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AAN publishes ethical guidance on patient care during the pandemic
The document, which was published online May 15 in Neurology, reviews adaptations to the inpatient and outpatient settings and addresses the need to develop protocols for the allocation of scarce medical resources. The guidance is the product of a joint committee of the AAN, the American Neurological Association, the Child Neurology Society, and the Neurocritical Care Society Ethics Committee.
“Now is one of the most challenging times of our careers as neurologists,” said James C. Stevens, MD, president of the AAN, in a press release. “Clinics and hospitals are adapting to caring for the most ill, managing scarce resources, and trying to protect people without the disease. As neurologists, we must continue to adapt our daily practice, continue to care for our most ill neurology patients, and help contribute to the care of those afflicted with COVID-19.”
The role of telehealth
The authors recommended that ordinary appointments be held using telehealth, which, they say, already has become part of patient care. Telehealth enables neurologists to continue providing care while reducing the risk of exposure to and spread of SARS-CoV-2. The disadvantages of telehealth are that it limits physical examinations and behavioral health examinations, the authors acknowledged. “Each clinician should decide, in concert with his or her patient, if an in-person evaluation warrants the risk of an encounter,” according to the guidance.
Neurologists also should advise their patients that their neurologic condition could affect their relative risk of hospitalization and death resulting from COVID-19. Patients with multiple sclerosis or myasthenia gravis, for example, may be receiving corticosteroids or immunomodulatory therapies that make them more vulnerable to COVID-19 infection. “Even if desired services are available, neurologists and their patients ought to consider whether their care plans can safely be delayed in order to mitigate risk,” wrote the authors. Neurologists must try to maintain the customary standard of care, however, for patients with neurologic disease severe enough to warrant hospitalization, such as stroke or epilepsy.
The potential need for triage
Resources such as ventilators and ICU beds are limited, and health care facilities have had to triage them during the pandemic. Patients with a neurologic disease that decreases their likelihood of survival from a respiratory illness may not be offered these resources. Neurologists should discuss with patients and decision makers the ways in which reduced resources might affect patient care. Neurologists must “be aware of the burden of disease in their local community and how healthcare leaders plan on coping with a surge,” according to the guidance.
Advance directives, which should be a standard part of clinical care, take on increased importance during the pandemic. Patients who have not completed advance care planning documents should be encouraged to do so, according to the authors. These documents include patients’ preferences for “do not attempt resuscitation” status. Nevertheless, “we must assure patients with chronic illness that diminished resources in this healthcare crisis will not restrict their access to comfort and palliative care,” the document states.
Scarce resource allocation protocols
In the event that a surge in patients overwhelms a hospital’s contingencies and forces it to operate in crisis mode, it should have a scarce resource allocation protocol in place.
“This will surely be the most challenging aspect of patient care during this pandemic public health emergency,” wrote the authors. To ensure transparency and to mitigate the emotional effect of these decisions on patients and clinicians, scarce resource allocation protocols should be developed by teams that include intensivists, clinical ethicists, and nursing representatives who are not directly involved in the care of the critically ill patients. The goal of these protocols is to maximize the number of lives saved. They generally include an initial patient assessment followed by regular reevaluations to determine whether patients using scarce resources are benefiting less than other patients who need the same resources. The protocols should consider not only patients with COVID-19 infection, but also patients with stroke, traumatic injury, influenza, and heart failure who may need the same resources. Race, gender, ethnicity, socioeconomics, and perceived social worth should not influence care decisions, according to the guidance. Validated mortality prediction scales, such as the Glasgow Outcome Scale, can contribute to care decisions. Obtaining community input into these protocols will ensure trust in the health care system.
“If the situation necessitates hard decisions, we need to be fair, objective, transparent, and adamantly preserve our professional integrity,” wrote the authors. “Through it all, we owe it to our patients and families, as well as ourselves, to maintain our own health and wellness.”
The guidance was developed without funding, and the authors reported no relevant disclosures.
SOURCE: Rubin MA et al. Neurology. 2020 May 15. doi: 10.1212/WNL.0000000000009744.
The document, which was published online May 15 in Neurology, reviews adaptations to the inpatient and outpatient settings and addresses the need to develop protocols for the allocation of scarce medical resources. The guidance is the product of a joint committee of the AAN, the American Neurological Association, the Child Neurology Society, and the Neurocritical Care Society Ethics Committee.
“Now is one of the most challenging times of our careers as neurologists,” said James C. Stevens, MD, president of the AAN, in a press release. “Clinics and hospitals are adapting to caring for the most ill, managing scarce resources, and trying to protect people without the disease. As neurologists, we must continue to adapt our daily practice, continue to care for our most ill neurology patients, and help contribute to the care of those afflicted with COVID-19.”
The role of telehealth
The authors recommended that ordinary appointments be held using telehealth, which, they say, already has become part of patient care. Telehealth enables neurologists to continue providing care while reducing the risk of exposure to and spread of SARS-CoV-2. The disadvantages of telehealth are that it limits physical examinations and behavioral health examinations, the authors acknowledged. “Each clinician should decide, in concert with his or her patient, if an in-person evaluation warrants the risk of an encounter,” according to the guidance.
Neurologists also should advise their patients that their neurologic condition could affect their relative risk of hospitalization and death resulting from COVID-19. Patients with multiple sclerosis or myasthenia gravis, for example, may be receiving corticosteroids or immunomodulatory therapies that make them more vulnerable to COVID-19 infection. “Even if desired services are available, neurologists and their patients ought to consider whether their care plans can safely be delayed in order to mitigate risk,” wrote the authors. Neurologists must try to maintain the customary standard of care, however, for patients with neurologic disease severe enough to warrant hospitalization, such as stroke or epilepsy.
The potential need for triage
Resources such as ventilators and ICU beds are limited, and health care facilities have had to triage them during the pandemic. Patients with a neurologic disease that decreases their likelihood of survival from a respiratory illness may not be offered these resources. Neurologists should discuss with patients and decision makers the ways in which reduced resources might affect patient care. Neurologists must “be aware of the burden of disease in their local community and how healthcare leaders plan on coping with a surge,” according to the guidance.
Advance directives, which should be a standard part of clinical care, take on increased importance during the pandemic. Patients who have not completed advance care planning documents should be encouraged to do so, according to the authors. These documents include patients’ preferences for “do not attempt resuscitation” status. Nevertheless, “we must assure patients with chronic illness that diminished resources in this healthcare crisis will not restrict their access to comfort and palliative care,” the document states.
Scarce resource allocation protocols
In the event that a surge in patients overwhelms a hospital’s contingencies and forces it to operate in crisis mode, it should have a scarce resource allocation protocol in place.
“This will surely be the most challenging aspect of patient care during this pandemic public health emergency,” wrote the authors. To ensure transparency and to mitigate the emotional effect of these decisions on patients and clinicians, scarce resource allocation protocols should be developed by teams that include intensivists, clinical ethicists, and nursing representatives who are not directly involved in the care of the critically ill patients. The goal of these protocols is to maximize the number of lives saved. They generally include an initial patient assessment followed by regular reevaluations to determine whether patients using scarce resources are benefiting less than other patients who need the same resources. The protocols should consider not only patients with COVID-19 infection, but also patients with stroke, traumatic injury, influenza, and heart failure who may need the same resources. Race, gender, ethnicity, socioeconomics, and perceived social worth should not influence care decisions, according to the guidance. Validated mortality prediction scales, such as the Glasgow Outcome Scale, can contribute to care decisions. Obtaining community input into these protocols will ensure trust in the health care system.
“If the situation necessitates hard decisions, we need to be fair, objective, transparent, and adamantly preserve our professional integrity,” wrote the authors. “Through it all, we owe it to our patients and families, as well as ourselves, to maintain our own health and wellness.”
The guidance was developed without funding, and the authors reported no relevant disclosures.
SOURCE: Rubin MA et al. Neurology. 2020 May 15. doi: 10.1212/WNL.0000000000009744.
The document, which was published online May 15 in Neurology, reviews adaptations to the inpatient and outpatient settings and addresses the need to develop protocols for the allocation of scarce medical resources. The guidance is the product of a joint committee of the AAN, the American Neurological Association, the Child Neurology Society, and the Neurocritical Care Society Ethics Committee.
“Now is one of the most challenging times of our careers as neurologists,” said James C. Stevens, MD, president of the AAN, in a press release. “Clinics and hospitals are adapting to caring for the most ill, managing scarce resources, and trying to protect people without the disease. As neurologists, we must continue to adapt our daily practice, continue to care for our most ill neurology patients, and help contribute to the care of those afflicted with COVID-19.”
The role of telehealth
The authors recommended that ordinary appointments be held using telehealth, which, they say, already has become part of patient care. Telehealth enables neurologists to continue providing care while reducing the risk of exposure to and spread of SARS-CoV-2. The disadvantages of telehealth are that it limits physical examinations and behavioral health examinations, the authors acknowledged. “Each clinician should decide, in concert with his or her patient, if an in-person evaluation warrants the risk of an encounter,” according to the guidance.
Neurologists also should advise their patients that their neurologic condition could affect their relative risk of hospitalization and death resulting from COVID-19. Patients with multiple sclerosis or myasthenia gravis, for example, may be receiving corticosteroids or immunomodulatory therapies that make them more vulnerable to COVID-19 infection. “Even if desired services are available, neurologists and their patients ought to consider whether their care plans can safely be delayed in order to mitigate risk,” wrote the authors. Neurologists must try to maintain the customary standard of care, however, for patients with neurologic disease severe enough to warrant hospitalization, such as stroke or epilepsy.
The potential need for triage
Resources such as ventilators and ICU beds are limited, and health care facilities have had to triage them during the pandemic. Patients with a neurologic disease that decreases their likelihood of survival from a respiratory illness may not be offered these resources. Neurologists should discuss with patients and decision makers the ways in which reduced resources might affect patient care. Neurologists must “be aware of the burden of disease in their local community and how healthcare leaders plan on coping with a surge,” according to the guidance.
Advance directives, which should be a standard part of clinical care, take on increased importance during the pandemic. Patients who have not completed advance care planning documents should be encouraged to do so, according to the authors. These documents include patients’ preferences for “do not attempt resuscitation” status. Nevertheless, “we must assure patients with chronic illness that diminished resources in this healthcare crisis will not restrict their access to comfort and palliative care,” the document states.
Scarce resource allocation protocols
In the event that a surge in patients overwhelms a hospital’s contingencies and forces it to operate in crisis mode, it should have a scarce resource allocation protocol in place.
“This will surely be the most challenging aspect of patient care during this pandemic public health emergency,” wrote the authors. To ensure transparency and to mitigate the emotional effect of these decisions on patients and clinicians, scarce resource allocation protocols should be developed by teams that include intensivists, clinical ethicists, and nursing representatives who are not directly involved in the care of the critically ill patients. The goal of these protocols is to maximize the number of lives saved. They generally include an initial patient assessment followed by regular reevaluations to determine whether patients using scarce resources are benefiting less than other patients who need the same resources. The protocols should consider not only patients with COVID-19 infection, but also patients with stroke, traumatic injury, influenza, and heart failure who may need the same resources. Race, gender, ethnicity, socioeconomics, and perceived social worth should not influence care decisions, according to the guidance. Validated mortality prediction scales, such as the Glasgow Outcome Scale, can contribute to care decisions. Obtaining community input into these protocols will ensure trust in the health care system.
“If the situation necessitates hard decisions, we need to be fair, objective, transparent, and adamantly preserve our professional integrity,” wrote the authors. “Through it all, we owe it to our patients and families, as well as ourselves, to maintain our own health and wellness.”
The guidance was developed without funding, and the authors reported no relevant disclosures.
SOURCE: Rubin MA et al. Neurology. 2020 May 15. doi: 10.1212/WNL.0000000000009744.
FROM NEUROLOGY
Blood pressure lowering lessens risk of dementia, cognitive decline
“Although observational studies report hypertension to be an important risk factor for dementia, the benefit of blood pressure lowering on dementia or cognitive impairment in clinical trials is modest and lower than the risk reduction for stroke,” wrote Diarmaid Hughes, MB, of the NUI Galway and Saolta University Hospital Group in Galway, Ireland, and coauthors. They added, however, that “these findings have the potential to inform public health strategies to reduce the burden of dementia globally.” The study was published online ahead of print May 19 in JAMA.
A rich data set
To assess the relationship between lowering blood pressure and cognitive issues, the researchers performed a systemic search of randomized, clinical trials that compared blood pressure lowering via antihypertensive agents with a control, had at least 1 year of follow-up, included more than 1,000 participants, and reported on either dementia, cognitive impairment, cognitive decline, or a change in cognitive test scores as outcomes. Of the 14 studies deemed eligible, 12 reported either the incidence of dementia (n = 9) or a composite of dementia or cognitive impairment (n = 3) at follow-up and thus were included in the primary meta-analysis. The other two studies were used for secondary outcomes only.
The studies included 96,158 participants in total – 42.2% were women – and their mean age was 69 years. At baseline, participants’ mean systolic blood pressure was 154 mm Hg and their mean diastolic blood pressure was 83.3 mm Hg. The mean duration of follow-up was 49.24 months.
In the 12 trials that reported dementia or cognitive impairment, blood pressure lowering via antihypertensive agents, compared with control, was significantly associated with a reduction in those two outcomes (7.0% vs. 7.5% over a mean trial follow-up of 4.1 years; odds ratio, 0.93; 95% confidence interval, 0.88-0.98; absolute risk reduction, 0.39%; 95% CI, 0.09%-0.68%). Blood pressure lowering, compared with control, was also significantly associated with a reduction in cognitive decline (20.2% vs. 21.1% over a mean trial follow-up of 4.1 years; OR, 0.93; 95% CI, 0.88-0.99; ARR, 0.71%; 95% CI, 0.19%-1.2%) in the eight trials that reported it as an outcome. An analysis of the eight trials that reported a change in cognitive scores did not find a significant association between that outcome and blood pressure lowering.
Subpopulations should be examined
“This is a very broad brush stroke study, albeit a definitive one,” Richard J. Caselli, MD, of the Mayo Clinic in Phoenix said in an interview. “With all the thousands of people in this meta-analysis, there are going to be subpopulations of patients with certain characteristics or common conditions in which blood pressure lowering might have a bigger or a lesser impact on their risk factor. Is there a difference between certain racial groups? Does it matter what antihypertensive strategies are used? You can look at the interactions between blood pressure lowering and other conditions: diabetes, head injuries, air pollution, certain genetic risk factors. There are a number of additional findings that could come from a very rich data set like this.”
The authors acknowledged their study’s limitations, including the challenges of performing a meta-analysis of studies that drew from different populations and had potentially different definitions of dementia, cognitive impairment, and cognitive decline outcomes. In addition, the low incidence of dementia across clinical trials limited the researchers, and its underdetection in trials and the potential of survivor bias for healthier participants with blood pressure reductions were noted as “unmeasured sources of potential error.”
Three authors reported receiving grants or personal fees from the Wellcome Trust and the Health Research Board, the Chief Scientist Office, and Bayer AG, respectively.
SOURCE: Hughes D et al. JAMA. 2020 May 19. doi: 10.1001/jama.2020.4249.
“Although observational studies report hypertension to be an important risk factor for dementia, the benefit of blood pressure lowering on dementia or cognitive impairment in clinical trials is modest and lower than the risk reduction for stroke,” wrote Diarmaid Hughes, MB, of the NUI Galway and Saolta University Hospital Group in Galway, Ireland, and coauthors. They added, however, that “these findings have the potential to inform public health strategies to reduce the burden of dementia globally.” The study was published online ahead of print May 19 in JAMA.
A rich data set
To assess the relationship between lowering blood pressure and cognitive issues, the researchers performed a systemic search of randomized, clinical trials that compared blood pressure lowering via antihypertensive agents with a control, had at least 1 year of follow-up, included more than 1,000 participants, and reported on either dementia, cognitive impairment, cognitive decline, or a change in cognitive test scores as outcomes. Of the 14 studies deemed eligible, 12 reported either the incidence of dementia (n = 9) or a composite of dementia or cognitive impairment (n = 3) at follow-up and thus were included in the primary meta-analysis. The other two studies were used for secondary outcomes only.
The studies included 96,158 participants in total – 42.2% were women – and their mean age was 69 years. At baseline, participants’ mean systolic blood pressure was 154 mm Hg and their mean diastolic blood pressure was 83.3 mm Hg. The mean duration of follow-up was 49.24 months.
In the 12 trials that reported dementia or cognitive impairment, blood pressure lowering via antihypertensive agents, compared with control, was significantly associated with a reduction in those two outcomes (7.0% vs. 7.5% over a mean trial follow-up of 4.1 years; odds ratio, 0.93; 95% confidence interval, 0.88-0.98; absolute risk reduction, 0.39%; 95% CI, 0.09%-0.68%). Blood pressure lowering, compared with control, was also significantly associated with a reduction in cognitive decline (20.2% vs. 21.1% over a mean trial follow-up of 4.1 years; OR, 0.93; 95% CI, 0.88-0.99; ARR, 0.71%; 95% CI, 0.19%-1.2%) in the eight trials that reported it as an outcome. An analysis of the eight trials that reported a change in cognitive scores did not find a significant association between that outcome and blood pressure lowering.
Subpopulations should be examined
“This is a very broad brush stroke study, albeit a definitive one,” Richard J. Caselli, MD, of the Mayo Clinic in Phoenix said in an interview. “With all the thousands of people in this meta-analysis, there are going to be subpopulations of patients with certain characteristics or common conditions in which blood pressure lowering might have a bigger or a lesser impact on their risk factor. Is there a difference between certain racial groups? Does it matter what antihypertensive strategies are used? You can look at the interactions between blood pressure lowering and other conditions: diabetes, head injuries, air pollution, certain genetic risk factors. There are a number of additional findings that could come from a very rich data set like this.”
The authors acknowledged their study’s limitations, including the challenges of performing a meta-analysis of studies that drew from different populations and had potentially different definitions of dementia, cognitive impairment, and cognitive decline outcomes. In addition, the low incidence of dementia across clinical trials limited the researchers, and its underdetection in trials and the potential of survivor bias for healthier participants with blood pressure reductions were noted as “unmeasured sources of potential error.”
Three authors reported receiving grants or personal fees from the Wellcome Trust and the Health Research Board, the Chief Scientist Office, and Bayer AG, respectively.
SOURCE: Hughes D et al. JAMA. 2020 May 19. doi: 10.1001/jama.2020.4249.
“Although observational studies report hypertension to be an important risk factor for dementia, the benefit of blood pressure lowering on dementia or cognitive impairment in clinical trials is modest and lower than the risk reduction for stroke,” wrote Diarmaid Hughes, MB, of the NUI Galway and Saolta University Hospital Group in Galway, Ireland, and coauthors. They added, however, that “these findings have the potential to inform public health strategies to reduce the burden of dementia globally.” The study was published online ahead of print May 19 in JAMA.
A rich data set
To assess the relationship between lowering blood pressure and cognitive issues, the researchers performed a systemic search of randomized, clinical trials that compared blood pressure lowering via antihypertensive agents with a control, had at least 1 year of follow-up, included more than 1,000 participants, and reported on either dementia, cognitive impairment, cognitive decline, or a change in cognitive test scores as outcomes. Of the 14 studies deemed eligible, 12 reported either the incidence of dementia (n = 9) or a composite of dementia or cognitive impairment (n = 3) at follow-up and thus were included in the primary meta-analysis. The other two studies were used for secondary outcomes only.
The studies included 96,158 participants in total – 42.2% were women – and their mean age was 69 years. At baseline, participants’ mean systolic blood pressure was 154 mm Hg and their mean diastolic blood pressure was 83.3 mm Hg. The mean duration of follow-up was 49.24 months.
In the 12 trials that reported dementia or cognitive impairment, blood pressure lowering via antihypertensive agents, compared with control, was significantly associated with a reduction in those two outcomes (7.0% vs. 7.5% over a mean trial follow-up of 4.1 years; odds ratio, 0.93; 95% confidence interval, 0.88-0.98; absolute risk reduction, 0.39%; 95% CI, 0.09%-0.68%). Blood pressure lowering, compared with control, was also significantly associated with a reduction in cognitive decline (20.2% vs. 21.1% over a mean trial follow-up of 4.1 years; OR, 0.93; 95% CI, 0.88-0.99; ARR, 0.71%; 95% CI, 0.19%-1.2%) in the eight trials that reported it as an outcome. An analysis of the eight trials that reported a change in cognitive scores did not find a significant association between that outcome and blood pressure lowering.
Subpopulations should be examined
“This is a very broad brush stroke study, albeit a definitive one,” Richard J. Caselli, MD, of the Mayo Clinic in Phoenix said in an interview. “With all the thousands of people in this meta-analysis, there are going to be subpopulations of patients with certain characteristics or common conditions in which blood pressure lowering might have a bigger or a lesser impact on their risk factor. Is there a difference between certain racial groups? Does it matter what antihypertensive strategies are used? You can look at the interactions between blood pressure lowering and other conditions: diabetes, head injuries, air pollution, certain genetic risk factors. There are a number of additional findings that could come from a very rich data set like this.”
The authors acknowledged their study’s limitations, including the challenges of performing a meta-analysis of studies that drew from different populations and had potentially different definitions of dementia, cognitive impairment, and cognitive decline outcomes. In addition, the low incidence of dementia across clinical trials limited the researchers, and its underdetection in trials and the potential of survivor bias for healthier participants with blood pressure reductions were noted as “unmeasured sources of potential error.”
Three authors reported receiving grants or personal fees from the Wellcome Trust and the Health Research Board, the Chief Scientist Office, and Bayer AG, respectively.
SOURCE: Hughes D et al. JAMA. 2020 May 19. doi: 10.1001/jama.2020.4249.
FROM JAMA
Frontal lobe glucose abnormalities may indicate increased SUDEP risk
, new research suggests.
“The data provide initial evidence that hypometabolism in certain parts of the frontal cortex may be associated with higher SUDEP risk,” said lead author Maysaa M. Basha, MD, associate professor of neurology and director of the Adult Comprehensive Epilepsy Program, Wayne State University/Detroit Medical Center, in Michigan.
If this research is validated, “it potentially can be used to screen patients for higher SUDEP risk,” she said. The idea is to identify those at high risk and then reduce that risk with more aggressive management of seizures or closer monitoring in certain cases, she added.
The research is being presented online as part of the 2020 American Academy of Neurology (AAN) Science Highlights.
Hypometabolism
Dr. Basha and colleagues were encouraged to pursue this new line of research after a pilot [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) study revealed frontal lobe hypometabolism among patients who subsequently died.
“We wanted to determine if such a metabolic abnormality is associated with SUDEP risk,” said Dr. Basha. She noted that no PET studies have addressed this question, only MRI studies.
In this new study, researchers aimed to identify specific patterns of objectively detected brain glucose metabolic abnormalities in patients with refractory focal epilepsy who were at risk for SUDEP.
The study included 80 patients (45 female patients) aged 16 to 61 years (mean age, 37 years) who underwent FDG-PET as part of their presurgical evaluation for epilepsy surgery. Patients with large brain lesions, such as an infarct or a large tumor, were excluded from the study; such lesions can affect the accuracy of an objective PET analysis, explained Dr. Basha.
The researchers assessed risk for SUDEP using the seven-item SUDEP inventory (SUDEP-7), which was developed as a marker of clinical SUDEP risk. The 0- to 10-point scale is used to evaluate the frequency of tonic-clonic and other seizures, the duration of epilepsy, the use of antiepileptic drugs, and intellectual disability.
The researchers calculated SUDEP-7 inventory scores as closely as possible to FDG-PET assessments. The mean score in the patient population was 3.6.
The investigators divided participants into two subgroups: 22 patients had a SUDEP score of 5 or greater; and 58 had a score of less than 5 (higher scores indicate higher risk for SUDEP).
The researchers compared PET scans of each of these subgroups to PET scans from healthy adults to determine whether they showed common areas of metabolic abnormality. For this, they used an image analytic software program called Statistical Parametric Mapping, which compares group values of metabolic activity measured in small units of the brain (voxels) with statistical methods.
The analysis showed that the higher-risk group displayed a common pattern of hypometabolism in certain brain areas.
“The epilepsy patient subgroup with high SUDEP risk showed areas of decreased metabolism, as compared to the control group, in portions of the frontal cortex,” said Dr. Basha. “The statistically most significant decreases were in the right frontal lobe area—both lateral convexity and medial cortex.”
Dr. Basha added that these group abnormalities were “remarkably similar” to the individual metabolic abnormalities found in the four SUDEP patients in the previous pilot study who underwent PET scanning and who subsequently died.
A similar group analysis showed that the group at low SUDEP risk displayed no common metabolic abnormalities.
MRI findings were normal for 40 patients.
Dr. Basha and colleagues believe that “this is the first PET study assessing the metabolic correlates of SUDEP risk on the group level.”
Common feature
Interictal glucose hypometabolism is “common in and around epileptic foci,” noted Dr. Basha. However, this could extend into nonepileptic regions—for example, to remote connected regions where seizures can spread from the primary focus and into subcortical gray matter structures, such the thalamus.
Some of these metabolic abnormalities may indicate subtle, microscopic, structural abnormalities in the affected brain, said Dr. Basha.
Abnormalities that are induced by epilepsy and that result from purely metabolic changes could be partly or fully reversed if seizures are controlled on a long-term basis, she said. “Some metabolic abnormalities can be reversed after better seizure control with antiepileptic drugs, epileptic surgery, or other antiepileptic treatment,” she said.
It’s “quite possible” that the same brain pattern would be evident in children with epilepsy, although her team has not performed the same analysis in a younger pediatric group, said Dr. Basha. She noted that it would be unethical to administer PET scans, which involve radiation, to young, healthy control persons.
It’s too early to recommend that all epilepsy patients undergo FDG-PET scanning to see whether this pattern of brain glucose hypometabolism is present, said Dr. Basha. “But if this is proven to be a good biomarker, the next step would be a prospective study” to see whether this brain marker is a true signal of SUDEP risk.
“I don’t think our single study would do that, but ultimately, that would be the goal,” she added.
One more piece of the SUDEP puzzle
Commenting on the study, William Davis Gaillard, MD, president of the American Epilepsy Society and chief of neurology, Children’s National Medical Center, Chevy Chase, Maryland, said this new information provides one more piece of the SUDEP puzzle but doesn’t complete the picture.
The study authors assessed PET scans of a group of patients and found common abnormalities that implicate the right medial frontal cortex. “That’s a pretty reasonable method” of investigation, said Dr. Gaillard.
“The challenge is that they’re looking at people they believe have a risk of SUDEP as opposed to people who died,” said Dr. Gaillard.
But he agreed that the results might signal “a biomarker” that “allows you to identify who’s at high risk, and then you may be able to intervene to save them.”
It’s not clear that people with frontal lobe epilepsy are at greater risk for SUDEP than those with temporal lobe epilepsy, he said.
“What you don’t know is whether this represents people with a seizure focus in that area or this represents a common network implicated in people with diverse forms of focal epilepsy; so you need to do some more work,” he said.
Dr. Gaillard pointed out that other research has implicated regions other than the mesial frontal cortex in SUDEP risk. These regions include the insula, the amygdala, the hippocampus, and the brain stem.
He also noted that the SUDEP-7, which has not been thoroughly validated, is designed for use only in adults.
In his own practice, he asks patients about the frequency of tonic-clonic seizures and whether they occur at night. The number of antiepileptic medications a patient takes reflects the difficulty of controlling seizures and may not be “an independent variable for risk,” said Dr. Gaillard.
“It’s clear one needs a better assessment and better idea of who is at risk,” he said.
The researchers have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Basha A et al. AAN 2020. Abstract P5.001.
, new research suggests.
“The data provide initial evidence that hypometabolism in certain parts of the frontal cortex may be associated with higher SUDEP risk,” said lead author Maysaa M. Basha, MD, associate professor of neurology and director of the Adult Comprehensive Epilepsy Program, Wayne State University/Detroit Medical Center, in Michigan.
If this research is validated, “it potentially can be used to screen patients for higher SUDEP risk,” she said. The idea is to identify those at high risk and then reduce that risk with more aggressive management of seizures or closer monitoring in certain cases, she added.
The research is being presented online as part of the 2020 American Academy of Neurology (AAN) Science Highlights.
Hypometabolism
Dr. Basha and colleagues were encouraged to pursue this new line of research after a pilot [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) study revealed frontal lobe hypometabolism among patients who subsequently died.
“We wanted to determine if such a metabolic abnormality is associated with SUDEP risk,” said Dr. Basha. She noted that no PET studies have addressed this question, only MRI studies.
In this new study, researchers aimed to identify specific patterns of objectively detected brain glucose metabolic abnormalities in patients with refractory focal epilepsy who were at risk for SUDEP.
The study included 80 patients (45 female patients) aged 16 to 61 years (mean age, 37 years) who underwent FDG-PET as part of their presurgical evaluation for epilepsy surgery. Patients with large brain lesions, such as an infarct or a large tumor, were excluded from the study; such lesions can affect the accuracy of an objective PET analysis, explained Dr. Basha.
The researchers assessed risk for SUDEP using the seven-item SUDEP inventory (SUDEP-7), which was developed as a marker of clinical SUDEP risk. The 0- to 10-point scale is used to evaluate the frequency of tonic-clonic and other seizures, the duration of epilepsy, the use of antiepileptic drugs, and intellectual disability.
The researchers calculated SUDEP-7 inventory scores as closely as possible to FDG-PET assessments. The mean score in the patient population was 3.6.
The investigators divided participants into two subgroups: 22 patients had a SUDEP score of 5 or greater; and 58 had a score of less than 5 (higher scores indicate higher risk for SUDEP).
The researchers compared PET scans of each of these subgroups to PET scans from healthy adults to determine whether they showed common areas of metabolic abnormality. For this, they used an image analytic software program called Statistical Parametric Mapping, which compares group values of metabolic activity measured in small units of the brain (voxels) with statistical methods.
The analysis showed that the higher-risk group displayed a common pattern of hypometabolism in certain brain areas.
“The epilepsy patient subgroup with high SUDEP risk showed areas of decreased metabolism, as compared to the control group, in portions of the frontal cortex,” said Dr. Basha. “The statistically most significant decreases were in the right frontal lobe area—both lateral convexity and medial cortex.”
Dr. Basha added that these group abnormalities were “remarkably similar” to the individual metabolic abnormalities found in the four SUDEP patients in the previous pilot study who underwent PET scanning and who subsequently died.
A similar group analysis showed that the group at low SUDEP risk displayed no common metabolic abnormalities.
MRI findings were normal for 40 patients.
Dr. Basha and colleagues believe that “this is the first PET study assessing the metabolic correlates of SUDEP risk on the group level.”
Common feature
Interictal glucose hypometabolism is “common in and around epileptic foci,” noted Dr. Basha. However, this could extend into nonepileptic regions—for example, to remote connected regions where seizures can spread from the primary focus and into subcortical gray matter structures, such the thalamus.
Some of these metabolic abnormalities may indicate subtle, microscopic, structural abnormalities in the affected brain, said Dr. Basha.
Abnormalities that are induced by epilepsy and that result from purely metabolic changes could be partly or fully reversed if seizures are controlled on a long-term basis, she said. “Some metabolic abnormalities can be reversed after better seizure control with antiepileptic drugs, epileptic surgery, or other antiepileptic treatment,” she said.
It’s “quite possible” that the same brain pattern would be evident in children with epilepsy, although her team has not performed the same analysis in a younger pediatric group, said Dr. Basha. She noted that it would be unethical to administer PET scans, which involve radiation, to young, healthy control persons.
It’s too early to recommend that all epilepsy patients undergo FDG-PET scanning to see whether this pattern of brain glucose hypometabolism is present, said Dr. Basha. “But if this is proven to be a good biomarker, the next step would be a prospective study” to see whether this brain marker is a true signal of SUDEP risk.
“I don’t think our single study would do that, but ultimately, that would be the goal,” she added.
One more piece of the SUDEP puzzle
Commenting on the study, William Davis Gaillard, MD, president of the American Epilepsy Society and chief of neurology, Children’s National Medical Center, Chevy Chase, Maryland, said this new information provides one more piece of the SUDEP puzzle but doesn’t complete the picture.
The study authors assessed PET scans of a group of patients and found common abnormalities that implicate the right medial frontal cortex. “That’s a pretty reasonable method” of investigation, said Dr. Gaillard.
“The challenge is that they’re looking at people they believe have a risk of SUDEP as opposed to people who died,” said Dr. Gaillard.
But he agreed that the results might signal “a biomarker” that “allows you to identify who’s at high risk, and then you may be able to intervene to save them.”
It’s not clear that people with frontal lobe epilepsy are at greater risk for SUDEP than those with temporal lobe epilepsy, he said.
“What you don’t know is whether this represents people with a seizure focus in that area or this represents a common network implicated in people with diverse forms of focal epilepsy; so you need to do some more work,” he said.
Dr. Gaillard pointed out that other research has implicated regions other than the mesial frontal cortex in SUDEP risk. These regions include the insula, the amygdala, the hippocampus, and the brain stem.
He also noted that the SUDEP-7, which has not been thoroughly validated, is designed for use only in adults.
In his own practice, he asks patients about the frequency of tonic-clonic seizures and whether they occur at night. The number of antiepileptic medications a patient takes reflects the difficulty of controlling seizures and may not be “an independent variable for risk,” said Dr. Gaillard.
“It’s clear one needs a better assessment and better idea of who is at risk,” he said.
The researchers have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Basha A et al. AAN 2020. Abstract P5.001.
, new research suggests.
“The data provide initial evidence that hypometabolism in certain parts of the frontal cortex may be associated with higher SUDEP risk,” said lead author Maysaa M. Basha, MD, associate professor of neurology and director of the Adult Comprehensive Epilepsy Program, Wayne State University/Detroit Medical Center, in Michigan.
If this research is validated, “it potentially can be used to screen patients for higher SUDEP risk,” she said. The idea is to identify those at high risk and then reduce that risk with more aggressive management of seizures or closer monitoring in certain cases, she added.
The research is being presented online as part of the 2020 American Academy of Neurology (AAN) Science Highlights.
Hypometabolism
Dr. Basha and colleagues were encouraged to pursue this new line of research after a pilot [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) study revealed frontal lobe hypometabolism among patients who subsequently died.
“We wanted to determine if such a metabolic abnormality is associated with SUDEP risk,” said Dr. Basha. She noted that no PET studies have addressed this question, only MRI studies.
In this new study, researchers aimed to identify specific patterns of objectively detected brain glucose metabolic abnormalities in patients with refractory focal epilepsy who were at risk for SUDEP.
The study included 80 patients (45 female patients) aged 16 to 61 years (mean age, 37 years) who underwent FDG-PET as part of their presurgical evaluation for epilepsy surgery. Patients with large brain lesions, such as an infarct or a large tumor, were excluded from the study; such lesions can affect the accuracy of an objective PET analysis, explained Dr. Basha.
The researchers assessed risk for SUDEP using the seven-item SUDEP inventory (SUDEP-7), which was developed as a marker of clinical SUDEP risk. The 0- to 10-point scale is used to evaluate the frequency of tonic-clonic and other seizures, the duration of epilepsy, the use of antiepileptic drugs, and intellectual disability.
The researchers calculated SUDEP-7 inventory scores as closely as possible to FDG-PET assessments. The mean score in the patient population was 3.6.
The investigators divided participants into two subgroups: 22 patients had a SUDEP score of 5 or greater; and 58 had a score of less than 5 (higher scores indicate higher risk for SUDEP).
The researchers compared PET scans of each of these subgroups to PET scans from healthy adults to determine whether they showed common areas of metabolic abnormality. For this, they used an image analytic software program called Statistical Parametric Mapping, which compares group values of metabolic activity measured in small units of the brain (voxels) with statistical methods.
The analysis showed that the higher-risk group displayed a common pattern of hypometabolism in certain brain areas.
“The epilepsy patient subgroup with high SUDEP risk showed areas of decreased metabolism, as compared to the control group, in portions of the frontal cortex,” said Dr. Basha. “The statistically most significant decreases were in the right frontal lobe area—both lateral convexity and medial cortex.”
Dr. Basha added that these group abnormalities were “remarkably similar” to the individual metabolic abnormalities found in the four SUDEP patients in the previous pilot study who underwent PET scanning and who subsequently died.
A similar group analysis showed that the group at low SUDEP risk displayed no common metabolic abnormalities.
MRI findings were normal for 40 patients.
Dr. Basha and colleagues believe that “this is the first PET study assessing the metabolic correlates of SUDEP risk on the group level.”
Common feature
Interictal glucose hypometabolism is “common in and around epileptic foci,” noted Dr. Basha. However, this could extend into nonepileptic regions—for example, to remote connected regions where seizures can spread from the primary focus and into subcortical gray matter structures, such the thalamus.
Some of these metabolic abnormalities may indicate subtle, microscopic, structural abnormalities in the affected brain, said Dr. Basha.
Abnormalities that are induced by epilepsy and that result from purely metabolic changes could be partly or fully reversed if seizures are controlled on a long-term basis, she said. “Some metabolic abnormalities can be reversed after better seizure control with antiepileptic drugs, epileptic surgery, or other antiepileptic treatment,” she said.
It’s “quite possible” that the same brain pattern would be evident in children with epilepsy, although her team has not performed the same analysis in a younger pediatric group, said Dr. Basha. She noted that it would be unethical to administer PET scans, which involve radiation, to young, healthy control persons.
It’s too early to recommend that all epilepsy patients undergo FDG-PET scanning to see whether this pattern of brain glucose hypometabolism is present, said Dr. Basha. “But if this is proven to be a good biomarker, the next step would be a prospective study” to see whether this brain marker is a true signal of SUDEP risk.
“I don’t think our single study would do that, but ultimately, that would be the goal,” she added.
One more piece of the SUDEP puzzle
Commenting on the study, William Davis Gaillard, MD, president of the American Epilepsy Society and chief of neurology, Children’s National Medical Center, Chevy Chase, Maryland, said this new information provides one more piece of the SUDEP puzzle but doesn’t complete the picture.
The study authors assessed PET scans of a group of patients and found common abnormalities that implicate the right medial frontal cortex. “That’s a pretty reasonable method” of investigation, said Dr. Gaillard.
“The challenge is that they’re looking at people they believe have a risk of SUDEP as opposed to people who died,” said Dr. Gaillard.
But he agreed that the results might signal “a biomarker” that “allows you to identify who’s at high risk, and then you may be able to intervene to save them.”
It’s not clear that people with frontal lobe epilepsy are at greater risk for SUDEP than those with temporal lobe epilepsy, he said.
“What you don’t know is whether this represents people with a seizure focus in that area or this represents a common network implicated in people with diverse forms of focal epilepsy; so you need to do some more work,” he said.
Dr. Gaillard pointed out that other research has implicated regions other than the mesial frontal cortex in SUDEP risk. These regions include the insula, the amygdala, the hippocampus, and the brain stem.
He also noted that the SUDEP-7, which has not been thoroughly validated, is designed for use only in adults.
In his own practice, he asks patients about the frequency of tonic-clonic seizures and whether they occur at night. The number of antiepileptic medications a patient takes reflects the difficulty of controlling seizures and may not be “an independent variable for risk,” said Dr. Gaillard.
“It’s clear one needs a better assessment and better idea of who is at risk,” he said.
The researchers have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Basha A et al. AAN 2020. Abstract P5.001.
Yoga is a good adjunct to migraine therapy
in Neurology.
The structured yoga program resulted in “remarkably improved” outcomes at 3 months of follow-up in CONTAIN, with both headache frequency and use of medications cut in half, compared with baseline, according to the investigators.
Compared with the control group on standard antimigraine medications alone, the yoga group demonstrated significantly greater reductions in pain intensity, headache frequency, pill counts, and validated measures of disability and headache impact on daily life (see graphic).
“The good news is that practicing something as simple and accessible as yoga may help much more than medications alone. And all you need is a mat,” observed Dr. Bhatia, professor of neurology at the All India Institute of Medical Sciences in New Delhi.
The single-center, open-label, blinded-assessment CONTAIN trial included 160 adult episodic migraine patients ages 18-50 years experiencing 4-14 headaches per month. They were randomized to prophylactic and acute rescue medications alone or in combination with yoga instruction by a qualified yoga therapist in a class that met at the medical center 3 days per week for 1 month. This was followed by practice of the hour-long yoga program at home 5 days per week for the next 2 months, with twice-monthly telephone calls from the yoga center to encourage adherence and encouragement to call if questions arose. Both groups received counseling about the importance of lifestyle changes that may help with migraine, including diet, physical activity, adequate sleep, and stress reduction. Outcomes were assessed in an intent-to-treat analysis.
The yoga program included specific relaxation exercises, breathing techniques, meditation, and yoga postures, or asanas. The migraine-tailored program was vetted by yoga experts at five renowned Indian yoga centers.
No safety issues arose with the yoga program.
The investigators noted that the 47% reduction in migraine medication pill count and 49% decrease in headache frequency over the course of 3 months in the adjunctive yoga group have important implications, not only in a limited-resource country such as India, but also in the United States, where Americans spend an estimated $3.2 billion annually on prescription and over the counter headache medications, and the indirect cost associated with lost productivity due to migraine has been put at $13 billion per year.
Dr. Bhatia and colleagues speculated that the observed benefits of add-on yoga in migraineurs may involve previously described improved vagal tone and parasympathetic drive coupled with decreased sympathetic tone, increased nitric oxide levels, and loosening of stiff muscles, which can trigger headaches.
Real-life goals
Commenting on the research, neurologist Holly Yancy, DO, a headache specialist at the Banner Health - University Medicine Neuroscience Institute in Phoenix, said she was impressed by the high quality of this well-designed, adequately powered study of a complementary and alternative therapy.
“The primary and secondary endpoints were real-life goals of migraine treatment that we strive to achieve in clinical practice – and they were met in the study,” she observed. “To start with a month of in-house yoga classes to instill a baseline competence in yoga prior to transitioning to home practice and to provide resources for ongoing assistance for questions were nice touches.”
She noted that the control group also experienced reductions in migraine frequency, severity, and disability scores, albeit of significantly lesser magnitude than in the yoga group. This underscores how important it is in clinical practice to spend time counseling migraine patients on lifestyle choices.
“A trial such as this provides neurologists and other health care providers with an accessible, evidence-based treatment for migraines that can be used with other preventive treatments to decrease the frequency and the amount of medication their patients are taking. In addition, it is a behavioral therapy that can decrease triggers and potentially help patients cope with pain,” Dr. Yancy said.
“I suspect I’ll not hesitate to recommend yoga as an adjunctive treatment for patients in my clinic that are physically capable. I think it would be logical to try to extrapolate the concept to a chronic migraine population as well, though it would be ideal to base that recommendation on another study conducted with a chronic migraine population.”
Dr. Bhatia and his coinvestigators reported having no financial conflicts regarding their study, funded by the Government of India and the All India Institute of Medical Sciences.
SOURCE: Kumar A et al. Neurology. 2020 May 6. doi: 10.1212/WNL.0000000000009473.
in Neurology.
The structured yoga program resulted in “remarkably improved” outcomes at 3 months of follow-up in CONTAIN, with both headache frequency and use of medications cut in half, compared with baseline, according to the investigators.
Compared with the control group on standard antimigraine medications alone, the yoga group demonstrated significantly greater reductions in pain intensity, headache frequency, pill counts, and validated measures of disability and headache impact on daily life (see graphic).
“The good news is that practicing something as simple and accessible as yoga may help much more than medications alone. And all you need is a mat,” observed Dr. Bhatia, professor of neurology at the All India Institute of Medical Sciences in New Delhi.
The single-center, open-label, blinded-assessment CONTAIN trial included 160 adult episodic migraine patients ages 18-50 years experiencing 4-14 headaches per month. They were randomized to prophylactic and acute rescue medications alone or in combination with yoga instruction by a qualified yoga therapist in a class that met at the medical center 3 days per week for 1 month. This was followed by practice of the hour-long yoga program at home 5 days per week for the next 2 months, with twice-monthly telephone calls from the yoga center to encourage adherence and encouragement to call if questions arose. Both groups received counseling about the importance of lifestyle changes that may help with migraine, including diet, physical activity, adequate sleep, and stress reduction. Outcomes were assessed in an intent-to-treat analysis.
The yoga program included specific relaxation exercises, breathing techniques, meditation, and yoga postures, or asanas. The migraine-tailored program was vetted by yoga experts at five renowned Indian yoga centers.
No safety issues arose with the yoga program.
The investigators noted that the 47% reduction in migraine medication pill count and 49% decrease in headache frequency over the course of 3 months in the adjunctive yoga group have important implications, not only in a limited-resource country such as India, but also in the United States, where Americans spend an estimated $3.2 billion annually on prescription and over the counter headache medications, and the indirect cost associated with lost productivity due to migraine has been put at $13 billion per year.
Dr. Bhatia and colleagues speculated that the observed benefits of add-on yoga in migraineurs may involve previously described improved vagal tone and parasympathetic drive coupled with decreased sympathetic tone, increased nitric oxide levels, and loosening of stiff muscles, which can trigger headaches.
Real-life goals
Commenting on the research, neurologist Holly Yancy, DO, a headache specialist at the Banner Health - University Medicine Neuroscience Institute in Phoenix, said she was impressed by the high quality of this well-designed, adequately powered study of a complementary and alternative therapy.
“The primary and secondary endpoints were real-life goals of migraine treatment that we strive to achieve in clinical practice – and they were met in the study,” she observed. “To start with a month of in-house yoga classes to instill a baseline competence in yoga prior to transitioning to home practice and to provide resources for ongoing assistance for questions were nice touches.”
She noted that the control group also experienced reductions in migraine frequency, severity, and disability scores, albeit of significantly lesser magnitude than in the yoga group. This underscores how important it is in clinical practice to spend time counseling migraine patients on lifestyle choices.
“A trial such as this provides neurologists and other health care providers with an accessible, evidence-based treatment for migraines that can be used with other preventive treatments to decrease the frequency and the amount of medication their patients are taking. In addition, it is a behavioral therapy that can decrease triggers and potentially help patients cope with pain,” Dr. Yancy said.
“I suspect I’ll not hesitate to recommend yoga as an adjunctive treatment for patients in my clinic that are physically capable. I think it would be logical to try to extrapolate the concept to a chronic migraine population as well, though it would be ideal to base that recommendation on another study conducted with a chronic migraine population.”
Dr. Bhatia and his coinvestigators reported having no financial conflicts regarding their study, funded by the Government of India and the All India Institute of Medical Sciences.
SOURCE: Kumar A et al. Neurology. 2020 May 6. doi: 10.1212/WNL.0000000000009473.
in Neurology.
The structured yoga program resulted in “remarkably improved” outcomes at 3 months of follow-up in CONTAIN, with both headache frequency and use of medications cut in half, compared with baseline, according to the investigators.
Compared with the control group on standard antimigraine medications alone, the yoga group demonstrated significantly greater reductions in pain intensity, headache frequency, pill counts, and validated measures of disability and headache impact on daily life (see graphic).
“The good news is that practicing something as simple and accessible as yoga may help much more than medications alone. And all you need is a mat,” observed Dr. Bhatia, professor of neurology at the All India Institute of Medical Sciences in New Delhi.
The single-center, open-label, blinded-assessment CONTAIN trial included 160 adult episodic migraine patients ages 18-50 years experiencing 4-14 headaches per month. They were randomized to prophylactic and acute rescue medications alone or in combination with yoga instruction by a qualified yoga therapist in a class that met at the medical center 3 days per week for 1 month. This was followed by practice of the hour-long yoga program at home 5 days per week for the next 2 months, with twice-monthly telephone calls from the yoga center to encourage adherence and encouragement to call if questions arose. Both groups received counseling about the importance of lifestyle changes that may help with migraine, including diet, physical activity, adequate sleep, and stress reduction. Outcomes were assessed in an intent-to-treat analysis.
The yoga program included specific relaxation exercises, breathing techniques, meditation, and yoga postures, or asanas. The migraine-tailored program was vetted by yoga experts at five renowned Indian yoga centers.
No safety issues arose with the yoga program.
The investigators noted that the 47% reduction in migraine medication pill count and 49% decrease in headache frequency over the course of 3 months in the adjunctive yoga group have important implications, not only in a limited-resource country such as India, but also in the United States, where Americans spend an estimated $3.2 billion annually on prescription and over the counter headache medications, and the indirect cost associated with lost productivity due to migraine has been put at $13 billion per year.
Dr. Bhatia and colleagues speculated that the observed benefits of add-on yoga in migraineurs may involve previously described improved vagal tone and parasympathetic drive coupled with decreased sympathetic tone, increased nitric oxide levels, and loosening of stiff muscles, which can trigger headaches.
Real-life goals
Commenting on the research, neurologist Holly Yancy, DO, a headache specialist at the Banner Health - University Medicine Neuroscience Institute in Phoenix, said she was impressed by the high quality of this well-designed, adequately powered study of a complementary and alternative therapy.
“The primary and secondary endpoints were real-life goals of migraine treatment that we strive to achieve in clinical practice – and they were met in the study,” she observed. “To start with a month of in-house yoga classes to instill a baseline competence in yoga prior to transitioning to home practice and to provide resources for ongoing assistance for questions were nice touches.”
She noted that the control group also experienced reductions in migraine frequency, severity, and disability scores, albeit of significantly lesser magnitude than in the yoga group. This underscores how important it is in clinical practice to spend time counseling migraine patients on lifestyle choices.
“A trial such as this provides neurologists and other health care providers with an accessible, evidence-based treatment for migraines that can be used with other preventive treatments to decrease the frequency and the amount of medication their patients are taking. In addition, it is a behavioral therapy that can decrease triggers and potentially help patients cope with pain,” Dr. Yancy said.
“I suspect I’ll not hesitate to recommend yoga as an adjunctive treatment for patients in my clinic that are physically capable. I think it would be logical to try to extrapolate the concept to a chronic migraine population as well, though it would be ideal to base that recommendation on another study conducted with a chronic migraine population.”
Dr. Bhatia and his coinvestigators reported having no financial conflicts regarding their study, funded by the Government of India and the All India Institute of Medical Sciences.
SOURCE: Kumar A et al. Neurology. 2020 May 6. doi: 10.1212/WNL.0000000000009473.
FROM NEUROLOGY
Incidental finding on brain MRI seen in 5% of older patients
New research shows that Knowing the expected prevalence of such incidental findings in the older general population is “extremely useful” for both researchers and clinicians, said study co-author Sarah Elisabeth Keuss, MBChB, clinical research associate, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
“In research, the knowledge helps to inform study protocols regarding how to manage incidental findings and enables study participants to be appropriately informed,” said Dr. Keuss. Greater awareness also helps clinicians make decisions about whether or not to scan a patient, she said, adding that imaging is increasingly available to them. It allows clinicians to counsel patients regarding the probability of an incidental finding and balance that risk against the potential benefits of having a test.
The research is being presented online as part of the American Academy of Neurology 2020 Science Highlights. The incidental findings also were published last year in BMJ Open.
The new findings are from the first wave of data collection for the Insight 46 study, a neuroimaging substudy of the MRC National Survey of Health and Development (NSHD) 1946 British birth cohort, a broadly representative sample of the population born in mainland Britain during 1946. The research uses detailed brain imaging, cognitive testing, and blood and other biomarkers to investigate genetic and life-course factors associated with Alzheimer’s disease and cerebrovascular disease.
The current study included 502 individuals, aged about 71 years at the time of the analysis, and 49% were women. Almost all (93.8%) participants underwent 1-day MRI scans. Some 4.5% of these participants had an incidental finding of brain abnormality as per a prespecified standardized protocol.
Suspected vascular malformations were present in 1.9%, and suspected intracranial mass lesions were present in 1.5%. The single most common vascular abnormality was a suspected cerebral aneurysm, which affected 1.1% of participants.
Suspected meningiomas were the most common intracranial lesion, affecting 0.6% of study participants.
Action plan
Participants and their primary care provider were informed of findings “that were deemed to be potentially serious, or life-threatening, or could have a major impact on quality of life,” said Dr. Keuss. Relevant experts “came up with a recommended clinical action plan to help the primary care provider decide what should be the next course of action with regard to investigation or referral to another specialist,” said Dr. Keuss.
The new results are important for clinical decision-making, said Dr. Keuss. “Clinicians should consider the possibility of detecting an incidental finding whenever they’re requesting a brain scan. They should balance that risk against the possible benefits of recommending a test.”
The prevalence of incidental findings on MRI reported in the literature varies because of different methods used to review scans. “However, comparing our study with similar studies, the prevalence of the key findings with regard to aneurysms and intracranial mass lesions are very similar,” said Dr. Keuss.
Dr. Keuss and colleagues do not recommend all elderly patients get a brain scan.
“We don’t know what the long-term consequences are of being informed you have an incidental finding of an abnormality; we don’t know if it improves their outcome, and it potentially could cause anxiety,” said Dr. Keuss.
Psychological impact
The researchers have not looked at the psychological impact of negative findings on study participants, but they could do so at a later date.
“It would be very important to look into that given the potential to cause anxiety,” said Dr. Keuss. “It’s important to find out the potential negative consequences to inform researchers in future about how best to manage these findings.”
From blood tests, the analysis found that more than a third (34.6%) of participants had at least one related abnormality. The most common of these were kidney impairment (about 9%), thyroid function abnormalities (between 4% and 5%), anemia (about 4%), and low vitamin B12 levels (about 3%).
However, few of these reached the prespecified threshold for urgent action, and Dr. Keuss noted these findings were not the focus of her AAN presentation.
A strength of the study was that participants were almost the exact same age.
Important issue
Commenting on the research, David S. Liebeskind, MD, professor of neurology and director, Neurovascular Imaging Research Core, University of California, Los Angeles, said it raises “a very interesting” and “important” public health issue.
“The question is whether we do things based around individual symptomatic status, or at a larger level in terms of public health, screening the larger population to figure out who is at risk for any particular disease or disorder.”
From the standpoint of imaging technologies like MRI that show details about brain structures, experts debate whether the population should be screened “before something occurs,” said Dr. Liebeskind. “Imaging has the capacity to tell us a tremendous amount; whether this implies we should therefore image everybody is a larger public health question.”
The issue is “fraught with a lot of difficulty and complexity” as treatment paradigms tend to be “built around symptomatic status,” he said. “When we sit in the office or with a patient at the bedside, we usually focus on that individual patient and not necessarily on the larger public.”
Dr. Liebeskind noted that the question of whether to put the emphasis on the individual patient or the public at large is also being discussed during the current COVID-19 pandemic.
He wasn’t surprised that the study uncovered incidental findings in almost 5% of the sample. “If you take an 80-year-old and study their brain, a good chunk, if not half or more, will have some abnormality,” he said.
Drs. Keuss and Liebeskind have reported no relevant financial relationships.
This article first appeared on Medscape.com.
New research shows that Knowing the expected prevalence of such incidental findings in the older general population is “extremely useful” for both researchers and clinicians, said study co-author Sarah Elisabeth Keuss, MBChB, clinical research associate, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
“In research, the knowledge helps to inform study protocols regarding how to manage incidental findings and enables study participants to be appropriately informed,” said Dr. Keuss. Greater awareness also helps clinicians make decisions about whether or not to scan a patient, she said, adding that imaging is increasingly available to them. It allows clinicians to counsel patients regarding the probability of an incidental finding and balance that risk against the potential benefits of having a test.
The research is being presented online as part of the American Academy of Neurology 2020 Science Highlights. The incidental findings also were published last year in BMJ Open.
The new findings are from the first wave of data collection for the Insight 46 study, a neuroimaging substudy of the MRC National Survey of Health and Development (NSHD) 1946 British birth cohort, a broadly representative sample of the population born in mainland Britain during 1946. The research uses detailed brain imaging, cognitive testing, and blood and other biomarkers to investigate genetic and life-course factors associated with Alzheimer’s disease and cerebrovascular disease.
The current study included 502 individuals, aged about 71 years at the time of the analysis, and 49% were women. Almost all (93.8%) participants underwent 1-day MRI scans. Some 4.5% of these participants had an incidental finding of brain abnormality as per a prespecified standardized protocol.
Suspected vascular malformations were present in 1.9%, and suspected intracranial mass lesions were present in 1.5%. The single most common vascular abnormality was a suspected cerebral aneurysm, which affected 1.1% of participants.
Suspected meningiomas were the most common intracranial lesion, affecting 0.6% of study participants.
Action plan
Participants and their primary care provider were informed of findings “that were deemed to be potentially serious, or life-threatening, or could have a major impact on quality of life,” said Dr. Keuss. Relevant experts “came up with a recommended clinical action plan to help the primary care provider decide what should be the next course of action with regard to investigation or referral to another specialist,” said Dr. Keuss.
The new results are important for clinical decision-making, said Dr. Keuss. “Clinicians should consider the possibility of detecting an incidental finding whenever they’re requesting a brain scan. They should balance that risk against the possible benefits of recommending a test.”
The prevalence of incidental findings on MRI reported in the literature varies because of different methods used to review scans. “However, comparing our study with similar studies, the prevalence of the key findings with regard to aneurysms and intracranial mass lesions are very similar,” said Dr. Keuss.
Dr. Keuss and colleagues do not recommend all elderly patients get a brain scan.
“We don’t know what the long-term consequences are of being informed you have an incidental finding of an abnormality; we don’t know if it improves their outcome, and it potentially could cause anxiety,” said Dr. Keuss.
Psychological impact
The researchers have not looked at the psychological impact of negative findings on study participants, but they could do so at a later date.
“It would be very important to look into that given the potential to cause anxiety,” said Dr. Keuss. “It’s important to find out the potential negative consequences to inform researchers in future about how best to manage these findings.”
From blood tests, the analysis found that more than a third (34.6%) of participants had at least one related abnormality. The most common of these were kidney impairment (about 9%), thyroid function abnormalities (between 4% and 5%), anemia (about 4%), and low vitamin B12 levels (about 3%).
However, few of these reached the prespecified threshold for urgent action, and Dr. Keuss noted these findings were not the focus of her AAN presentation.
A strength of the study was that participants were almost the exact same age.
Important issue
Commenting on the research, David S. Liebeskind, MD, professor of neurology and director, Neurovascular Imaging Research Core, University of California, Los Angeles, said it raises “a very interesting” and “important” public health issue.
“The question is whether we do things based around individual symptomatic status, or at a larger level in terms of public health, screening the larger population to figure out who is at risk for any particular disease or disorder.”
From the standpoint of imaging technologies like MRI that show details about brain structures, experts debate whether the population should be screened “before something occurs,” said Dr. Liebeskind. “Imaging has the capacity to tell us a tremendous amount; whether this implies we should therefore image everybody is a larger public health question.”
The issue is “fraught with a lot of difficulty and complexity” as treatment paradigms tend to be “built around symptomatic status,” he said. “When we sit in the office or with a patient at the bedside, we usually focus on that individual patient and not necessarily on the larger public.”
Dr. Liebeskind noted that the question of whether to put the emphasis on the individual patient or the public at large is also being discussed during the current COVID-19 pandemic.
He wasn’t surprised that the study uncovered incidental findings in almost 5% of the sample. “If you take an 80-year-old and study their brain, a good chunk, if not half or more, will have some abnormality,” he said.
Drs. Keuss and Liebeskind have reported no relevant financial relationships.
This article first appeared on Medscape.com.
New research shows that Knowing the expected prevalence of such incidental findings in the older general population is “extremely useful” for both researchers and clinicians, said study co-author Sarah Elisabeth Keuss, MBChB, clinical research associate, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
“In research, the knowledge helps to inform study protocols regarding how to manage incidental findings and enables study participants to be appropriately informed,” said Dr. Keuss. Greater awareness also helps clinicians make decisions about whether or not to scan a patient, she said, adding that imaging is increasingly available to them. It allows clinicians to counsel patients regarding the probability of an incidental finding and balance that risk against the potential benefits of having a test.
The research is being presented online as part of the American Academy of Neurology 2020 Science Highlights. The incidental findings also were published last year in BMJ Open.
The new findings are from the first wave of data collection for the Insight 46 study, a neuroimaging substudy of the MRC National Survey of Health and Development (NSHD) 1946 British birth cohort, a broadly representative sample of the population born in mainland Britain during 1946. The research uses detailed brain imaging, cognitive testing, and blood and other biomarkers to investigate genetic and life-course factors associated with Alzheimer’s disease and cerebrovascular disease.
The current study included 502 individuals, aged about 71 years at the time of the analysis, and 49% were women. Almost all (93.8%) participants underwent 1-day MRI scans. Some 4.5% of these participants had an incidental finding of brain abnormality as per a prespecified standardized protocol.
Suspected vascular malformations were present in 1.9%, and suspected intracranial mass lesions were present in 1.5%. The single most common vascular abnormality was a suspected cerebral aneurysm, which affected 1.1% of participants.
Suspected meningiomas were the most common intracranial lesion, affecting 0.6% of study participants.
Action plan
Participants and their primary care provider were informed of findings “that were deemed to be potentially serious, or life-threatening, or could have a major impact on quality of life,” said Dr. Keuss. Relevant experts “came up with a recommended clinical action plan to help the primary care provider decide what should be the next course of action with regard to investigation or referral to another specialist,” said Dr. Keuss.
The new results are important for clinical decision-making, said Dr. Keuss. “Clinicians should consider the possibility of detecting an incidental finding whenever they’re requesting a brain scan. They should balance that risk against the possible benefits of recommending a test.”
The prevalence of incidental findings on MRI reported in the literature varies because of different methods used to review scans. “However, comparing our study with similar studies, the prevalence of the key findings with regard to aneurysms and intracranial mass lesions are very similar,” said Dr. Keuss.
Dr. Keuss and colleagues do not recommend all elderly patients get a brain scan.
“We don’t know what the long-term consequences are of being informed you have an incidental finding of an abnormality; we don’t know if it improves their outcome, and it potentially could cause anxiety,” said Dr. Keuss.
Psychological impact
The researchers have not looked at the psychological impact of negative findings on study participants, but they could do so at a later date.
“It would be very important to look into that given the potential to cause anxiety,” said Dr. Keuss. “It’s important to find out the potential negative consequences to inform researchers in future about how best to manage these findings.”
From blood tests, the analysis found that more than a third (34.6%) of participants had at least one related abnormality. The most common of these were kidney impairment (about 9%), thyroid function abnormalities (between 4% and 5%), anemia (about 4%), and low vitamin B12 levels (about 3%).
However, few of these reached the prespecified threshold for urgent action, and Dr. Keuss noted these findings were not the focus of her AAN presentation.
A strength of the study was that participants were almost the exact same age.
Important issue
Commenting on the research, David S. Liebeskind, MD, professor of neurology and director, Neurovascular Imaging Research Core, University of California, Los Angeles, said it raises “a very interesting” and “important” public health issue.
“The question is whether we do things based around individual symptomatic status, or at a larger level in terms of public health, screening the larger population to figure out who is at risk for any particular disease or disorder.”
From the standpoint of imaging technologies like MRI that show details about brain structures, experts debate whether the population should be screened “before something occurs,” said Dr. Liebeskind. “Imaging has the capacity to tell us a tremendous amount; whether this implies we should therefore image everybody is a larger public health question.”
The issue is “fraught with a lot of difficulty and complexity” as treatment paradigms tend to be “built around symptomatic status,” he said. “When we sit in the office or with a patient at the bedside, we usually focus on that individual patient and not necessarily on the larger public.”
Dr. Liebeskind noted that the question of whether to put the emphasis on the individual patient or the public at large is also being discussed during the current COVID-19 pandemic.
He wasn’t surprised that the study uncovered incidental findings in almost 5% of the sample. “If you take an 80-year-old and study their brain, a good chunk, if not half or more, will have some abnormality,” he said.
Drs. Keuss and Liebeskind have reported no relevant financial relationships.
This article first appeared on Medscape.com.
New ‘atlas’ maps links between mental disorders, physical illnesses
Mental illnesses are associated with a significantly increased risk of subsequent physical diseases, new research shows.
An international team of researchers has created an “atlas” that maps the relationship between specific mental disorders and the risk of subsequent physical illnesses.
The researchers found that, following the diagnosis of a mental disorder, psychiatric patients are significantly more likely than the general population to develop potentially life-threatening conditions, including heart disease and stroke.
These findings, the investigators noted, highlight the need for better medical care in this vulnerable population. They have created a website with detailed information about the risks of specific physical ailments and the link to particular mental disorders.
“We found that women with anxiety disorders have a 50% increased risk of developing a heart condition or stroke – over 15 years, one in three women with anxiety disorders will develop these medical disorders,” lead investigator John McGrath, MD, PhD, University of Queensland’s Brain Institute, Brisbane, Australia, and Aarhus (Denmark) University, said in a statement.
“We also looked at men with substance use disorders such as alcohol-related disorders and found they have a 400% increased risk of gut or liver disorders, while over 15 years, one in five of them will develop gut or liver conditions,” he added.
The study was published in the New England Journal of Medicine.
New ‘atlas’
It’s well known that patients with mental disorders have decreased quality of life, increased health care utilization, and a shorter life expectancy than individuals in the general population – about 10 years for men and 7 years for women.
However, the investigators noted, previous research examining the relationship between mental disorders and medical conditions only focused on “particular pairs or a small set of mental disorders and medical conditions.”
“We needed a comprehensive study to map the links between different types of mental disorders versus different types of general medical conditions. Our study has provided this atlas,” Dr. McGrath said in an interview.
The clinical utility of such a map could provide comprehensive data on relative and absolute risks of various medical conditions after a diagnosis of a mental disorder. This information, the researchers noted, would “help clinicians and health care planners identify the primary prevention needs of their patients.”
The study included 5.9 million people born in Denmark between 1900 and 2015 and followed them from 2000 to 2016, a total of 83.9 million person-years. The researchers followed patients for up to 17 years (2000-2016) for medical diagnoses and up to 48 years (1969-2016) for diagnoses of mental disorders.
The study’s large sample size allowed investigators to assess 10 broad types of mental disorders and 9 broad categories of medical conditions that encompassed 31 specific conditions.
Categories of medical conditions included circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, neurologic, and cancer. Mental disorder categories included organic disorders such as Alzheimer’s, substance abuse disorders, schizophrenia, mood disorders, neurotic disorders, eating disorders, personality disorders, developmental disorders, behavioral/emotional disorders, and intellectual disabilities.
The researchers estimated associations between 90 pairs of mental disorders and broad-category medical conditions, as well as 310 pairs of mental disorders and specific medical conditions.
‘Curious’ finding
Individuals with mental disorders showed a higher risk of medical conditions in 76 out of 90 specific mental disorder–medical condition pairs.
After adjusting for sex, age, calendar time, and previous coexisting mental disorders, the median hazard ratio for a subsequent medical condition was 1.37 in patients with a mental disorder.
The lowest HR was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval, 0.80-0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11-4.22). On the other hand, schizophrenia was associated with a reduced risk of developing musculoskeletal conditions (HR, 0.87; 95% CI, 0.84-0.91).
Dr. McGrath described this finding as “curious” and speculated it “may be related to underlying genetic risk factors.”
compared with the matched reference group without a mood disorder (40.9% vs. 32.6%, respectively).
The risk of developing subsequent medical conditions after a mental disorder diagnosis did not remain steady over time. For instance, although mood disorders were associated with an increased risk of developing circulatory problems (HR, 1.32; 95% CI, 1.31-1.34), the highest risk occurred during the first 6 months following diagnosis and gradually decreased over the next 15 years (HR, 2.39; 95% CI, 2.29-2.48 and HR, 1.18; 95% CI, 1.17-1.20, respectively).
“Many people with mental disorders have unhealthy lifestyle, including low exercise, poor diet, smoking, and alcohol, which may account for the increased risk of physical illness, and also they may not seek and/or may not get quick treatment for their health conditions,” said Dr. McGrath.
Additionally, “perhaps some genetic and early life exposures, such as trauma, may increase the risk of both medical conditions and mental disorders,” he added. “We need better treatments for mental disorders, so that they do not slip into unemployment or poverty.”
A strong case
In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto and head of the mood disorders psychopharmacology unit, University Health Network, said that the research “really makes a strong case for the fact that persons who have mental disorders are at higher risk of chronic diseases, and it’s the chronic diseases that decrease their lifespan.”
Dr. McIntyre, who is also director of the Depression and Bipolar Support Alliance, said that the “takeaway message is that mental disorders are not just brain disorders but are multisystem disorders.”
For this reason, “the most appropriate way to provide care would be to provide a holistic approach to treat and prevent the chronic diseases that lead to increase in mortality,” recommended Dr. McIntyre, who was not involved with the current study.
The study was supported by grants from the Danish National Research Foundation, the National Health and Medical Research Council, the Novo Nordisk Foundation , the European Union’s Horizon 2020 Research and Innovation Program, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the European Commission, Helsefonden, the Danish Council for Independent Research, the Independent Research Fund Denmark, the National Health and Medical Research Council of Australia, and the National Institute on Drug Abuse.
Dr. McGrath has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reports receiving grants from Stanley Medical Research Institute; the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation; and receiving speaking/consultation fees from Lundbeck, Janssen, Shire, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, and Minerva.
A version of this article originally appeared on Medscape.com.
Mental illnesses are associated with a significantly increased risk of subsequent physical diseases, new research shows.
An international team of researchers has created an “atlas” that maps the relationship between specific mental disorders and the risk of subsequent physical illnesses.
The researchers found that, following the diagnosis of a mental disorder, psychiatric patients are significantly more likely than the general population to develop potentially life-threatening conditions, including heart disease and stroke.
These findings, the investigators noted, highlight the need for better medical care in this vulnerable population. They have created a website with detailed information about the risks of specific physical ailments and the link to particular mental disorders.
“We found that women with anxiety disorders have a 50% increased risk of developing a heart condition or stroke – over 15 years, one in three women with anxiety disorders will develop these medical disorders,” lead investigator John McGrath, MD, PhD, University of Queensland’s Brain Institute, Brisbane, Australia, and Aarhus (Denmark) University, said in a statement.
“We also looked at men with substance use disorders such as alcohol-related disorders and found they have a 400% increased risk of gut or liver disorders, while over 15 years, one in five of them will develop gut or liver conditions,” he added.
The study was published in the New England Journal of Medicine.
New ‘atlas’
It’s well known that patients with mental disorders have decreased quality of life, increased health care utilization, and a shorter life expectancy than individuals in the general population – about 10 years for men and 7 years for women.
However, the investigators noted, previous research examining the relationship between mental disorders and medical conditions only focused on “particular pairs or a small set of mental disorders and medical conditions.”
“We needed a comprehensive study to map the links between different types of mental disorders versus different types of general medical conditions. Our study has provided this atlas,” Dr. McGrath said in an interview.
The clinical utility of such a map could provide comprehensive data on relative and absolute risks of various medical conditions after a diagnosis of a mental disorder. This information, the researchers noted, would “help clinicians and health care planners identify the primary prevention needs of their patients.”
The study included 5.9 million people born in Denmark between 1900 and 2015 and followed them from 2000 to 2016, a total of 83.9 million person-years. The researchers followed patients for up to 17 years (2000-2016) for medical diagnoses and up to 48 years (1969-2016) for diagnoses of mental disorders.
The study’s large sample size allowed investigators to assess 10 broad types of mental disorders and 9 broad categories of medical conditions that encompassed 31 specific conditions.
Categories of medical conditions included circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, neurologic, and cancer. Mental disorder categories included organic disorders such as Alzheimer’s, substance abuse disorders, schizophrenia, mood disorders, neurotic disorders, eating disorders, personality disorders, developmental disorders, behavioral/emotional disorders, and intellectual disabilities.
The researchers estimated associations between 90 pairs of mental disorders and broad-category medical conditions, as well as 310 pairs of mental disorders and specific medical conditions.
‘Curious’ finding
Individuals with mental disorders showed a higher risk of medical conditions in 76 out of 90 specific mental disorder–medical condition pairs.
After adjusting for sex, age, calendar time, and previous coexisting mental disorders, the median hazard ratio for a subsequent medical condition was 1.37 in patients with a mental disorder.
The lowest HR was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval, 0.80-0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11-4.22). On the other hand, schizophrenia was associated with a reduced risk of developing musculoskeletal conditions (HR, 0.87; 95% CI, 0.84-0.91).
Dr. McGrath described this finding as “curious” and speculated it “may be related to underlying genetic risk factors.”
compared with the matched reference group without a mood disorder (40.9% vs. 32.6%, respectively).
The risk of developing subsequent medical conditions after a mental disorder diagnosis did not remain steady over time. For instance, although mood disorders were associated with an increased risk of developing circulatory problems (HR, 1.32; 95% CI, 1.31-1.34), the highest risk occurred during the first 6 months following diagnosis and gradually decreased over the next 15 years (HR, 2.39; 95% CI, 2.29-2.48 and HR, 1.18; 95% CI, 1.17-1.20, respectively).
“Many people with mental disorders have unhealthy lifestyle, including low exercise, poor diet, smoking, and alcohol, which may account for the increased risk of physical illness, and also they may not seek and/or may not get quick treatment for their health conditions,” said Dr. McGrath.
Additionally, “perhaps some genetic and early life exposures, such as trauma, may increase the risk of both medical conditions and mental disorders,” he added. “We need better treatments for mental disorders, so that they do not slip into unemployment or poverty.”
A strong case
In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto and head of the mood disorders psychopharmacology unit, University Health Network, said that the research “really makes a strong case for the fact that persons who have mental disorders are at higher risk of chronic diseases, and it’s the chronic diseases that decrease their lifespan.”
Dr. McIntyre, who is also director of the Depression and Bipolar Support Alliance, said that the “takeaway message is that mental disorders are not just brain disorders but are multisystem disorders.”
For this reason, “the most appropriate way to provide care would be to provide a holistic approach to treat and prevent the chronic diseases that lead to increase in mortality,” recommended Dr. McIntyre, who was not involved with the current study.
The study was supported by grants from the Danish National Research Foundation, the National Health and Medical Research Council, the Novo Nordisk Foundation , the European Union’s Horizon 2020 Research and Innovation Program, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the European Commission, Helsefonden, the Danish Council for Independent Research, the Independent Research Fund Denmark, the National Health and Medical Research Council of Australia, and the National Institute on Drug Abuse.
Dr. McGrath has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reports receiving grants from Stanley Medical Research Institute; the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation; and receiving speaking/consultation fees from Lundbeck, Janssen, Shire, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, and Minerva.
A version of this article originally appeared on Medscape.com.
Mental illnesses are associated with a significantly increased risk of subsequent physical diseases, new research shows.
An international team of researchers has created an “atlas” that maps the relationship between specific mental disorders and the risk of subsequent physical illnesses.
The researchers found that, following the diagnosis of a mental disorder, psychiatric patients are significantly more likely than the general population to develop potentially life-threatening conditions, including heart disease and stroke.
These findings, the investigators noted, highlight the need for better medical care in this vulnerable population. They have created a website with detailed information about the risks of specific physical ailments and the link to particular mental disorders.
“We found that women with anxiety disorders have a 50% increased risk of developing a heart condition or stroke – over 15 years, one in three women with anxiety disorders will develop these medical disorders,” lead investigator John McGrath, MD, PhD, University of Queensland’s Brain Institute, Brisbane, Australia, and Aarhus (Denmark) University, said in a statement.
“We also looked at men with substance use disorders such as alcohol-related disorders and found they have a 400% increased risk of gut or liver disorders, while over 15 years, one in five of them will develop gut or liver conditions,” he added.
The study was published in the New England Journal of Medicine.
New ‘atlas’
It’s well known that patients with mental disorders have decreased quality of life, increased health care utilization, and a shorter life expectancy than individuals in the general population – about 10 years for men and 7 years for women.
However, the investigators noted, previous research examining the relationship between mental disorders and medical conditions only focused on “particular pairs or a small set of mental disorders and medical conditions.”
“We needed a comprehensive study to map the links between different types of mental disorders versus different types of general medical conditions. Our study has provided this atlas,” Dr. McGrath said in an interview.
The clinical utility of such a map could provide comprehensive data on relative and absolute risks of various medical conditions after a diagnosis of a mental disorder. This information, the researchers noted, would “help clinicians and health care planners identify the primary prevention needs of their patients.”
The study included 5.9 million people born in Denmark between 1900 and 2015 and followed them from 2000 to 2016, a total of 83.9 million person-years. The researchers followed patients for up to 17 years (2000-2016) for medical diagnoses and up to 48 years (1969-2016) for diagnoses of mental disorders.
The study’s large sample size allowed investigators to assess 10 broad types of mental disorders and 9 broad categories of medical conditions that encompassed 31 specific conditions.
Categories of medical conditions included circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, neurologic, and cancer. Mental disorder categories included organic disorders such as Alzheimer’s, substance abuse disorders, schizophrenia, mood disorders, neurotic disorders, eating disorders, personality disorders, developmental disorders, behavioral/emotional disorders, and intellectual disabilities.
The researchers estimated associations between 90 pairs of mental disorders and broad-category medical conditions, as well as 310 pairs of mental disorders and specific medical conditions.
‘Curious’ finding
Individuals with mental disorders showed a higher risk of medical conditions in 76 out of 90 specific mental disorder–medical condition pairs.
After adjusting for sex, age, calendar time, and previous coexisting mental disorders, the median hazard ratio for a subsequent medical condition was 1.37 in patients with a mental disorder.
The lowest HR was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval, 0.80-0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11-4.22). On the other hand, schizophrenia was associated with a reduced risk of developing musculoskeletal conditions (HR, 0.87; 95% CI, 0.84-0.91).
Dr. McGrath described this finding as “curious” and speculated it “may be related to underlying genetic risk factors.”
compared with the matched reference group without a mood disorder (40.9% vs. 32.6%, respectively).
The risk of developing subsequent medical conditions after a mental disorder diagnosis did not remain steady over time. For instance, although mood disorders were associated with an increased risk of developing circulatory problems (HR, 1.32; 95% CI, 1.31-1.34), the highest risk occurred during the first 6 months following diagnosis and gradually decreased over the next 15 years (HR, 2.39; 95% CI, 2.29-2.48 and HR, 1.18; 95% CI, 1.17-1.20, respectively).
“Many people with mental disorders have unhealthy lifestyle, including low exercise, poor diet, smoking, and alcohol, which may account for the increased risk of physical illness, and also they may not seek and/or may not get quick treatment for their health conditions,” said Dr. McGrath.
Additionally, “perhaps some genetic and early life exposures, such as trauma, may increase the risk of both medical conditions and mental disorders,” he added. “We need better treatments for mental disorders, so that they do not slip into unemployment or poverty.”
A strong case
In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto and head of the mood disorders psychopharmacology unit, University Health Network, said that the research “really makes a strong case for the fact that persons who have mental disorders are at higher risk of chronic diseases, and it’s the chronic diseases that decrease their lifespan.”
Dr. McIntyre, who is also director of the Depression and Bipolar Support Alliance, said that the “takeaway message is that mental disorders are not just brain disorders but are multisystem disorders.”
For this reason, “the most appropriate way to provide care would be to provide a holistic approach to treat and prevent the chronic diseases that lead to increase in mortality,” recommended Dr. McIntyre, who was not involved with the current study.
The study was supported by grants from the Danish National Research Foundation, the National Health and Medical Research Council, the Novo Nordisk Foundation , the European Union’s Horizon 2020 Research and Innovation Program, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the European Commission, Helsefonden, the Danish Council for Independent Research, the Independent Research Fund Denmark, the National Health and Medical Research Council of Australia, and the National Institute on Drug Abuse.
Dr. McGrath has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reports receiving grants from Stanley Medical Research Institute; the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation; and receiving speaking/consultation fees from Lundbeck, Janssen, Shire, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, and Minerva.
A version of this article originally appeared on Medscape.com.
Depression linked to neuro dysfunction, brain lesions in MS
Depression is associated with decreased neurologic function and new brain lesions in patients with multiple sclerosis (MS), new research suggests.
In an observational study of more than 2500 patients with relapsing-remitting MS (RRMS), participants with self-reported depression were more likely to have worse scores on neuroperformance measures, such as processing speed tests, than their peers without depression.
At baseline, the group with depression also had greater odds of having at least one new contrast-enhancing lesion on MRI.
“Our results suggest that depression is not merely a reactive symptom but indicates increased risk of future MS disease activity,” the investigators note.
Lead author Jenny Feng, MD, clinical associate at the Mellen Center for MS Treatment and Research at Cleveland Clinic, added that depression should be routinely screened for in all patients with MS, something done routinely at her center.
“Every single patient that comes through the door with newly diagnosed MS, we refer to neuropsychology to screen for depression; and if there is depression, then we actively manage it because it does have an effect” on patients, she told Medscape Medical News.
“Depression isn’t just a neuropsychiatric disease,” Feng added. As shown in their study, “it may have effects on MS, especially with regards to performance in neurological function testing.”
The research is presented on AAN.com as part of the American Academy of Neurology 2020 Science Highlights. Because of the COVID-19 pandemic, the AAN had to cancel its 2020 annual meeting.
Associations Have Been “Unclear”
Although inflammatory, psychosocial, and neurodegenerative factors “have been hypothesized as etiologies” for why depression is commonly found in patients with MS,
For the current study, they assessed data from the Partners Advancing Technology and Health Solutions (MS-PATHS) database, an ongoing collaborative network of seven MS centers in the United States and three in Europe.
MS disease history and MRI data were examined, as well as 12-month scores on neuroperformance tests measuring processing speed (Symbol Digit Modalities Test), walking speed (Timed 25-Foot Walk), and manual dexterity (Nine-Hole Peg Test).
Patient-reported outcomes (PROs), as measured with the Quality of Life in Neurological Disorders (Neuro-QoL) and patient-determined disease steps, were also assessed. Depression was defined as a depression T score at baseline greater than “the 50th percentile” on the Neuro-QoL.
In the patient sample, 1333 of the participants with RRMS were classified as “not depressed” (73.7% women; mean age, 45.6 years; disease duration, 13.7 years) while 1172 were “depressed” (78.4% women; mean age, 45.9 years; disease duration, 14.3 years).
“To balance for baseline variances in the observational cohort between group with depression and group without depression, propensity score analysis was used to adjust for potential confounding factors,” the investigators report.
Worse Performance
After adjustment for baseline covariates, results showed that the depressed patients performed worse on the walking speed test (0.48; 95% confidence interval, 0.038-0.918) and processing speed test (–1.899; 95% CI, –3.548 to –0.250).
The depressed group also had increased odds at baseline of having new contrast-enhancing lesions (odds ratio, 5.89; 95% CI, 2.236-15.517). This demonstrated an “association of depression and neuroinflammatory activity” in the central nervous system, the investigators note.
At 12 months, processing speed continued to be worse in the depressed group (–1.68; 95% CI, –3.254 to –0.105).
There were trends, albeit insignificant, for decreased walking speed scores at 12 months and for decreased manual dexterity scores at both baseline and at 12 months for the participants who were depressed.
Interestingly, there were “no significant differences in PROs at month 12, despite worsening neuroperformance,” the investigators report.
“This means that patients themselves may not even realize that they were getting worse,” Feng said.
Underpowered Study?
Further results showed nonsignificant trends for increased T2 lesion volume and white matter fraction and decreased brain volume, gray matter fraction, and cortical gray matter volume at baseline and at 12 months in the depressed group.
The researchers note that study limitations include the unavailability of information on treatment compliance for depression or date of depression onset.
Feng added that because this was an observational study, other missing data included depression status for some patients at year 1 and some MRI metrics.
“So this may have been underpowered to detect some of the results. The power may have been inadequate to detect all changes,” she said.
The investigators write that future research should assess larger sample sizes with longer follow-ups and should use more advanced MRI measures, such as diffusion tensor imaging or functional MRI.
In addition, they will continue examining data from MS-PATHS. “With the newest data cut, we have new patients that we can analyze. So perhaps that can provide sufficient power to detect [more MRI] changes,” Feng said.
Unusual, Intriguing Findings
Commenting on the study for Medscape Medical News, Mark Freedman, MD, professor of neurology at the University of Ottawa and director of the Multiple Sclerosis Research Clinic at the Ottawa Hospital Research Institute, noted that he wasn’t terribly surprised” by the overall findings.
“We’ve known for years that patients who are depressed don’t do as well on our performance methods,” said Freedman, who was not involved with the research.
However, the current investigators “took a huge number of patients in this multicenter study and started using some of the statistical methods we’ve seen in the use of real-world evidence,” he noted.
“So you’re looking at some outcome measures and you have to ask yourself, ‘Why would it influence that?’ and ‘Did it happen by chance or not?’ And you ask why it is that depressed people might actually have more lesions on their MRI, which is something that is unusual,” Freedman said.
“When you start to look at this, even when you’re trying to standardize things for the differences that we know of, there are some stuff that comes out as intriguing. In general, I think those depressed patients did worse on several outcome measures that one would say, ‘That’s somewhat surprising.’ That’s why this group was very careful to not conclude absolutely that depression drives this disease. But it was consistently trending in the direction that it looks like there was more inflammatory activity in these people,” he said.
He echoed the investigators’ note that drug adherence and which depression treatment was used wasn’t controlled for; and he added that depression in the study was not based on receiving a diagnosis of clinical depression but on self-report.
Still, the patients classified as depressed “did worse. They didn’t walk as fast, which was interesting; and we know that cognitive performance is often damped because of poor concentration. But how do you get worse MRIs? This study is raising a question and [the researchers] conclude that it may be that depression might be an independent factor” for that outcome, Freedman said.
“It might be that you could get more out of a particular [MS] medicine if you pay attention to depression; and if that’s the investigators’ conclusion, and I think it is, then I certainly agree with it.”
Freedman noted that, instead of a blanket recommendation that all patients with MS should be screened for depression, he thinks clinicians, especially those at smaller centers, should focus on what’s best for treating all aspects of an individual patient.
“Don’t try to manage them if you’re not going to manage the entire picture. Looking at depression and mood and other things is very important. And if you have the capacity for an official screening, I think it’s wonderful; but not everybody does,” he said.
Feng and Freedman have disclosed no relevant financial relationships. Freedman is currently a member of the Medscape Neurology Advisory Board.
This article appeared on Medscape.com.
Depression is associated with decreased neurologic function and new brain lesions in patients with multiple sclerosis (MS), new research suggests.
In an observational study of more than 2500 patients with relapsing-remitting MS (RRMS), participants with self-reported depression were more likely to have worse scores on neuroperformance measures, such as processing speed tests, than their peers without depression.
At baseline, the group with depression also had greater odds of having at least one new contrast-enhancing lesion on MRI.
“Our results suggest that depression is not merely a reactive symptom but indicates increased risk of future MS disease activity,” the investigators note.
Lead author Jenny Feng, MD, clinical associate at the Mellen Center for MS Treatment and Research at Cleveland Clinic, added that depression should be routinely screened for in all patients with MS, something done routinely at her center.
“Every single patient that comes through the door with newly diagnosed MS, we refer to neuropsychology to screen for depression; and if there is depression, then we actively manage it because it does have an effect” on patients, she told Medscape Medical News.
“Depression isn’t just a neuropsychiatric disease,” Feng added. As shown in their study, “it may have effects on MS, especially with regards to performance in neurological function testing.”
The research is presented on AAN.com as part of the American Academy of Neurology 2020 Science Highlights. Because of the COVID-19 pandemic, the AAN had to cancel its 2020 annual meeting.
Associations Have Been “Unclear”
Although inflammatory, psychosocial, and neurodegenerative factors “have been hypothesized as etiologies” for why depression is commonly found in patients with MS,
For the current study, they assessed data from the Partners Advancing Technology and Health Solutions (MS-PATHS) database, an ongoing collaborative network of seven MS centers in the United States and three in Europe.
MS disease history and MRI data were examined, as well as 12-month scores on neuroperformance tests measuring processing speed (Symbol Digit Modalities Test), walking speed (Timed 25-Foot Walk), and manual dexterity (Nine-Hole Peg Test).
Patient-reported outcomes (PROs), as measured with the Quality of Life in Neurological Disorders (Neuro-QoL) and patient-determined disease steps, were also assessed. Depression was defined as a depression T score at baseline greater than “the 50th percentile” on the Neuro-QoL.
In the patient sample, 1333 of the participants with RRMS were classified as “not depressed” (73.7% women; mean age, 45.6 years; disease duration, 13.7 years) while 1172 were “depressed” (78.4% women; mean age, 45.9 years; disease duration, 14.3 years).
“To balance for baseline variances in the observational cohort between group with depression and group without depression, propensity score analysis was used to adjust for potential confounding factors,” the investigators report.
Worse Performance
After adjustment for baseline covariates, results showed that the depressed patients performed worse on the walking speed test (0.48; 95% confidence interval, 0.038-0.918) and processing speed test (–1.899; 95% CI, –3.548 to –0.250).
The depressed group also had increased odds at baseline of having new contrast-enhancing lesions (odds ratio, 5.89; 95% CI, 2.236-15.517). This demonstrated an “association of depression and neuroinflammatory activity” in the central nervous system, the investigators note.
At 12 months, processing speed continued to be worse in the depressed group (–1.68; 95% CI, –3.254 to –0.105).
There were trends, albeit insignificant, for decreased walking speed scores at 12 months and for decreased manual dexterity scores at both baseline and at 12 months for the participants who were depressed.
Interestingly, there were “no significant differences in PROs at month 12, despite worsening neuroperformance,” the investigators report.
“This means that patients themselves may not even realize that they were getting worse,” Feng said.
Underpowered Study?
Further results showed nonsignificant trends for increased T2 lesion volume and white matter fraction and decreased brain volume, gray matter fraction, and cortical gray matter volume at baseline and at 12 months in the depressed group.
The researchers note that study limitations include the unavailability of information on treatment compliance for depression or date of depression onset.
Feng added that because this was an observational study, other missing data included depression status for some patients at year 1 and some MRI metrics.
“So this may have been underpowered to detect some of the results. The power may have been inadequate to detect all changes,” she said.
The investigators write that future research should assess larger sample sizes with longer follow-ups and should use more advanced MRI measures, such as diffusion tensor imaging or functional MRI.
In addition, they will continue examining data from MS-PATHS. “With the newest data cut, we have new patients that we can analyze. So perhaps that can provide sufficient power to detect [more MRI] changes,” Feng said.
Unusual, Intriguing Findings
Commenting on the study for Medscape Medical News, Mark Freedman, MD, professor of neurology at the University of Ottawa and director of the Multiple Sclerosis Research Clinic at the Ottawa Hospital Research Institute, noted that he wasn’t terribly surprised” by the overall findings.
“We’ve known for years that patients who are depressed don’t do as well on our performance methods,” said Freedman, who was not involved with the research.
However, the current investigators “took a huge number of patients in this multicenter study and started using some of the statistical methods we’ve seen in the use of real-world evidence,” he noted.
“So you’re looking at some outcome measures and you have to ask yourself, ‘Why would it influence that?’ and ‘Did it happen by chance or not?’ And you ask why it is that depressed people might actually have more lesions on their MRI, which is something that is unusual,” Freedman said.
“When you start to look at this, even when you’re trying to standardize things for the differences that we know of, there are some stuff that comes out as intriguing. In general, I think those depressed patients did worse on several outcome measures that one would say, ‘That’s somewhat surprising.’ That’s why this group was very careful to not conclude absolutely that depression drives this disease. But it was consistently trending in the direction that it looks like there was more inflammatory activity in these people,” he said.
He echoed the investigators’ note that drug adherence and which depression treatment was used wasn’t controlled for; and he added that depression in the study was not based on receiving a diagnosis of clinical depression but on self-report.
Still, the patients classified as depressed “did worse. They didn’t walk as fast, which was interesting; and we know that cognitive performance is often damped because of poor concentration. But how do you get worse MRIs? This study is raising a question and [the researchers] conclude that it may be that depression might be an independent factor” for that outcome, Freedman said.
“It might be that you could get more out of a particular [MS] medicine if you pay attention to depression; and if that’s the investigators’ conclusion, and I think it is, then I certainly agree with it.”
Freedman noted that, instead of a blanket recommendation that all patients with MS should be screened for depression, he thinks clinicians, especially those at smaller centers, should focus on what’s best for treating all aspects of an individual patient.
“Don’t try to manage them if you’re not going to manage the entire picture. Looking at depression and mood and other things is very important. And if you have the capacity for an official screening, I think it’s wonderful; but not everybody does,” he said.
Feng and Freedman have disclosed no relevant financial relationships. Freedman is currently a member of the Medscape Neurology Advisory Board.
This article appeared on Medscape.com.
Depression is associated with decreased neurologic function and new brain lesions in patients with multiple sclerosis (MS), new research suggests.
In an observational study of more than 2500 patients with relapsing-remitting MS (RRMS), participants with self-reported depression were more likely to have worse scores on neuroperformance measures, such as processing speed tests, than their peers without depression.
At baseline, the group with depression also had greater odds of having at least one new contrast-enhancing lesion on MRI.
“Our results suggest that depression is not merely a reactive symptom but indicates increased risk of future MS disease activity,” the investigators note.
Lead author Jenny Feng, MD, clinical associate at the Mellen Center for MS Treatment and Research at Cleveland Clinic, added that depression should be routinely screened for in all patients with MS, something done routinely at her center.
“Every single patient that comes through the door with newly diagnosed MS, we refer to neuropsychology to screen for depression; and if there is depression, then we actively manage it because it does have an effect” on patients, she told Medscape Medical News.
“Depression isn’t just a neuropsychiatric disease,” Feng added. As shown in their study, “it may have effects on MS, especially with regards to performance in neurological function testing.”
The research is presented on AAN.com as part of the American Academy of Neurology 2020 Science Highlights. Because of the COVID-19 pandemic, the AAN had to cancel its 2020 annual meeting.
Associations Have Been “Unclear”
Although inflammatory, psychosocial, and neurodegenerative factors “have been hypothesized as etiologies” for why depression is commonly found in patients with MS,
For the current study, they assessed data from the Partners Advancing Technology and Health Solutions (MS-PATHS) database, an ongoing collaborative network of seven MS centers in the United States and three in Europe.
MS disease history and MRI data were examined, as well as 12-month scores on neuroperformance tests measuring processing speed (Symbol Digit Modalities Test), walking speed (Timed 25-Foot Walk), and manual dexterity (Nine-Hole Peg Test).
Patient-reported outcomes (PROs), as measured with the Quality of Life in Neurological Disorders (Neuro-QoL) and patient-determined disease steps, were also assessed. Depression was defined as a depression T score at baseline greater than “the 50th percentile” on the Neuro-QoL.
In the patient sample, 1333 of the participants with RRMS were classified as “not depressed” (73.7% women; mean age, 45.6 years; disease duration, 13.7 years) while 1172 were “depressed” (78.4% women; mean age, 45.9 years; disease duration, 14.3 years).
“To balance for baseline variances in the observational cohort between group with depression and group without depression, propensity score analysis was used to adjust for potential confounding factors,” the investigators report.
Worse Performance
After adjustment for baseline covariates, results showed that the depressed patients performed worse on the walking speed test (0.48; 95% confidence interval, 0.038-0.918) and processing speed test (–1.899; 95% CI, –3.548 to –0.250).
The depressed group also had increased odds at baseline of having new contrast-enhancing lesions (odds ratio, 5.89; 95% CI, 2.236-15.517). This demonstrated an “association of depression and neuroinflammatory activity” in the central nervous system, the investigators note.
At 12 months, processing speed continued to be worse in the depressed group (–1.68; 95% CI, –3.254 to –0.105).
There were trends, albeit insignificant, for decreased walking speed scores at 12 months and for decreased manual dexterity scores at both baseline and at 12 months for the participants who were depressed.
Interestingly, there were “no significant differences in PROs at month 12, despite worsening neuroperformance,” the investigators report.
“This means that patients themselves may not even realize that they were getting worse,” Feng said.
Underpowered Study?
Further results showed nonsignificant trends for increased T2 lesion volume and white matter fraction and decreased brain volume, gray matter fraction, and cortical gray matter volume at baseline and at 12 months in the depressed group.
The researchers note that study limitations include the unavailability of information on treatment compliance for depression or date of depression onset.
Feng added that because this was an observational study, other missing data included depression status for some patients at year 1 and some MRI metrics.
“So this may have been underpowered to detect some of the results. The power may have been inadequate to detect all changes,” she said.
The investigators write that future research should assess larger sample sizes with longer follow-ups and should use more advanced MRI measures, such as diffusion tensor imaging or functional MRI.
In addition, they will continue examining data from MS-PATHS. “With the newest data cut, we have new patients that we can analyze. So perhaps that can provide sufficient power to detect [more MRI] changes,” Feng said.
Unusual, Intriguing Findings
Commenting on the study for Medscape Medical News, Mark Freedman, MD, professor of neurology at the University of Ottawa and director of the Multiple Sclerosis Research Clinic at the Ottawa Hospital Research Institute, noted that he wasn’t terribly surprised” by the overall findings.
“We’ve known for years that patients who are depressed don’t do as well on our performance methods,” said Freedman, who was not involved with the research.
However, the current investigators “took a huge number of patients in this multicenter study and started using some of the statistical methods we’ve seen in the use of real-world evidence,” he noted.
“So you’re looking at some outcome measures and you have to ask yourself, ‘Why would it influence that?’ and ‘Did it happen by chance or not?’ And you ask why it is that depressed people might actually have more lesions on their MRI, which is something that is unusual,” Freedman said.
“When you start to look at this, even when you’re trying to standardize things for the differences that we know of, there are some stuff that comes out as intriguing. In general, I think those depressed patients did worse on several outcome measures that one would say, ‘That’s somewhat surprising.’ That’s why this group was very careful to not conclude absolutely that depression drives this disease. But it was consistently trending in the direction that it looks like there was more inflammatory activity in these people,” he said.
He echoed the investigators’ note that drug adherence and which depression treatment was used wasn’t controlled for; and he added that depression in the study was not based on receiving a diagnosis of clinical depression but on self-report.
Still, the patients classified as depressed “did worse. They didn’t walk as fast, which was interesting; and we know that cognitive performance is often damped because of poor concentration. But how do you get worse MRIs? This study is raising a question and [the researchers] conclude that it may be that depression might be an independent factor” for that outcome, Freedman said.
“It might be that you could get more out of a particular [MS] medicine if you pay attention to depression; and if that’s the investigators’ conclusion, and I think it is, then I certainly agree with it.”
Freedman noted that, instead of a blanket recommendation that all patients with MS should be screened for depression, he thinks clinicians, especially those at smaller centers, should focus on what’s best for treating all aspects of an individual patient.
“Don’t try to manage them if you’re not going to manage the entire picture. Looking at depression and mood and other things is very important. And if you have the capacity for an official screening, I think it’s wonderful; but not everybody does,” he said.
Feng and Freedman have disclosed no relevant financial relationships. Freedman is currently a member of the Medscape Neurology Advisory Board.
This article appeared on Medscape.com.
USPSTF round-up
In 2019, the US Preventive Services Task Force published 19 recommendation statements on 11 topics. Two of the topics are new; 9 are topics the Task Force had previously reviewed and has updated (TABLE 1). Three of these topics have been covered in Practice Alert podcasts (mdedge.com/familymedicine) and will not be discussed here: risk assessment, genetic counseling, and genetic testing for breast cancer susceptibility gene mutations (October 2019); medications to reduce the risk of breast cancer (December 2019); and preexposure prophylaxis to prevent HIV infections (January 2020).
Of the 19 recommendation statements made in 2019 (TABLE 2), 5 were rated “A” and 5 were “B,” meaning the evidence shows that benefits outweigh harms and these interventions should be offered in primary care practice. There were 5 “D” recommendations for interventions that should not be offered because they are either ineffective or harms exceed benefits. There were 3 “I” statements on interventions having insufficient evidence on benefits or harms to warrant a recommendation. Only 1 recommendation was rated “C” (selectively offer based on individual factors); this assessment is the hardest one to interpret and implement. Keep in mind that all “A” and “B” recommendations must be covered by commercial health plans with no out-of-pocket cost to the patient (ie, no co-pay or deductible).
New recommendation on preventing perinatal depression
One of 2 new topics reviewed in 2019 was the prevention of perinatal depression. (As noted, the other on preexposure prophylaxis to prevent HIV infection has already been covered in a Practice Alert podcast.) The Task Force found that the prevalence of depression is estimated at 8.9% among pregnant women and 37% at any point in the first year postpartum.1
Depression during pregnancy and the postpartum period is associated with adverse effects on the mother and infant, including higher rates of suicide and suicidal ideation and thoughts of harming the infant.1 Women with perinatal depression are also more likely to exhibit significantly lower levels of positive maternal behaviors, such as praising and playing with their child,2 and higher rates of negative maternal behaviors.2 Perinatal depression is also associated with increased rates of preterm birth and low birth weight.3
Mothers with postpartum depression have higher rates of early termination of breast feeding and lower adherence for recommended child preventive services including vaccination.1 Children of mothers with perinatal depression develop more behavior problems, have lower cognitive functioning, and have an increased risk of psychiatric disorders than do children of mothers without this condition.4,5
A number of risk factors are associated with perinatal depression, but no screening tool was found to have enough predictive value to be recommended. In deciding who should receive an offer or referral for counseling, the Task Force recommends as a practical approach providing “counseling interventions to women with 1 or more of the following: a history of depression, current depressive symptoms (that do not reach a diagnostic threshold), certain socioeconomic risk factors such as low income or adolescent or single parenthood, recent intimate partner violence, or mental health-related factors such as elevated anxiety symptoms or a history of significant negative life events.”1
There is no conclusive evidence to guide timing of counseling interventions, but most studies reviewed started them in the second trimester. These studies included cognitive behavioral therapy and interpersonal therapy and involved counseling sessions that ranged from 4 to 20 sessions and lasted for 4 to 70 weeks. They involved group and individual sessions, mostly in-person visits, and were provided by a variety of health professionals.6
Continue to: The studies reviewed showed...
The studies reviewed showed that counseling interventions reduced the likelihood of developing depression symptoms by 39%, with a number needed to treat of 13.5.6 Studies that looked at pregnancy and maternal and infant clinical outcomes were mixed but usually found little to no difference with counseling.6 Even so, the Task Force felt that a reduction in depression itself was enough to warrant a “B” recommendation.
Screening for abdominal aortic aneurisms
Ultrasound is underused in screening for abdominal aortic aneurisms (AAA) and preventing death from their rupture. (See “Whom should you screen for abdominal aortic aneurysm?”) The prevalence of AAA is the United States is unknown; in other western countries it varies from 1.2% to 3.3% in men and is declining due to decreased rates of smoking, the primary risk factor.
The risk of AAA rupture is related to the size of the aneurism, and surgical repair (either endovascular or open repair) is usually reserved for lesions > 5.5 cm in diameter or for smaller ones that are rapidly increasing in size. The standard of care for most aneurysms < 5.5 cm is to periodically monitor growth using ultrasound.
The 2019 recommendations on AAA screening are essentially the same as those made in 2004; evaluation of new evidence supported the previous recommendations. The Task Force recommends one-time screening for men ages 65 to 75 years who have ever smoked (B recommendation). Selective screening is recommended for men in this age group who have never smoked, based mainly on personal factors such as a family history of AAA, the presence of other arterial aneurisms, and the number of risk factors for cardiovascular disease (C recommendation).
The Task Force recommends against screening women ages 65 to 75 years with no history of smoking or family history of AAA, while the evidence was felt to be insufficient to make a recommendation for women in this age range who have either risk factor. This is problematic for family physicians since women with these risk factors are at increased risk of AAA compared with women without risk factors.8 And aneurisms in women appear to rupture more frequently at smaller sizes, although at a later age than in men.8 Operative mortality is also higher in women than in men8 and there is no direct evidence that screening improves outcomes for women.
Continue to: Screening for asymptomatic bacteriuria
Screening for asymptomatic bacteriuria
The Task Force re-examined and reconfirmed its previous recommendations on screening for asymptomatic bacteriuria in adults. It recommends in favor of it for pregnant women, using a urine culture to screen, and against it for all other adults. There is good evidence that treating screen-detected asymptomatic bacteriuria in pregnant women reduces the incidence of pyelonephritis in pregnancy.
The Task Force made this a “B” recommendation based on a lower prevalence of pyelonephritis found in more recent studies, making the overall magnitude of benefits moderate. There is also good evidence that treating asymptomatic bacteriuria in nonpregnant adults offers no benefits.9 The Task Force has re-examined this topic 5 times since 1996 with essentially the same results.
Screening for elevated lead levels in children and pregnant women
In 2019 the Task Force changed its 2006 recommendation on screening for elevated lead levels. The earlier recommendation advised against screening both children ages 1 to 5 years and pregnant women at average risk for elevated blood lead levels. In 2006 the Task Force also felt that evidence was insufficient to make a recommendation regarding children ages 1 to 5 years at elevated risk.
The Task Force now believes the evidence is insufficient to make a recommendation for all children ages 1 to 5 years and for pregnant women, thus moving from a “D” to an “I” recommendation for children and pregnant women with average risk. Even though there is little evidence to support screening for elevated lead levels in children ages 1 to 5 years and in pregnant women, the Task Force apparently did not feel comfortable recommending against testing, given that the cutoff for elevated blood lead levels has been lowered from 10 to 5 mcg/dL and that other sources of lead may now be more prevalent than in 2006.10
Remember that the Medicaid Early and Periodic Screening, Diagnostic, and Treatment program requires that all children receive a blood lead test twice, at ages 12 and 24 months, and that previously unscreened children ages 36 to 72 months must be tested once.
Continue to: Additional updates with no recommendation changes
Additional updates with no recommendation changes
Four other topics were re-examined by the Task Force in 2019, resulting in no significant changes to recommendations (TABLE 2):
- Screen for hepatitis B infection in pregnant women at the first prenatal visit (A recommendation; updated from 2009).
- Screen for HIV infection in adolescents and adults ages 15 to 65 years, and in those younger and older who are at high risk, and during pregnancy (A recommendation; updated from 2013).
- Provide topical medication for all newborns to prevent gonococcal ophthalmia neonatorum (A recommendation; first recommendation in 1996, updated in 2005 and 2011).
- Avoid screening for pancreatic cancer in asymptomatic adults (D recommendation; updated from 2004).
Affirmation of USPSTF’s value
In only 1 out of 9 reassessments of past topics did the Task Force modify its previous recommendations in any significant way. This demonstrates that recommendations will usually stand the test of time if they are made using robust, evidence-based methods (that consider both benefits and harms) and they are not made when evidence is insufficient. That only 2 new topics could be addressed in 2019 may reflect a need for more resources for the Task Force.
1. USPSTF. Interventions to prevent perinatal depression: US Preventive Services Task Force recommendation statement. 2019;321:580-587.
2. Lovejoy MC, Graczyk PA, O’Hare E, et al. Maternal depression and parenting behavior: a meta-analytic review. Clin Psychol Rev. 2000;20:561-592.
3. Szegda K, Markenson G, Bertone-Johnson ER, et al. Depression during pregnancy: a risk factor for adverse neonatal outcomes? A critical review of the literature. J Matern Fetal Neonatal Med. 2014;27:960-967.
4. Beck CT. The effects of postpartum depression on child development: a meta-analysis. Arch Psychiatr Nurs. 1998;12:12-20.
5. Santos IS, Matijasevich A, Barros AJ, et al. Antenatal and postnatal maternal mood symptoms and psychiatric disorders in pre-school children from the 2004 Pelotas Birth Cohort. J Affect Disord. 2014;164:112-117.
6. O’Connor E, Senger CA, Henniger ML, et al. Interventions to prevent perinatal depression. Evidence report and systematic review for the US preventive services task force. JAMA. 2019;321:588-601.
7. USPSTF. Screening for abdominal aortic aneurysm: US Preventive Services Task Force recommendation statement. 2019;322:2211-2218.
8. Guirguis-Blake JM, Beil TL, Senger CA, et al. Primary care screening for abdominal aortic aneurysm: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2019;322:2219-2238.
9. USPSTF. Owens DK, Davidson KW, Krist AH, et al. Screening for asymptomatic bacteriuria in adults: US Preventive Services Task Force recommendation statement. 2019;322:1188-1194.
10. USPSTF. Screening for elevated blood lead levels in children and pregnant women: US Preventive Services Task Force recommendation statement. 2019;321:1502-1509.
In 2019, the US Preventive Services Task Force published 19 recommendation statements on 11 topics. Two of the topics are new; 9 are topics the Task Force had previously reviewed and has updated (TABLE 1). Three of these topics have been covered in Practice Alert podcasts (mdedge.com/familymedicine) and will not be discussed here: risk assessment, genetic counseling, and genetic testing for breast cancer susceptibility gene mutations (October 2019); medications to reduce the risk of breast cancer (December 2019); and preexposure prophylaxis to prevent HIV infections (January 2020).
Of the 19 recommendation statements made in 2019 (TABLE 2), 5 were rated “A” and 5 were “B,” meaning the evidence shows that benefits outweigh harms and these interventions should be offered in primary care practice. There were 5 “D” recommendations for interventions that should not be offered because they are either ineffective or harms exceed benefits. There were 3 “I” statements on interventions having insufficient evidence on benefits or harms to warrant a recommendation. Only 1 recommendation was rated “C” (selectively offer based on individual factors); this assessment is the hardest one to interpret and implement. Keep in mind that all “A” and “B” recommendations must be covered by commercial health plans with no out-of-pocket cost to the patient (ie, no co-pay or deductible).
New recommendation on preventing perinatal depression
One of 2 new topics reviewed in 2019 was the prevention of perinatal depression. (As noted, the other on preexposure prophylaxis to prevent HIV infection has already been covered in a Practice Alert podcast.) The Task Force found that the prevalence of depression is estimated at 8.9% among pregnant women and 37% at any point in the first year postpartum.1
Depression during pregnancy and the postpartum period is associated with adverse effects on the mother and infant, including higher rates of suicide and suicidal ideation and thoughts of harming the infant.1 Women with perinatal depression are also more likely to exhibit significantly lower levels of positive maternal behaviors, such as praising and playing with their child,2 and higher rates of negative maternal behaviors.2 Perinatal depression is also associated with increased rates of preterm birth and low birth weight.3
Mothers with postpartum depression have higher rates of early termination of breast feeding and lower adherence for recommended child preventive services including vaccination.1 Children of mothers with perinatal depression develop more behavior problems, have lower cognitive functioning, and have an increased risk of psychiatric disorders than do children of mothers without this condition.4,5
A number of risk factors are associated with perinatal depression, but no screening tool was found to have enough predictive value to be recommended. In deciding who should receive an offer or referral for counseling, the Task Force recommends as a practical approach providing “counseling interventions to women with 1 or more of the following: a history of depression, current depressive symptoms (that do not reach a diagnostic threshold), certain socioeconomic risk factors such as low income or adolescent or single parenthood, recent intimate partner violence, or mental health-related factors such as elevated anxiety symptoms or a history of significant negative life events.”1
There is no conclusive evidence to guide timing of counseling interventions, but most studies reviewed started them in the second trimester. These studies included cognitive behavioral therapy and interpersonal therapy and involved counseling sessions that ranged from 4 to 20 sessions and lasted for 4 to 70 weeks. They involved group and individual sessions, mostly in-person visits, and were provided by a variety of health professionals.6
Continue to: The studies reviewed showed...
The studies reviewed showed that counseling interventions reduced the likelihood of developing depression symptoms by 39%, with a number needed to treat of 13.5.6 Studies that looked at pregnancy and maternal and infant clinical outcomes were mixed but usually found little to no difference with counseling.6 Even so, the Task Force felt that a reduction in depression itself was enough to warrant a “B” recommendation.
Screening for abdominal aortic aneurisms
Ultrasound is underused in screening for abdominal aortic aneurisms (AAA) and preventing death from their rupture. (See “Whom should you screen for abdominal aortic aneurysm?”) The prevalence of AAA is the United States is unknown; in other western countries it varies from 1.2% to 3.3% in men and is declining due to decreased rates of smoking, the primary risk factor.
The risk of AAA rupture is related to the size of the aneurism, and surgical repair (either endovascular or open repair) is usually reserved for lesions > 5.5 cm in diameter or for smaller ones that are rapidly increasing in size. The standard of care for most aneurysms < 5.5 cm is to periodically monitor growth using ultrasound.
The 2019 recommendations on AAA screening are essentially the same as those made in 2004; evaluation of new evidence supported the previous recommendations. The Task Force recommends one-time screening for men ages 65 to 75 years who have ever smoked (B recommendation). Selective screening is recommended for men in this age group who have never smoked, based mainly on personal factors such as a family history of AAA, the presence of other arterial aneurisms, and the number of risk factors for cardiovascular disease (C recommendation).
The Task Force recommends against screening women ages 65 to 75 years with no history of smoking or family history of AAA, while the evidence was felt to be insufficient to make a recommendation for women in this age range who have either risk factor. This is problematic for family physicians since women with these risk factors are at increased risk of AAA compared with women without risk factors.8 And aneurisms in women appear to rupture more frequently at smaller sizes, although at a later age than in men.8 Operative mortality is also higher in women than in men8 and there is no direct evidence that screening improves outcomes for women.
Continue to: Screening for asymptomatic bacteriuria
Screening for asymptomatic bacteriuria
The Task Force re-examined and reconfirmed its previous recommendations on screening for asymptomatic bacteriuria in adults. It recommends in favor of it for pregnant women, using a urine culture to screen, and against it for all other adults. There is good evidence that treating screen-detected asymptomatic bacteriuria in pregnant women reduces the incidence of pyelonephritis in pregnancy.
The Task Force made this a “B” recommendation based on a lower prevalence of pyelonephritis found in more recent studies, making the overall magnitude of benefits moderate. There is also good evidence that treating asymptomatic bacteriuria in nonpregnant adults offers no benefits.9 The Task Force has re-examined this topic 5 times since 1996 with essentially the same results.
Screening for elevated lead levels in children and pregnant women
In 2019 the Task Force changed its 2006 recommendation on screening for elevated lead levels. The earlier recommendation advised against screening both children ages 1 to 5 years and pregnant women at average risk for elevated blood lead levels. In 2006 the Task Force also felt that evidence was insufficient to make a recommendation regarding children ages 1 to 5 years at elevated risk.
The Task Force now believes the evidence is insufficient to make a recommendation for all children ages 1 to 5 years and for pregnant women, thus moving from a “D” to an “I” recommendation for children and pregnant women with average risk. Even though there is little evidence to support screening for elevated lead levels in children ages 1 to 5 years and in pregnant women, the Task Force apparently did not feel comfortable recommending against testing, given that the cutoff for elevated blood lead levels has been lowered from 10 to 5 mcg/dL and that other sources of lead may now be more prevalent than in 2006.10
Remember that the Medicaid Early and Periodic Screening, Diagnostic, and Treatment program requires that all children receive a blood lead test twice, at ages 12 and 24 months, and that previously unscreened children ages 36 to 72 months must be tested once.
Continue to: Additional updates with no recommendation changes
Additional updates with no recommendation changes
Four other topics were re-examined by the Task Force in 2019, resulting in no significant changes to recommendations (TABLE 2):
- Screen for hepatitis B infection in pregnant women at the first prenatal visit (A recommendation; updated from 2009).
- Screen for HIV infection in adolescents and adults ages 15 to 65 years, and in those younger and older who are at high risk, and during pregnancy (A recommendation; updated from 2013).
- Provide topical medication for all newborns to prevent gonococcal ophthalmia neonatorum (A recommendation; first recommendation in 1996, updated in 2005 and 2011).
- Avoid screening for pancreatic cancer in asymptomatic adults (D recommendation; updated from 2004).
Affirmation of USPSTF’s value
In only 1 out of 9 reassessments of past topics did the Task Force modify its previous recommendations in any significant way. This demonstrates that recommendations will usually stand the test of time if they are made using robust, evidence-based methods (that consider both benefits and harms) and they are not made when evidence is insufficient. That only 2 new topics could be addressed in 2019 may reflect a need for more resources for the Task Force.
In 2019, the US Preventive Services Task Force published 19 recommendation statements on 11 topics. Two of the topics are new; 9 are topics the Task Force had previously reviewed and has updated (TABLE 1). Three of these topics have been covered in Practice Alert podcasts (mdedge.com/familymedicine) and will not be discussed here: risk assessment, genetic counseling, and genetic testing for breast cancer susceptibility gene mutations (October 2019); medications to reduce the risk of breast cancer (December 2019); and preexposure prophylaxis to prevent HIV infections (January 2020).
Of the 19 recommendation statements made in 2019 (TABLE 2), 5 were rated “A” and 5 were “B,” meaning the evidence shows that benefits outweigh harms and these interventions should be offered in primary care practice. There were 5 “D” recommendations for interventions that should not be offered because they are either ineffective or harms exceed benefits. There were 3 “I” statements on interventions having insufficient evidence on benefits or harms to warrant a recommendation. Only 1 recommendation was rated “C” (selectively offer based on individual factors); this assessment is the hardest one to interpret and implement. Keep in mind that all “A” and “B” recommendations must be covered by commercial health plans with no out-of-pocket cost to the patient (ie, no co-pay or deductible).
New recommendation on preventing perinatal depression
One of 2 new topics reviewed in 2019 was the prevention of perinatal depression. (As noted, the other on preexposure prophylaxis to prevent HIV infection has already been covered in a Practice Alert podcast.) The Task Force found that the prevalence of depression is estimated at 8.9% among pregnant women and 37% at any point in the first year postpartum.1
Depression during pregnancy and the postpartum period is associated with adverse effects on the mother and infant, including higher rates of suicide and suicidal ideation and thoughts of harming the infant.1 Women with perinatal depression are also more likely to exhibit significantly lower levels of positive maternal behaviors, such as praising and playing with their child,2 and higher rates of negative maternal behaviors.2 Perinatal depression is also associated with increased rates of preterm birth and low birth weight.3
Mothers with postpartum depression have higher rates of early termination of breast feeding and lower adherence for recommended child preventive services including vaccination.1 Children of mothers with perinatal depression develop more behavior problems, have lower cognitive functioning, and have an increased risk of psychiatric disorders than do children of mothers without this condition.4,5
A number of risk factors are associated with perinatal depression, but no screening tool was found to have enough predictive value to be recommended. In deciding who should receive an offer or referral for counseling, the Task Force recommends as a practical approach providing “counseling interventions to women with 1 or more of the following: a history of depression, current depressive symptoms (that do not reach a diagnostic threshold), certain socioeconomic risk factors such as low income or adolescent or single parenthood, recent intimate partner violence, or mental health-related factors such as elevated anxiety symptoms or a history of significant negative life events.”1
There is no conclusive evidence to guide timing of counseling interventions, but most studies reviewed started them in the second trimester. These studies included cognitive behavioral therapy and interpersonal therapy and involved counseling sessions that ranged from 4 to 20 sessions and lasted for 4 to 70 weeks. They involved group and individual sessions, mostly in-person visits, and were provided by a variety of health professionals.6
Continue to: The studies reviewed showed...
The studies reviewed showed that counseling interventions reduced the likelihood of developing depression symptoms by 39%, with a number needed to treat of 13.5.6 Studies that looked at pregnancy and maternal and infant clinical outcomes were mixed but usually found little to no difference with counseling.6 Even so, the Task Force felt that a reduction in depression itself was enough to warrant a “B” recommendation.
Screening for abdominal aortic aneurisms
Ultrasound is underused in screening for abdominal aortic aneurisms (AAA) and preventing death from their rupture. (See “Whom should you screen for abdominal aortic aneurysm?”) The prevalence of AAA is the United States is unknown; in other western countries it varies from 1.2% to 3.3% in men and is declining due to decreased rates of smoking, the primary risk factor.
The risk of AAA rupture is related to the size of the aneurism, and surgical repair (either endovascular or open repair) is usually reserved for lesions > 5.5 cm in diameter or for smaller ones that are rapidly increasing in size. The standard of care for most aneurysms < 5.5 cm is to periodically monitor growth using ultrasound.
The 2019 recommendations on AAA screening are essentially the same as those made in 2004; evaluation of new evidence supported the previous recommendations. The Task Force recommends one-time screening for men ages 65 to 75 years who have ever smoked (B recommendation). Selective screening is recommended for men in this age group who have never smoked, based mainly on personal factors such as a family history of AAA, the presence of other arterial aneurisms, and the number of risk factors for cardiovascular disease (C recommendation).
The Task Force recommends against screening women ages 65 to 75 years with no history of smoking or family history of AAA, while the evidence was felt to be insufficient to make a recommendation for women in this age range who have either risk factor. This is problematic for family physicians since women with these risk factors are at increased risk of AAA compared with women without risk factors.8 And aneurisms in women appear to rupture more frequently at smaller sizes, although at a later age than in men.8 Operative mortality is also higher in women than in men8 and there is no direct evidence that screening improves outcomes for women.
Continue to: Screening for asymptomatic bacteriuria
Screening for asymptomatic bacteriuria
The Task Force re-examined and reconfirmed its previous recommendations on screening for asymptomatic bacteriuria in adults. It recommends in favor of it for pregnant women, using a urine culture to screen, and against it for all other adults. There is good evidence that treating screen-detected asymptomatic bacteriuria in pregnant women reduces the incidence of pyelonephritis in pregnancy.
The Task Force made this a “B” recommendation based on a lower prevalence of pyelonephritis found in more recent studies, making the overall magnitude of benefits moderate. There is also good evidence that treating asymptomatic bacteriuria in nonpregnant adults offers no benefits.9 The Task Force has re-examined this topic 5 times since 1996 with essentially the same results.
Screening for elevated lead levels in children and pregnant women
In 2019 the Task Force changed its 2006 recommendation on screening for elevated lead levels. The earlier recommendation advised against screening both children ages 1 to 5 years and pregnant women at average risk for elevated blood lead levels. In 2006 the Task Force also felt that evidence was insufficient to make a recommendation regarding children ages 1 to 5 years at elevated risk.
The Task Force now believes the evidence is insufficient to make a recommendation for all children ages 1 to 5 years and for pregnant women, thus moving from a “D” to an “I” recommendation for children and pregnant women with average risk. Even though there is little evidence to support screening for elevated lead levels in children ages 1 to 5 years and in pregnant women, the Task Force apparently did not feel comfortable recommending against testing, given that the cutoff for elevated blood lead levels has been lowered from 10 to 5 mcg/dL and that other sources of lead may now be more prevalent than in 2006.10
Remember that the Medicaid Early and Periodic Screening, Diagnostic, and Treatment program requires that all children receive a blood lead test twice, at ages 12 and 24 months, and that previously unscreened children ages 36 to 72 months must be tested once.
Continue to: Additional updates with no recommendation changes
Additional updates with no recommendation changes
Four other topics were re-examined by the Task Force in 2019, resulting in no significant changes to recommendations (TABLE 2):
- Screen for hepatitis B infection in pregnant women at the first prenatal visit (A recommendation; updated from 2009).
- Screen for HIV infection in adolescents and adults ages 15 to 65 years, and in those younger and older who are at high risk, and during pregnancy (A recommendation; updated from 2013).
- Provide topical medication for all newborns to prevent gonococcal ophthalmia neonatorum (A recommendation; first recommendation in 1996, updated in 2005 and 2011).
- Avoid screening for pancreatic cancer in asymptomatic adults (D recommendation; updated from 2004).
Affirmation of USPSTF’s value
In only 1 out of 9 reassessments of past topics did the Task Force modify its previous recommendations in any significant way. This demonstrates that recommendations will usually stand the test of time if they are made using robust, evidence-based methods (that consider both benefits and harms) and they are not made when evidence is insufficient. That only 2 new topics could be addressed in 2019 may reflect a need for more resources for the Task Force.
1. USPSTF. Interventions to prevent perinatal depression: US Preventive Services Task Force recommendation statement. 2019;321:580-587.
2. Lovejoy MC, Graczyk PA, O’Hare E, et al. Maternal depression and parenting behavior: a meta-analytic review. Clin Psychol Rev. 2000;20:561-592.
3. Szegda K, Markenson G, Bertone-Johnson ER, et al. Depression during pregnancy: a risk factor for adverse neonatal outcomes? A critical review of the literature. J Matern Fetal Neonatal Med. 2014;27:960-967.
4. Beck CT. The effects of postpartum depression on child development: a meta-analysis. Arch Psychiatr Nurs. 1998;12:12-20.
5. Santos IS, Matijasevich A, Barros AJ, et al. Antenatal and postnatal maternal mood symptoms and psychiatric disorders in pre-school children from the 2004 Pelotas Birth Cohort. J Affect Disord. 2014;164:112-117.
6. O’Connor E, Senger CA, Henniger ML, et al. Interventions to prevent perinatal depression. Evidence report and systematic review for the US preventive services task force. JAMA. 2019;321:588-601.
7. USPSTF. Screening for abdominal aortic aneurysm: US Preventive Services Task Force recommendation statement. 2019;322:2211-2218.
8. Guirguis-Blake JM, Beil TL, Senger CA, et al. Primary care screening for abdominal aortic aneurysm: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2019;322:2219-2238.
9. USPSTF. Owens DK, Davidson KW, Krist AH, et al. Screening for asymptomatic bacteriuria in adults: US Preventive Services Task Force recommendation statement. 2019;322:1188-1194.
10. USPSTF. Screening for elevated blood lead levels in children and pregnant women: US Preventive Services Task Force recommendation statement. 2019;321:1502-1509.
1. USPSTF. Interventions to prevent perinatal depression: US Preventive Services Task Force recommendation statement. 2019;321:580-587.
2. Lovejoy MC, Graczyk PA, O’Hare E, et al. Maternal depression and parenting behavior: a meta-analytic review. Clin Psychol Rev. 2000;20:561-592.
3. Szegda K, Markenson G, Bertone-Johnson ER, et al. Depression during pregnancy: a risk factor for adverse neonatal outcomes? A critical review of the literature. J Matern Fetal Neonatal Med. 2014;27:960-967.
4. Beck CT. The effects of postpartum depression on child development: a meta-analysis. Arch Psychiatr Nurs. 1998;12:12-20.
5. Santos IS, Matijasevich A, Barros AJ, et al. Antenatal and postnatal maternal mood symptoms and psychiatric disorders in pre-school children from the 2004 Pelotas Birth Cohort. J Affect Disord. 2014;164:112-117.
6. O’Connor E, Senger CA, Henniger ML, et al. Interventions to prevent perinatal depression. Evidence report and systematic review for the US preventive services task force. JAMA. 2019;321:588-601.
7. USPSTF. Screening for abdominal aortic aneurysm: US Preventive Services Task Force recommendation statement. 2019;322:2211-2218.
8. Guirguis-Blake JM, Beil TL, Senger CA, et al. Primary care screening for abdominal aortic aneurysm: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2019;322:2219-2238.
9. USPSTF. Owens DK, Davidson KW, Krist AH, et al. Screening for asymptomatic bacteriuria in adults: US Preventive Services Task Force recommendation statement. 2019;322:1188-1194.
10. USPSTF. Screening for elevated blood lead levels in children and pregnant women: US Preventive Services Task Force recommendation statement. 2019;321:1502-1509.
Silent brain infarcts found in 3% of AFib patients, tied to cognitive decline
Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.
The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.
“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.
Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.
This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.
These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.
“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.
The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.
Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.
Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.
SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.
Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.
The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.
“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.
Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.
This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.
These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.
“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.
The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.
Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.
Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.
SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.
Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.
The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.
“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.
Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.
This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.
These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.
“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.
The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.
Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.
Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.
SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.
FROM HEART RHYTHM 2020
Serum NfL in early MS can help predict clinical course
research suggests. The study showed that patients with higher sNfL within 5 years of MS diagnosis had a higher risk of long term-clinical disability and higher risk of developing progressive MS. The level of sNfL also predicted the rate of increase over time in the Expanded Disability Status Scale (EDSS).
Serum NfL levels can provide “useful information in both directions, adding to both an overall reassuring picture or worrying picture both at first presentation and then on subsequent visits,” said Simon Thebault, MBBCh, a neurology resident at the University of Ottawa and the Ottawa Hospital Research Institute, Canada.
This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
Prognostication from day one
Many studies have shown a correlation between MS disease activity (clinical relapses, EDSS progression, MRI lesions) and elevated sNfL. Other studies have also looked at the prognostic value of NfL in serum and cerebrospinal fluid (CSF), but the data are limited by the lack of long-term biobanked samples and subsequent follow-up, Dr. Thebault explained.
The new study took advantage of the Ottawa MS biobank, which contains carefully frozen and stored samples from more than 3,000 patients with MS going back up to 25 years.
The team identified patients with serum collected within 5 years of first MS symptom onset (baseline) who were followed for a median of 18.9 years (range 15.0 to 27.0 years). They quantified levels of sNfL in 67 patients and 37 matched controls.
In patients with MS, the median baseline sNfL level was 10.1 pg/mL – 38.5% higher than the median level in controls (7.26 pg/mL, P = 0.004).
The baseline sNfL level was “most helpful as a sensitive predictive marker to rule out disease progression,” the researchers reported in their meeting abstract.
Patients with baseline sNfL levels less than 7.62 pg/mL were 4.3 times less likely to develop significant disability (EDSS score ≥ 4; P = 0.001) and 7.1 times less likely to develop progressive MS by end of follow-up (P = 0.054).
The most rapid disease progression was seen in patients with the highest baseline NfL levels (3rd-tertile, > 13.2 pg/mL). Higher baseline sNfL level was associated with faster rate of EDSS progression even after adjusting for confounders of age, sex, and disease-modifying treatment.
“We were able to show that serum neurofilament levels collected very early in the disease, usually at the time of first diagnosis, were predictive of the clinical progression [by EDSS score] and the risk of evolving to secondary progressive MS on average 19 years later,” Dr. Thebault said. A baseline level less than 7.6 pg/mL was “reassuring.”
“Prognostication in MS from day one is important,” he emphasized.
“If we know someone is on a bad trajectory, neurologists might recommend more aggressive therapies up front. Equally, if a patient has a very reassuring picture, then maybe it is more appropriate to start with safer treatments [the so called ‘platform therapies’] that may serve a patient well for many years, as they did for many in the years before higher-efficacy therapies were available,” Dr. Thebault said.
“In the hands of an expert MS neurologist who understands both the pearls and pitfalls of this test ... serum neurofilament is already a useful clinical tool, and we have implemented it in our daily practice in Ottawa,” he concluded.
Noteworthy study
Commenting on the study, Asaff Harel, MD, neurologist at Lenox Hill Hospital in New York City, said the findings in this study are “noteworthy, as there is a relative lack of effective prognostic biomarkers in the field of MS.”
“It remains to be seen whether this improves risk stratification of patients above what can be achieved by looking at other prognostic factors, such as age, gender, baseline EDSS, and severity and frequency of relapses during early disease course,” Dr. Harel cautioned.
“This was a relatively small study and further research is necessary,” Dr. Harel added. It’s also worth noting, he said, that out of the 67 patients who met criteria to be included in the study (i.e., those with blood samples taken during “early MS,” more than 15 years ago), almost half were lost to follow-up, which could potentially open the study to error.
It is also “unclear whether early NfL level is a better prognostic marker than severity of early disease course and baseline EDSS, both of which were not addressed in the study, and this will be interesting to determine in the future,” Dr. Harel commented.
Funding for the study was provided by The Ottawa Hospital Pilot Project Grant. Thebault and Harel have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
research suggests. The study showed that patients with higher sNfL within 5 years of MS diagnosis had a higher risk of long term-clinical disability and higher risk of developing progressive MS. The level of sNfL also predicted the rate of increase over time in the Expanded Disability Status Scale (EDSS).
Serum NfL levels can provide “useful information in both directions, adding to both an overall reassuring picture or worrying picture both at first presentation and then on subsequent visits,” said Simon Thebault, MBBCh, a neurology resident at the University of Ottawa and the Ottawa Hospital Research Institute, Canada.
This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
Prognostication from day one
Many studies have shown a correlation between MS disease activity (clinical relapses, EDSS progression, MRI lesions) and elevated sNfL. Other studies have also looked at the prognostic value of NfL in serum and cerebrospinal fluid (CSF), but the data are limited by the lack of long-term biobanked samples and subsequent follow-up, Dr. Thebault explained.
The new study took advantage of the Ottawa MS biobank, which contains carefully frozen and stored samples from more than 3,000 patients with MS going back up to 25 years.
The team identified patients with serum collected within 5 years of first MS symptom onset (baseline) who were followed for a median of 18.9 years (range 15.0 to 27.0 years). They quantified levels of sNfL in 67 patients and 37 matched controls.
In patients with MS, the median baseline sNfL level was 10.1 pg/mL – 38.5% higher than the median level in controls (7.26 pg/mL, P = 0.004).
The baseline sNfL level was “most helpful as a sensitive predictive marker to rule out disease progression,” the researchers reported in their meeting abstract.
Patients with baseline sNfL levels less than 7.62 pg/mL were 4.3 times less likely to develop significant disability (EDSS score ≥ 4; P = 0.001) and 7.1 times less likely to develop progressive MS by end of follow-up (P = 0.054).
The most rapid disease progression was seen in patients with the highest baseline NfL levels (3rd-tertile, > 13.2 pg/mL). Higher baseline sNfL level was associated with faster rate of EDSS progression even after adjusting for confounders of age, sex, and disease-modifying treatment.
“We were able to show that serum neurofilament levels collected very early in the disease, usually at the time of first diagnosis, were predictive of the clinical progression [by EDSS score] and the risk of evolving to secondary progressive MS on average 19 years later,” Dr. Thebault said. A baseline level less than 7.6 pg/mL was “reassuring.”
“Prognostication in MS from day one is important,” he emphasized.
“If we know someone is on a bad trajectory, neurologists might recommend more aggressive therapies up front. Equally, if a patient has a very reassuring picture, then maybe it is more appropriate to start with safer treatments [the so called ‘platform therapies’] that may serve a patient well for many years, as they did for many in the years before higher-efficacy therapies were available,” Dr. Thebault said.
“In the hands of an expert MS neurologist who understands both the pearls and pitfalls of this test ... serum neurofilament is already a useful clinical tool, and we have implemented it in our daily practice in Ottawa,” he concluded.
Noteworthy study
Commenting on the study, Asaff Harel, MD, neurologist at Lenox Hill Hospital in New York City, said the findings in this study are “noteworthy, as there is a relative lack of effective prognostic biomarkers in the field of MS.”
“It remains to be seen whether this improves risk stratification of patients above what can be achieved by looking at other prognostic factors, such as age, gender, baseline EDSS, and severity and frequency of relapses during early disease course,” Dr. Harel cautioned.
“This was a relatively small study and further research is necessary,” Dr. Harel added. It’s also worth noting, he said, that out of the 67 patients who met criteria to be included in the study (i.e., those with blood samples taken during “early MS,” more than 15 years ago), almost half were lost to follow-up, which could potentially open the study to error.
It is also “unclear whether early NfL level is a better prognostic marker than severity of early disease course and baseline EDSS, both of which were not addressed in the study, and this will be interesting to determine in the future,” Dr. Harel commented.
Funding for the study was provided by The Ottawa Hospital Pilot Project Grant. Thebault and Harel have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
research suggests. The study showed that patients with higher sNfL within 5 years of MS diagnosis had a higher risk of long term-clinical disability and higher risk of developing progressive MS. The level of sNfL also predicted the rate of increase over time in the Expanded Disability Status Scale (EDSS).
Serum NfL levels can provide “useful information in both directions, adding to both an overall reassuring picture or worrying picture both at first presentation and then on subsequent visits,” said Simon Thebault, MBBCh, a neurology resident at the University of Ottawa and the Ottawa Hospital Research Institute, Canada.
This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
Prognostication from day one
Many studies have shown a correlation between MS disease activity (clinical relapses, EDSS progression, MRI lesions) and elevated sNfL. Other studies have also looked at the prognostic value of NfL in serum and cerebrospinal fluid (CSF), but the data are limited by the lack of long-term biobanked samples and subsequent follow-up, Dr. Thebault explained.
The new study took advantage of the Ottawa MS biobank, which contains carefully frozen and stored samples from more than 3,000 patients with MS going back up to 25 years.
The team identified patients with serum collected within 5 years of first MS symptom onset (baseline) who were followed for a median of 18.9 years (range 15.0 to 27.0 years). They quantified levels of sNfL in 67 patients and 37 matched controls.
In patients with MS, the median baseline sNfL level was 10.1 pg/mL – 38.5% higher than the median level in controls (7.26 pg/mL, P = 0.004).
The baseline sNfL level was “most helpful as a sensitive predictive marker to rule out disease progression,” the researchers reported in their meeting abstract.
Patients with baseline sNfL levels less than 7.62 pg/mL were 4.3 times less likely to develop significant disability (EDSS score ≥ 4; P = 0.001) and 7.1 times less likely to develop progressive MS by end of follow-up (P = 0.054).
The most rapid disease progression was seen in patients with the highest baseline NfL levels (3rd-tertile, > 13.2 pg/mL). Higher baseline sNfL level was associated with faster rate of EDSS progression even after adjusting for confounders of age, sex, and disease-modifying treatment.
“We were able to show that serum neurofilament levels collected very early in the disease, usually at the time of first diagnosis, were predictive of the clinical progression [by EDSS score] and the risk of evolving to secondary progressive MS on average 19 years later,” Dr. Thebault said. A baseline level less than 7.6 pg/mL was “reassuring.”
“Prognostication in MS from day one is important,” he emphasized.
“If we know someone is on a bad trajectory, neurologists might recommend more aggressive therapies up front. Equally, if a patient has a very reassuring picture, then maybe it is more appropriate to start with safer treatments [the so called ‘platform therapies’] that may serve a patient well for many years, as they did for many in the years before higher-efficacy therapies were available,” Dr. Thebault said.
“In the hands of an expert MS neurologist who understands both the pearls and pitfalls of this test ... serum neurofilament is already a useful clinical tool, and we have implemented it in our daily practice in Ottawa,” he concluded.
Noteworthy study
Commenting on the study, Asaff Harel, MD, neurologist at Lenox Hill Hospital in New York City, said the findings in this study are “noteworthy, as there is a relative lack of effective prognostic biomarkers in the field of MS.”
“It remains to be seen whether this improves risk stratification of patients above what can be achieved by looking at other prognostic factors, such as age, gender, baseline EDSS, and severity and frequency of relapses during early disease course,” Dr. Harel cautioned.
“This was a relatively small study and further research is necessary,” Dr. Harel added. It’s also worth noting, he said, that out of the 67 patients who met criteria to be included in the study (i.e., those with blood samples taken during “early MS,” more than 15 years ago), almost half were lost to follow-up, which could potentially open the study to error.
It is also “unclear whether early NfL level is a better prognostic marker than severity of early disease course and baseline EDSS, both of which were not addressed in the study, and this will be interesting to determine in the future,” Dr. Harel commented.
Funding for the study was provided by The Ottawa Hospital Pilot Project Grant. Thebault and Harel have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.