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DBS may improve nonmotor symptoms in Parkinson’s disease
LAS VEGAS – , according to a small study presented at the annual meeting of the North American Neuromodulation Society. DBS of the subthalamic nucleus (STN), however, does not significantly improve these symptoms.
“Further work will be needed to confirm whether DBS needs to be bilateral ... and whether demographic differences are significant,” said Michael Gillogly, RN, clinical research nurse in the department of neurosurgery at Albany (New York) Medical Center. “The pilot data suggest that, if all else is equal, and the patient has significant urinary dysfunction as a major complaint, GPI DBS may be preferentially considered.”
The benefits of DBS on motor symptoms in Parkinson’s disease are well documented in the literature, but the technique’s effects on nonmotor symptoms are less clear. Nonmotor symptoms – such as cognitive deficits, gastrointestinal dysfunction, genitourinary dysfunction, and sleep disturbance – are common in all stages of Parkinson’s disease and significantly impair quality of life. Data indicate that speech and neuropsychological symptoms worsen with DBS of the STN, but research into the effect of DBS of the GPI on nonmotor symptoms is limited.
Mr. Gillogly and his colleagues considered all surgical candidates at their facility for enrollment into a study evaluating nonmotor outcomes in Parkinson’s disease at baseline, before implantation, and at 6 months after DBS. Study outcomes were patient perception of urinary, swallowing, and gastrointestinal function at 6 months after DBS of the GPI, compared with DBS of the STN.
The researchers chose two tools each to measure sialorrhea, dysphagia, and genitourinary dysfunction. These tools included the Drooling Severity and Frequency Scale (DSFS), the Swallowing Disturbance Questionnaire, and the International Prostate Symptom Score (IPSS). The investigators also collected demographic information, including sex, age at the time of surgery, duration of illness, neuropsychological profile, and medication inventory.
In all, 34 patients (12 women) were enrolled in the study and completed each outcome measure preoperatively and at 6 months postoperatively. The mean age of our subjects at the time of surgery was 64 years. Eight received DBS of the GPI, and 26 received DBS of the STN. Mr. Gillogly and his colleagues observed a significant 31% improvement in DSFS score and a significant 24% improvement on the IPSS among GPI-targeted patients. They found no significant improvements among patients who had STN targeting. When the investigators compared patients with unilateral lead placement and those with bilateral lead placement, they observed that all of the significant improvement among patients with GPI targeting occurred when treatment was bilateral.
The small sample size is a notable limitation of the study, and subset analyses were limited, said Mr. Gillogly. In addition, it was difficult to determine whether the symptoms studied were directly related to Parkinson’s disease, because they often arise as part of the natural aging process. “Other limitations of the study include lack of objective measurements, as these are all patient perception, and the innate limitations of self-reported questionnaires,” said Mr. Gillogly.
Two of the researchers reported having consulted for Medtronic, which markets a DBS system. One author received grant funding and consulting fees from Boston Scientific, Medtronic, and Abbott, all of which make DBS devices.
LAS VEGAS – , according to a small study presented at the annual meeting of the North American Neuromodulation Society. DBS of the subthalamic nucleus (STN), however, does not significantly improve these symptoms.
“Further work will be needed to confirm whether DBS needs to be bilateral ... and whether demographic differences are significant,” said Michael Gillogly, RN, clinical research nurse in the department of neurosurgery at Albany (New York) Medical Center. “The pilot data suggest that, if all else is equal, and the patient has significant urinary dysfunction as a major complaint, GPI DBS may be preferentially considered.”
The benefits of DBS on motor symptoms in Parkinson’s disease are well documented in the literature, but the technique’s effects on nonmotor symptoms are less clear. Nonmotor symptoms – such as cognitive deficits, gastrointestinal dysfunction, genitourinary dysfunction, and sleep disturbance – are common in all stages of Parkinson’s disease and significantly impair quality of life. Data indicate that speech and neuropsychological symptoms worsen with DBS of the STN, but research into the effect of DBS of the GPI on nonmotor symptoms is limited.
Mr. Gillogly and his colleagues considered all surgical candidates at their facility for enrollment into a study evaluating nonmotor outcomes in Parkinson’s disease at baseline, before implantation, and at 6 months after DBS. Study outcomes were patient perception of urinary, swallowing, and gastrointestinal function at 6 months after DBS of the GPI, compared with DBS of the STN.
The researchers chose two tools each to measure sialorrhea, dysphagia, and genitourinary dysfunction. These tools included the Drooling Severity and Frequency Scale (DSFS), the Swallowing Disturbance Questionnaire, and the International Prostate Symptom Score (IPSS). The investigators also collected demographic information, including sex, age at the time of surgery, duration of illness, neuropsychological profile, and medication inventory.
In all, 34 patients (12 women) were enrolled in the study and completed each outcome measure preoperatively and at 6 months postoperatively. The mean age of our subjects at the time of surgery was 64 years. Eight received DBS of the GPI, and 26 received DBS of the STN. Mr. Gillogly and his colleagues observed a significant 31% improvement in DSFS score and a significant 24% improvement on the IPSS among GPI-targeted patients. They found no significant improvements among patients who had STN targeting. When the investigators compared patients with unilateral lead placement and those with bilateral lead placement, they observed that all of the significant improvement among patients with GPI targeting occurred when treatment was bilateral.
The small sample size is a notable limitation of the study, and subset analyses were limited, said Mr. Gillogly. In addition, it was difficult to determine whether the symptoms studied were directly related to Parkinson’s disease, because they often arise as part of the natural aging process. “Other limitations of the study include lack of objective measurements, as these are all patient perception, and the innate limitations of self-reported questionnaires,” said Mr. Gillogly.
Two of the researchers reported having consulted for Medtronic, which markets a DBS system. One author received grant funding and consulting fees from Boston Scientific, Medtronic, and Abbott, all of which make DBS devices.
LAS VEGAS – , according to a small study presented at the annual meeting of the North American Neuromodulation Society. DBS of the subthalamic nucleus (STN), however, does not significantly improve these symptoms.
“Further work will be needed to confirm whether DBS needs to be bilateral ... and whether demographic differences are significant,” said Michael Gillogly, RN, clinical research nurse in the department of neurosurgery at Albany (New York) Medical Center. “The pilot data suggest that, if all else is equal, and the patient has significant urinary dysfunction as a major complaint, GPI DBS may be preferentially considered.”
The benefits of DBS on motor symptoms in Parkinson’s disease are well documented in the literature, but the technique’s effects on nonmotor symptoms are less clear. Nonmotor symptoms – such as cognitive deficits, gastrointestinal dysfunction, genitourinary dysfunction, and sleep disturbance – are common in all stages of Parkinson’s disease and significantly impair quality of life. Data indicate that speech and neuropsychological symptoms worsen with DBS of the STN, but research into the effect of DBS of the GPI on nonmotor symptoms is limited.
Mr. Gillogly and his colleagues considered all surgical candidates at their facility for enrollment into a study evaluating nonmotor outcomes in Parkinson’s disease at baseline, before implantation, and at 6 months after DBS. Study outcomes were patient perception of urinary, swallowing, and gastrointestinal function at 6 months after DBS of the GPI, compared with DBS of the STN.
The researchers chose two tools each to measure sialorrhea, dysphagia, and genitourinary dysfunction. These tools included the Drooling Severity and Frequency Scale (DSFS), the Swallowing Disturbance Questionnaire, and the International Prostate Symptom Score (IPSS). The investigators also collected demographic information, including sex, age at the time of surgery, duration of illness, neuropsychological profile, and medication inventory.
In all, 34 patients (12 women) were enrolled in the study and completed each outcome measure preoperatively and at 6 months postoperatively. The mean age of our subjects at the time of surgery was 64 years. Eight received DBS of the GPI, and 26 received DBS of the STN. Mr. Gillogly and his colleagues observed a significant 31% improvement in DSFS score and a significant 24% improvement on the IPSS among GPI-targeted patients. They found no significant improvements among patients who had STN targeting. When the investigators compared patients with unilateral lead placement and those with bilateral lead placement, they observed that all of the significant improvement among patients with GPI targeting occurred when treatment was bilateral.
The small sample size is a notable limitation of the study, and subset analyses were limited, said Mr. Gillogly. In addition, it was difficult to determine whether the symptoms studied were directly related to Parkinson’s disease, because they often arise as part of the natural aging process. “Other limitations of the study include lack of objective measurements, as these are all patient perception, and the innate limitations of self-reported questionnaires,” said Mr. Gillogly.
Two of the researchers reported having consulted for Medtronic, which markets a DBS system. One author received grant funding and consulting fees from Boston Scientific, Medtronic, and Abbott, all of which make DBS devices.
REPORTING FROM NANS 2019
Key clinical point: Bilateral stimulation of the globus pallidus internus reduces sialorrhea and improves genitourinary symptoms.
Major finding: Patients reported 31% improvement in sialorrhea and 24% improvement in urinary function.
Study details: A prospective study of 34 patients receiving DBS of the STN or GPI.
Disclosures: No funding was reported.
AF ablation referral
Also today, a theory of relativity for rosacea patients, long-term opioid use is substantial in elderly adults prior to total joint replacement, and pediatricians get more guidance to be proactive on the use of e-cigarettes among youth.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Also today, a theory of relativity for rosacea patients, long-term opioid use is substantial in elderly adults prior to total joint replacement, and pediatricians get more guidance to be proactive on the use of e-cigarettes among youth.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Also today, a theory of relativity for rosacea patients, long-term opioid use is substantial in elderly adults prior to total joint replacement, and pediatricians get more guidance to be proactive on the use of e-cigarettes among youth.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
SPRINT MIND published: Extension trial to add 2 years’ follow-up
A new iteration of the SPRINT MIND hypertension trial will seek to prove conclusively the original study’s tantalizing suggestion: that intensive blood pressure control decreases the risk of developing mild cognitive impairment (MCI) and, eventually, dementia.
SPRINT MIND 2.0 will re-recruit SPRINT MIND subjects and enable another follow-up cognitive assessment and other clinical tests as they remain on their standard of care blood pressure regimen. It is largely funded by an $800,000 grant from the Alzheimer’s Association.
Initially released last July at the Alzheimer’s Association International Conference, the results of the SPRINT MIND have now appeared online in JAMA. Although it failed to meet its primary endpoint of reducing dementia incidence, the study did score on two secondary endpoints. Patients who reduced their systolic blood pressure to less than 120 mm Hg were 19% less likely to develop MCI and 17% less likely to be diagnosed with all-cause dementia than were those who achieved a hypertension target of less than 140 mm Hg.
The secondary results, and positive movement in the primary results, sparked excitement in the dementia research community last summer. They have suggested that the median 5-year follow-up just wasn’t long enough to show any significant effects on dementia, which can take years to fully manifest. Adding 2 more years with SPRINT MIND 2.0 should be long enough to discern those benefits, if indeed they exist.
“SPRINT MIND 2.0 and the work leading up to it offers genuine, concrete hope,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a press statement. “MCI is a known risk factor for dementia, and everyone who experiences dementia passes through MCI. When you prevent new cases of MCI, you are preventing new cases of dementia. The Alzheimer’s Association finds these data to be compelling and is committed to getting clarity and certainty on the dementia outcome by following participants for a longer period of time.”
The study strengthens the new and energetic push to find ways to prevent dementia, which has proven itself intractable in every drug study to date.
“This study is in line with where the field of dementia research is going: preventing memory loss earlier,” said Laurie Ryan, PhD, chief of the dementias of aging branch in the National Institute on Aging. “Much like we have research-based interventions for heart health and cancer prevention, we hope to have guidance based on this and subsequent studies that will more definitively show how to slow or even stop dementia well before symptoms appear.”
NIA director Richard J. Hodes, MD, agreed.
“Dementia continues to be a large public health challenge, and based on the primary results of this study, we still have yet to find an intervention strategy proven to reduce the risk of dementia,” he said in a press statement. “Nevertheless, the secondary results showing that intensive lowering of blood pressure may reduce risk for MCI, a known risk factor for dementia, gives us additional avenues to explore on the path to prevention.”
SPRINT MIND was a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT). It compared two strategies for managing hypertension in older adults. The intensive strategy had a target of less than 120 mm Hg, while standard care had a target of less than 140 mm Hg. SPRINT showed that more intensive blood pressure control produced a 25% reduction in the composite primary composite endpoint of cardiovascular events, stroke, and cardiovascular death. The intensive arm was so successful that SPRINT helped inform the 2017 high blood pressure clinical guidelines from the American Heart Association and American College of Cardiology.
The SPRINT MIND substudy, headed by Jeff D. Williamson, MD, of Wake Forest University, Winston-Salem, NC, asked whether intensive management had any effect on probable all-cause dementia or MCI, as well as imaging evidence of changes in white matter lesions and brain volume. It followed patients for up to 7 years and comprised 9,361 SPRINT subjects at least 50 years old (mean, 68 years) with at least one cardiovascular risk factor. Nearly a third (30%) were black, and 10% Hispanic. The primary outcome was incident probable dementia. Secondary outcomes were MCI and a composite of MCI and/or probable dementia. About a third had a SBP of 132 mm Hg or less, another third had a systolic pressure of 132-145 mm Hg, and the remainder had a systolic pressure greater than 145 mm Hg.
Physicians could use their choice of antihypertensive treatments. The study protocol encouraged, but did not mandate, thiazide-type diuretics as a first-line agent, followed by loop diuretics and beta-adrenergic blockers. Chlorthalidone was encouraged as the primary thiazide-type diuretic, and amlodipine as the preferred calcium-channel blocker.
The interventions did successfully control blood pressure, with a significant difference between the treatment groups. The mean SBP was 121.6 mm Hg in the intensive therapy group and 134.8 mm Hg in the standard group – a statistically significant difference of 13.3 mm Hg.
Dementia developed in 149 in the aggressive control group and 176 in the standard group – a nonsignificant difference of 17% (hazard ratio, 0.83). MCI developed in 287 in the intensive group and 353 in the standard treatment group. This amounted to a statistically significant 19% reduction. There was also a significant 15% reduction in the composite outcome of MCI or probable dementia in favor of intensive treatment.
As evidenced by the Alzheimer’s Association grant, dementia researchers chose to focus on SPRINT MIND’s positive secondary endpoints. At the AAIC meeting, Dr. Williamson even suggested that antihypertensive medications could be seen as disease-modifying agents for cognitive decline. Data support his claim: No dementia intervention yet tested has approached this level of success.
“I think we can say this is the first disease-modifying strategy to reduce the risk of MCI,” Dr. Williamson said during a press briefing. And although the primary endpoint – the 17% relative risk reduction for probable all-cause dementia – didn’t meet statistical significance, “It’s comforting to see that the benefit went in the same direction and was of the same magnitude..”
SOURCE: Williamson JD et al. JAMA 2019 Jan 28. doi:10.1001/jama.2018.21442.
SPRINT MIND offers hope that a very achievable blood pressure goal can dramatically alter the trajectory from mild cognitive impairment to dementia, Kristine Yaffe, MD, wrote in an accompanying editorial. But at this point, it’s impossible to make specific clinical recommendations.
Additionally it is not possible, right now, to know which hypertension treatment regimens were most effective in improved cognitive outcomes.
“Information necessary to compare the effects of classes of antihypertensive agents on cognitive outcomes is also not provided. SPRINT used a quasi-pragmatic approach with suggestions for treatment choice, but practitioners approached SBP control individually, and most participants were taking multiple drugs.”
Nevertheless, the positive secondary findings and the encouraging trajectory on dementia risk should fix blood pressure management squarely into a cornerstone of dementia prevention algorithms.
“The SPRINT MIND study may not be the final approach for prevention of AD or other cognitive impairment, but it represents a major leap forward in what has emerged as a marathon journey.”
Dr. Kristine Yaffe is professor of psychiatry, neurology and epidemiology and the Roy and Marie Scola Endowed Chair at the University of California, San Francisco.
SPRINT MIND offers hope that a very achievable blood pressure goal can dramatically alter the trajectory from mild cognitive impairment to dementia, Kristine Yaffe, MD, wrote in an accompanying editorial. But at this point, it’s impossible to make specific clinical recommendations.
Additionally it is not possible, right now, to know which hypertension treatment regimens were most effective in improved cognitive outcomes.
“Information necessary to compare the effects of classes of antihypertensive agents on cognitive outcomes is also not provided. SPRINT used a quasi-pragmatic approach with suggestions for treatment choice, but practitioners approached SBP control individually, and most participants were taking multiple drugs.”
Nevertheless, the positive secondary findings and the encouraging trajectory on dementia risk should fix blood pressure management squarely into a cornerstone of dementia prevention algorithms.
“The SPRINT MIND study may not be the final approach for prevention of AD or other cognitive impairment, but it represents a major leap forward in what has emerged as a marathon journey.”
Dr. Kristine Yaffe is professor of psychiatry, neurology and epidemiology and the Roy and Marie Scola Endowed Chair at the University of California, San Francisco.
SPRINT MIND offers hope that a very achievable blood pressure goal can dramatically alter the trajectory from mild cognitive impairment to dementia, Kristine Yaffe, MD, wrote in an accompanying editorial. But at this point, it’s impossible to make specific clinical recommendations.
Additionally it is not possible, right now, to know which hypertension treatment regimens were most effective in improved cognitive outcomes.
“Information necessary to compare the effects of classes of antihypertensive agents on cognitive outcomes is also not provided. SPRINT used a quasi-pragmatic approach with suggestions for treatment choice, but practitioners approached SBP control individually, and most participants were taking multiple drugs.”
Nevertheless, the positive secondary findings and the encouraging trajectory on dementia risk should fix blood pressure management squarely into a cornerstone of dementia prevention algorithms.
“The SPRINT MIND study may not be the final approach for prevention of AD or other cognitive impairment, but it represents a major leap forward in what has emerged as a marathon journey.”
Dr. Kristine Yaffe is professor of psychiatry, neurology and epidemiology and the Roy and Marie Scola Endowed Chair at the University of California, San Francisco.
A new iteration of the SPRINT MIND hypertension trial will seek to prove conclusively the original study’s tantalizing suggestion: that intensive blood pressure control decreases the risk of developing mild cognitive impairment (MCI) and, eventually, dementia.
SPRINT MIND 2.0 will re-recruit SPRINT MIND subjects and enable another follow-up cognitive assessment and other clinical tests as they remain on their standard of care blood pressure regimen. It is largely funded by an $800,000 grant from the Alzheimer’s Association.
Initially released last July at the Alzheimer’s Association International Conference, the results of the SPRINT MIND have now appeared online in JAMA. Although it failed to meet its primary endpoint of reducing dementia incidence, the study did score on two secondary endpoints. Patients who reduced their systolic blood pressure to less than 120 mm Hg were 19% less likely to develop MCI and 17% less likely to be diagnosed with all-cause dementia than were those who achieved a hypertension target of less than 140 mm Hg.
The secondary results, and positive movement in the primary results, sparked excitement in the dementia research community last summer. They have suggested that the median 5-year follow-up just wasn’t long enough to show any significant effects on dementia, which can take years to fully manifest. Adding 2 more years with SPRINT MIND 2.0 should be long enough to discern those benefits, if indeed they exist.
“SPRINT MIND 2.0 and the work leading up to it offers genuine, concrete hope,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a press statement. “MCI is a known risk factor for dementia, and everyone who experiences dementia passes through MCI. When you prevent new cases of MCI, you are preventing new cases of dementia. The Alzheimer’s Association finds these data to be compelling and is committed to getting clarity and certainty on the dementia outcome by following participants for a longer period of time.”
The study strengthens the new and energetic push to find ways to prevent dementia, which has proven itself intractable in every drug study to date.
“This study is in line with where the field of dementia research is going: preventing memory loss earlier,” said Laurie Ryan, PhD, chief of the dementias of aging branch in the National Institute on Aging. “Much like we have research-based interventions for heart health and cancer prevention, we hope to have guidance based on this and subsequent studies that will more definitively show how to slow or even stop dementia well before symptoms appear.”
NIA director Richard J. Hodes, MD, agreed.
“Dementia continues to be a large public health challenge, and based on the primary results of this study, we still have yet to find an intervention strategy proven to reduce the risk of dementia,” he said in a press statement. “Nevertheless, the secondary results showing that intensive lowering of blood pressure may reduce risk for MCI, a known risk factor for dementia, gives us additional avenues to explore on the path to prevention.”
SPRINT MIND was a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT). It compared two strategies for managing hypertension in older adults. The intensive strategy had a target of less than 120 mm Hg, while standard care had a target of less than 140 mm Hg. SPRINT showed that more intensive blood pressure control produced a 25% reduction in the composite primary composite endpoint of cardiovascular events, stroke, and cardiovascular death. The intensive arm was so successful that SPRINT helped inform the 2017 high blood pressure clinical guidelines from the American Heart Association and American College of Cardiology.
The SPRINT MIND substudy, headed by Jeff D. Williamson, MD, of Wake Forest University, Winston-Salem, NC, asked whether intensive management had any effect on probable all-cause dementia or MCI, as well as imaging evidence of changes in white matter lesions and brain volume. It followed patients for up to 7 years and comprised 9,361 SPRINT subjects at least 50 years old (mean, 68 years) with at least one cardiovascular risk factor. Nearly a third (30%) were black, and 10% Hispanic. The primary outcome was incident probable dementia. Secondary outcomes were MCI and a composite of MCI and/or probable dementia. About a third had a SBP of 132 mm Hg or less, another third had a systolic pressure of 132-145 mm Hg, and the remainder had a systolic pressure greater than 145 mm Hg.
Physicians could use their choice of antihypertensive treatments. The study protocol encouraged, but did not mandate, thiazide-type diuretics as a first-line agent, followed by loop diuretics and beta-adrenergic blockers. Chlorthalidone was encouraged as the primary thiazide-type diuretic, and amlodipine as the preferred calcium-channel blocker.
The interventions did successfully control blood pressure, with a significant difference between the treatment groups. The mean SBP was 121.6 mm Hg in the intensive therapy group and 134.8 mm Hg in the standard group – a statistically significant difference of 13.3 mm Hg.
Dementia developed in 149 in the aggressive control group and 176 in the standard group – a nonsignificant difference of 17% (hazard ratio, 0.83). MCI developed in 287 in the intensive group and 353 in the standard treatment group. This amounted to a statistically significant 19% reduction. There was also a significant 15% reduction in the composite outcome of MCI or probable dementia in favor of intensive treatment.
As evidenced by the Alzheimer’s Association grant, dementia researchers chose to focus on SPRINT MIND’s positive secondary endpoints. At the AAIC meeting, Dr. Williamson even suggested that antihypertensive medications could be seen as disease-modifying agents for cognitive decline. Data support his claim: No dementia intervention yet tested has approached this level of success.
“I think we can say this is the first disease-modifying strategy to reduce the risk of MCI,” Dr. Williamson said during a press briefing. And although the primary endpoint – the 17% relative risk reduction for probable all-cause dementia – didn’t meet statistical significance, “It’s comforting to see that the benefit went in the same direction and was of the same magnitude..”
SOURCE: Williamson JD et al. JAMA 2019 Jan 28. doi:10.1001/jama.2018.21442.
A new iteration of the SPRINT MIND hypertension trial will seek to prove conclusively the original study’s tantalizing suggestion: that intensive blood pressure control decreases the risk of developing mild cognitive impairment (MCI) and, eventually, dementia.
SPRINT MIND 2.0 will re-recruit SPRINT MIND subjects and enable another follow-up cognitive assessment and other clinical tests as they remain on their standard of care blood pressure regimen. It is largely funded by an $800,000 grant from the Alzheimer’s Association.
Initially released last July at the Alzheimer’s Association International Conference, the results of the SPRINT MIND have now appeared online in JAMA. Although it failed to meet its primary endpoint of reducing dementia incidence, the study did score on two secondary endpoints. Patients who reduced their systolic blood pressure to less than 120 mm Hg were 19% less likely to develop MCI and 17% less likely to be diagnosed with all-cause dementia than were those who achieved a hypertension target of less than 140 mm Hg.
The secondary results, and positive movement in the primary results, sparked excitement in the dementia research community last summer. They have suggested that the median 5-year follow-up just wasn’t long enough to show any significant effects on dementia, which can take years to fully manifest. Adding 2 more years with SPRINT MIND 2.0 should be long enough to discern those benefits, if indeed they exist.
“SPRINT MIND 2.0 and the work leading up to it offers genuine, concrete hope,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a press statement. “MCI is a known risk factor for dementia, and everyone who experiences dementia passes through MCI. When you prevent new cases of MCI, you are preventing new cases of dementia. The Alzheimer’s Association finds these data to be compelling and is committed to getting clarity and certainty on the dementia outcome by following participants for a longer period of time.”
The study strengthens the new and energetic push to find ways to prevent dementia, which has proven itself intractable in every drug study to date.
“This study is in line with where the field of dementia research is going: preventing memory loss earlier,” said Laurie Ryan, PhD, chief of the dementias of aging branch in the National Institute on Aging. “Much like we have research-based interventions for heart health and cancer prevention, we hope to have guidance based on this and subsequent studies that will more definitively show how to slow or even stop dementia well before symptoms appear.”
NIA director Richard J. Hodes, MD, agreed.
“Dementia continues to be a large public health challenge, and based on the primary results of this study, we still have yet to find an intervention strategy proven to reduce the risk of dementia,” he said in a press statement. “Nevertheless, the secondary results showing that intensive lowering of blood pressure may reduce risk for MCI, a known risk factor for dementia, gives us additional avenues to explore on the path to prevention.”
SPRINT MIND was a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT). It compared two strategies for managing hypertension in older adults. The intensive strategy had a target of less than 120 mm Hg, while standard care had a target of less than 140 mm Hg. SPRINT showed that more intensive blood pressure control produced a 25% reduction in the composite primary composite endpoint of cardiovascular events, stroke, and cardiovascular death. The intensive arm was so successful that SPRINT helped inform the 2017 high blood pressure clinical guidelines from the American Heart Association and American College of Cardiology.
The SPRINT MIND substudy, headed by Jeff D. Williamson, MD, of Wake Forest University, Winston-Salem, NC, asked whether intensive management had any effect on probable all-cause dementia or MCI, as well as imaging evidence of changes in white matter lesions and brain volume. It followed patients for up to 7 years and comprised 9,361 SPRINT subjects at least 50 years old (mean, 68 years) with at least one cardiovascular risk factor. Nearly a third (30%) were black, and 10% Hispanic. The primary outcome was incident probable dementia. Secondary outcomes were MCI and a composite of MCI and/or probable dementia. About a third had a SBP of 132 mm Hg or less, another third had a systolic pressure of 132-145 mm Hg, and the remainder had a systolic pressure greater than 145 mm Hg.
Physicians could use their choice of antihypertensive treatments. The study protocol encouraged, but did not mandate, thiazide-type diuretics as a first-line agent, followed by loop diuretics and beta-adrenergic blockers. Chlorthalidone was encouraged as the primary thiazide-type diuretic, and amlodipine as the preferred calcium-channel blocker.
The interventions did successfully control blood pressure, with a significant difference between the treatment groups. The mean SBP was 121.6 mm Hg in the intensive therapy group and 134.8 mm Hg in the standard group – a statistically significant difference of 13.3 mm Hg.
Dementia developed in 149 in the aggressive control group and 176 in the standard group – a nonsignificant difference of 17% (hazard ratio, 0.83). MCI developed in 287 in the intensive group and 353 in the standard treatment group. This amounted to a statistically significant 19% reduction. There was also a significant 15% reduction in the composite outcome of MCI or probable dementia in favor of intensive treatment.
As evidenced by the Alzheimer’s Association grant, dementia researchers chose to focus on SPRINT MIND’s positive secondary endpoints. At the AAIC meeting, Dr. Williamson even suggested that antihypertensive medications could be seen as disease-modifying agents for cognitive decline. Data support his claim: No dementia intervention yet tested has approached this level of success.
“I think we can say this is the first disease-modifying strategy to reduce the risk of MCI,” Dr. Williamson said during a press briefing. And although the primary endpoint – the 17% relative risk reduction for probable all-cause dementia – didn’t meet statistical significance, “It’s comforting to see that the benefit went in the same direction and was of the same magnitude..”
SOURCE: Williamson JD et al. JAMA 2019 Jan 28. doi:10.1001/jama.2018.21442.
FROM JAMA
Key clinical point: Keeping systolic blood pressure lower than 120 mm Hg did not significantly reduce the risk of all-cause dementia in patients with hypertension, but it did lower the risk of mild cognitive impairment and probable dementia.
Major finding: The intensively treated group had a nonsignificant 17% lower risk of dementia, and significant reductions in the risk of MCI (19%) and probable dementia (15%).
Study details: SPRINT MIND was a substudy of the SPRINT antihypertension trial.
Source: Williamson JD et al. JAMA 2019 Jan 28. doi:10.1001/jama.2018.21442.
Peripheral nerve stimulation reduces hand tremor
LAS VEGAS – In addition, sensors worn on the wrist can provide objective measures of tremor in the home environment, said the investigators, who presented their research at the annual meeting of the North American Neuromodulation Society.
The current hypothesis is that tremulous activity within a central tremor network causes essential tremor, but the specific mechanisms are unknown. Research suggests that invasive neuromodulation of deep brain structures within this tremor network provides clinical benefit. The question of whether noninvasive neuromodulation of the peripheral nerve inputs connected to this network is beneficial has received comparatively little attention, however.
Rajesh Pahwa, MD, movement disorders division chief at the University of Kansas Medical Center in Kansas City, and his colleagues examined the safety and efficacy of noninvasive neuromodulation for hand tremor in patients with essential tremor. To provide treatment, they used a wristband with three electrodes that targeted the median and radial nerves. The stimulation pattern was adjusted to interrupt each patient’s tremulous signal in the clinical setting and at home. Participants were asked to hold a certain posture for 20 seconds while the device recorded tremor frequency. After determining the peak tremor frequency, the device was able to adapt stimulation parameters to each patient.
Dr. Pahwa and his colleagues conducted an acute in-office study and an at-home study. In the in-office study, 77 participants were randomized to peripheral nerve treatment or sham stimulation of the tremor-dominant hand. The researchers evaluated tremor before and after one stimulation session using the Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Tremor Scale and the TETRAS Archimedes Spiral Rating Scale. In the at-home study, 61 participants were randomized to stimulation, sham, or standard of care for 2 weeks. After that point, all participants underwent two to five 40-minute stimulation sessions daily for 2 weeks. Patients in the treatment and sham groups had at least two sessions per day.
In the in-office study, the researchers randomized 40 patients to stimulation and 37 patients to sham. Dr. Pahwa and his colleagues determined that participants had been blinded successfully. The investigators observed a mean improvement in forward posture of approximately 0.75 points among treated patients, compared with a mean improvement of 0.3 points in the sham group. The difference between groups was statistically significant. Treated patients had significant improvements in upper limb tremor score and total performance score, compared with the sham group. The investigators also observed greater mean improvements in spiral drawing, lateral posture, and movement among treated patients, compared with the sham group, but the differences were not statistically significant.
Participants in the in-office study rated their improvement on activities of daily living. Average improvement across tasks was significantly greater for the treated group, compared to the sham group. Improvement on each individual task also was greater for the treated group than the sham group. The differences in improvement were significant for holding a cup of tea, dialing a telephone, picking up change, and unlocking a door with a key.
In the at-home study, the decrease in tremor amplitude, as measured by the wrist-worn device, was significantly greater among participants who received stimulation than in the sham group. “These randomized, controlled studies suggest that noninvasive peripheral neuromodulation may offer meaningful symptomatic relief from hand tremor in essential tremor with a favorable safety profile, compared to other available therapies,” noted Dr. Pahwa and his colleagues. “At-home monitoring may provide key insights into evaluating and treating tremor,” they added.
The studies were supported by Cala Health.
LAS VEGAS – In addition, sensors worn on the wrist can provide objective measures of tremor in the home environment, said the investigators, who presented their research at the annual meeting of the North American Neuromodulation Society.
The current hypothesis is that tremulous activity within a central tremor network causes essential tremor, but the specific mechanisms are unknown. Research suggests that invasive neuromodulation of deep brain structures within this tremor network provides clinical benefit. The question of whether noninvasive neuromodulation of the peripheral nerve inputs connected to this network is beneficial has received comparatively little attention, however.
Rajesh Pahwa, MD, movement disorders division chief at the University of Kansas Medical Center in Kansas City, and his colleagues examined the safety and efficacy of noninvasive neuromodulation for hand tremor in patients with essential tremor. To provide treatment, they used a wristband with three electrodes that targeted the median and radial nerves. The stimulation pattern was adjusted to interrupt each patient’s tremulous signal in the clinical setting and at home. Participants were asked to hold a certain posture for 20 seconds while the device recorded tremor frequency. After determining the peak tremor frequency, the device was able to adapt stimulation parameters to each patient.
Dr. Pahwa and his colleagues conducted an acute in-office study and an at-home study. In the in-office study, 77 participants were randomized to peripheral nerve treatment or sham stimulation of the tremor-dominant hand. The researchers evaluated tremor before and after one stimulation session using the Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Tremor Scale and the TETRAS Archimedes Spiral Rating Scale. In the at-home study, 61 participants were randomized to stimulation, sham, or standard of care for 2 weeks. After that point, all participants underwent two to five 40-minute stimulation sessions daily for 2 weeks. Patients in the treatment and sham groups had at least two sessions per day.
In the in-office study, the researchers randomized 40 patients to stimulation and 37 patients to sham. Dr. Pahwa and his colleagues determined that participants had been blinded successfully. The investigators observed a mean improvement in forward posture of approximately 0.75 points among treated patients, compared with a mean improvement of 0.3 points in the sham group. The difference between groups was statistically significant. Treated patients had significant improvements in upper limb tremor score and total performance score, compared with the sham group. The investigators also observed greater mean improvements in spiral drawing, lateral posture, and movement among treated patients, compared with the sham group, but the differences were not statistically significant.
Participants in the in-office study rated their improvement on activities of daily living. Average improvement across tasks was significantly greater for the treated group, compared to the sham group. Improvement on each individual task also was greater for the treated group than the sham group. The differences in improvement were significant for holding a cup of tea, dialing a telephone, picking up change, and unlocking a door with a key.
In the at-home study, the decrease in tremor amplitude, as measured by the wrist-worn device, was significantly greater among participants who received stimulation than in the sham group. “These randomized, controlled studies suggest that noninvasive peripheral neuromodulation may offer meaningful symptomatic relief from hand tremor in essential tremor with a favorable safety profile, compared to other available therapies,” noted Dr. Pahwa and his colleagues. “At-home monitoring may provide key insights into evaluating and treating tremor,” they added.
The studies were supported by Cala Health.
LAS VEGAS – In addition, sensors worn on the wrist can provide objective measures of tremor in the home environment, said the investigators, who presented their research at the annual meeting of the North American Neuromodulation Society.
The current hypothesis is that tremulous activity within a central tremor network causes essential tremor, but the specific mechanisms are unknown. Research suggests that invasive neuromodulation of deep brain structures within this tremor network provides clinical benefit. The question of whether noninvasive neuromodulation of the peripheral nerve inputs connected to this network is beneficial has received comparatively little attention, however.
Rajesh Pahwa, MD, movement disorders division chief at the University of Kansas Medical Center in Kansas City, and his colleagues examined the safety and efficacy of noninvasive neuromodulation for hand tremor in patients with essential tremor. To provide treatment, they used a wristband with three electrodes that targeted the median and radial nerves. The stimulation pattern was adjusted to interrupt each patient’s tremulous signal in the clinical setting and at home. Participants were asked to hold a certain posture for 20 seconds while the device recorded tremor frequency. After determining the peak tremor frequency, the device was able to adapt stimulation parameters to each patient.
Dr. Pahwa and his colleagues conducted an acute in-office study and an at-home study. In the in-office study, 77 participants were randomized to peripheral nerve treatment or sham stimulation of the tremor-dominant hand. The researchers evaluated tremor before and after one stimulation session using the Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Tremor Scale and the TETRAS Archimedes Spiral Rating Scale. In the at-home study, 61 participants were randomized to stimulation, sham, or standard of care for 2 weeks. After that point, all participants underwent two to five 40-minute stimulation sessions daily for 2 weeks. Patients in the treatment and sham groups had at least two sessions per day.
In the in-office study, the researchers randomized 40 patients to stimulation and 37 patients to sham. Dr. Pahwa and his colleagues determined that participants had been blinded successfully. The investigators observed a mean improvement in forward posture of approximately 0.75 points among treated patients, compared with a mean improvement of 0.3 points in the sham group. The difference between groups was statistically significant. Treated patients had significant improvements in upper limb tremor score and total performance score, compared with the sham group. The investigators also observed greater mean improvements in spiral drawing, lateral posture, and movement among treated patients, compared with the sham group, but the differences were not statistically significant.
Participants in the in-office study rated their improvement on activities of daily living. Average improvement across tasks was significantly greater for the treated group, compared to the sham group. Improvement on each individual task also was greater for the treated group than the sham group. The differences in improvement were significant for holding a cup of tea, dialing a telephone, picking up change, and unlocking a door with a key.
In the at-home study, the decrease in tremor amplitude, as measured by the wrist-worn device, was significantly greater among participants who received stimulation than in the sham group. “These randomized, controlled studies suggest that noninvasive peripheral neuromodulation may offer meaningful symptomatic relief from hand tremor in essential tremor with a favorable safety profile, compared to other available therapies,” noted Dr. Pahwa and his colleagues. “At-home monitoring may provide key insights into evaluating and treating tremor,” they added.
The studies were supported by Cala Health.
REPORTING FROM NANS 2019
Key clinical point: Two randomized trials indicate that peripheral nerve stimulation provides clinical benefits in essential tremor.
Major finding: Peripheral nerve stimulation reduced hand tremor and improved activities of daily living.
Study details: Two randomized, controlled studies including 138 patients with essential tremor and hand tremor.
Disclosures: Cala Health supported the studies.
Benefit of thrombectomy may be universal
The location of the arterial occlusive lesion and the imaging technique used to select patients for the procedure also do not influence the therapy’s benefits, the researchers said. Although the proportional benefit of thrombectomy plus medical management is uniform across subgroups, compared with medical management alone, patients may have different amounts of absolute benefit.
The results of the DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial, which were published in 2018, indicated that endovascular thrombectomy provided clinical benefits for patients with acute ischemic stroke if administered at 6-16 hours after stroke onset. As part of the trial’s prespecified analyses, Maarten G. Lansberg, MD, PhD, associate professor of neurology and neurological sciences at Stanford (Calif.) University Medical Center in California, and his colleagues sought to determine whether thrombectomy had uniform benefit among various patient subgroups (e.g., elderly people, patients with mild symptoms, and those who present late after onset).
A total of 296 patients were enrolled in the randomized, open-label, blinded-endpoint DEFUSE 3 trial at 38 sites in the United States. Eligible participants had acute ischemic stroke resulting from an occlusion of the internal carotid artery or middle cerebral artery and evidence of salvageable tissue on perfusion CT or MRI. In all, 182 patients met these criteria and were randomized and included in the intention-to-treat analysis. The researchers stopped DEFUSE 3 early because of efficacy.
The study’s primary endpoint was functional outcome at day 90, as measured with the modified Rankin Scale. Dr. Lansberg and his colleagues performed multivariate ordinal logistic regression to calculate the adjusted proportional association between endovascular treatment and clinical outcome among participants of various ages, baseline stroke severities, periods between onset and treatment, locations of the arterial occlusion, and imaging modalities, such as CT or MRI, used to identify salvageable tissue.
The population’s median age was 70 years, and 51% of participants were women. The median National Institutes of Health Stroke Scale score was 16. When the researchers considered the whole sample, they found that younger age, lower baseline NIHSS score, and lower serum glucose level independently predicted better functional outcome. The common odds ratio for improved functional outcome with endovascular therapy, adjusted for these variables, was 3.1. Age, NIHSS score, time to randomization, imaging modality, and location of the arterial occlusion did not interact significantly with treatment effect.
“Our results indicate that advanced age, up to 90 years, should not be considered a contraindication to thrombectomy, provided that the patient is fully independent prior to stroke onset,” said the researchers. “Although age did not modify the treatment effect, it was a strong independent predictor of 90-day disability, which is consistent with prior studies of both tissue plasminogen activator and endovascular therapy.”
The trial’s small sample size may have allowed small differences between groups to pass unnoticed, said the reseachers. Other trials of late-window thrombectomy will be required to validate these results, they concluded.
The National Institute for Neurological Disorders and Stroke supported the study through grants. Several investigators received consulting fees from and hold shares in iSchemaView, which manufactures the software that the investigators used for postprocessing of CT and MRI perfusion studies. Other authors received consulting fees from various pharmaceutical and medical device companies, including Genentech, Medtronic, Pfizer, and Stryker Neurovascular.
SOURCE: Lansberg MG et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4587.
The location of the arterial occlusive lesion and the imaging technique used to select patients for the procedure also do not influence the therapy’s benefits, the researchers said. Although the proportional benefit of thrombectomy plus medical management is uniform across subgroups, compared with medical management alone, patients may have different amounts of absolute benefit.
The results of the DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial, which were published in 2018, indicated that endovascular thrombectomy provided clinical benefits for patients with acute ischemic stroke if administered at 6-16 hours after stroke onset. As part of the trial’s prespecified analyses, Maarten G. Lansberg, MD, PhD, associate professor of neurology and neurological sciences at Stanford (Calif.) University Medical Center in California, and his colleagues sought to determine whether thrombectomy had uniform benefit among various patient subgroups (e.g., elderly people, patients with mild symptoms, and those who present late after onset).
A total of 296 patients were enrolled in the randomized, open-label, blinded-endpoint DEFUSE 3 trial at 38 sites in the United States. Eligible participants had acute ischemic stroke resulting from an occlusion of the internal carotid artery or middle cerebral artery and evidence of salvageable tissue on perfusion CT or MRI. In all, 182 patients met these criteria and were randomized and included in the intention-to-treat analysis. The researchers stopped DEFUSE 3 early because of efficacy.
The study’s primary endpoint was functional outcome at day 90, as measured with the modified Rankin Scale. Dr. Lansberg and his colleagues performed multivariate ordinal logistic regression to calculate the adjusted proportional association between endovascular treatment and clinical outcome among participants of various ages, baseline stroke severities, periods between onset and treatment, locations of the arterial occlusion, and imaging modalities, such as CT or MRI, used to identify salvageable tissue.
The population’s median age was 70 years, and 51% of participants were women. The median National Institutes of Health Stroke Scale score was 16. When the researchers considered the whole sample, they found that younger age, lower baseline NIHSS score, and lower serum glucose level independently predicted better functional outcome. The common odds ratio for improved functional outcome with endovascular therapy, adjusted for these variables, was 3.1. Age, NIHSS score, time to randomization, imaging modality, and location of the arterial occlusion did not interact significantly with treatment effect.
“Our results indicate that advanced age, up to 90 years, should not be considered a contraindication to thrombectomy, provided that the patient is fully independent prior to stroke onset,” said the researchers. “Although age did not modify the treatment effect, it was a strong independent predictor of 90-day disability, which is consistent with prior studies of both tissue plasminogen activator and endovascular therapy.”
The trial’s small sample size may have allowed small differences between groups to pass unnoticed, said the reseachers. Other trials of late-window thrombectomy will be required to validate these results, they concluded.
The National Institute for Neurological Disorders and Stroke supported the study through grants. Several investigators received consulting fees from and hold shares in iSchemaView, which manufactures the software that the investigators used for postprocessing of CT and MRI perfusion studies. Other authors received consulting fees from various pharmaceutical and medical device companies, including Genentech, Medtronic, Pfizer, and Stryker Neurovascular.
SOURCE: Lansberg MG et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4587.
The location of the arterial occlusive lesion and the imaging technique used to select patients for the procedure also do not influence the therapy’s benefits, the researchers said. Although the proportional benefit of thrombectomy plus medical management is uniform across subgroups, compared with medical management alone, patients may have different amounts of absolute benefit.
The results of the DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial, which were published in 2018, indicated that endovascular thrombectomy provided clinical benefits for patients with acute ischemic stroke if administered at 6-16 hours after stroke onset. As part of the trial’s prespecified analyses, Maarten G. Lansberg, MD, PhD, associate professor of neurology and neurological sciences at Stanford (Calif.) University Medical Center in California, and his colleagues sought to determine whether thrombectomy had uniform benefit among various patient subgroups (e.g., elderly people, patients with mild symptoms, and those who present late after onset).
A total of 296 patients were enrolled in the randomized, open-label, blinded-endpoint DEFUSE 3 trial at 38 sites in the United States. Eligible participants had acute ischemic stroke resulting from an occlusion of the internal carotid artery or middle cerebral artery and evidence of salvageable tissue on perfusion CT or MRI. In all, 182 patients met these criteria and were randomized and included in the intention-to-treat analysis. The researchers stopped DEFUSE 3 early because of efficacy.
The study’s primary endpoint was functional outcome at day 90, as measured with the modified Rankin Scale. Dr. Lansberg and his colleagues performed multivariate ordinal logistic regression to calculate the adjusted proportional association between endovascular treatment and clinical outcome among participants of various ages, baseline stroke severities, periods between onset and treatment, locations of the arterial occlusion, and imaging modalities, such as CT or MRI, used to identify salvageable tissue.
The population’s median age was 70 years, and 51% of participants were women. The median National Institutes of Health Stroke Scale score was 16. When the researchers considered the whole sample, they found that younger age, lower baseline NIHSS score, and lower serum glucose level independently predicted better functional outcome. The common odds ratio for improved functional outcome with endovascular therapy, adjusted for these variables, was 3.1. Age, NIHSS score, time to randomization, imaging modality, and location of the arterial occlusion did not interact significantly with treatment effect.
“Our results indicate that advanced age, up to 90 years, should not be considered a contraindication to thrombectomy, provided that the patient is fully independent prior to stroke onset,” said the researchers. “Although age did not modify the treatment effect, it was a strong independent predictor of 90-day disability, which is consistent with prior studies of both tissue plasminogen activator and endovascular therapy.”
The trial’s small sample size may have allowed small differences between groups to pass unnoticed, said the reseachers. Other trials of late-window thrombectomy will be required to validate these results, they concluded.
The National Institute for Neurological Disorders and Stroke supported the study through grants. Several investigators received consulting fees from and hold shares in iSchemaView, which manufactures the software that the investigators used for postprocessing of CT and MRI perfusion studies. Other authors received consulting fees from various pharmaceutical and medical device companies, including Genentech, Medtronic, Pfizer, and Stryker Neurovascular.
SOURCE: Lansberg MG et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4587.
FROM JAMA NEUROLOGY
Key clinical point: Age, symptom severity, and serum glucose do not influence the benefit of thrombectomy for acute ischemic stroke.
Major finding: The adjusted common odds ratio for improved functional outcome with endovascular therapy was 3.1.
Study details: The randomized, open-label, blinded-end-point DEFUSE 3 trial included 182 patients.
Disclosures: The National Institute for Neurological Disorders and Stroke funded the study through grants.
Source: Lansberg MG et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4587.
Anxiety, depression, burnout higher in physician mothers caring for others at home
Physicians who are also mothers have a higher risk of burnout and mood and anxiety disorders if they are also caring for someone with a serious illness or disability outside of work, according to a cross-sectional survey reported in a letter in JAMA Internal Medicine.
“Our findings highlight the additional caregiving responsibilities of some women physicians and the potential consequences of these additional responsibilities for their behavioral health and careers,” wrote Veronica Yank, MD, of the department of medicine at the University of California, San Francisco, and her colleagues.
“To reduce burnout and improve workforce retention, health care systems should develop new approaches to identify and address the needs of these physician mothers,” they wrote.
The researchers used data from a June-July 2016 online survey of respondents from the Physicians Moms Group online community. Approximately 16,059 members saw the posting for the survey, and 5,613 United States–based mothers participated.
Among the questions was one on non–work related caregiving responsibilities that asked whether the respondent provided “regular care or assistance to a friend or family member with a serious health problem, long-term illness or disability” during the last year. Other questions assessed alcohol and drug use, history of a mood or anxiety disorder, career satisfaction and burnout.
Among the 16.4% of respondents who had additional caregiving responsibilities outside of work for someone chronically or seriously ill or disabled, nearly half (48.3%) said they cared for ill parents, 16.9% for children or infants, 7.7% for a partner, and 28.6% for another relative. In addition, 16.7% of respondents had such caregiving responsibilities for more than one person.
The women with these extra caregiving responsibilities were 21% more likely to have a mood or anxiety disorder (adjusted relative risk, 1.21; P = .02) and 25% more likely to report burnout (aRR, 1.25; P = .007), compared with those who did not have such extra responsibilities.
There were no significant differences, however, on rates of career satisfaction, risky drinking behaviors, or substance abuse between physician mothers who did have additional caregiving responsibilities and those who did not.
Among the study’s limitations were its cross-sectional nature, use of a convenience sample that may not be generalizable or representative, and lack of data on fathers or non-parent physicians for comparison.
SOURCE: Yank V et al. JAMA Intern Med. 2019 Jan 28. doi: 10.1001/jamainternmed.2018.6411.
Physicians who are also mothers have a higher risk of burnout and mood and anxiety disorders if they are also caring for someone with a serious illness or disability outside of work, according to a cross-sectional survey reported in a letter in JAMA Internal Medicine.
“Our findings highlight the additional caregiving responsibilities of some women physicians and the potential consequences of these additional responsibilities for their behavioral health and careers,” wrote Veronica Yank, MD, of the department of medicine at the University of California, San Francisco, and her colleagues.
“To reduce burnout and improve workforce retention, health care systems should develop new approaches to identify and address the needs of these physician mothers,” they wrote.
The researchers used data from a June-July 2016 online survey of respondents from the Physicians Moms Group online community. Approximately 16,059 members saw the posting for the survey, and 5,613 United States–based mothers participated.
Among the questions was one on non–work related caregiving responsibilities that asked whether the respondent provided “regular care or assistance to a friend or family member with a serious health problem, long-term illness or disability” during the last year. Other questions assessed alcohol and drug use, history of a mood or anxiety disorder, career satisfaction and burnout.
Among the 16.4% of respondents who had additional caregiving responsibilities outside of work for someone chronically or seriously ill or disabled, nearly half (48.3%) said they cared for ill parents, 16.9% for children or infants, 7.7% for a partner, and 28.6% for another relative. In addition, 16.7% of respondents had such caregiving responsibilities for more than one person.
The women with these extra caregiving responsibilities were 21% more likely to have a mood or anxiety disorder (adjusted relative risk, 1.21; P = .02) and 25% more likely to report burnout (aRR, 1.25; P = .007), compared with those who did not have such extra responsibilities.
There were no significant differences, however, on rates of career satisfaction, risky drinking behaviors, or substance abuse between physician mothers who did have additional caregiving responsibilities and those who did not.
Among the study’s limitations were its cross-sectional nature, use of a convenience sample that may not be generalizable or representative, and lack of data on fathers or non-parent physicians for comparison.
SOURCE: Yank V et al. JAMA Intern Med. 2019 Jan 28. doi: 10.1001/jamainternmed.2018.6411.
Physicians who are also mothers have a higher risk of burnout and mood and anxiety disorders if they are also caring for someone with a serious illness or disability outside of work, according to a cross-sectional survey reported in a letter in JAMA Internal Medicine.
“Our findings highlight the additional caregiving responsibilities of some women physicians and the potential consequences of these additional responsibilities for their behavioral health and careers,” wrote Veronica Yank, MD, of the department of medicine at the University of California, San Francisco, and her colleagues.
“To reduce burnout and improve workforce retention, health care systems should develop new approaches to identify and address the needs of these physician mothers,” they wrote.
The researchers used data from a June-July 2016 online survey of respondents from the Physicians Moms Group online community. Approximately 16,059 members saw the posting for the survey, and 5,613 United States–based mothers participated.
Among the questions was one on non–work related caregiving responsibilities that asked whether the respondent provided “regular care or assistance to a friend or family member with a serious health problem, long-term illness or disability” during the last year. Other questions assessed alcohol and drug use, history of a mood or anxiety disorder, career satisfaction and burnout.
Among the 16.4% of respondents who had additional caregiving responsibilities outside of work for someone chronically or seriously ill or disabled, nearly half (48.3%) said they cared for ill parents, 16.9% for children or infants, 7.7% for a partner, and 28.6% for another relative. In addition, 16.7% of respondents had such caregiving responsibilities for more than one person.
The women with these extra caregiving responsibilities were 21% more likely to have a mood or anxiety disorder (adjusted relative risk, 1.21; P = .02) and 25% more likely to report burnout (aRR, 1.25; P = .007), compared with those who did not have such extra responsibilities.
There were no significant differences, however, on rates of career satisfaction, risky drinking behaviors, or substance abuse between physician mothers who did have additional caregiving responsibilities and those who did not.
Among the study’s limitations were its cross-sectional nature, use of a convenience sample that may not be generalizable or representative, and lack of data on fathers or non-parent physicians for comparison.
SOURCE: Yank V et al. JAMA Intern Med. 2019 Jan 28. doi: 10.1001/jamainternmed.2018.6411.
FROM JAMA INTERNAL MEDICINE
Key clinical point:
Major finding: Risk of anxiety and mood disorders is 21% higher and burnout is 25% higher among physician mothers with extra caregiving at home.
Study details: The findings are based on an online cross-sectional survey of 5,613 United States–based physician mothers conducted from June to July 2016.
Disclosures: No single entity directly funded the study, but the authors were supported by a variety of grants from foundations and the National Institutes of Health at the time it was completed. One coauthor is founder of Equity Quotient, a company that provides gender equity culture analytics for institutions, and another has consulted for Amgen and Vizient and receives stock options as an Equity Quotient advisory board member.
Source: Yank V et al. JAMA Internal Medicine. 2018 Jan 28. doi: 10.1001/jamainternmed.2018.6411.
Routine clinical data may predict psychiatric adverse effects from levetiracetam
Among patients with epilepsy, a simple model that incorporates factors such as a patient’s sex and history of depression, anxiety, and recreational drug use may help predict the risk of a psychiatric adverse effect from levetiracetam, according to a study published in JAMA Neurology.
“This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam” and can “guide prescription in clinical practice,” said Colin B. Josephson, MD, of the department of clinical neurosciences at the University of Calgary (Canada) and his research colleagues.
Levetiracetam is a commonly used first-line treatment for epilepsy because of its ease of use, broad spectrum of action, and safety profile, the researchers said. Still, psychiatric adverse reactions occur in as many as 16% of patients and frequently require treatment discontinuation.
To evaluate whether routine clinical data can predict which patients with epilepsy will experience a psychiatric adverse event from levetiracetam, the investigators analyzed data from The Health Improvement Network (THIN) database, which includes anonymized patient records from general practices in the United Kingdom. They assessed 21 variables for possible inclusion in prediction models. They identified these variables by searching the literature and weighing input from a panel of experts.
Their analysis included data from Jan. 1, 2000–May 31, 2012. Among the more than 11 million patients in THIN, the researchers identified 7,300 incident cases of epilepsy. The researchers examined when patients received a first prescription for levetiracetam and whether patients experienced a psychiatric symptom or disorder within 2 years of the prescription.
Among 1,173 patients with epilepsy receiving levetiracetam, the median age was 39 years; about half were women. In all, 14.1% experienced a psychiatric symptom or disorder within 2 years of prescription. Women were more likely to report a psychiatric symptom (odds ratio, 1.41), as were patients with a history of social deprivation (OR, 1.15), anxiety (OR, 1.74), recreational drug use (OR, 2.02), or depression (OR, 2.20).
The final model included female sex, history of depression, history of anxiety, and history of recreational drug use. Low socioeconomic status was not included because “it would be challenging to assign this score in clinic,” the authors said.
“There was a gradient in risk probabilities increasing from 8% for 0 risk factors to 11%-17% for 1, 17% to 31% for 2, 30%-42% for 3, and 49% when all risk factors were present,” Dr. Josephson and his colleagues indicated. “The discovered incremental probability of reporting a psychiatric sign can help generate an index of suspicion to counsel patients.”
Using the example of a woman patient with depression, the model “suggests she would be at risk,” with a 22% chance of a psychiatric adverse event in the 2 years after receiving a levetiracetam prescription.
The researchers created a second prediction algorithm based on data from patients without documentation of a mental health sign, symptom, or disorder prior to their levetiracetam prescription. This model incorporated age, sex, recreational drug use, and levetiracetam daily dose; it performed comparably well and might be used to determine safety of prescription, according to Dr. Josephson and his colleagues.
The authors noted that the study was limited by an inability to evaluate medication adherence and seizure type and frequency. One advantage of the study’s design is that it may have circumvented expectation bias because general practitioners were not prone to anticipating psychiatric adverse events or to have a lower threshold for diagnosing them.
The authors disclosed research fellowships and support from foundations and federal agencies.
SOURCE: Josephson CB et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4561.
Among patients with epilepsy, a simple model that incorporates factors such as a patient’s sex and history of depression, anxiety, and recreational drug use may help predict the risk of a psychiatric adverse effect from levetiracetam, according to a study published in JAMA Neurology.
“This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam” and can “guide prescription in clinical practice,” said Colin B. Josephson, MD, of the department of clinical neurosciences at the University of Calgary (Canada) and his research colleagues.
Levetiracetam is a commonly used first-line treatment for epilepsy because of its ease of use, broad spectrum of action, and safety profile, the researchers said. Still, psychiatric adverse reactions occur in as many as 16% of patients and frequently require treatment discontinuation.
To evaluate whether routine clinical data can predict which patients with epilepsy will experience a psychiatric adverse event from levetiracetam, the investigators analyzed data from The Health Improvement Network (THIN) database, which includes anonymized patient records from general practices in the United Kingdom. They assessed 21 variables for possible inclusion in prediction models. They identified these variables by searching the literature and weighing input from a panel of experts.
Their analysis included data from Jan. 1, 2000–May 31, 2012. Among the more than 11 million patients in THIN, the researchers identified 7,300 incident cases of epilepsy. The researchers examined when patients received a first prescription for levetiracetam and whether patients experienced a psychiatric symptom or disorder within 2 years of the prescription.
Among 1,173 patients with epilepsy receiving levetiracetam, the median age was 39 years; about half were women. In all, 14.1% experienced a psychiatric symptom or disorder within 2 years of prescription. Women were more likely to report a psychiatric symptom (odds ratio, 1.41), as were patients with a history of social deprivation (OR, 1.15), anxiety (OR, 1.74), recreational drug use (OR, 2.02), or depression (OR, 2.20).
The final model included female sex, history of depression, history of anxiety, and history of recreational drug use. Low socioeconomic status was not included because “it would be challenging to assign this score in clinic,” the authors said.
“There was a gradient in risk probabilities increasing from 8% for 0 risk factors to 11%-17% for 1, 17% to 31% for 2, 30%-42% for 3, and 49% when all risk factors were present,” Dr. Josephson and his colleagues indicated. “The discovered incremental probability of reporting a psychiatric sign can help generate an index of suspicion to counsel patients.”
Using the example of a woman patient with depression, the model “suggests she would be at risk,” with a 22% chance of a psychiatric adverse event in the 2 years after receiving a levetiracetam prescription.
The researchers created a second prediction algorithm based on data from patients without documentation of a mental health sign, symptom, or disorder prior to their levetiracetam prescription. This model incorporated age, sex, recreational drug use, and levetiracetam daily dose; it performed comparably well and might be used to determine safety of prescription, according to Dr. Josephson and his colleagues.
The authors noted that the study was limited by an inability to evaluate medication adherence and seizure type and frequency. One advantage of the study’s design is that it may have circumvented expectation bias because general practitioners were not prone to anticipating psychiatric adverse events or to have a lower threshold for diagnosing them.
The authors disclosed research fellowships and support from foundations and federal agencies.
SOURCE: Josephson CB et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4561.
Among patients with epilepsy, a simple model that incorporates factors such as a patient’s sex and history of depression, anxiety, and recreational drug use may help predict the risk of a psychiatric adverse effect from levetiracetam, according to a study published in JAMA Neurology.
“This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam” and can “guide prescription in clinical practice,” said Colin B. Josephson, MD, of the department of clinical neurosciences at the University of Calgary (Canada) and his research colleagues.
Levetiracetam is a commonly used first-line treatment for epilepsy because of its ease of use, broad spectrum of action, and safety profile, the researchers said. Still, psychiatric adverse reactions occur in as many as 16% of patients and frequently require treatment discontinuation.
To evaluate whether routine clinical data can predict which patients with epilepsy will experience a psychiatric adverse event from levetiracetam, the investigators analyzed data from The Health Improvement Network (THIN) database, which includes anonymized patient records from general practices in the United Kingdom. They assessed 21 variables for possible inclusion in prediction models. They identified these variables by searching the literature and weighing input from a panel of experts.
Their analysis included data from Jan. 1, 2000–May 31, 2012. Among the more than 11 million patients in THIN, the researchers identified 7,300 incident cases of epilepsy. The researchers examined when patients received a first prescription for levetiracetam and whether patients experienced a psychiatric symptom or disorder within 2 years of the prescription.
Among 1,173 patients with epilepsy receiving levetiracetam, the median age was 39 years; about half were women. In all, 14.1% experienced a psychiatric symptom or disorder within 2 years of prescription. Women were more likely to report a psychiatric symptom (odds ratio, 1.41), as were patients with a history of social deprivation (OR, 1.15), anxiety (OR, 1.74), recreational drug use (OR, 2.02), or depression (OR, 2.20).
The final model included female sex, history of depression, history of anxiety, and history of recreational drug use. Low socioeconomic status was not included because “it would be challenging to assign this score in clinic,” the authors said.
“There was a gradient in risk probabilities increasing from 8% for 0 risk factors to 11%-17% for 1, 17% to 31% for 2, 30%-42% for 3, and 49% when all risk factors were present,” Dr. Josephson and his colleagues indicated. “The discovered incremental probability of reporting a psychiatric sign can help generate an index of suspicion to counsel patients.”
Using the example of a woman patient with depression, the model “suggests she would be at risk,” with a 22% chance of a psychiatric adverse event in the 2 years after receiving a levetiracetam prescription.
The researchers created a second prediction algorithm based on data from patients without documentation of a mental health sign, symptom, or disorder prior to their levetiracetam prescription. This model incorporated age, sex, recreational drug use, and levetiracetam daily dose; it performed comparably well and might be used to determine safety of prescription, according to Dr. Josephson and his colleagues.
The authors noted that the study was limited by an inability to evaluate medication adherence and seizure type and frequency. One advantage of the study’s design is that it may have circumvented expectation bias because general practitioners were not prone to anticipating psychiatric adverse events or to have a lower threshold for diagnosing them.
The authors disclosed research fellowships and support from foundations and federal agencies.
SOURCE: Josephson CB et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4561.
FROM JAMA NEUROLOGY
Key clinical point: Among patients with epilepsy, a simple model may help predict the risk of a psychiatric adverse effect from levetiracetam.
Major finding: The likelihood of a psychiatric adverse event increases from 8% for patients with no risk factors to 49% with all risk factors present.
Study details: A retrospective open cohort study of 1,173 patients with epilepsy receiving levetiracetam in the United Kingdom.
Disclosures: The authors disclosed research fellowships and support from foundations and federal agencies.
Source: Josephson CB et al. JAMA Neurol. 2019 Jan 28. doi: 10.1001/jamaneurol.2018.4561
Polysomnography beats Fitbit
Also today, there is no evidence for the disease-modifying effect of levodopa in Parkinson’s Disease, and ablation surpassed drugs for raising quality of life for atrial fibrillation.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Also today, there is no evidence for the disease-modifying effect of levodopa in Parkinson’s Disease, and ablation surpassed drugs for raising quality of life for atrial fibrillation.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Also today, there is no evidence for the disease-modifying effect of levodopa in Parkinson’s Disease, and ablation surpassed drugs for raising quality of life for atrial fibrillation.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Before you refer for AF ablation
SNOWMASS, COLO. – Appropriate in the way of benefit, along with instilling awareness of the warning signals heralding serious late complications, Samuel J. Asirvatham, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“Who to steer toward ablation? You have to have a symptomatic patient – that’s a given. For the ones who are paroxysmal, the ones with a relatively normal heart, there’s a much better chance that you’ll help manage their symptoms with ablation than if they have persistent or permanent A-fib. Notice I do not use the word ‘cure’ for A-fib. We talk about controlling symptoms and decreasing frequency, because the longer follow-up you have with intensive monitoring, the more you realize that patients still tend to have some A-fib,” explained Dr. Asirvatham, an electrophysiologist who is professor of medicine and pediatrics at the Mayo Clinic in Rochester, Minn.
The rationale for early atrial fibrillation (AF) ablation in younger patients with troublesome symptoms of paroxysmal AF despite pharmacologic attempts at rate or rhythm control is that it will arrest the progression from an atrial arrhythmia that has just a few triggers readily neutralized by pulmonary vein isolation to persistent AF with a diseased heart and a multitude of arrhythmia trigger points coming from many directions.
A solid candidate for ablation of paroxysmal AF has about a 75% likelihood of having a successful first ablation procedure, with substantial improvement in symptoms and no need for medication. Another 9%-10% will achieve marked reduction in symptom burden upon addition of antiarrhythmic agents that weren’t effective before ablation.
Late complications can be deceptive
Periprocedural stroke/transient ischemic attack, tamponade, or bleeding on the table are infrequent complications readily recognized by the interventionalist. More problematic are several late complications which are often misinterpreted, with the resultant delay causing major harm.
- Pulmonary vein stenosis. This complication of inadvertent ablation inside the pulmonary vein manifests as shortness of breath, typically beginning about 4 weeks post ablation.
“This is very different from the shortness of breath they had with atrial fibrillation. They almost always have a cough that they didn’t have before, and they may have hemoptysis. It’s very important to recognize this promptly, because before it closes completely we can do an angioplasty and stent the vein with good results. But once it closes completely, it becomes an extremely complicated procedure to try to reopen that vein,” according to Dr. Asirvatham.
Very often the patient’s general cardiologist, chest physician, or primary care physician fails to recognize what’s happening. He cited an example: He recently had a patient with a cough who was first referred to an infectious disease specialist, who ordered a bronchoalveolar lavage. The specimen grew atypical actinomycetes. That prompted a referral to thoracic surgery for an open-lung biopsy. But that procedure required cardiac clearance beforehand. It was a cardiologist who said, ‘Wait – all this started after you had an ablation?’
“That patient had pulmonary vein stenosis. And, unfortunately, that complication has not gone away. Being a referral center for pulmonary vein isolation, we see just as many cases of pulmonary vein stenosis today as we did a few years ago,” he said.
- Atrial esophageal fistula. The hallmark of this complication is onset of a plethora of what Dr. Asirvatham called “funny symptoms” more than a month post ablation. These include fever, transient ischemic attacks (TIAs), sepsislike symptoms, discomfort in swallowing, and in some cases hemoptysis.
“The predominant picture is endocarditis/TIA/stroke. If you see this, and the patient has had ablation, immediately refer to surgery to have the fistula between the esophagus and heart fixed. This is not a patient where you say, ‘Nothing by mouth, give some antibiotics, and see what happens.’ I can tell you what will happen: The patient will die,” the cardiologist said.
- Atrial stiffness. This typically occurs about a month after a second or third ablation procedure, when the patient develops shortness of breath that keeps worsening.
“You think ‘pulmonary vein stenosis,’ but the CT scan shows the veins are wide open. Many of these patients will get misdiagnosed as having heart failure with preserved ejection fraction even though they never had it before. The problem here is the atrium has become too stiff from the ablation, and this stiff atrium causes increased pressure, resulting in the shortness of breath. Sometimes patients feel better over time, but sometimes it’s very difficult to treat. But it’s important to recognize atrial stiffness and exclude other causes like pulmonary vein stenosis,” Dr. Asirvatham continued.
- Gastroparesis. This occurs because of injury to the vagus nerve branches located at the top of the esophagus, with resultant delayed gastric emptying.
“It’s an uncomfortable feeling of fullness all the time. The patient will say, ‘It seems like I just ate, even though I ate 8 hours ago,” the electrophysiologist said. “Most of these patients will recover in about 6 months. They may feel better on a gastric motility agent, like a macrolide antibiotic. I personally have not seen a patient who did not feel better within 6-8 months.”
Novel treatment approaches: “A-fib may be an autonomic epilepsy of the heart”
“Patients sometimes will ask you, ‘What is this ablation? What does that mean?’ You have to be truthful and tell them that it’s just a fancy word for burning,” the electrophysiologist said.
Achievement of AF ablation without radiofrequency or cryoablation, instead utilizing nonthermal direct-current pulsed electrical fields, is “the hottest topic in the field of electrophysiology,” according to Dr. Asirvatham.
These electrical fields result in irreversible electroporation of targeted myocardial cell membranes, leading to cell death. It is a tissue-specific intervention, so it’s much less likely than conventional ablation to cause collateral damage to the esophagus and other structures.
“Direct current electroporation has transitioned from proof-of-concept studies to three relatively large patient trials. This is potentially an important breakthrough because if we don’t heat, a lot of the complications of A-fib ablation will probably decrease,” he explained.
Two other promising outside-the-box approaches to the treatment of AF are autonomic nervous system modulation at sites distant from the heart and particle beam ablation without need for cardiac catheters.
“If you put electrodes everywhere in the body to see where A-fib starts, it’s not in the atrium, not in the pulmonary veins, it’s in the nerves behind the pulmonary veins, and before those nerves it’s in some other area of the autonomic nervous system. This has given rise to the notion that A-fib may be an autonomic epilepsy of the heart,” according to the electrophysiologist.
This concept has given rise to a completely different approach to treatment of AF through neurostimulation. That’s how acupuncture works. Also, headphones have been used successfully to terminate and prevent AF by stimulating autonomic nerve centers near the ears. Low-level electrical stimulation of the vagus nerve in order to reduce stellate ganglion activity is under study. So is the application of botulinum toxin at key points in the autonomic nervous system.
“Catheters, drugs, and devices that target these areas, maybe without any ablation in the heart itself, is an exciting area of future management of A-fib,” he said.
Another promising approach is borrowed from radiation oncology: particulate ablation using beams of carbon atoms, protons, or photons.
“The first patients have now been treated for ventricular tachycardia and A-fib. It really is quite amazing how precise the lesion formation is. And with no catheters in the heart, clot can’t form on catheters,” he observed.
Dr. Asirvatham reported having no financial conflicts regarding his presentation, although he serves as a consultant to a handful of medical startup companies and holds patents on intellectual property, the royalties for which go directly to the Mayo Clinic.
SNOWMASS, COLO. – Appropriate in the way of benefit, along with instilling awareness of the warning signals heralding serious late complications, Samuel J. Asirvatham, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“Who to steer toward ablation? You have to have a symptomatic patient – that’s a given. For the ones who are paroxysmal, the ones with a relatively normal heart, there’s a much better chance that you’ll help manage their symptoms with ablation than if they have persistent or permanent A-fib. Notice I do not use the word ‘cure’ for A-fib. We talk about controlling symptoms and decreasing frequency, because the longer follow-up you have with intensive monitoring, the more you realize that patients still tend to have some A-fib,” explained Dr. Asirvatham, an electrophysiologist who is professor of medicine and pediatrics at the Mayo Clinic in Rochester, Minn.
The rationale for early atrial fibrillation (AF) ablation in younger patients with troublesome symptoms of paroxysmal AF despite pharmacologic attempts at rate or rhythm control is that it will arrest the progression from an atrial arrhythmia that has just a few triggers readily neutralized by pulmonary vein isolation to persistent AF with a diseased heart and a multitude of arrhythmia trigger points coming from many directions.
A solid candidate for ablation of paroxysmal AF has about a 75% likelihood of having a successful first ablation procedure, with substantial improvement in symptoms and no need for medication. Another 9%-10% will achieve marked reduction in symptom burden upon addition of antiarrhythmic agents that weren’t effective before ablation.
Late complications can be deceptive
Periprocedural stroke/transient ischemic attack, tamponade, or bleeding on the table are infrequent complications readily recognized by the interventionalist. More problematic are several late complications which are often misinterpreted, with the resultant delay causing major harm.
- Pulmonary vein stenosis. This complication of inadvertent ablation inside the pulmonary vein manifests as shortness of breath, typically beginning about 4 weeks post ablation.
“This is very different from the shortness of breath they had with atrial fibrillation. They almost always have a cough that they didn’t have before, and they may have hemoptysis. It’s very important to recognize this promptly, because before it closes completely we can do an angioplasty and stent the vein with good results. But once it closes completely, it becomes an extremely complicated procedure to try to reopen that vein,” according to Dr. Asirvatham.
Very often the patient’s general cardiologist, chest physician, or primary care physician fails to recognize what’s happening. He cited an example: He recently had a patient with a cough who was first referred to an infectious disease specialist, who ordered a bronchoalveolar lavage. The specimen grew atypical actinomycetes. That prompted a referral to thoracic surgery for an open-lung biopsy. But that procedure required cardiac clearance beforehand. It was a cardiologist who said, ‘Wait – all this started after you had an ablation?’
“That patient had pulmonary vein stenosis. And, unfortunately, that complication has not gone away. Being a referral center for pulmonary vein isolation, we see just as many cases of pulmonary vein stenosis today as we did a few years ago,” he said.
- Atrial esophageal fistula. The hallmark of this complication is onset of a plethora of what Dr. Asirvatham called “funny symptoms” more than a month post ablation. These include fever, transient ischemic attacks (TIAs), sepsislike symptoms, discomfort in swallowing, and in some cases hemoptysis.
“The predominant picture is endocarditis/TIA/stroke. If you see this, and the patient has had ablation, immediately refer to surgery to have the fistula between the esophagus and heart fixed. This is not a patient where you say, ‘Nothing by mouth, give some antibiotics, and see what happens.’ I can tell you what will happen: The patient will die,” the cardiologist said.
- Atrial stiffness. This typically occurs about a month after a second or third ablation procedure, when the patient develops shortness of breath that keeps worsening.
“You think ‘pulmonary vein stenosis,’ but the CT scan shows the veins are wide open. Many of these patients will get misdiagnosed as having heart failure with preserved ejection fraction even though they never had it before. The problem here is the atrium has become too stiff from the ablation, and this stiff atrium causes increased pressure, resulting in the shortness of breath. Sometimes patients feel better over time, but sometimes it’s very difficult to treat. But it’s important to recognize atrial stiffness and exclude other causes like pulmonary vein stenosis,” Dr. Asirvatham continued.
- Gastroparesis. This occurs because of injury to the vagus nerve branches located at the top of the esophagus, with resultant delayed gastric emptying.
“It’s an uncomfortable feeling of fullness all the time. The patient will say, ‘It seems like I just ate, even though I ate 8 hours ago,” the electrophysiologist said. “Most of these patients will recover in about 6 months. They may feel better on a gastric motility agent, like a macrolide antibiotic. I personally have not seen a patient who did not feel better within 6-8 months.”
Novel treatment approaches: “A-fib may be an autonomic epilepsy of the heart”
“Patients sometimes will ask you, ‘What is this ablation? What does that mean?’ You have to be truthful and tell them that it’s just a fancy word for burning,” the electrophysiologist said.
Achievement of AF ablation without radiofrequency or cryoablation, instead utilizing nonthermal direct-current pulsed electrical fields, is “the hottest topic in the field of electrophysiology,” according to Dr. Asirvatham.
These electrical fields result in irreversible electroporation of targeted myocardial cell membranes, leading to cell death. It is a tissue-specific intervention, so it’s much less likely than conventional ablation to cause collateral damage to the esophagus and other structures.
“Direct current electroporation has transitioned from proof-of-concept studies to three relatively large patient trials. This is potentially an important breakthrough because if we don’t heat, a lot of the complications of A-fib ablation will probably decrease,” he explained.
Two other promising outside-the-box approaches to the treatment of AF are autonomic nervous system modulation at sites distant from the heart and particle beam ablation without need for cardiac catheters.
“If you put electrodes everywhere in the body to see where A-fib starts, it’s not in the atrium, not in the pulmonary veins, it’s in the nerves behind the pulmonary veins, and before those nerves it’s in some other area of the autonomic nervous system. This has given rise to the notion that A-fib may be an autonomic epilepsy of the heart,” according to the electrophysiologist.
This concept has given rise to a completely different approach to treatment of AF through neurostimulation. That’s how acupuncture works. Also, headphones have been used successfully to terminate and prevent AF by stimulating autonomic nerve centers near the ears. Low-level electrical stimulation of the vagus nerve in order to reduce stellate ganglion activity is under study. So is the application of botulinum toxin at key points in the autonomic nervous system.
“Catheters, drugs, and devices that target these areas, maybe without any ablation in the heart itself, is an exciting area of future management of A-fib,” he said.
Another promising approach is borrowed from radiation oncology: particulate ablation using beams of carbon atoms, protons, or photons.
“The first patients have now been treated for ventricular tachycardia and A-fib. It really is quite amazing how precise the lesion formation is. And with no catheters in the heart, clot can’t form on catheters,” he observed.
Dr. Asirvatham reported having no financial conflicts regarding his presentation, although he serves as a consultant to a handful of medical startup companies and holds patents on intellectual property, the royalties for which go directly to the Mayo Clinic.
SNOWMASS, COLO. – Appropriate in the way of benefit, along with instilling awareness of the warning signals heralding serious late complications, Samuel J. Asirvatham, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
“Who to steer toward ablation? You have to have a symptomatic patient – that’s a given. For the ones who are paroxysmal, the ones with a relatively normal heart, there’s a much better chance that you’ll help manage their symptoms with ablation than if they have persistent or permanent A-fib. Notice I do not use the word ‘cure’ for A-fib. We talk about controlling symptoms and decreasing frequency, because the longer follow-up you have with intensive monitoring, the more you realize that patients still tend to have some A-fib,” explained Dr. Asirvatham, an electrophysiologist who is professor of medicine and pediatrics at the Mayo Clinic in Rochester, Minn.
The rationale for early atrial fibrillation (AF) ablation in younger patients with troublesome symptoms of paroxysmal AF despite pharmacologic attempts at rate or rhythm control is that it will arrest the progression from an atrial arrhythmia that has just a few triggers readily neutralized by pulmonary vein isolation to persistent AF with a diseased heart and a multitude of arrhythmia trigger points coming from many directions.
A solid candidate for ablation of paroxysmal AF has about a 75% likelihood of having a successful first ablation procedure, with substantial improvement in symptoms and no need for medication. Another 9%-10% will achieve marked reduction in symptom burden upon addition of antiarrhythmic agents that weren’t effective before ablation.
Late complications can be deceptive
Periprocedural stroke/transient ischemic attack, tamponade, or bleeding on the table are infrequent complications readily recognized by the interventionalist. More problematic are several late complications which are often misinterpreted, with the resultant delay causing major harm.
- Pulmonary vein stenosis. This complication of inadvertent ablation inside the pulmonary vein manifests as shortness of breath, typically beginning about 4 weeks post ablation.
“This is very different from the shortness of breath they had with atrial fibrillation. They almost always have a cough that they didn’t have before, and they may have hemoptysis. It’s very important to recognize this promptly, because before it closes completely we can do an angioplasty and stent the vein with good results. But once it closes completely, it becomes an extremely complicated procedure to try to reopen that vein,” according to Dr. Asirvatham.
Very often the patient’s general cardiologist, chest physician, or primary care physician fails to recognize what’s happening. He cited an example: He recently had a patient with a cough who was first referred to an infectious disease specialist, who ordered a bronchoalveolar lavage. The specimen grew atypical actinomycetes. That prompted a referral to thoracic surgery for an open-lung biopsy. But that procedure required cardiac clearance beforehand. It was a cardiologist who said, ‘Wait – all this started after you had an ablation?’
“That patient had pulmonary vein stenosis. And, unfortunately, that complication has not gone away. Being a referral center for pulmonary vein isolation, we see just as many cases of pulmonary vein stenosis today as we did a few years ago,” he said.
- Atrial esophageal fistula. The hallmark of this complication is onset of a plethora of what Dr. Asirvatham called “funny symptoms” more than a month post ablation. These include fever, transient ischemic attacks (TIAs), sepsislike symptoms, discomfort in swallowing, and in some cases hemoptysis.
“The predominant picture is endocarditis/TIA/stroke. If you see this, and the patient has had ablation, immediately refer to surgery to have the fistula between the esophagus and heart fixed. This is not a patient where you say, ‘Nothing by mouth, give some antibiotics, and see what happens.’ I can tell you what will happen: The patient will die,” the cardiologist said.
- Atrial stiffness. This typically occurs about a month after a second or third ablation procedure, when the patient develops shortness of breath that keeps worsening.
“You think ‘pulmonary vein stenosis,’ but the CT scan shows the veins are wide open. Many of these patients will get misdiagnosed as having heart failure with preserved ejection fraction even though they never had it before. The problem here is the atrium has become too stiff from the ablation, and this stiff atrium causes increased pressure, resulting in the shortness of breath. Sometimes patients feel better over time, but sometimes it’s very difficult to treat. But it’s important to recognize atrial stiffness and exclude other causes like pulmonary vein stenosis,” Dr. Asirvatham continued.
- Gastroparesis. This occurs because of injury to the vagus nerve branches located at the top of the esophagus, with resultant delayed gastric emptying.
“It’s an uncomfortable feeling of fullness all the time. The patient will say, ‘It seems like I just ate, even though I ate 8 hours ago,” the electrophysiologist said. “Most of these patients will recover in about 6 months. They may feel better on a gastric motility agent, like a macrolide antibiotic. I personally have not seen a patient who did not feel better within 6-8 months.”
Novel treatment approaches: “A-fib may be an autonomic epilepsy of the heart”
“Patients sometimes will ask you, ‘What is this ablation? What does that mean?’ You have to be truthful and tell them that it’s just a fancy word for burning,” the electrophysiologist said.
Achievement of AF ablation without radiofrequency or cryoablation, instead utilizing nonthermal direct-current pulsed electrical fields, is “the hottest topic in the field of electrophysiology,” according to Dr. Asirvatham.
These electrical fields result in irreversible electroporation of targeted myocardial cell membranes, leading to cell death. It is a tissue-specific intervention, so it’s much less likely than conventional ablation to cause collateral damage to the esophagus and other structures.
“Direct current electroporation has transitioned from proof-of-concept studies to three relatively large patient trials. This is potentially an important breakthrough because if we don’t heat, a lot of the complications of A-fib ablation will probably decrease,” he explained.
Two other promising outside-the-box approaches to the treatment of AF are autonomic nervous system modulation at sites distant from the heart and particle beam ablation without need for cardiac catheters.
“If you put electrodes everywhere in the body to see where A-fib starts, it’s not in the atrium, not in the pulmonary veins, it’s in the nerves behind the pulmonary veins, and before those nerves it’s in some other area of the autonomic nervous system. This has given rise to the notion that A-fib may be an autonomic epilepsy of the heart,” according to the electrophysiologist.
This concept has given rise to a completely different approach to treatment of AF through neurostimulation. That’s how acupuncture works. Also, headphones have been used successfully to terminate and prevent AF by stimulating autonomic nerve centers near the ears. Low-level electrical stimulation of the vagus nerve in order to reduce stellate ganglion activity is under study. So is the application of botulinum toxin at key points in the autonomic nervous system.
“Catheters, drugs, and devices that target these areas, maybe without any ablation in the heart itself, is an exciting area of future management of A-fib,” he said.
Another promising approach is borrowed from radiation oncology: particulate ablation using beams of carbon atoms, protons, or photons.
“The first patients have now been treated for ventricular tachycardia and A-fib. It really is quite amazing how precise the lesion formation is. And with no catheters in the heart, clot can’t form on catheters,” he observed.
Dr. Asirvatham reported having no financial conflicts regarding his presentation, although he serves as a consultant to a handful of medical startup companies and holds patents on intellectual property, the royalties for which go directly to the Mayo Clinic.
REPORTING FROM ACC SNOWMASS 2019
Diagnosing OSA: Polysomnography beats Fitbit, apps
CORONADO, CALIF. –
“Currently, the gold standard for diagnosis is a polysomnography (PSG), which is basically a sleep study test,” one of the study authors, Daniel Chung, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “While it is very thorough, it is expensive, intrusive, and gives data on only 1 night of sleep and cannot give information on a patient’s sleep pattern over several days. Using wrist-worn devices such as Fitbit products or smartphone applications such as Sleep Cycle would be much cheaper alternatives with little distraction that can provide continuous data over several days if accurate.”
According to Dr. Chung, an otolaryngology head and neck surgery resident in the department of surgery at the George Washington University, Washington, previous studies about this topic are inconclusive.
“Most have been studied only in the pediatric population, and in general, show that Fitbit overestimates PSG measurements,” he said. “Also, prior studies have looked into 20-60 patients, depending on the study.”
In an effort to address these limitations, he and his colleagues prospectively evaluated 180 adult patients who were already scheduled to undergo a PSG with or without CPAP testing from the sleep lab. The overnight test was performed with a Fitbit Alta HR on their wrist of choice and a smartphone at their bedside. Each smartphone was randomly assigned and had a popular sleep application installed, with Sleep as Android on the Android phone and Sleep Cycle on the Apple iPhone. For the main outcomes of interest, the researchers collected the total sleep time, sleep efficiency, and apnea-hypopnea index (AHI) from the PSG and compared them with their equivalents from Fitbit and smartphone applications. For statistical analysis, they performed Bland-Altman plots, paired t-tests, and regression lines to assess R2, slope, and Y-intercept.
Dr. Chung and his colleagues found that both Fitbit Alta HR (P = .0014) and smartphone applications (P less than .0001) significantly overestimated the total sleep time, compared with PSG, while moderate correlation for sleep efficiency was observed between PSG and Fitbit (r = 0.38). Other findings of note were that the number of times awake recorded by Fitbit significantly underestimated the PSG AHI (P less than .0001), the snoring noise measurements from Sleep as Android had strong associations with PSG AHI (R2 = 0.43), and those from Sleep Cycle had modest associations with PSG AHI (R2 = 0.12). However, Bland-Altman plots showed wide limits of agreement for total sleep time and sleep efficiency, though as sleep efficiency approached 100%, the discrepancy between the PSG and Fitbit decreased.
“While there are various tools out right now that claim to measure sleep in a more comforting setting, we cannot recommend any product to act as a screening device or replacement for the PSG at this time,” Dr. Chung said.
He acknowledged certain limitations of the study, including the fact that Fitbit is unable to fully record sleep data if the wearer is asleep for fewer than 3 hours, which can happen in patients with severe OSA. In addition, the smartphone applications require the user to begin and conclude the recording. “This was performed only by the sleep technicians and not the patients, and can be a significant source of error, particularly with the Sleep as Android application, as it had a less intuitive interface,” he noted. “This lead to multiple unusable data points. There were also incidences where the Fitbit Alta HR failed to record sleep data even though it was fully charged and correctly placed, which led to only a smaller number of patients having both measurements at the same time.”
Dr. Chung reported having no financial disclosures. The meeting was jointly sponsored by the Triological Society and the American College of Surgeons.
SOURCE: Chung D et al. Triological CSM, Abstracts.
CORONADO, CALIF. –
“Currently, the gold standard for diagnosis is a polysomnography (PSG), which is basically a sleep study test,” one of the study authors, Daniel Chung, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “While it is very thorough, it is expensive, intrusive, and gives data on only 1 night of sleep and cannot give information on a patient’s sleep pattern over several days. Using wrist-worn devices such as Fitbit products or smartphone applications such as Sleep Cycle would be much cheaper alternatives with little distraction that can provide continuous data over several days if accurate.”
According to Dr. Chung, an otolaryngology head and neck surgery resident in the department of surgery at the George Washington University, Washington, previous studies about this topic are inconclusive.
“Most have been studied only in the pediatric population, and in general, show that Fitbit overestimates PSG measurements,” he said. “Also, prior studies have looked into 20-60 patients, depending on the study.”
In an effort to address these limitations, he and his colleagues prospectively evaluated 180 adult patients who were already scheduled to undergo a PSG with or without CPAP testing from the sleep lab. The overnight test was performed with a Fitbit Alta HR on their wrist of choice and a smartphone at their bedside. Each smartphone was randomly assigned and had a popular sleep application installed, with Sleep as Android on the Android phone and Sleep Cycle on the Apple iPhone. For the main outcomes of interest, the researchers collected the total sleep time, sleep efficiency, and apnea-hypopnea index (AHI) from the PSG and compared them with their equivalents from Fitbit and smartphone applications. For statistical analysis, they performed Bland-Altman plots, paired t-tests, and regression lines to assess R2, slope, and Y-intercept.
Dr. Chung and his colleagues found that both Fitbit Alta HR (P = .0014) and smartphone applications (P less than .0001) significantly overestimated the total sleep time, compared with PSG, while moderate correlation for sleep efficiency was observed between PSG and Fitbit (r = 0.38). Other findings of note were that the number of times awake recorded by Fitbit significantly underestimated the PSG AHI (P less than .0001), the snoring noise measurements from Sleep as Android had strong associations with PSG AHI (R2 = 0.43), and those from Sleep Cycle had modest associations with PSG AHI (R2 = 0.12). However, Bland-Altman plots showed wide limits of agreement for total sleep time and sleep efficiency, though as sleep efficiency approached 100%, the discrepancy between the PSG and Fitbit decreased.
“While there are various tools out right now that claim to measure sleep in a more comforting setting, we cannot recommend any product to act as a screening device or replacement for the PSG at this time,” Dr. Chung said.
He acknowledged certain limitations of the study, including the fact that Fitbit is unable to fully record sleep data if the wearer is asleep for fewer than 3 hours, which can happen in patients with severe OSA. In addition, the smartphone applications require the user to begin and conclude the recording. “This was performed only by the sleep technicians and not the patients, and can be a significant source of error, particularly with the Sleep as Android application, as it had a less intuitive interface,” he noted. “This lead to multiple unusable data points. There were also incidences where the Fitbit Alta HR failed to record sleep data even though it was fully charged and correctly placed, which led to only a smaller number of patients having both measurements at the same time.”
Dr. Chung reported having no financial disclosures. The meeting was jointly sponsored by the Triological Society and the American College of Surgeons.
SOURCE: Chung D et al. Triological CSM, Abstracts.
CORONADO, CALIF. –
“Currently, the gold standard for diagnosis is a polysomnography (PSG), which is basically a sleep study test,” one of the study authors, Daniel Chung, MD, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “While it is very thorough, it is expensive, intrusive, and gives data on only 1 night of sleep and cannot give information on a patient’s sleep pattern over several days. Using wrist-worn devices such as Fitbit products or smartphone applications such as Sleep Cycle would be much cheaper alternatives with little distraction that can provide continuous data over several days if accurate.”
According to Dr. Chung, an otolaryngology head and neck surgery resident in the department of surgery at the George Washington University, Washington, previous studies about this topic are inconclusive.
“Most have been studied only in the pediatric population, and in general, show that Fitbit overestimates PSG measurements,” he said. “Also, prior studies have looked into 20-60 patients, depending on the study.”
In an effort to address these limitations, he and his colleagues prospectively evaluated 180 adult patients who were already scheduled to undergo a PSG with or without CPAP testing from the sleep lab. The overnight test was performed with a Fitbit Alta HR on their wrist of choice and a smartphone at their bedside. Each smartphone was randomly assigned and had a popular sleep application installed, with Sleep as Android on the Android phone and Sleep Cycle on the Apple iPhone. For the main outcomes of interest, the researchers collected the total sleep time, sleep efficiency, and apnea-hypopnea index (AHI) from the PSG and compared them with their equivalents from Fitbit and smartphone applications. For statistical analysis, they performed Bland-Altman plots, paired t-tests, and regression lines to assess R2, slope, and Y-intercept.
Dr. Chung and his colleagues found that both Fitbit Alta HR (P = .0014) and smartphone applications (P less than .0001) significantly overestimated the total sleep time, compared with PSG, while moderate correlation for sleep efficiency was observed between PSG and Fitbit (r = 0.38). Other findings of note were that the number of times awake recorded by Fitbit significantly underestimated the PSG AHI (P less than .0001), the snoring noise measurements from Sleep as Android had strong associations with PSG AHI (R2 = 0.43), and those from Sleep Cycle had modest associations with PSG AHI (R2 = 0.12). However, Bland-Altman plots showed wide limits of agreement for total sleep time and sleep efficiency, though as sleep efficiency approached 100%, the discrepancy between the PSG and Fitbit decreased.
“While there are various tools out right now that claim to measure sleep in a more comforting setting, we cannot recommend any product to act as a screening device or replacement for the PSG at this time,” Dr. Chung said.
He acknowledged certain limitations of the study, including the fact that Fitbit is unable to fully record sleep data if the wearer is asleep for fewer than 3 hours, which can happen in patients with severe OSA. In addition, the smartphone applications require the user to begin and conclude the recording. “This was performed only by the sleep technicians and not the patients, and can be a significant source of error, particularly with the Sleep as Android application, as it had a less intuitive interface,” he noted. “This lead to multiple unusable data points. There were also incidences where the Fitbit Alta HR failed to record sleep data even though it was fully charged and correctly placed, which led to only a smaller number of patients having both measurements at the same time.”
Dr. Chung reported having no financial disclosures. The meeting was jointly sponsored by the Triological Society and the American College of Surgeons.
SOURCE: Chung D et al. Triological CSM, Abstracts.
REPORTING FROM THE TRIOLOGICAL CSM
Key clinical point: To date, no wrist-worn device or smartphone app can be recommended as a replacement for polysomnography to diagnose OSA.
Major finding: Both Fitbit Alta HR (P = .0014) and smart phone applications (P less than .0001) significantly overestimated the total sleep time, compared to PSG.
Study details: A prospective study of 180 adult patients.
Disclosures: Dr. Chung reported having no financial disclosures.
Source: Chung D et al. Triological CSM, Abstracts.