². This compared with median differences of 7.2 with the CKiD U25 equation and 4.9 mL/min per 1.73 m² with the EKFC equation. The disparity in bias was greatest among those with eGFR values in the range of 60-90 mL/min per 1.73 m² and was also greatest for those 18-25 years old.

The CKD-EPI equation results also showed the greatest consistency of bias across the entire 18- to 40-year-old range. Between-group differences were small for the percentage of eGFR values that fell within 30% of measured GFR, with all three equations scoring in the range of 88%-90%.

The study received no commercial funding. Dr. Inker is a consultant to Diamtrix and her department receives research funding from Chinook, Omeros, Reata, and Tricida. Dr. Coresh is a consultant to Healthy.io and SomaLogic and he has an ownership interest in Healthy.io.

PHOENIX – Artificial intelligence (AI) is poised to dramatically alter health care, and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.

Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.

He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.

Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.

It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.

Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
 

Trust, but verify

Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.

AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
 

Limitations

The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.

Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.

Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.

There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.

Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.

Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.

He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.

For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”

Dr. Morren has no relevant financial disclosures.

PHOENIX – Artificial intelligence (AI) is poised to dramatically alter health care, and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.

Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.

He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.

Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.

It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.

Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
 

Trust, but verify

Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.

AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
 

Limitations

The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.

Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.

Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.

There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.

Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.

Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.

He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.

For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”

Dr. Morren has no relevant financial disclosures.

PHOENIX – Artificial intelligence (AI) is poised to dramatically alter health care, and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.

Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.

He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.

Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.

It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.

Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
 

Trust, but verify

Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.

AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
 

Limitations

The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.

Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.

Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.

There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.

Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.

Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.

He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.

For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”

Dr. Morren has no relevant financial disclosures.

Pelvic floor disorders are embarrassing, annoying, painful, and extremely disruptive to a woman’s life, often resulting in depression, anxiety, and a poor self-image. According to a 2021 study, approximately 75% of peripartum women and 68% of postmenopausal women feel insufficiently informed about pelvic floor disorders.¹

Consequently, a large majority of women are not seeking care for these disorders. This drives health care costs higher as women wait until their symptoms are unbearable until finally seeking help. Many of these women don’t know they have options.
 

Who is at risk?

To understand the scope of this growing problem, it is vital to see who is most at risk. Parity, age, body mass index, and race are significant factors, although any woman can have a pelvic floor disorder (PFD).

Urinary incontinence (UI), pelvic floor prolapses (POP), and fecal incontinence (FI) are three of the most common pelvic floor disorders. Pregnancy and childbirth, specifically a vaginal birth, greatly contribute to this population’s risk. In pregnancy, the increase in plasma volume and glomerular filtration rate, along with hormone changes impacting urethral pressure and the growing gravid uterus, cause urinary frequency and nocturia. This can result in urinary incontinence during and after pregnancy.

Indeed, 76% of women with urinary incontinence at 3 months postpartum report it 12 years later.¹ Third- and fourth-degree lacerations during delivery are uncommon (3.3%), but can cause fecal incontinence, often requiring surgery.¹ Independently, all of these symptoms have been correlated with sexual dysfunction and postpartum depression.

One-third of all women and 50% of women over the age of 55 are currently affected by a PFD. Contributing factors include hormone changes with menopause that affect the pelvic floor muscles and connective tissue, prior childbirth and pregnancy, constipation, heavy lifting, prior pelvic surgery, and obesity. These women are vulnerable to pelvic organ prolapse from the weakened pelvic floor muscles. They will often present with a vague complaint of “something is protruding out of my vagina.” These women also present with urinary incontinence or leakage, proclaiming they have to wear a diaper or a pad. Without proper knowledge, aging women think these issues are normal and nothing can be done.

The woman with a BMI above 30 may have damaged tissues supporting the uterus and bladder, weakening those organs, and causing a prolapse. Incontinence is a result of poor muscle and connective tissue of the vagina that support the urethra. Obese women can suffer from both urinary and bowel incontinence. By the year 2030, it is projected that one in two adults will be obese.² This will greatly impact health care costs.

To date, there is little conclusive evidence on the impact of race on pelvic floor disorders. A study in Scientific Reports did find that Asian women have a significantly lower risk for any PFD.² Some research has found that Black and Hispanic women have less risk for UI but are at higher risk for FI and other PFDs.³ Understandably, women of certain cultures and demographics may be less likely to report incontinence to their clinicians and may be less informed as well.
 

What can we do?

The American College of Obstetricians and Gynecologists (ACOG) has acknowledged the deficiencies and lack of standard care of pelvic health in pregnancy and postpartum.¹ There are differences in definitions across clinical practice and in the medical literature. Inconsistent patient reporting of PFD symptoms occurs due to nonstandard methods (questionnaire, interview, physical exam). With the often-short time allotted for visits with health care providers, women may neglect to discuss their symptoms, especially if they have other more pressing matters to address.

What would really help improve treatment of PFDs is early education in pregnancy. At the first OB appointment, a pregnant woman should be given information on what are normal and abnormal symptoms, from the beginning through postpartum. At each visit, she should be given ample opportunity to discuss symptoms of pelvic health. Clinicians should continue assessing, questioning, and discussing treatment options as applicable. Women need to know that early recognition and treatment can have a positive affect on their pelvic health for years to come.

ACOG recommends all postpartum patients see an obstetric provider within 3 weeks of delivery.¹ Most are seen at 6 weeks. Pelvic health should be discussed at this final postpartum appointment, including normal and abnormal symptoms within the next few months and beyond.

Regardless of pregnancy status, women need a safe and supportive place to describe their pelvic floor issues. There is a validated questionnaire tool available for postpartum, but one is desperately needed for all women, especially women at risk. A pelvic health assessment must be included in every annual exam.

Women need to know there are multiple treatment modalities including simple exercises, physical therapy, a variety of pessaries, medications, and surgery. Sometimes, all that is needed are a few lifestyle changes: avoiding pushing or straining while urinating or having a bowel movement, maintaining a healthy diet rich in high fiber foods, and drinking plenty of fluids.

The National Public Health Service in the United Kingdom recently announced a government-funded program for pelvic health services to begin in April 2024.⁴ This program will address the pelvic floor needs, assessment, education and treatment for women after childbirth.

There are multiple clinics in the United States focusing on women’s health that feature urogynecologists – specialists in pelvic floor disorders. These specialists do a thorough health and physical assessment, explain types of pelvic floor disorders, and suggest appropriate treatment options. Most importantly, urogynecologists listen and address a woman’s concerns and fears.

There is no reason for women to feel compromised at any age. We, as health care providers, just need to assess, educate, treat, and follow up.

Ms. Barnett is a registered nurse in the department of obstetrics, Mills-Peninsula Medical Center, Burlingame, Calif. She has disclosed no relevant financial relationships.

References

1. Madsen AM et al. Recognition and management of pelvic floor disorders in pregnancy and the postpartum period. Obstet Gynecol Clin North Am. 2021 Sep;48(3):571-84. doi: 10.1016/j.ogc.2021.05.009.

2. Kenne KA et al. Prevalence of pelvic floor disorders in adult women being seen in a primary care setting and associated risk factors. Sci Rep. 2022 June; (12):9878. doi: 10.1038/s41598-022-13501-w.

3. Nygaard I et al. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008;300(11):1311-6. doi: 10.1001/jama.300.11.1311.

4. United Kingdom Department of Health and Social Care. “National pelvic health service to support women.” 2023 Oct 19.

Pelvic floor disorders are embarrassing, annoying, painful, and extremely disruptive to a woman’s life, often resulting in depression, anxiety, and a poor self-image. According to a 2021 study, approximately 75% of peripartum women and 68% of postmenopausal women feel insufficiently informed about pelvic floor disorders.¹

Consequently, a large majority of women are not seeking care for these disorders. This drives health care costs higher as women wait until their symptoms are unbearable until finally seeking help. Many of these women don’t know they have options.
 

Who is at risk?

To understand the scope of this growing problem, it is vital to see who is most at risk. Parity, age, body mass index, and race are significant factors, although any woman can have a pelvic floor disorder (PFD).

Urinary incontinence (UI), pelvic floor prolapses (POP), and fecal incontinence (FI) are three of the most common pelvic floor disorders. Pregnancy and childbirth, specifically a vaginal birth, greatly contribute to this population’s risk. In pregnancy, the increase in plasma volume and glomerular filtration rate, along with hormone changes impacting urethral pressure and the growing gravid uterus, cause urinary frequency and nocturia. This can result in urinary incontinence during and after pregnancy.

Indeed, 76% of women with urinary incontinence at 3 months postpartum report it 12 years later.¹ Third- and fourth-degree lacerations during delivery are uncommon (3.3%), but can cause fecal incontinence, often requiring surgery.¹ Independently, all of these symptoms have been correlated with sexual dysfunction and postpartum depression.

One-third of all women and 50% of women over the age of 55 are currently affected by a PFD. Contributing factors include hormone changes with menopause that affect the pelvic floor muscles and connective tissue, prior childbirth and pregnancy, constipation, heavy lifting, prior pelvic surgery, and obesity. These women are vulnerable to pelvic organ prolapse from the weakened pelvic floor muscles. They will often present with a vague complaint of “something is protruding out of my vagina.” These women also present with urinary incontinence or leakage, proclaiming they have to wear a diaper or a pad. Without proper knowledge, aging women think these issues are normal and nothing can be done.

The woman with a BMI above 30 may have damaged tissues supporting the uterus and bladder, weakening those organs, and causing a prolapse. Incontinence is a result of poor muscle and connective tissue of the vagina that support the urethra. Obese women can suffer from both urinary and bowel incontinence. By the year 2030, it is projected that one in two adults will be obese.² This will greatly impact health care costs.

To date, there is little conclusive evidence on the impact of race on pelvic floor disorders. A study in Scientific Reports did find that Asian women have a significantly lower risk for any PFD.² Some research has found that Black and Hispanic women have less risk for UI but are at higher risk for FI and other PFDs.³ Understandably, women of certain cultures and demographics may be less likely to report incontinence to their clinicians and may be less informed as well.
 

What can we do?

The American College of Obstetricians and Gynecologists (ACOG) has acknowledged the deficiencies and lack of standard care of pelvic health in pregnancy and postpartum.¹ There are differences in definitions across clinical practice and in the medical literature. Inconsistent patient reporting of PFD symptoms occurs due to nonstandard methods (questionnaire, interview, physical exam). With the often-short time allotted for visits with health care providers, women may neglect to discuss their symptoms, especially if they have other more pressing matters to address.

What would really help improve treatment of PFDs is early education in pregnancy. At the first OB appointment, a pregnant woman should be given information on what are normal and abnormal symptoms, from the beginning through postpartum. At each visit, she should be given ample opportunity to discuss symptoms of pelvic health. Clinicians should continue assessing, questioning, and discussing treatment options as applicable. Women need to know that early recognition and treatment can have a positive affect on their pelvic health for years to come.

ACOG recommends all postpartum patients see an obstetric provider within 3 weeks of delivery.¹ Most are seen at 6 weeks. Pelvic health should be discussed at this final postpartum appointment, including normal and abnormal symptoms within the next few months and beyond.

Regardless of pregnancy status, women need a safe and supportive place to describe their pelvic floor issues. There is a validated questionnaire tool available for postpartum, but one is desperately needed for all women, especially women at risk. A pelvic health assessment must be included in every annual exam.

Women need to know there are multiple treatment modalities including simple exercises, physical therapy, a variety of pessaries, medications, and surgery. Sometimes, all that is needed are a few lifestyle changes: avoiding pushing or straining while urinating or having a bowel movement, maintaining a healthy diet rich in high fiber foods, and drinking plenty of fluids.

The National Public Health Service in the United Kingdom recently announced a government-funded program for pelvic health services to begin in April 2024.⁴ This program will address the pelvic floor needs, assessment, education and treatment for women after childbirth.

There are multiple clinics in the United States focusing on women’s health that feature urogynecologists – specialists in pelvic floor disorders. These specialists do a thorough health and physical assessment, explain types of pelvic floor disorders, and suggest appropriate treatment options. Most importantly, urogynecologists listen and address a woman’s concerns and fears.

There is no reason for women to feel compromised at any age. We, as health care providers, just need to assess, educate, treat, and follow up.

Ms. Barnett is a registered nurse in the department of obstetrics, Mills-Peninsula Medical Center, Burlingame, Calif. She has disclosed no relevant financial relationships.

References

1. Madsen AM et al. Recognition and management of pelvic floor disorders in pregnancy and the postpartum period. Obstet Gynecol Clin North Am. 2021 Sep;48(3):571-84. doi: 10.1016/j.ogc.2021.05.009.

2. Kenne KA et al. Prevalence of pelvic floor disorders in adult women being seen in a primary care setting and associated risk factors. Sci Rep. 2022 June; (12):9878. doi: 10.1038/s41598-022-13501-w.

3. Nygaard I et al. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008;300(11):1311-6. doi: 10.1001/jama.300.11.1311.

4. United Kingdom Department of Health and Social Care. “National pelvic health service to support women.” 2023 Oct 19.

Pelvic floor disorders are embarrassing, annoying, painful, and extremely disruptive to a woman’s life, often resulting in depression, anxiety, and a poor self-image. According to a 2021 study, approximately 75% of peripartum women and 68% of postmenopausal women feel insufficiently informed about pelvic floor disorders.¹

Consequently, a large majority of women are not seeking care for these disorders. This drives health care costs higher as women wait until their symptoms are unbearable until finally seeking help. Many of these women don’t know they have options.
 

Who is at risk?

To understand the scope of this growing problem, it is vital to see who is most at risk. Parity, age, body mass index, and race are significant factors, although any woman can have a pelvic floor disorder (PFD).

Urinary incontinence (UI), pelvic floor prolapses (POP), and fecal incontinence (FI) are three of the most common pelvic floor disorders. Pregnancy and childbirth, specifically a vaginal birth, greatly contribute to this population’s risk. In pregnancy, the increase in plasma volume and glomerular filtration rate, along with hormone changes impacting urethral pressure and the growing gravid uterus, cause urinary frequency and nocturia. This can result in urinary incontinence during and after pregnancy.

Indeed, 76% of women with urinary incontinence at 3 months postpartum report it 12 years later.¹ Third- and fourth-degree lacerations during delivery are uncommon (3.3%), but can cause fecal incontinence, often requiring surgery.¹ Independently, all of these symptoms have been correlated with sexual dysfunction and postpartum depression.

One-third of all women and 50% of women over the age of 55 are currently affected by a PFD. Contributing factors include hormone changes with menopause that affect the pelvic floor muscles and connective tissue, prior childbirth and pregnancy, constipation, heavy lifting, prior pelvic surgery, and obesity. These women are vulnerable to pelvic organ prolapse from the weakened pelvic floor muscles. They will often present with a vague complaint of “something is protruding out of my vagina.” These women also present with urinary incontinence or leakage, proclaiming they have to wear a diaper or a pad. Without proper knowledge, aging women think these issues are normal and nothing can be done.

The woman with a BMI above 30 may have damaged tissues supporting the uterus and bladder, weakening those organs, and causing a prolapse. Incontinence is a result of poor muscle and connective tissue of the vagina that support the urethra. Obese women can suffer from both urinary and bowel incontinence. By the year 2030, it is projected that one in two adults will be obese.² This will greatly impact health care costs.

To date, there is little conclusive evidence on the impact of race on pelvic floor disorders. A study in Scientific Reports did find that Asian women have a significantly lower risk for any PFD.² Some research has found that Black and Hispanic women have less risk for UI but are at higher risk for FI and other PFDs.³ Understandably, women of certain cultures and demographics may be less likely to report incontinence to their clinicians and may be less informed as well.
 

What can we do?

The American College of Obstetricians and Gynecologists (ACOG) has acknowledged the deficiencies and lack of standard care of pelvic health in pregnancy and postpartum.¹ There are differences in definitions across clinical practice and in the medical literature. Inconsistent patient reporting of PFD symptoms occurs due to nonstandard methods (questionnaire, interview, physical exam). With the often-short time allotted for visits with health care providers, women may neglect to discuss their symptoms, especially if they have other more pressing matters to address.

What would really help improve treatment of PFDs is early education in pregnancy. At the first OB appointment, a pregnant woman should be given information on what are normal and abnormal symptoms, from the beginning through postpartum. At each visit, she should be given ample opportunity to discuss symptoms of pelvic health. Clinicians should continue assessing, questioning, and discussing treatment options as applicable. Women need to know that early recognition and treatment can have a positive affect on their pelvic health for years to come.

ACOG recommends all postpartum patients see an obstetric provider within 3 weeks of delivery.¹ Most are seen at 6 weeks. Pelvic health should be discussed at this final postpartum appointment, including normal and abnormal symptoms within the next few months and beyond.

Regardless of pregnancy status, women need a safe and supportive place to describe their pelvic floor issues. There is a validated questionnaire tool available for postpartum, but one is desperately needed for all women, especially women at risk. A pelvic health assessment must be included in every annual exam.

Women need to know there are multiple treatment modalities including simple exercises, physical therapy, a variety of pessaries, medications, and surgery. Sometimes, all that is needed are a few lifestyle changes: avoiding pushing or straining while urinating or having a bowel movement, maintaining a healthy diet rich in high fiber foods, and drinking plenty of fluids.

The National Public Health Service in the United Kingdom recently announced a government-funded program for pelvic health services to begin in April 2024.⁴ This program will address the pelvic floor needs, assessment, education and treatment for women after childbirth.

There are multiple clinics in the United States focusing on women’s health that feature urogynecologists – specialists in pelvic floor disorders. These specialists do a thorough health and physical assessment, explain types of pelvic floor disorders, and suggest appropriate treatment options. Most importantly, urogynecologists listen and address a woman’s concerns and fears.

There is no reason for women to feel compromised at any age. We, as health care providers, just need to assess, educate, treat, and follow up.

Ms. Barnett is a registered nurse in the department of obstetrics, Mills-Peninsula Medical Center, Burlingame, Calif. She has disclosed no relevant financial relationships.

References

1. Madsen AM et al. Recognition and management of pelvic floor disorders in pregnancy and the postpartum period. Obstet Gynecol Clin North Am. 2021 Sep;48(3):571-84. doi: 10.1016/j.ogc.2021.05.009.

2. Kenne KA et al. Prevalence of pelvic floor disorders in adult women being seen in a primary care setting and associated risk factors. Sci Rep. 2022 June; (12):9878. doi: 10.1038/s41598-022-13501-w.

3. Nygaard I et al. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008;300(11):1311-6. doi: 10.1001/jama.300.11.1311.

4. United Kingdom Department of Health and Social Care. “National pelvic health service to support women.” 2023 Oct 19.

ANAHEIM, CALIF. – Patients with uncontrolled asthma are seen more often by primary care providers (PCPs) than by allergists, but a survey has found that 42% of PCPs are unfamiliar with the biologics that have markedly improved asthma treatment options over the past 2 decades.

Bijalben Patel, MD, with the department of internal medicine, University of South Florida, Tampa, said in an interview that in addition to the considerable lack of knowledge of biologics in primary care, she was surprised that 77% of survey participants stated they only referred patients to specialists after two or more exacerbations.

“This is important because these patients are considered to have exacerbation-prone asthma, which should be managed by specialists,” she said.

She said that being “unfamiliar” with biologics meant that the healthcare provider may have heard of biologics but did not know the various types, initiation criteria, or side effects.

The researchers administered a REDCap (Research Electronic Data Capture) survey by email to primary care attending and resident physicians in the departments of internal medicine, family medicine, and pediatrics, and 85 responded. Responses were compared using Chi-square tests.

Patel presented the results of the survey at the annual meeting of the American College of Allergy, Asthma & Immunology.

82% do not order labs

Familiarity did not vary in primary care with number of patients with asthma seen per month, the researchers noted.

“Also, the frequency of PCP referrals to a specialist did not change familiarity with biologics (P = .260) or eligibility criteria (P = .393),” the researchers said.

In addition, they found that 82% of those surveyed do not order labs, and 90% do not use absolute eosinophil count to guide care.

Dr. Patel explained that lab work such as obtaining IgE levels and a complete blood count with a differential and examining the absolute eosinophil count help identify patients who are at high risk for future exacerbation and also treatable phenotypic traits, which can be targeted with biologic therapy. 

Angela Duff Hogan, MD, vice chair of the ACAAI Asthma Committee and professor of pediatrics at Eastern Virginia Medical School, Norfolk, said in an interview that she finds the delay on referrals the most concerning finding in the survey results.

“I’m not as concerned they are not obtaining labs,” said Dr. Hogan, who was not part of the study. “The specialist can do that. It’s more concerning they wait so long to refer a patient with poorly controlled asthma. We know that asthma patients treated by an allergist have better asthma control, better quality of life, and reduced health care costs.”
 

Asthma specialists ‘need better marketing’

Dr. Hogan said that the results show the need for more studies to demonstrate that asthma specialists can improve outcomes and reduce healthcare costs.

“Objective data is more convincing than subjective data,” she noted. “As a specialty, we need to disseminate more information about asthma management, the “new” asthma guidelines, SMART/MART therapy, and the importance of biologicals in asthma. We need better marketing as a specialty in asthma care.”

Dr. Patel said that their goal with the study is to raise awareness about the available asthma biologic therapies, which have been improving care for 2 decades.

“The results of the survey point to the need to improve the communication between primary care physicians and asthma care specialists, including regarding use of biologics,” senior author Juan Carlos Cardet, MD, MPH, also an allergy specialist at USF, added in a press release. “Biologics have become an important tool in the treatment of asthma and other allergic diseases such as atopic dermatitis (eczema), chronic rhinosinusitis with nasal polyps and eosinophilic esophagitis, and can prevent substantial ill results from occurring in patients who are eligible for them.”

The study authors and Dr. Hogan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

ANAHEIM, CALIF. – Patients with uncontrolled asthma are seen more often by primary care providers (PCPs) than by allergists, but a survey has found that 42% of PCPs are unfamiliar with the biologics that have markedly improved asthma treatment options over the past 2 decades.

Bijalben Patel, MD, with the department of internal medicine, University of South Florida, Tampa, said in an interview that in addition to the considerable lack of knowledge of biologics in primary care, she was surprised that 77% of survey participants stated they only referred patients to specialists after two or more exacerbations.

“This is important because these patients are considered to have exacerbation-prone asthma, which should be managed by specialists,” she said.

She said that being “unfamiliar” with biologics meant that the healthcare provider may have heard of biologics but did not know the various types, initiation criteria, or side effects.

The researchers administered a REDCap (Research Electronic Data Capture) survey by email to primary care attending and resident physicians in the departments of internal medicine, family medicine, and pediatrics, and 85 responded. Responses were compared using Chi-square tests.

Patel presented the results of the survey at the annual meeting of the American College of Allergy, Asthma & Immunology.

82% do not order labs

Familiarity did not vary in primary care with number of patients with asthma seen per month, the researchers noted.

“Also, the frequency of PCP referrals to a specialist did not change familiarity with biologics (P = .260) or eligibility criteria (P = .393),” the researchers said.

In addition, they found that 82% of those surveyed do not order labs, and 90% do not use absolute eosinophil count to guide care.

Dr. Patel explained that lab work such as obtaining IgE levels and a complete blood count with a differential and examining the absolute eosinophil count help identify patients who are at high risk for future exacerbation and also treatable phenotypic traits, which can be targeted with biologic therapy. 

Angela Duff Hogan, MD, vice chair of the ACAAI Asthma Committee and professor of pediatrics at Eastern Virginia Medical School, Norfolk, said in an interview that she finds the delay on referrals the most concerning finding in the survey results.

“I’m not as concerned they are not obtaining labs,” said Dr. Hogan, who was not part of the study. “The specialist can do that. It’s more concerning they wait so long to refer a patient with poorly controlled asthma. We know that asthma patients treated by an allergist have better asthma control, better quality of life, and reduced health care costs.”
 

Asthma specialists ‘need better marketing’

Dr. Hogan said that the results show the need for more studies to demonstrate that asthma specialists can improve outcomes and reduce healthcare costs.

“Objective data is more convincing than subjective data,” she noted. “As a specialty, we need to disseminate more information about asthma management, the “new” asthma guidelines, SMART/MART therapy, and the importance of biologicals in asthma. We need better marketing as a specialty in asthma care.”

Dr. Patel said that their goal with the study is to raise awareness about the available asthma biologic therapies, which have been improving care for 2 decades.

“The results of the survey point to the need to improve the communication between primary care physicians and asthma care specialists, including regarding use of biologics,” senior author Juan Carlos Cardet, MD, MPH, also an allergy specialist at USF, added in a press release. “Biologics have become an important tool in the treatment of asthma and other allergic diseases such as atopic dermatitis (eczema), chronic rhinosinusitis with nasal polyps and eosinophilic esophagitis, and can prevent substantial ill results from occurring in patients who are eligible for them.”

The study authors and Dr. Hogan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

ANAHEIM, CALIF. – Patients with uncontrolled asthma are seen more often by primary care providers (PCPs) than by allergists, but a survey has found that 42% of PCPs are unfamiliar with the biologics that have markedly improved asthma treatment options over the past 2 decades.

Bijalben Patel, MD, with the department of internal medicine, University of South Florida, Tampa, said in an interview that in addition to the considerable lack of knowledge of biologics in primary care, she was surprised that 77% of survey participants stated they only referred patients to specialists after two or more exacerbations.

“This is important because these patients are considered to have exacerbation-prone asthma, which should be managed by specialists,” she said.

She said that being “unfamiliar” with biologics meant that the healthcare provider may have heard of biologics but did not know the various types, initiation criteria, or side effects.

The researchers administered a REDCap (Research Electronic Data Capture) survey by email to primary care attending and resident physicians in the departments of internal medicine, family medicine, and pediatrics, and 85 responded. Responses were compared using Chi-square tests.

Patel presented the results of the survey at the annual meeting of the American College of Allergy, Asthma & Immunology.

82% do not order labs

Familiarity did not vary in primary care with number of patients with asthma seen per month, the researchers noted.

“Also, the frequency of PCP referrals to a specialist did not change familiarity with biologics (P = .260) or eligibility criteria (P = .393),” the researchers said.

In addition, they found that 82% of those surveyed do not order labs, and 90% do not use absolute eosinophil count to guide care.

Dr. Patel explained that lab work such as obtaining IgE levels and a complete blood count with a differential and examining the absolute eosinophil count help identify patients who are at high risk for future exacerbation and also treatable phenotypic traits, which can be targeted with biologic therapy. 

Angela Duff Hogan, MD, vice chair of the ACAAI Asthma Committee and professor of pediatrics at Eastern Virginia Medical School, Norfolk, said in an interview that she finds the delay on referrals the most concerning finding in the survey results.

“I’m not as concerned they are not obtaining labs,” said Dr. Hogan, who was not part of the study. “The specialist can do that. It’s more concerning they wait so long to refer a patient with poorly controlled asthma. We know that asthma patients treated by an allergist have better asthma control, better quality of life, and reduced health care costs.”
 

Asthma specialists ‘need better marketing’

Dr. Hogan said that the results show the need for more studies to demonstrate that asthma specialists can improve outcomes and reduce healthcare costs.

“Objective data is more convincing than subjective data,” she noted. “As a specialty, we need to disseminate more information about asthma management, the “new” asthma guidelines, SMART/MART therapy, and the importance of biologicals in asthma. We need better marketing as a specialty in asthma care.”

Dr. Patel said that their goal with the study is to raise awareness about the available asthma biologic therapies, which have been improving care for 2 decades.

“The results of the survey point to the need to improve the communication between primary care physicians and asthma care specialists, including regarding use of biologics,” senior author Juan Carlos Cardet, MD, MPH, also an allergy specialist at USF, added in a press release. “Biologics have become an important tool in the treatment of asthma and other allergic diseases such as atopic dermatitis (eczema), chronic rhinosinusitis with nasal polyps and eosinophilic esophagitis, and can prevent substantial ill results from occurring in patients who are eligible for them.”

The study authors and Dr. Hogan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Older adults with actinic keratoses (AKs) have a higher risk for skin cancers, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.

METHODOLOGY:

• AKs have been associated with a small risk for cutaneous SCC, but associations with risk for other skin cancers have not been well studied.
• AKs may be a marker of overall skin cancer risk, but guidelines for AK management lack recommendations for follow-up cancer surveillance.
• The researchers reviewed data from a random sample of 5 million fee-for-service Medicare beneficiaries treated for AKs from 2009 through 2018 in the United States. Patients with seborrheic keratoses (SKs) were included as comparators, and patients with a history of skin cancer were excluded.
• The primary outcome was the first surgically treated skin cancer, including SCC, BCC, and melanoma.

TAKEAWAY:

• A total of 555,945 adults with AKs and 481,024 with SKs were included. The mean age was approximately 74.0 years. More than half were female. Most were non-Hispanic White.
• Among patients with AKs, the absolute risk for any skin cancer after the first AK was 6.3%, 18.4%, and 28.5% at 1, 3, and 5 years, respectively.
• Patients with AKs had a significantly increased relative risk for any skin cancer compared with those with SKs (adjusted hazard ratio [aHR], 2.17) and separately for keratinocyte carcinoma (aHR, 2.20), SCC (aHR, 2.63), BCC (aHR, 1.85), and melanoma (aHR, 1.67).
• Although AKs are not considered a biological precursor of melanoma or BCC, the results suggest that AKs may be clinical indicators of increased UV exposure that subsequently increases the risk for skin cancer.

IN PRACTICE:

“The present results highlight the importance of developing evidence-based guidelines for follow-up skin cancer surveillance in patients with AKs, optimally including measures of AK burden,” the researchers wrote.

SOURCE:

The lead author on the study was Cassandra Mohr, BS, with corresponding author Mackenzie R. Wehner, MD, MPhil, of The University of Texas MD Anderson Cancer Center, Houston. The study was published online in JAMA Dermatology .

LIMITATIONS:

The study population of Medicare beneficiaries aged 65 years or older may not be a nationally representative sample, and surveillance bias may contribute to the increased risk for skin cancer in patients with AKs. The use of both ICD and CPT codes may underestimate the number of skin cancers because of cases that were treated nonsurgically.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and The University of Texas Rising STARS program. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Older adults with actinic keratoses (AKs) have a higher risk for skin cancers, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.

METHODOLOGY:

• AKs have been associated with a small risk for cutaneous SCC, but associations with risk for other skin cancers have not been well studied.
• AKs may be a marker of overall skin cancer risk, but guidelines for AK management lack recommendations for follow-up cancer surveillance.
• The researchers reviewed data from a random sample of 5 million fee-for-service Medicare beneficiaries treated for AKs from 2009 through 2018 in the United States. Patients with seborrheic keratoses (SKs) were included as comparators, and patients with a history of skin cancer were excluded.
• The primary outcome was the first surgically treated skin cancer, including SCC, BCC, and melanoma.

TAKEAWAY:

• A total of 555,945 adults with AKs and 481,024 with SKs were included. The mean age was approximately 74.0 years. More than half were female. Most were non-Hispanic White.
• Among patients with AKs, the absolute risk for any skin cancer after the first AK was 6.3%, 18.4%, and 28.5% at 1, 3, and 5 years, respectively.
• Patients with AKs had a significantly increased relative risk for any skin cancer compared with those with SKs (adjusted hazard ratio [aHR], 2.17) and separately for keratinocyte carcinoma (aHR, 2.20), SCC (aHR, 2.63), BCC (aHR, 1.85), and melanoma (aHR, 1.67).
• Although AKs are not considered a biological precursor of melanoma or BCC, the results suggest that AKs may be clinical indicators of increased UV exposure that subsequently increases the risk for skin cancer.

IN PRACTICE:

“The present results highlight the importance of developing evidence-based guidelines for follow-up skin cancer surveillance in patients with AKs, optimally including measures of AK burden,” the researchers wrote.

SOURCE:

The lead author on the study was Cassandra Mohr, BS, with corresponding author Mackenzie R. Wehner, MD, MPhil, of The University of Texas MD Anderson Cancer Center, Houston. The study was published online in JAMA Dermatology .

LIMITATIONS:

The study population of Medicare beneficiaries aged 65 years or older may not be a nationally representative sample, and surveillance bias may contribute to the increased risk for skin cancer in patients with AKs. The use of both ICD and CPT codes may underestimate the number of skin cancers because of cases that were treated nonsurgically.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and The University of Texas Rising STARS program. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Older adults with actinic keratoses (AKs) have a higher risk for skin cancers, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.

METHODOLOGY:

• AKs have been associated with a small risk for cutaneous SCC, but associations with risk for other skin cancers have not been well studied.
• AKs may be a marker of overall skin cancer risk, but guidelines for AK management lack recommendations for follow-up cancer surveillance.
• The researchers reviewed data from a random sample of 5 million fee-for-service Medicare beneficiaries treated for AKs from 2009 through 2018 in the United States. Patients with seborrheic keratoses (SKs) were included as comparators, and patients with a history of skin cancer were excluded.
• The primary outcome was the first surgically treated skin cancer, including SCC, BCC, and melanoma.

TAKEAWAY:

• A total of 555,945 adults with AKs and 481,024 with SKs were included. The mean age was approximately 74.0 years. More than half were female. Most were non-Hispanic White.
• Among patients with AKs, the absolute risk for any skin cancer after the first AK was 6.3%, 18.4%, and 28.5% at 1, 3, and 5 years, respectively.
• Patients with AKs had a significantly increased relative risk for any skin cancer compared with those with SKs (adjusted hazard ratio [aHR], 2.17) and separately for keratinocyte carcinoma (aHR, 2.20), SCC (aHR, 2.63), BCC (aHR, 1.85), and melanoma (aHR, 1.67).
• Although AKs are not considered a biological precursor of melanoma or BCC, the results suggest that AKs may be clinical indicators of increased UV exposure that subsequently increases the risk for skin cancer.

IN PRACTICE:

“The present results highlight the importance of developing evidence-based guidelines for follow-up skin cancer surveillance in patients with AKs, optimally including measures of AK burden,” the researchers wrote.

SOURCE:

The lead author on the study was Cassandra Mohr, BS, with corresponding author Mackenzie R. Wehner, MD, MPhil, of The University of Texas MD Anderson Cancer Center, Houston. The study was published online in JAMA Dermatology .

LIMITATIONS:

The study population of Medicare beneficiaries aged 65 years or older may not be a nationally representative sample, and surveillance bias may contribute to the increased risk for skin cancer in patients with AKs. The use of both ICD and CPT codes may underestimate the number of skin cancers because of cases that were treated nonsurgically.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and The University of Texas Rising STARS program. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Incipient ulceration in primary cutaneous melanoma may represent a more biologically aggressive disease population than truly nonulcerated tumors.

METHODOLOGY:

• The final cohort included 40 cases of incipient ulceration that were matched 1:2 with 80 nonulcerated controls and 80 ulcerated controls.
• The prognostic significance of incipient ulceration in cutaneous melanoma is unclear.
• Current American Joint Committee on Cancer (AJCC) guidelines classify incipient ulceration as nonulcerated.
• In a retrospective case-control study, researchers drew from the Melanoma Institute Australia database to identify resected primary cutaneous melanomas diagnosed between 2005 and 2015 that had slides available at Royal Prince Alfred Hospital in Sydney and a Breslow thickness greater than 0 mm.
• Clinical outcomes compared between cases and controls were recurrence-free survival (RFS), melanoma-specific survival (MSS), and overall survival (OS).

TAKEAWAY:

• The median Breslow depth was 2.8 mm for incipient cases, compared with 1.0 mm for nonulcerated melanomas and 5.3 mm for ulcerated melanomas, while the median tumor mitotic rate was 5.0 per mm² for incipient cases, compared with 1 per mm² in nonulcerated controls and 9 per mm² in ulcerated controls.
• On univariable analyses, compared with patients with incipiently ulcerated cases, patients with nonulcerated tumors had significantly better OS (hazard ratio [HR], 0.49) and RFS (HR, 0.37), while patients with ulcerated tumors showed worse RFS (HR, 1.67).
• On multivariable analyses, no differences in survival outcomes were observed, perhaps due to the moderate number of incipient ulceration cases included in the study, the authors wrote.

IN PRACTICE:

“Future editions of the AJCC staging system should consider acknowledging this interpretive challenge and provide guidance on how primary melanomas with incipient ulceration should be classified,” the researchers wrote.

SOURCE:

Richard A. Scolyer, MD, a pathologist at Royal Prince Alfred Hospital, Camperdown, Australia, is the senior author on the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations of the study include its retrospective design and the relatively small number of cases that met criteria for inclusion.

DISCLOSURES:

Dr. Scolyer disclosed that he has received grants from the Australian National Health and Medical Research Council and personal fees from MetaOptima, F. Hoffmann-La Roche, Evaxion, Provectus, QBiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline, all outside the submitted work. Four coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Incipient ulceration in primary cutaneous melanoma may represent a more biologically aggressive disease population than truly nonulcerated tumors.

METHODOLOGY:

• The final cohort included 40 cases of incipient ulceration that were matched 1:2 with 80 nonulcerated controls and 80 ulcerated controls.
• The prognostic significance of incipient ulceration in cutaneous melanoma is unclear.
• Current American Joint Committee on Cancer (AJCC) guidelines classify incipient ulceration as nonulcerated.
• In a retrospective case-control study, researchers drew from the Melanoma Institute Australia database to identify resected primary cutaneous melanomas diagnosed between 2005 and 2015 that had slides available at Royal Prince Alfred Hospital in Sydney and a Breslow thickness greater than 0 mm.
• Clinical outcomes compared between cases and controls were recurrence-free survival (RFS), melanoma-specific survival (MSS), and overall survival (OS).

TAKEAWAY:

• The median Breslow depth was 2.8 mm for incipient cases, compared with 1.0 mm for nonulcerated melanomas and 5.3 mm for ulcerated melanomas, while the median tumor mitotic rate was 5.0 per mm² for incipient cases, compared with 1 per mm² in nonulcerated controls and 9 per mm² in ulcerated controls.
• On univariable analyses, compared with patients with incipiently ulcerated cases, patients with nonulcerated tumors had significantly better OS (hazard ratio [HR], 0.49) and RFS (HR, 0.37), while patients with ulcerated tumors showed worse RFS (HR, 1.67).
• On multivariable analyses, no differences in survival outcomes were observed, perhaps due to the moderate number of incipient ulceration cases included in the study, the authors wrote.

IN PRACTICE:

“Future editions of the AJCC staging system should consider acknowledging this interpretive challenge and provide guidance on how primary melanomas with incipient ulceration should be classified,” the researchers wrote.

SOURCE:

Richard A. Scolyer, MD, a pathologist at Royal Prince Alfred Hospital, Camperdown, Australia, is the senior author on the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations of the study include its retrospective design and the relatively small number of cases that met criteria for inclusion.

DISCLOSURES:

Dr. Scolyer disclosed that he has received grants from the Australian National Health and Medical Research Council and personal fees from MetaOptima, F. Hoffmann-La Roche, Evaxion, Provectus, QBiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline, all outside the submitted work. Four coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Incipient ulceration in primary cutaneous melanoma may represent a more biologically aggressive disease population than truly nonulcerated tumors.

METHODOLOGY:

• The final cohort included 40 cases of incipient ulceration that were matched 1:2 with 80 nonulcerated controls and 80 ulcerated controls.
• The prognostic significance of incipient ulceration in cutaneous melanoma is unclear.
• Current American Joint Committee on Cancer (AJCC) guidelines classify incipient ulceration as nonulcerated.
• In a retrospective case-control study, researchers drew from the Melanoma Institute Australia database to identify resected primary cutaneous melanomas diagnosed between 2005 and 2015 that had slides available at Royal Prince Alfred Hospital in Sydney and a Breslow thickness greater than 0 mm.
• Clinical outcomes compared between cases and controls were recurrence-free survival (RFS), melanoma-specific survival (MSS), and overall survival (OS).

TAKEAWAY:

• The median Breslow depth was 2.8 mm for incipient cases, compared with 1.0 mm for nonulcerated melanomas and 5.3 mm for ulcerated melanomas, while the median tumor mitotic rate was 5.0 per mm² for incipient cases, compared with 1 per mm² in nonulcerated controls and 9 per mm² in ulcerated controls.
• On univariable analyses, compared with patients with incipiently ulcerated cases, patients with nonulcerated tumors had significantly better OS (hazard ratio [HR], 0.49) and RFS (HR, 0.37), while patients with ulcerated tumors showed worse RFS (HR, 1.67).
• On multivariable analyses, no differences in survival outcomes were observed, perhaps due to the moderate number of incipient ulceration cases included in the study, the authors wrote.

IN PRACTICE:

“Future editions of the AJCC staging system should consider acknowledging this interpretive challenge and provide guidance on how primary melanomas with incipient ulceration should be classified,” the researchers wrote.

SOURCE:

Richard A. Scolyer, MD, a pathologist at Royal Prince Alfred Hospital, Camperdown, Australia, is the senior author on the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations of the study include its retrospective design and the relatively small number of cases that met criteria for inclusion.

DISCLOSURES:

Dr. Scolyer disclosed that he has received grants from the Australian National Health and Medical Research Council and personal fees from MetaOptima, F. Hoffmann-La Roche, Evaxion, Provectus, QBiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline, all outside the submitted work. Four coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

PHILADELPHIA – As an initial treatment strategy for treatment of atrial fibrillation (AF) in patients with obesity, dual energy cardioversion is substantially more reliable and just as safe as conventional single energy cardioversion, a multicenter randomized trial shows.

When treated with dual direct current cardioversion (DCCV), only 2% of patients with obesity failed to cardiovert on the first shock versus 14% (P = .002) of those treated with a conventional single DCCV, reported Joshua D. Aymond, MD, a fellow in electrophysiology at Ochsner Health, New Orleans.

Of the 14 patients in the single DCCV arm who did not convert on the first shock, 12 cardioverted when switched to dual energy. The remaining two cardioverted on the second dual shock.

In the dual DCCV group, of the two patients who did not cardiovert on the first dual shock, one did on the second. The other also cardioverted on a second shock, but this second shock was not delivered for 2 weeks, during which time the patient received a course of amiodarone-based anti-arrhythmic therapy.

No disadvantages seen with dual energy

The greater efficacy of a first shock with dual DCCV was achieved with no apparent disadvantages. There were no differences in post-procedure chest discomfort and no procedure-related adverse events in either arm, Dr. Aymond said.

The rising prevalence of obesity in the United States has created the need for a more effective first-line strategy for AF, noted Dr. Aymond, who presented the results of this study at the annual scientific sessions of the American Heart Association.

Cardioversion, which he characterized as the treatment of choice for AF, “fails to restore sinus rhythm in 20% to 35% of obese patients versus less than 10% of non-obese patients,” he said. The higher failure rate in patients with obesity is becoming a more common clinical issue not only due to the rising rates of obesity but a corresponding rise in AF, which is a related phenomenon.

“The risk of atrial fibrillation is increased by 50% relative to those who are not obese,” Dr. Aymond explained.

In this study, 200 patients at three participating centers were randomized to single DCCV or double DCCV after exclusions that included ventricular tachycardia and respiratory instability. The baseline characteristics were comparable. All 101 patients in the single DCCV group and 99 patients in the dual DCCV group were available for the intention-to-treat analysis.

200 vs. 400 joules delivered across the heart

In the study protocol, patients were fitted with four chest pads, two located adjacent but above the heart and two adjacent but below the heart. For single DCCV, 200 joules of energy were delivered from the upper right pad to the lower left pad across the heart. For dual DCCV, another 200 joules were delivered simultaneously from the upper left to the lower right across the heart. The total dose in the dual DCCV group was 400 joules.

The primary outcome was restoration of sinus rhythm of any duration immediately after DCCV. Safety, including clinical events, was a secondary outcome. Only the patients were blinded to the energy they received.

On univariate analysis, the odds ratio for successful cardioversion with dual DCCV was nearly eightfold higher (OR 7.8; P = .008) than single DCCV. On a simple multivariable analysis, when the researchers controlled for just age, sex, and body mass index, the odds ratio rose (OR 8.5; P = .007).

On a comprehensive multivariable analysis adding control for such characteristics as left ventricular ejection fraction (LVEF), obstructive sleep apnea, and antiarrhythmic drugs, the advantage of dual DCCV climbed above 12-fold (OR 12.6; P = .03).

The study is addressing a relevant and persistent question, said the AHA-invited discussant Jose A. Joglar, MD, program director, Clinical Cardiac Electrophysiology Fellowship, University of Texas Southwestern Medical Center, Dallas.

Dr. Joglar pointed out that alternatives to single DCCV for patients more difficult to cardiovert have been “sought for decades.” He noted that a variety of techniques, including dual DCCV, have been evaluated in small studies and case reports.

Alternatives for obese outlined

Several have shown promise, Dr. Joglar said. As one of several examples, he cited a 20-patient study that randomized patients to adhesive patches, like those employed in the Aymond trial, or handheld paddles. Both patches and paddles were applied with manual pressure while a 200-joule shock was delivered. The proportion of patients who cardioverted on the first shock was almost two times higher in the group after the first shock with the paddles (50% vs. 27%; P = .01). Dr. Joglar said the study supports the principle that 200 joules delivered by adhesive patches is inadequate for treatment of AF in many patients with obesity.

Dr. Joglar also cited studies suggesting that single DCCV delivered with higher energy than 200 joules appears to improve cardioversion success rates, but he indicated that this study with dual DCCV in the front-line setting provides evidence for another alternative.

“This is the first such trial with dual defibrillators as an initial strategy,” he said, calling the groups well matched and the superiority of dual DCCV “impressive.” He cautioned that the study size was well powered for the endpoint but perhaps small for evaluating relative safety.

Yet, “the study adds credibility and confidence for the use of dual DCCV, especially in difficult or refractory patients,” he said. He is less certain that it establishes dual DCCV as a standard first-line therapy in all patients with obesity. This would require additional studies to compare it to other types of strategies such as those he mentioned.

As an option for improving cardioversion in first-line treatment, dual DCCV “can be added to a list of other techniques, such as manual pressure or a higher initial dose with single DCCV,” he said.

Dr. Aymond and Dr. Joglar report no potential conflicts of interest.

PHILADELPHIA – As an initial treatment strategy for treatment of atrial fibrillation (AF) in patients with obesity, dual energy cardioversion is substantially more reliable and just as safe as conventional single energy cardioversion, a multicenter randomized trial shows.

When treated with dual direct current cardioversion (DCCV), only 2% of patients with obesity failed to cardiovert on the first shock versus 14% (P = .002) of those treated with a conventional single DCCV, reported Joshua D. Aymond, MD, a fellow in electrophysiology at Ochsner Health, New Orleans.

Of the 14 patients in the single DCCV arm who did not convert on the first shock, 12 cardioverted when switched to dual energy. The remaining two cardioverted on the second dual shock.

In the dual DCCV group, of the two patients who did not cardiovert on the first dual shock, one did on the second. The other also cardioverted on a second shock, but this second shock was not delivered for 2 weeks, during which time the patient received a course of amiodarone-based anti-arrhythmic therapy.

No disadvantages seen with dual energy

The greater efficacy of a first shock with dual DCCV was achieved with no apparent disadvantages. There were no differences in post-procedure chest discomfort and no procedure-related adverse events in either arm, Dr. Aymond said.

The rising prevalence of obesity in the United States has created the need for a more effective first-line strategy for AF, noted Dr. Aymond, who presented the results of this study at the annual scientific sessions of the American Heart Association.

Cardioversion, which he characterized as the treatment of choice for AF, “fails to restore sinus rhythm in 20% to 35% of obese patients versus less than 10% of non-obese patients,” he said. The higher failure rate in patients with obesity is becoming a more common clinical issue not only due to the rising rates of obesity but a corresponding rise in AF, which is a related phenomenon.

“The risk of atrial fibrillation is increased by 50% relative to those who are not obese,” Dr. Aymond explained.

In this study, 200 patients at three participating centers were randomized to single DCCV or double DCCV after exclusions that included ventricular tachycardia and respiratory instability. The baseline characteristics were comparable. All 101 patients in the single DCCV group and 99 patients in the dual DCCV group were available for the intention-to-treat analysis.

200 vs. 400 joules delivered across the heart

In the study protocol, patients were fitted with four chest pads, two located adjacent but above the heart and two adjacent but below the heart. For single DCCV, 200 joules of energy were delivered from the upper right pad to the lower left pad across the heart. For dual DCCV, another 200 joules were delivered simultaneously from the upper left to the lower right across the heart. The total dose in the dual DCCV group was 400 joules.

The primary outcome was restoration of sinus rhythm of any duration immediately after DCCV. Safety, including clinical events, was a secondary outcome. Only the patients were blinded to the energy they received.

On univariate analysis, the odds ratio for successful cardioversion with dual DCCV was nearly eightfold higher (OR 7.8; P = .008) than single DCCV. On a simple multivariable analysis, when the researchers controlled for just age, sex, and body mass index, the odds ratio rose (OR 8.5; P = .007).

On a comprehensive multivariable analysis adding control for such characteristics as left ventricular ejection fraction (LVEF), obstructive sleep apnea, and antiarrhythmic drugs, the advantage of dual DCCV climbed above 12-fold (OR 12.6; P = .03).

The study is addressing a relevant and persistent question, said the AHA-invited discussant Jose A. Joglar, MD, program director, Clinical Cardiac Electrophysiology Fellowship, University of Texas Southwestern Medical Center, Dallas.

Dr. Joglar pointed out that alternatives to single DCCV for patients more difficult to cardiovert have been “sought for decades.” He noted that a variety of techniques, including dual DCCV, have been evaluated in small studies and case reports.

Alternatives for obese outlined

Several have shown promise, Dr. Joglar said. As one of several examples, he cited a 20-patient study that randomized patients to adhesive patches, like those employed in the Aymond trial, or handheld paddles. Both patches and paddles were applied with manual pressure while a 200-joule shock was delivered. The proportion of patients who cardioverted on the first shock was almost two times higher in the group after the first shock with the paddles (50% vs. 27%; P = .01). Dr. Joglar said the study supports the principle that 200 joules delivered by adhesive patches is inadequate for treatment of AF in many patients with obesity.

Dr. Joglar also cited studies suggesting that single DCCV delivered with higher energy than 200 joules appears to improve cardioversion success rates, but he indicated that this study with dual DCCV in the front-line setting provides evidence for another alternative.

“This is the first such trial with dual defibrillators as an initial strategy,” he said, calling the groups well matched and the superiority of dual DCCV “impressive.” He cautioned that the study size was well powered for the endpoint but perhaps small for evaluating relative safety.

Yet, “the study adds credibility and confidence for the use of dual DCCV, especially in difficult or refractory patients,” he said. He is less certain that it establishes dual DCCV as a standard first-line therapy in all patients with obesity. This would require additional studies to compare it to other types of strategies such as those he mentioned.

As an option for improving cardioversion in first-line treatment, dual DCCV “can be added to a list of other techniques, such as manual pressure or a higher initial dose with single DCCV,” he said.

Dr. Aymond and Dr. Joglar report no potential conflicts of interest.

PHILADELPHIA – As an initial treatment strategy for treatment of atrial fibrillation (AF) in patients with obesity, dual energy cardioversion is substantially more reliable and just as safe as conventional single energy cardioversion, a multicenter randomized trial shows.

When treated with dual direct current cardioversion (DCCV), only 2% of patients with obesity failed to cardiovert on the first shock versus 14% (P = .002) of those treated with a conventional single DCCV, reported Joshua D. Aymond, MD, a fellow in electrophysiology at Ochsner Health, New Orleans.

Of the 14 patients in the single DCCV arm who did not convert on the first shock, 12 cardioverted when switched to dual energy. The remaining two cardioverted on the second dual shock.

In the dual DCCV group, of the two patients who did not cardiovert on the first dual shock, one did on the second. The other also cardioverted on a second shock, but this second shock was not delivered for 2 weeks, during which time the patient received a course of amiodarone-based anti-arrhythmic therapy.

No disadvantages seen with dual energy

The greater efficacy of a first shock with dual DCCV was achieved with no apparent disadvantages. There were no differences in post-procedure chest discomfort and no procedure-related adverse events in either arm, Dr. Aymond said.

The rising prevalence of obesity in the United States has created the need for a more effective first-line strategy for AF, noted Dr. Aymond, who presented the results of this study at the annual scientific sessions of the American Heart Association.

Cardioversion, which he characterized as the treatment of choice for AF, “fails to restore sinus rhythm in 20% to 35% of obese patients versus less than 10% of non-obese patients,” he said. The higher failure rate in patients with obesity is becoming a more common clinical issue not only due to the rising rates of obesity but a corresponding rise in AF, which is a related phenomenon.

“The risk of atrial fibrillation is increased by 50% relative to those who are not obese,” Dr. Aymond explained.

In this study, 200 patients at three participating centers were randomized to single DCCV or double DCCV after exclusions that included ventricular tachycardia and respiratory instability. The baseline characteristics were comparable. All 101 patients in the single DCCV group and 99 patients in the dual DCCV group were available for the intention-to-treat analysis.

200 vs. 400 joules delivered across the heart

In the study protocol, patients were fitted with four chest pads, two located adjacent but above the heart and two adjacent but below the heart. For single DCCV, 200 joules of energy were delivered from the upper right pad to the lower left pad across the heart. For dual DCCV, another 200 joules were delivered simultaneously from the upper left to the lower right across the heart. The total dose in the dual DCCV group was 400 joules.

The primary outcome was restoration of sinus rhythm of any duration immediately after DCCV. Safety, including clinical events, was a secondary outcome. Only the patients were blinded to the energy they received.

On univariate analysis, the odds ratio for successful cardioversion with dual DCCV was nearly eightfold higher (OR 7.8; P = .008) than single DCCV. On a simple multivariable analysis, when the researchers controlled for just age, sex, and body mass index, the odds ratio rose (OR 8.5; P = .007).

On a comprehensive multivariable analysis adding control for such characteristics as left ventricular ejection fraction (LVEF), obstructive sleep apnea, and antiarrhythmic drugs, the advantage of dual DCCV climbed above 12-fold (OR 12.6; P = .03).

The study is addressing a relevant and persistent question, said the AHA-invited discussant Jose A. Joglar, MD, program director, Clinical Cardiac Electrophysiology Fellowship, University of Texas Southwestern Medical Center, Dallas.

Dr. Joglar pointed out that alternatives to single DCCV for patients more difficult to cardiovert have been “sought for decades.” He noted that a variety of techniques, including dual DCCV, have been evaluated in small studies and case reports.

Alternatives for obese outlined

Several have shown promise, Dr. Joglar said. As one of several examples, he cited a 20-patient study that randomized patients to adhesive patches, like those employed in the Aymond trial, or handheld paddles. Both patches and paddles were applied with manual pressure while a 200-joule shock was delivered. The proportion of patients who cardioverted on the first shock was almost two times higher in the group after the first shock with the paddles (50% vs. 27%; P = .01). Dr. Joglar said the study supports the principle that 200 joules delivered by adhesive patches is inadequate for treatment of AF in many patients with obesity.

Dr. Joglar also cited studies suggesting that single DCCV delivered with higher energy than 200 joules appears to improve cardioversion success rates, but he indicated that this study with dual DCCV in the front-line setting provides evidence for another alternative.

“This is the first such trial with dual defibrillators as an initial strategy,” he said, calling the groups well matched and the superiority of dual DCCV “impressive.” He cautioned that the study size was well powered for the endpoint but perhaps small for evaluating relative safety.

Yet, “the study adds credibility and confidence for the use of dual DCCV, especially in difficult or refractory patients,” he said. He is less certain that it establishes dual DCCV as a standard first-line therapy in all patients with obesity. This would require additional studies to compare it to other types of strategies such as those he mentioned.

As an option for improving cardioversion in first-line treatment, dual DCCV “can be added to a list of other techniques, such as manual pressure or a higher initial dose with single DCCV,” he said.

Dr. Aymond and Dr. Joglar report no potential conflicts of interest.

Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.

All-cause dementia, the primary outcome, was significantly reduced by 15% in the intervention group, compared with usual care, and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.

“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”

He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.

Target organ damage

Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”

The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.

Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”

So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”

Public health priority

It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”

Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.

This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.

It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.

Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.

All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.

The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.

Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.

Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.

At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.

The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.

Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.

The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.

At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.

The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).

Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.

Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.

The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.

First definitive evidence

Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.

The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.

Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”

Since it is the first of its kind though, replication of the results will be important, he noted.

The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.

The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.

All-cause dementia, the primary outcome, was significantly reduced by 15% in the intervention group, compared with usual care, and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.

“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”

He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.

Target organ damage

Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”

The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.

Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”

So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”

Public health priority

It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”

Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.

This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.

It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.

Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.

All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.

The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.

Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.

Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.

At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.

The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.

Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.

The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.

At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.

The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).

Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.

Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.

The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.

First definitive evidence

Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.

The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.

Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”

Since it is the first of its kind though, replication of the results will be important, he noted.

The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.

The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.

All-cause dementia, the primary outcome, was significantly reduced by 15% in the intervention group, compared with usual care, and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.

“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”

He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.

Target organ damage

Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”

The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.

Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”

So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”

Public health priority

It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”

Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.

This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.

It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.

Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.

All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.

The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.

Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.

Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.

At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.

The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.

Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.

The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.

At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.

The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).

Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.

Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.

The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.

First definitive evidence

Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.

The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.

Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”

Since it is the first of its kind though, replication of the results will be important, he noted.

The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.

The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

These skin findings were the latest manifestation of a condition that the patient had been diagnosed with at age 32: basal cell nevus syndrome (BCNS), also called Gorlin syndrome. This syndrome is characterized by multiple biopsy-proven BCCs, palmar pitting, frontal bossing, scoliosis, and gum cysts. This patient had had gum cysts since she was 8 years old; her sister and mother had similar gum cysts and her mother had at least 1 BCC. BCNS is caused by an inheritable defect in the Patched 1 (PTCH1) gene, leading to various findings—including numerous BCCs at a young age.¹

The Oncology team started the patient on the oral small-molecule chemotherapy agent vismodegib, 150 mg/d. The patient was also referred to Medical Genetics and Wound Care. Although her diagnosis had been made clinically years earlier, genetic testing was performed and confirmed a defect in the PTCH1 gene. This helped with surveillance plans. A computed tomography scan of the head revealed a nasal dermoid cyst of the ethmoid sinus that the Ear, Nose, & Throat and Neurology teams felt safe to observe.

After 3 months of therapy with vismodegib, the patient had significant improvement of facial lesions and significant re-epithelialization of the crown.

Patients on vismodegib often deal with adverse effects, but adjusted dosing regimens have proved to improve tolerability. This patient had substantial adverse effects including fatigue, hair loss, loss of taste, and weight loss (26 lbs). Because of these adverse effects, her regimen was adjusted to 1 month of every other day active treatment and 2 months off treatment, cycled continuously. With this regimen, her weight returned to normal and her sense of taste returned for most days in the treatment cycle.

She has been tolerating this regimen for 3 years with continued control of BCCs.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

These skin findings were the latest manifestation of a condition that the patient had been diagnosed with at age 32: basal cell nevus syndrome (BCNS), also called Gorlin syndrome. This syndrome is characterized by multiple biopsy-proven BCCs, palmar pitting, frontal bossing, scoliosis, and gum cysts. This patient had had gum cysts since she was 8 years old; her sister and mother had similar gum cysts and her mother had at least 1 BCC. BCNS is caused by an inheritable defect in the Patched 1 (PTCH1) gene, leading to various findings—including numerous BCCs at a young age.¹

The Oncology team started the patient on the oral small-molecule chemotherapy agent vismodegib, 150 mg/d. The patient was also referred to Medical Genetics and Wound Care. Although her diagnosis had been made clinically years earlier, genetic testing was performed and confirmed a defect in the PTCH1 gene. This helped with surveillance plans. A computed tomography scan of the head revealed a nasal dermoid cyst of the ethmoid sinus that the Ear, Nose, & Throat and Neurology teams felt safe to observe.

After 3 months of therapy with vismodegib, the patient had significant improvement of facial lesions and significant re-epithelialization of the crown.

Patients on vismodegib often deal with adverse effects, but adjusted dosing regimens have proved to improve tolerability. This patient had substantial adverse effects including fatigue, hair loss, loss of taste, and weight loss (26 lbs). Because of these adverse effects, her regimen was adjusted to 1 month of every other day active treatment and 2 months off treatment, cycled continuously. With this regimen, her weight returned to normal and her sense of taste returned for most days in the treatment cycle.

She has been tolerating this regimen for 3 years with continued control of BCCs.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

These skin findings were the latest manifestation of a condition that the patient had been diagnosed with at age 32: basal cell nevus syndrome (BCNS), also called Gorlin syndrome. This syndrome is characterized by multiple biopsy-proven BCCs, palmar pitting, frontal bossing, scoliosis, and gum cysts. This patient had had gum cysts since she was 8 years old; her sister and mother had similar gum cysts and her mother had at least 1 BCC. BCNS is caused by an inheritable defect in the Patched 1 (PTCH1) gene, leading to various findings—including numerous BCCs at a young age.¹

The Oncology team started the patient on the oral small-molecule chemotherapy agent vismodegib, 150 mg/d. The patient was also referred to Medical Genetics and Wound Care. Although her diagnosis had been made clinically years earlier, genetic testing was performed and confirmed a defect in the PTCH1 gene. This helped with surveillance plans. A computed tomography scan of the head revealed a nasal dermoid cyst of the ethmoid sinus that the Ear, Nose, & Throat and Neurology teams felt safe to observe.

After 3 months of therapy with vismodegib, the patient had significant improvement of facial lesions and significant re-epithelialization of the crown.

Patients on vismodegib often deal with adverse effects, but adjusted dosing regimens have proved to improve tolerability. This patient had substantial adverse effects including fatigue, hair loss, loss of taste, and weight loss (26 lbs). Because of these adverse effects, her regimen was adjusted to 1 month of every other day active treatment and 2 months off treatment, cycled continuously. With this regimen, her weight returned to normal and her sense of taste returned for most days in the treatment cycle.

She has been tolerating this regimen for 3 years with continued control of BCCs.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.