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iPad app puts cognitive screening in the hands of MS patients
NASHVILLE, TENN. – A new computer tablet application puts cognitive screening literally in the hands of patients with multiple sclerosis.
The Multiple Sclerosis Performance Test (MSPT), created specifically for iPad, presents patients with four assessments that they can complete in a short time before any clinic visit, according to Stephen M. Rao, PhD, who helped develop the tool. After patients complete the test battery, the program translates their results into adjusted normative data and feeds them directly into the individual electronic medical record. When the clinic visit begins, everything is ready for the physician and patient to review together. The program not only provides a solid baseline assessment, but can also, over time, create a longitudinal profile of a patient’s cognitive status, and help to guide management decisions, Dr. Rao said at the annual meeting of the Consortium of Multiple Sclerosis Centers.
“About half of people with MS do have cognitive problems, which, above and beyond the physical problems, can result in major challenges with work, the ability to engage in social activities, and the need for personal assistance,” said Dr. Rao, who is the Ralph and Luci Schey Chair and director of the Schey Center for Cognitive Neuroimaging at the Cleveland Clinic. “But despite that, even comprehensive MS care centers rarely screen for cognitive dysfunction using objective neuropsychological tests.”
Time is the issue for most clinics, he said. Although the paper-and-pencil screening tools out there take only 10 minutes or so, most centers don’t have the luxury of carving out those extra moments or dedicating a staff member to administer the test and handle the data.
The MSPT attempts to sidestep the problem of time and manpower. In Dr. Rao’s center and the other 10 in the United States and Europe that now use the tool, patients simply arrive a bit early for their appointment and complete the three components: a structured patient history; the Neurological Quality of Life assessment; and an electronic adaptation of the MS Functional Composite.
It assesses cognition with a processing speed test based on the Symbol Digit Modalities Test, which has long been validated for MS patients. A contrast sensitivity test assesses visual acuity. A simple manual-dexterity test, in which patients move peg symbols into “holes,” tests upper extremity function, and a video-recorded walking speed test assesses lower extremity function.
The system was validated in 165 patients with MS and 217 healthy controls. It correlated well with the paper-and-pencil Symbol Digits Modalities Test, and correlated more highly than that test with cerebral T2 lesion load (MS Journal. 2017;23:1929-37).
The MSPT is part of a Biogen-sponsored project that Dr. Rao and colleagues unveiled at the American Academy of Neurology annual meeting in April, called the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS). It will gather longitudinal data on 11,000 patients using the MSPT program, and correlate it to multiple clinical and socioeconomic outcomes, Dr. Rao said.
The processing speed test portion of MS PATHS isn’t only available to PATHS centers, he added. Any clinician can obtain it by simply registering with Biogen and downloading the standalone version, which is called CogEval.
After downloading, the clinician must register with Biogen, which then will email a code to unlock the program. CogEval can be used on any iPad system that runs iOS 11 or higher. Results don’t get uploaded automatically into an EHR, but they can be entered manually or printed.
Dr. Rao disclosed that he received financial support from Biogen for the research and development of the MSPT program.
SOURCE: Rao SM et al. CMSC 2018. doi: 10.1177/1352458516688955
NASHVILLE, TENN. – A new computer tablet application puts cognitive screening literally in the hands of patients with multiple sclerosis.
The Multiple Sclerosis Performance Test (MSPT), created specifically for iPad, presents patients with four assessments that they can complete in a short time before any clinic visit, according to Stephen M. Rao, PhD, who helped develop the tool. After patients complete the test battery, the program translates their results into adjusted normative data and feeds them directly into the individual electronic medical record. When the clinic visit begins, everything is ready for the physician and patient to review together. The program not only provides a solid baseline assessment, but can also, over time, create a longitudinal profile of a patient’s cognitive status, and help to guide management decisions, Dr. Rao said at the annual meeting of the Consortium of Multiple Sclerosis Centers.
“About half of people with MS do have cognitive problems, which, above and beyond the physical problems, can result in major challenges with work, the ability to engage in social activities, and the need for personal assistance,” said Dr. Rao, who is the Ralph and Luci Schey Chair and director of the Schey Center for Cognitive Neuroimaging at the Cleveland Clinic. “But despite that, even comprehensive MS care centers rarely screen for cognitive dysfunction using objective neuropsychological tests.”
Time is the issue for most clinics, he said. Although the paper-and-pencil screening tools out there take only 10 minutes or so, most centers don’t have the luxury of carving out those extra moments or dedicating a staff member to administer the test and handle the data.
The MSPT attempts to sidestep the problem of time and manpower. In Dr. Rao’s center and the other 10 in the United States and Europe that now use the tool, patients simply arrive a bit early for their appointment and complete the three components: a structured patient history; the Neurological Quality of Life assessment; and an electronic adaptation of the MS Functional Composite.
It assesses cognition with a processing speed test based on the Symbol Digit Modalities Test, which has long been validated for MS patients. A contrast sensitivity test assesses visual acuity. A simple manual-dexterity test, in which patients move peg symbols into “holes,” tests upper extremity function, and a video-recorded walking speed test assesses lower extremity function.
The system was validated in 165 patients with MS and 217 healthy controls. It correlated well with the paper-and-pencil Symbol Digits Modalities Test, and correlated more highly than that test with cerebral T2 lesion load (MS Journal. 2017;23:1929-37).
The MSPT is part of a Biogen-sponsored project that Dr. Rao and colleagues unveiled at the American Academy of Neurology annual meeting in April, called the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS). It will gather longitudinal data on 11,000 patients using the MSPT program, and correlate it to multiple clinical and socioeconomic outcomes, Dr. Rao said.
The processing speed test portion of MS PATHS isn’t only available to PATHS centers, he added. Any clinician can obtain it by simply registering with Biogen and downloading the standalone version, which is called CogEval.
After downloading, the clinician must register with Biogen, which then will email a code to unlock the program. CogEval can be used on any iPad system that runs iOS 11 or higher. Results don’t get uploaded automatically into an EHR, but they can be entered manually or printed.
Dr. Rao disclosed that he received financial support from Biogen for the research and development of the MSPT program.
SOURCE: Rao SM et al. CMSC 2018. doi: 10.1177/1352458516688955
NASHVILLE, TENN. – A new computer tablet application puts cognitive screening literally in the hands of patients with multiple sclerosis.
The Multiple Sclerosis Performance Test (MSPT), created specifically for iPad, presents patients with four assessments that they can complete in a short time before any clinic visit, according to Stephen M. Rao, PhD, who helped develop the tool. After patients complete the test battery, the program translates their results into adjusted normative data and feeds them directly into the individual electronic medical record. When the clinic visit begins, everything is ready for the physician and patient to review together. The program not only provides a solid baseline assessment, but can also, over time, create a longitudinal profile of a patient’s cognitive status, and help to guide management decisions, Dr. Rao said at the annual meeting of the Consortium of Multiple Sclerosis Centers.
“About half of people with MS do have cognitive problems, which, above and beyond the physical problems, can result in major challenges with work, the ability to engage in social activities, and the need for personal assistance,” said Dr. Rao, who is the Ralph and Luci Schey Chair and director of the Schey Center for Cognitive Neuroimaging at the Cleveland Clinic. “But despite that, even comprehensive MS care centers rarely screen for cognitive dysfunction using objective neuropsychological tests.”
Time is the issue for most clinics, he said. Although the paper-and-pencil screening tools out there take only 10 minutes or so, most centers don’t have the luxury of carving out those extra moments or dedicating a staff member to administer the test and handle the data.
The MSPT attempts to sidestep the problem of time and manpower. In Dr. Rao’s center and the other 10 in the United States and Europe that now use the tool, patients simply arrive a bit early for their appointment and complete the three components: a structured patient history; the Neurological Quality of Life assessment; and an electronic adaptation of the MS Functional Composite.
It assesses cognition with a processing speed test based on the Symbol Digit Modalities Test, which has long been validated for MS patients. A contrast sensitivity test assesses visual acuity. A simple manual-dexterity test, in which patients move peg symbols into “holes,” tests upper extremity function, and a video-recorded walking speed test assesses lower extremity function.
The system was validated in 165 patients with MS and 217 healthy controls. It correlated well with the paper-and-pencil Symbol Digits Modalities Test, and correlated more highly than that test with cerebral T2 lesion load (MS Journal. 2017;23:1929-37).
The MSPT is part of a Biogen-sponsored project that Dr. Rao and colleagues unveiled at the American Academy of Neurology annual meeting in April, called the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS). It will gather longitudinal data on 11,000 patients using the MSPT program, and correlate it to multiple clinical and socioeconomic outcomes, Dr. Rao said.
The processing speed test portion of MS PATHS isn’t only available to PATHS centers, he added. Any clinician can obtain it by simply registering with Biogen and downloading the standalone version, which is called CogEval.
After downloading, the clinician must register with Biogen, which then will email a code to unlock the program. CogEval can be used on any iPad system that runs iOS 11 or higher. Results don’t get uploaded automatically into an EHR, but they can be entered manually or printed.
Dr. Rao disclosed that he received financial support from Biogen for the research and development of the MSPT program.
SOURCE: Rao SM et al. CMSC 2018. doi: 10.1177/1352458516688955
REPORTING FROM THE CMSC ANNUAL MEETING
Peer mentorship, groups help combat burnout in female physicians
NEW YORK – Female physicians are at higher risk for burnout compared with their male counterparts, and the reasons and potential solutions for the problem were addressed at a symposium during the annual meeting of the American Psychiatric Association.
The work environment for women has improved over time, but lingering implicit and unconscious biases are part of the reason for the high burnout rate among women who are physicians, as are some inherent biological differences, according to Cynthia M. Stonnington, MD, of the Mayo Clinic, Phoenix.
In this video interview, Dr. Stonnington, symposium chair, discussed potential solutions, including facilitated peer mentorship and group support. She also reviewed recent data on how group support can be of benefit, and noted that “there is power in numbers.
“ ,” she said.
Dr. Stonnington reported having no disclosures.
NEW YORK – Female physicians are at higher risk for burnout compared with their male counterparts, and the reasons and potential solutions for the problem were addressed at a symposium during the annual meeting of the American Psychiatric Association.
The work environment for women has improved over time, but lingering implicit and unconscious biases are part of the reason for the high burnout rate among women who are physicians, as are some inherent biological differences, according to Cynthia M. Stonnington, MD, of the Mayo Clinic, Phoenix.
In this video interview, Dr. Stonnington, symposium chair, discussed potential solutions, including facilitated peer mentorship and group support. She also reviewed recent data on how group support can be of benefit, and noted that “there is power in numbers.
“ ,” she said.
Dr. Stonnington reported having no disclosures.
NEW YORK – Female physicians are at higher risk for burnout compared with their male counterparts, and the reasons and potential solutions for the problem were addressed at a symposium during the annual meeting of the American Psychiatric Association.
The work environment for women has improved over time, but lingering implicit and unconscious biases are part of the reason for the high burnout rate among women who are physicians, as are some inherent biological differences, according to Cynthia M. Stonnington, MD, of the Mayo Clinic, Phoenix.
In this video interview, Dr. Stonnington, symposium chair, discussed potential solutions, including facilitated peer mentorship and group support. She also reviewed recent data on how group support can be of benefit, and noted that “there is power in numbers.
“ ,” she said.
Dr. Stonnington reported having no disclosures.
REPORTING FROM APA
New agents may bring hope for SLE patients
SANDESTIN, FLA. – Several drugs approved for other conditions may also have good effect in patients with systemic lupus erythematosus, Michelle Petri, MD, said in an interview at the annual Congress of Clinical Rheumatology.
The molecules target several different disease pathways, said Dr. Petri, director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.
Ustekinumab (Stelara) has accumulated the most data so far. A phase 2 study presented last fall at the annual meeting of the American College of Rheumatology found that it conferred significant benefits relative to placebo, including a 60% responder rate (29% better than placebo), a significantly lower flare rate, and improvements in musculoskeletal and mucocutaneous disease features. The rate of serious adverse events was acceptable (8.3% vs. 9.5% for placebo).
Baricitinib is also being investigated in SLE, Dr. Petri said. A phase 2 study conducted by Eli Lilly closed late last year and will be reported on June 13 at the European League Against Rheumatism’s opening plenary session (Wallace et al. EULAR 2018 abstract OP0019).
The three-armed, placebo-controlled study comprised 314 patients who were randomized to placebo or one of two baricitinib doses, given orally for 24 weeks. The primary outcome was remission of arthritis and/or rash as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Secondary endpoints included responder rate, change from baseline in the SLEDAI-2K, change in the Global Assessment of Disease Activity score, and pharmacokinetic measures.
Dr. Petri disclosed relationships with Amgen, Boston Pharmaceuticals, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, and GlaxoSmithKline.
SANDESTIN, FLA. – Several drugs approved for other conditions may also have good effect in patients with systemic lupus erythematosus, Michelle Petri, MD, said in an interview at the annual Congress of Clinical Rheumatology.
The molecules target several different disease pathways, said Dr. Petri, director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.
Ustekinumab (Stelara) has accumulated the most data so far. A phase 2 study presented last fall at the annual meeting of the American College of Rheumatology found that it conferred significant benefits relative to placebo, including a 60% responder rate (29% better than placebo), a significantly lower flare rate, and improvements in musculoskeletal and mucocutaneous disease features. The rate of serious adverse events was acceptable (8.3% vs. 9.5% for placebo).
Baricitinib is also being investigated in SLE, Dr. Petri said. A phase 2 study conducted by Eli Lilly closed late last year and will be reported on June 13 at the European League Against Rheumatism’s opening plenary session (Wallace et al. EULAR 2018 abstract OP0019).
The three-armed, placebo-controlled study comprised 314 patients who were randomized to placebo or one of two baricitinib doses, given orally for 24 weeks. The primary outcome was remission of arthritis and/or rash as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Secondary endpoints included responder rate, change from baseline in the SLEDAI-2K, change in the Global Assessment of Disease Activity score, and pharmacokinetic measures.
Dr. Petri disclosed relationships with Amgen, Boston Pharmaceuticals, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, and GlaxoSmithKline.
SANDESTIN, FLA. – Several drugs approved for other conditions may also have good effect in patients with systemic lupus erythematosus, Michelle Petri, MD, said in an interview at the annual Congress of Clinical Rheumatology.
The molecules target several different disease pathways, said Dr. Petri, director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.
Ustekinumab (Stelara) has accumulated the most data so far. A phase 2 study presented last fall at the annual meeting of the American College of Rheumatology found that it conferred significant benefits relative to placebo, including a 60% responder rate (29% better than placebo), a significantly lower flare rate, and improvements in musculoskeletal and mucocutaneous disease features. The rate of serious adverse events was acceptable (8.3% vs. 9.5% for placebo).
Baricitinib is also being investigated in SLE, Dr. Petri said. A phase 2 study conducted by Eli Lilly closed late last year and will be reported on June 13 at the European League Against Rheumatism’s opening plenary session (Wallace et al. EULAR 2018 abstract OP0019).
The three-armed, placebo-controlled study comprised 314 patients who were randomized to placebo or one of two baricitinib doses, given orally for 24 weeks. The primary outcome was remission of arthritis and/or rash as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Secondary endpoints included responder rate, change from baseline in the SLEDAI-2K, change in the Global Assessment of Disease Activity score, and pharmacokinetic measures.
Dr. Petri disclosed relationships with Amgen, Boston Pharmaceuticals, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, and GlaxoSmithKline.
EXPERT ANALYSIS FROM CCR 18
Link between alcohol consumption, neuroinflammation has possible treatment implications
NEW YORK – Recent discoveries regarding the relationship between alcohol consumption and neuroinflammation suggest a possible role for adjunctive treatments and supplements in addiction treatment, according to Shram Shukla, MD.
For example, a qualitative review of the literature over the past 2-3 years showed that the “neuroinflammatory process in and of itself drives epigenetic changes, which ultimately upregulate neuroinflammation of the brain,” according to Dr. Shukla of Walter Reed National Military Medical Center, Bethesda, Md., who reported the findings in a poster at the annual meeting of the American Psychiatric Association.
In this video interview, he explained that this finding is important because “neuroinflammation leads to neurotoxicity, which leads to neuronal degeneration.”
“As we know, with patients who chronically abuse alcohol, they do have a level of cortical degeneration that we often see on imaging, so there is, perhaps, a role that this may play in that,” he added.
Dr. Shukla said he also found that the neuroinflammatory process, when it drives the epigenetic changes, affects the amygdala, which is known as a “high stress part of the brain.”
“What we found in animal models so far is that if we can impact where that epigenetic change occurs, we can prevent the anxiogenic behaviors we often see in alcohol withdrawal and abstinence; we associate that, in humans, to be the high-stress state we often see in patients when they ... are withdrawing from alcohol.”
This raised questions about whether certain medications and supplements, including vitamin C, pioglitazone, infliximab, and omega-3 fatty acids, could be of benefit, and it was shown that these do affect neuroinflammation and stop neurotoxicity from occurring – and also, in turn, prevent the epigenetic changes, he said.
The take-away is that
“Now we have something, potentially ... that can do some of the ancillary stuff, working on the withdrawal effects, helping with the behavioral response that we see in patients that are suffering from addiction,” he said.
Dr. Shukla reported having no disclosures.
SOURCE: Shukla S et al. APA Poster Session 4, Poster 3.
NEW YORK – Recent discoveries regarding the relationship between alcohol consumption and neuroinflammation suggest a possible role for adjunctive treatments and supplements in addiction treatment, according to Shram Shukla, MD.
For example, a qualitative review of the literature over the past 2-3 years showed that the “neuroinflammatory process in and of itself drives epigenetic changes, which ultimately upregulate neuroinflammation of the brain,” according to Dr. Shukla of Walter Reed National Military Medical Center, Bethesda, Md., who reported the findings in a poster at the annual meeting of the American Psychiatric Association.
In this video interview, he explained that this finding is important because “neuroinflammation leads to neurotoxicity, which leads to neuronal degeneration.”
“As we know, with patients who chronically abuse alcohol, they do have a level of cortical degeneration that we often see on imaging, so there is, perhaps, a role that this may play in that,” he added.
Dr. Shukla said he also found that the neuroinflammatory process, when it drives the epigenetic changes, affects the amygdala, which is known as a “high stress part of the brain.”
“What we found in animal models so far is that if we can impact where that epigenetic change occurs, we can prevent the anxiogenic behaviors we often see in alcohol withdrawal and abstinence; we associate that, in humans, to be the high-stress state we often see in patients when they ... are withdrawing from alcohol.”
This raised questions about whether certain medications and supplements, including vitamin C, pioglitazone, infliximab, and omega-3 fatty acids, could be of benefit, and it was shown that these do affect neuroinflammation and stop neurotoxicity from occurring – and also, in turn, prevent the epigenetic changes, he said.
The take-away is that
“Now we have something, potentially ... that can do some of the ancillary stuff, working on the withdrawal effects, helping with the behavioral response that we see in patients that are suffering from addiction,” he said.
Dr. Shukla reported having no disclosures.
SOURCE: Shukla S et al. APA Poster Session 4, Poster 3.
NEW YORK – Recent discoveries regarding the relationship between alcohol consumption and neuroinflammation suggest a possible role for adjunctive treatments and supplements in addiction treatment, according to Shram Shukla, MD.
For example, a qualitative review of the literature over the past 2-3 years showed that the “neuroinflammatory process in and of itself drives epigenetic changes, which ultimately upregulate neuroinflammation of the brain,” according to Dr. Shukla of Walter Reed National Military Medical Center, Bethesda, Md., who reported the findings in a poster at the annual meeting of the American Psychiatric Association.
In this video interview, he explained that this finding is important because “neuroinflammation leads to neurotoxicity, which leads to neuronal degeneration.”
“As we know, with patients who chronically abuse alcohol, they do have a level of cortical degeneration that we often see on imaging, so there is, perhaps, a role that this may play in that,” he added.
Dr. Shukla said he also found that the neuroinflammatory process, when it drives the epigenetic changes, affects the amygdala, which is known as a “high stress part of the brain.”
“What we found in animal models so far is that if we can impact where that epigenetic change occurs, we can prevent the anxiogenic behaviors we often see in alcohol withdrawal and abstinence; we associate that, in humans, to be the high-stress state we often see in patients when they ... are withdrawing from alcohol.”
This raised questions about whether certain medications and supplements, including vitamin C, pioglitazone, infliximab, and omega-3 fatty acids, could be of benefit, and it was shown that these do affect neuroinflammation and stop neurotoxicity from occurring – and also, in turn, prevent the epigenetic changes, he said.
The take-away is that
“Now we have something, potentially ... that can do some of the ancillary stuff, working on the withdrawal effects, helping with the behavioral response that we see in patients that are suffering from addiction,” he said.
Dr. Shukla reported having no disclosures.
SOURCE: Shukla S et al. APA Poster Session 4, Poster 3.
REPORTING FROM APA
Genes, not adiposity, may be driving appetite differences in obesity
BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.
“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.
Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.
Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m2.
On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.
Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.
Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.
“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.
However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.
As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.
Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.
The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.
BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.
“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.
Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.
Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m2.
On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.
Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.
Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.
“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.
However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.
As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.
Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.
The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.
BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.
“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.
Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.
Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m2.
On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.
Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.
Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.
“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.
However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.
As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.
Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.
The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.
REPORTING FROM AACE 2018
A fib ablation in HFrEF patients gains momentum
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“The CASTLE-AF data confirmed that I can improve heart failure outcomes in patients with AF. You might think that the heart failure patients are too sick, but ablation is the appropriate treatment; you make their heart failure better,” said Andrea M. Russo, MD, professor and director of the electrophysiology and arrhythmia service at Cooper University Health Care in Camden, N.J.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“The CASTLE-AF data confirmed that I can improve heart failure outcomes in patients with AF. You might think that the heart failure patients are too sick, but ablation is the appropriate treatment; you make their heart failure better,” said Andrea M. Russo, MD, professor and director of the electrophysiology and arrhythmia service at Cooper University Health Care in Camden, N.J.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“The CASTLE-AF data confirmed that I can improve heart failure outcomes in patients with AF. You might think that the heart failure patients are too sick, but ablation is the appropriate treatment; you make their heart failure better,” said Andrea M. Russo, MD, professor and director of the electrophysiology and arrhythmia service at Cooper University Health Care in Camden, N.J.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
EXPERT ANALYSIS FROM HEART RHYTHM 2018
Prevention of ovarian remnant syndrome: Adnexal adhesiolysis from the pelvic sidewall
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SAMHSA’s new general embarks on a new mission
Elinore F. McCance-Katz, MD, PhD, is by turns passionate and impatient, empathetic and brusquely no-nonsense. She is a person who knows what she wants to do and knows how to do it.
Accomplishing that on the idealogic battlefield of a presidential appointment is the focus of her considerable energy.
Dr. McCance-Katz carries the newly minted banner of assistant secretary for mental health and substance use. Her troops comprise more than 100 related federal agencies. Her charge is at once simple and mind-numbingly complex: Overhaul the nation’s mental health care system. for their illnesses before they can begin to heal.
It’s the precise opposite of the Substance Abuse and Mental Health Services Administration’s prior targeting, which focused heavily on providing healthy social support for patients with mental health and substance abuse disorders. To Dr. McCance-Katz’s way of thinking, dollars spent on such are largely wasted, because terribly ill people simply can’t function in healthy ways until they begin to get better. Why, she reasoned, should the government waste money on peer-support services while ignoring – or even openly rejecting – evidence-based psychiatric treatment paradigms that are proven to help heal?
It’s this philosophical dichotomy – combined with what she perceived as a palpable dismissal of psychiatric science – that drove her away from her first SAMHSA appointment as the agency’s first chief medical officer. She aired her frustration in an editorial, published 2 years ago in Psychiatric Times.
“There is a perceptible hostility toward psychiatric medicine: a resistance to addressing the treatment needs of those with serious mental illness and a questioning by some at SAMHSA as to whether mental disorders even exist – for example, is psychosis just a ‘different way of thinking for some experiencing stress?’ … Nowhere in SAMHSA’s strategic initiatives is psychiatric treatment of mental illness a priority. The occasional vague reference to treatment is no substitute for the urgent need for programs that address these issues.”
In the same letter, she outlined a new battle plan, one that includes funding for better outpatient treatments, more psychiatric hospital beds, clinician education and support, and money to beef up the dwindling supply of psychiatrists, advanced-practice psychiatric nurses, and psychologists.
In an exclusive video interview, Dr. McCance-Katz sat down with MDedge Psychiatry to discuss the path that brought her to this station and the long road ahead.
Elinore F. McCance-Katz, MD, PhD, is by turns passionate and impatient, empathetic and brusquely no-nonsense. She is a person who knows what she wants to do and knows how to do it.
Accomplishing that on the idealogic battlefield of a presidential appointment is the focus of her considerable energy.
Dr. McCance-Katz carries the newly minted banner of assistant secretary for mental health and substance use. Her troops comprise more than 100 related federal agencies. Her charge is at once simple and mind-numbingly complex: Overhaul the nation’s mental health care system. for their illnesses before they can begin to heal.
It’s the precise opposite of the Substance Abuse and Mental Health Services Administration’s prior targeting, which focused heavily on providing healthy social support for patients with mental health and substance abuse disorders. To Dr. McCance-Katz’s way of thinking, dollars spent on such are largely wasted, because terribly ill people simply can’t function in healthy ways until they begin to get better. Why, she reasoned, should the government waste money on peer-support services while ignoring – or even openly rejecting – evidence-based psychiatric treatment paradigms that are proven to help heal?
It’s this philosophical dichotomy – combined with what she perceived as a palpable dismissal of psychiatric science – that drove her away from her first SAMHSA appointment as the agency’s first chief medical officer. She aired her frustration in an editorial, published 2 years ago in Psychiatric Times.
“There is a perceptible hostility toward psychiatric medicine: a resistance to addressing the treatment needs of those with serious mental illness and a questioning by some at SAMHSA as to whether mental disorders even exist – for example, is psychosis just a ‘different way of thinking for some experiencing stress?’ … Nowhere in SAMHSA’s strategic initiatives is psychiatric treatment of mental illness a priority. The occasional vague reference to treatment is no substitute for the urgent need for programs that address these issues.”
In the same letter, she outlined a new battle plan, one that includes funding for better outpatient treatments, more psychiatric hospital beds, clinician education and support, and money to beef up the dwindling supply of psychiatrists, advanced-practice psychiatric nurses, and psychologists.
In an exclusive video interview, Dr. McCance-Katz sat down with MDedge Psychiatry to discuss the path that brought her to this station and the long road ahead.
Elinore F. McCance-Katz, MD, PhD, is by turns passionate and impatient, empathetic and brusquely no-nonsense. She is a person who knows what she wants to do and knows how to do it.
Accomplishing that on the idealogic battlefield of a presidential appointment is the focus of her considerable energy.
Dr. McCance-Katz carries the newly minted banner of assistant secretary for mental health and substance use. Her troops comprise more than 100 related federal agencies. Her charge is at once simple and mind-numbingly complex: Overhaul the nation’s mental health care system. for their illnesses before they can begin to heal.
It’s the precise opposite of the Substance Abuse and Mental Health Services Administration’s prior targeting, which focused heavily on providing healthy social support for patients with mental health and substance abuse disorders. To Dr. McCance-Katz’s way of thinking, dollars spent on such are largely wasted, because terribly ill people simply can’t function in healthy ways until they begin to get better. Why, she reasoned, should the government waste money on peer-support services while ignoring – or even openly rejecting – evidence-based psychiatric treatment paradigms that are proven to help heal?
It’s this philosophical dichotomy – combined with what she perceived as a palpable dismissal of psychiatric science – that drove her away from her first SAMHSA appointment as the agency’s first chief medical officer. She aired her frustration in an editorial, published 2 years ago in Psychiatric Times.
“There is a perceptible hostility toward psychiatric medicine: a resistance to addressing the treatment needs of those with serious mental illness and a questioning by some at SAMHSA as to whether mental disorders even exist – for example, is psychosis just a ‘different way of thinking for some experiencing stress?’ … Nowhere in SAMHSA’s strategic initiatives is psychiatric treatment of mental illness a priority. The occasional vague reference to treatment is no substitute for the urgent need for programs that address these issues.”
In the same letter, she outlined a new battle plan, one that includes funding for better outpatient treatments, more psychiatric hospital beds, clinician education and support, and money to beef up the dwindling supply of psychiatrists, advanced-practice psychiatric nurses, and psychologists.
In an exclusive video interview, Dr. McCance-Katz sat down with MDedge Psychiatry to discuss the path that brought her to this station and the long road ahead.
SUSTAIN-7: GLP-1 receptor agonists effective in elderly
BOSTON – Efficacy and safety of two glucagonlike peptide 1 (GLP-1) receptor agonists in type 2 diabetes mellitus were similar between older and younger adults, according to a post hoc analysis of the SUSTAIN 7 clinical trial data.
However, Vanita Aroda, MD, associate director for clinical diabetes research at Brigham and Women’s Hospital, Boston.
said the study’s first author,The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The SUSTAIN 7 trial compared low-dose semaglutide (0.5 mg) with low-dose dulaglutide (0.75 mg), and high-dose semaglutide (1.0 mg) with high-dose dulaglutide (1.5 mg) as add-on therapy to metformin for adults with type 2 diabetes. All medications were given as once-weekly subcutaneous injections.
Dr. Aroda and her collaborators performed a subgroup analysis of the SUSTAIN 7 data that compared 260 patients aged 65 years and older (mean, 69.3 years) with 939 patients younger than 65 years (mean, 51.9 years).
“What we found is that the efficacy results … were similar to what we saw in the general population. We did not lose the efficacy in the older adult population,” said Dr. Aroda in an interview at the annual meeting of the American Association for Clinical Endocrinology.
Weight loss was similar in older and younger patients, though there was “maybe a tiny bit more in the older adults,” said Dr. Aroda: Older participants had a 4.4-kg reduction in weight, compared with 4.9-kg reduction in the younger population, on low-dose semaglutide. For low-dose dulaglutide, losses were an average 2.6 kg in the elderly versus 2.2 kg in the younger participants.
The higher doses of each resulted in greater weight loss, up to a mean 6.7 kg in elderly participants on high-dose semaglutide, with the same marginally greater losses seen in older participants.
Both agents were efficacious in the older population, Dr. Aroda said, with slightly better efficacy than in younger patients. As a caveat, she noted that the older patients came into the study with slightly better glycemic control and slightly lower body weight.
An array of endpoints for the 40-week study included achieving hemoglobin A1c less than 7%, less than or equal to 6.5%, and less than 7% without weight gain or hypoglycemia. A higher proportion of elderly patients met these endpoints; for example, 83% of elderly patients on high-dose semaglutide reached the composite endpoint of HbA1c less than 7% with no weight gain or hypoglycemia, compared to 72.1% of younger participants.
The analysis also looked at safety data for SUSTAIN 7. “The next question is, are you seeing this efficacy in terms of glycemic change and weight loss, at any cost of hypoglycemia? And the answer to that was no,” said Dr. Aroda. There were very rare to zero hypoglycemic events in the various study arms, she said.
However, older adults taking the higher doses of both GLP-1 receptor agonists had a high incidence of nausea, vomiting, and other gastrointestinal disturbances. These adverse events were seen in 52.8% of older patients on high-dose semaglutide and 52.2% of those on high-dose dulaglutide. Rates for the younger study population at these doses were 42.5% for semaglutide and 46.6% for dulaglutide.
The clinical take-home message? Don’t be afraid to reach for a GLP-1 receptor agonist for an older patient who’s not reaching target on metformin. “You have good efficacy with both of the therapies … but you just need to watch out for tolerability at the higher doses,” said Dr. Aroda.
Dr. Aroda reported receiving research funding from AstraZeneca, Calibri, Eisai, Novo Nordisk, Sanofi, and Theracos. She was formerly affiliated with Medstar Health Research Institute, Hyattsville, Md.
SOURCE: Aroda V et al. AACE 2018. Abstract 245.
BOSTON – Efficacy and safety of two glucagonlike peptide 1 (GLP-1) receptor agonists in type 2 diabetes mellitus were similar between older and younger adults, according to a post hoc analysis of the SUSTAIN 7 clinical trial data.
However, Vanita Aroda, MD, associate director for clinical diabetes research at Brigham and Women’s Hospital, Boston.
said the study’s first author,The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The SUSTAIN 7 trial compared low-dose semaglutide (0.5 mg) with low-dose dulaglutide (0.75 mg), and high-dose semaglutide (1.0 mg) with high-dose dulaglutide (1.5 mg) as add-on therapy to metformin for adults with type 2 diabetes. All medications were given as once-weekly subcutaneous injections.
Dr. Aroda and her collaborators performed a subgroup analysis of the SUSTAIN 7 data that compared 260 patients aged 65 years and older (mean, 69.3 years) with 939 patients younger than 65 years (mean, 51.9 years).
“What we found is that the efficacy results … were similar to what we saw in the general population. We did not lose the efficacy in the older adult population,” said Dr. Aroda in an interview at the annual meeting of the American Association for Clinical Endocrinology.
Weight loss was similar in older and younger patients, though there was “maybe a tiny bit more in the older adults,” said Dr. Aroda: Older participants had a 4.4-kg reduction in weight, compared with 4.9-kg reduction in the younger population, on low-dose semaglutide. For low-dose dulaglutide, losses were an average 2.6 kg in the elderly versus 2.2 kg in the younger participants.
The higher doses of each resulted in greater weight loss, up to a mean 6.7 kg in elderly participants on high-dose semaglutide, with the same marginally greater losses seen in older participants.
Both agents were efficacious in the older population, Dr. Aroda said, with slightly better efficacy than in younger patients. As a caveat, she noted that the older patients came into the study with slightly better glycemic control and slightly lower body weight.
An array of endpoints for the 40-week study included achieving hemoglobin A1c less than 7%, less than or equal to 6.5%, and less than 7% without weight gain or hypoglycemia. A higher proportion of elderly patients met these endpoints; for example, 83% of elderly patients on high-dose semaglutide reached the composite endpoint of HbA1c less than 7% with no weight gain or hypoglycemia, compared to 72.1% of younger participants.
The analysis also looked at safety data for SUSTAIN 7. “The next question is, are you seeing this efficacy in terms of glycemic change and weight loss, at any cost of hypoglycemia? And the answer to that was no,” said Dr. Aroda. There were very rare to zero hypoglycemic events in the various study arms, she said.
However, older adults taking the higher doses of both GLP-1 receptor agonists had a high incidence of nausea, vomiting, and other gastrointestinal disturbances. These adverse events were seen in 52.8% of older patients on high-dose semaglutide and 52.2% of those on high-dose dulaglutide. Rates for the younger study population at these doses were 42.5% for semaglutide and 46.6% for dulaglutide.
The clinical take-home message? Don’t be afraid to reach for a GLP-1 receptor agonist for an older patient who’s not reaching target on metformin. “You have good efficacy with both of the therapies … but you just need to watch out for tolerability at the higher doses,” said Dr. Aroda.
Dr. Aroda reported receiving research funding from AstraZeneca, Calibri, Eisai, Novo Nordisk, Sanofi, and Theracos. She was formerly affiliated with Medstar Health Research Institute, Hyattsville, Md.
SOURCE: Aroda V et al. AACE 2018. Abstract 245.
BOSTON – Efficacy and safety of two glucagonlike peptide 1 (GLP-1) receptor agonists in type 2 diabetes mellitus were similar between older and younger adults, according to a post hoc analysis of the SUSTAIN 7 clinical trial data.
However, Vanita Aroda, MD, associate director for clinical diabetes research at Brigham and Women’s Hospital, Boston.
said the study’s first author,The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The SUSTAIN 7 trial compared low-dose semaglutide (0.5 mg) with low-dose dulaglutide (0.75 mg), and high-dose semaglutide (1.0 mg) with high-dose dulaglutide (1.5 mg) as add-on therapy to metformin for adults with type 2 diabetes. All medications were given as once-weekly subcutaneous injections.
Dr. Aroda and her collaborators performed a subgroup analysis of the SUSTAIN 7 data that compared 260 patients aged 65 years and older (mean, 69.3 years) with 939 patients younger than 65 years (mean, 51.9 years).
“What we found is that the efficacy results … were similar to what we saw in the general population. We did not lose the efficacy in the older adult population,” said Dr. Aroda in an interview at the annual meeting of the American Association for Clinical Endocrinology.
Weight loss was similar in older and younger patients, though there was “maybe a tiny bit more in the older adults,” said Dr. Aroda: Older participants had a 4.4-kg reduction in weight, compared with 4.9-kg reduction in the younger population, on low-dose semaglutide. For low-dose dulaglutide, losses were an average 2.6 kg in the elderly versus 2.2 kg in the younger participants.
The higher doses of each resulted in greater weight loss, up to a mean 6.7 kg in elderly participants on high-dose semaglutide, with the same marginally greater losses seen in older participants.
Both agents were efficacious in the older population, Dr. Aroda said, with slightly better efficacy than in younger patients. As a caveat, she noted that the older patients came into the study with slightly better glycemic control and slightly lower body weight.
An array of endpoints for the 40-week study included achieving hemoglobin A1c less than 7%, less than or equal to 6.5%, and less than 7% without weight gain or hypoglycemia. A higher proportion of elderly patients met these endpoints; for example, 83% of elderly patients on high-dose semaglutide reached the composite endpoint of HbA1c less than 7% with no weight gain or hypoglycemia, compared to 72.1% of younger participants.
The analysis also looked at safety data for SUSTAIN 7. “The next question is, are you seeing this efficacy in terms of glycemic change and weight loss, at any cost of hypoglycemia? And the answer to that was no,” said Dr. Aroda. There were very rare to zero hypoglycemic events in the various study arms, she said.
However, older adults taking the higher doses of both GLP-1 receptor agonists had a high incidence of nausea, vomiting, and other gastrointestinal disturbances. These adverse events were seen in 52.8% of older patients on high-dose semaglutide and 52.2% of those on high-dose dulaglutide. Rates for the younger study population at these doses were 42.5% for semaglutide and 46.6% for dulaglutide.
The clinical take-home message? Don’t be afraid to reach for a GLP-1 receptor agonist for an older patient who’s not reaching target on metformin. “You have good efficacy with both of the therapies … but you just need to watch out for tolerability at the higher doses,” said Dr. Aroda.
Dr. Aroda reported receiving research funding from AstraZeneca, Calibri, Eisai, Novo Nordisk, Sanofi, and Theracos. She was formerly affiliated with Medstar Health Research Institute, Hyattsville, Md.
SOURCE: Aroda V et al. AACE 2018. Abstract 245.
REPORTING FROM AACE 2018
Atopic dermatitis severity reduced by topical microbiome treatment
The Beginning Assessment of Cutaneous Treatment Efficacy of Roseomonas in Atopic Dermatitis trial; BACTERiAD I/II study, an open-label phase I/II trial, first looked at the therapeutic use of R. mucosa in 10 adults aged 18 years or older. Three sucrose mixtures with increasing doses of live R. mucosa bacteria were topically applied to two body areas – the antecubital fossae and a body surface of their choice – twice per week for 2 weeks per dose. At 6 weeks, the patients stopped using the mixtures and followed a 4-week washout phase.
Treatment was found to reduce mean antecubital SCORAD (SCORing Atopic Dermatitis) scores by 59.8%. Reduction in pruritus was even more pronounced, with a mean decrease of 78.5%. Treating the hands did not improve disease severity, even in patients whose symptoms improved in other body areas. One explanation may be the increased exposure of the hands to topical antimicrobials and environmental exposures, the researchers noted.
With the success in the adult cohort, the researchers enrolled five children aged 7-17 years in the study. These patients were treated twice weekly for 16 weeks. The pediatric patients experienced a mean decrease of 70.3% in their SCORAD scores. The mean decrease in pruritis was 78.8%.
All adults who responded continued to report improved symptoms after the washout period. The pediatric patients are now being evaluated in a washout period.
Four patients did not respond; three of them had a family history of AD persisting into adulthood. “The association between these complex medical histories and the lack of clinical response suggests that differences in heritable host and/or microbial factors may impact treatment responses,” wrote Ian A. Myles, MD, and his colleagues.
“Overall, our findings suggest the safety of topical R. mucosa therapy and justify continuation of our ongoing trial to assess safety and activity in a pediatric cohort of patients with AD. These studies will additionally assess changes in host serum markers, skin metabolomics, and the skin microbiota by culture and genomic methods.”
The researchers noted that expanding to the pediatric population will deepen understanding of topical microbiome transplantation and lay the foundation for placebo-controlled trials to assess efficacy.
This work was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases and the National Institutes of Health. The researchers had no disclosures.
SOURCE: Myles IA et al. JCI Insight. 2018 May 3. doi: 10.1172/jci.insight.120608.
The Beginning Assessment of Cutaneous Treatment Efficacy of Roseomonas in Atopic Dermatitis trial; BACTERiAD I/II study, an open-label phase I/II trial, first looked at the therapeutic use of R. mucosa in 10 adults aged 18 years or older. Three sucrose mixtures with increasing doses of live R. mucosa bacteria were topically applied to two body areas – the antecubital fossae and a body surface of their choice – twice per week for 2 weeks per dose. At 6 weeks, the patients stopped using the mixtures and followed a 4-week washout phase.
Treatment was found to reduce mean antecubital SCORAD (SCORing Atopic Dermatitis) scores by 59.8%. Reduction in pruritus was even more pronounced, with a mean decrease of 78.5%. Treating the hands did not improve disease severity, even in patients whose symptoms improved in other body areas. One explanation may be the increased exposure of the hands to topical antimicrobials and environmental exposures, the researchers noted.
With the success in the adult cohort, the researchers enrolled five children aged 7-17 years in the study. These patients were treated twice weekly for 16 weeks. The pediatric patients experienced a mean decrease of 70.3% in their SCORAD scores. The mean decrease in pruritis was 78.8%.
All adults who responded continued to report improved symptoms after the washout period. The pediatric patients are now being evaluated in a washout period.
Four patients did not respond; three of them had a family history of AD persisting into adulthood. “The association between these complex medical histories and the lack of clinical response suggests that differences in heritable host and/or microbial factors may impact treatment responses,” wrote Ian A. Myles, MD, and his colleagues.
“Overall, our findings suggest the safety of topical R. mucosa therapy and justify continuation of our ongoing trial to assess safety and activity in a pediatric cohort of patients with AD. These studies will additionally assess changes in host serum markers, skin metabolomics, and the skin microbiota by culture and genomic methods.”
The researchers noted that expanding to the pediatric population will deepen understanding of topical microbiome transplantation and lay the foundation for placebo-controlled trials to assess efficacy.
This work was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases and the National Institutes of Health. The researchers had no disclosures.
SOURCE: Myles IA et al. JCI Insight. 2018 May 3. doi: 10.1172/jci.insight.120608.
The Beginning Assessment of Cutaneous Treatment Efficacy of Roseomonas in Atopic Dermatitis trial; BACTERiAD I/II study, an open-label phase I/II trial, first looked at the therapeutic use of R. mucosa in 10 adults aged 18 years or older. Three sucrose mixtures with increasing doses of live R. mucosa bacteria were topically applied to two body areas – the antecubital fossae and a body surface of their choice – twice per week for 2 weeks per dose. At 6 weeks, the patients stopped using the mixtures and followed a 4-week washout phase.
Treatment was found to reduce mean antecubital SCORAD (SCORing Atopic Dermatitis) scores by 59.8%. Reduction in pruritus was even more pronounced, with a mean decrease of 78.5%. Treating the hands did not improve disease severity, even in patients whose symptoms improved in other body areas. One explanation may be the increased exposure of the hands to topical antimicrobials and environmental exposures, the researchers noted.
With the success in the adult cohort, the researchers enrolled five children aged 7-17 years in the study. These patients were treated twice weekly for 16 weeks. The pediatric patients experienced a mean decrease of 70.3% in their SCORAD scores. The mean decrease in pruritis was 78.8%.
All adults who responded continued to report improved symptoms after the washout period. The pediatric patients are now being evaluated in a washout period.
Four patients did not respond; three of them had a family history of AD persisting into adulthood. “The association between these complex medical histories and the lack of clinical response suggests that differences in heritable host and/or microbial factors may impact treatment responses,” wrote Ian A. Myles, MD, and his colleagues.
“Overall, our findings suggest the safety of topical R. mucosa therapy and justify continuation of our ongoing trial to assess safety and activity in a pediatric cohort of patients with AD. These studies will additionally assess changes in host serum markers, skin metabolomics, and the skin microbiota by culture and genomic methods.”
The researchers noted that expanding to the pediatric population will deepen understanding of topical microbiome transplantation and lay the foundation for placebo-controlled trials to assess efficacy.
This work was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases and the National Institutes of Health. The researchers had no disclosures.
SOURCE: Myles IA et al. JCI Insight. 2018 May 3. doi: 10.1172/jci.insight.120608.
FROM JCI INSIGHT
Key clinical point: Roseomonas mucosa reduces disease severity.
Major finding: There were reductions in SCORAD scores of 78.5% and 70.3% in the adult and pediatric cohorts, respectively.
Study details: Case study of 10 adult and 5 pediatric patients with atopic dermatitis.
Disclosures: No relevant financial disclosures were reported.
Source: Myles IA et al. JCI Insight. 2018 May 3. doi: 10.1172/jci.insight.120608.