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Basal ganglia microcircuits offer clues to Parkinson’s symptoms
, according to a new study using a mouse model of disease.
Parkinson’s disease is characterized by a range of cognitive and motor symptoms, which appear at different disease stages. While recent research has pointed to specific neuronal subpopulations, or microcircuits, operating in the basal ganglia, researchers lacked a clear understanding of how they might correspond with specific symptom domains.
In a study published online March 15 in Nature Neuroscience, lead author Varoth Lilascharoen, PhD, of the University of California, San Diego, and colleagues reported that two different neuronal subpopulations within the external globus pallidus, an important nucleus within the basal ganglia, are associated, respectively, with movement and with reversal learning (having to adapt to a reward pattern that is the reverse of a previous pattern). This is the first time, the investigators said, that the contributions of specific microcircuits in the basal ganglia have been linked to different behaviors.
Using electrophysiology, viral tracing, and other approaches, Dr. Lilascharoen and colleagues demonstrated that two microcircuits or populations of parvalbumin-expressing neurons could be manipulated to exacerbate or alleviate the motor or cognitive deficits in the dopamine-depleted mice.
One of these microcircuits, made up of substantia nigra pars reticulata-projecting GPe-PV neurons, could be manipulated in ways that promoted or inhibited the mice’s movement. The other, which comprises parafascicular thalamus-projecting GPe-PV neurons, could be manipulated to affect reversal learning, the researchers found. Activation or inhibition of either circuit was not seen affecting function in the other.
The results shed light on the functional organization of the different basal ganglia nuclei at the circuit level, and suggest, the authors argued, that differences in how different neuronal subpopulations adapt to dopamine loss could explain some of the patterns of progression seen in Parkinson’s disease.
The findings “establish the differential contributions from two distinct GPe-PV microcircuits in specific Parkinsonian-like behaviors linked to early and late stages of the disease,” Dr. Lilascharoen and colleagues wrote in their analysis. “[F]urther elucidation of the detailed connectivity of GPe subpopulations to their downstream targets … is needed to fully define the function of each microcircuit and design better therapeutic strategies for the various behavioral impairments of Parkinson’s disease.”
Commenting on the research, Stefan Lang, MD, PhD, of the University of Calgary in Alberta said, “While Parkinson’s disease is often referred to as a movement disorder, it is well known that nonmotor symptoms, including cognitive and behavioral impairment, are common and debilitating. Impairment of basal ganglia function is known to contribute to these different symptom domains, though the specific circuits have never been elucidated. [Dr.] Lilascharoen et al. tease apart specific basal ganglia circuits associated with motor and behavioral symptoms, thereby providing evidence that distinct microcircuits might contribute to unique behaviours. As technological advances in neuromodulatory therapies continue to improve the spatial and temporal resolution of stimulation, future treatments may allow for specific targeting of behavioral impairment symptoms in Parkinson’s disease.”
Dr. Lilascharoen and Dr. Lang did not report outside funding or conflicts of interest.
, according to a new study using a mouse model of disease.
Parkinson’s disease is characterized by a range of cognitive and motor symptoms, which appear at different disease stages. While recent research has pointed to specific neuronal subpopulations, or microcircuits, operating in the basal ganglia, researchers lacked a clear understanding of how they might correspond with specific symptom domains.
In a study published online March 15 in Nature Neuroscience, lead author Varoth Lilascharoen, PhD, of the University of California, San Diego, and colleagues reported that two different neuronal subpopulations within the external globus pallidus, an important nucleus within the basal ganglia, are associated, respectively, with movement and with reversal learning (having to adapt to a reward pattern that is the reverse of a previous pattern). This is the first time, the investigators said, that the contributions of specific microcircuits in the basal ganglia have been linked to different behaviors.
Using electrophysiology, viral tracing, and other approaches, Dr. Lilascharoen and colleagues demonstrated that two microcircuits or populations of parvalbumin-expressing neurons could be manipulated to exacerbate or alleviate the motor or cognitive deficits in the dopamine-depleted mice.
One of these microcircuits, made up of substantia nigra pars reticulata-projecting GPe-PV neurons, could be manipulated in ways that promoted or inhibited the mice’s movement. The other, which comprises parafascicular thalamus-projecting GPe-PV neurons, could be manipulated to affect reversal learning, the researchers found. Activation or inhibition of either circuit was not seen affecting function in the other.
The results shed light on the functional organization of the different basal ganglia nuclei at the circuit level, and suggest, the authors argued, that differences in how different neuronal subpopulations adapt to dopamine loss could explain some of the patterns of progression seen in Parkinson’s disease.
The findings “establish the differential contributions from two distinct GPe-PV microcircuits in specific Parkinsonian-like behaviors linked to early and late stages of the disease,” Dr. Lilascharoen and colleagues wrote in their analysis. “[F]urther elucidation of the detailed connectivity of GPe subpopulations to their downstream targets … is needed to fully define the function of each microcircuit and design better therapeutic strategies for the various behavioral impairments of Parkinson’s disease.”
Commenting on the research, Stefan Lang, MD, PhD, of the University of Calgary in Alberta said, “While Parkinson’s disease is often referred to as a movement disorder, it is well known that nonmotor symptoms, including cognitive and behavioral impairment, are common and debilitating. Impairment of basal ganglia function is known to contribute to these different symptom domains, though the specific circuits have never been elucidated. [Dr.] Lilascharoen et al. tease apart specific basal ganglia circuits associated with motor and behavioral symptoms, thereby providing evidence that distinct microcircuits might contribute to unique behaviours. As technological advances in neuromodulatory therapies continue to improve the spatial and temporal resolution of stimulation, future treatments may allow for specific targeting of behavioral impairment symptoms in Parkinson’s disease.”
Dr. Lilascharoen and Dr. Lang did not report outside funding or conflicts of interest.
, according to a new study using a mouse model of disease.
Parkinson’s disease is characterized by a range of cognitive and motor symptoms, which appear at different disease stages. While recent research has pointed to specific neuronal subpopulations, or microcircuits, operating in the basal ganglia, researchers lacked a clear understanding of how they might correspond with specific symptom domains.
In a study published online March 15 in Nature Neuroscience, lead author Varoth Lilascharoen, PhD, of the University of California, San Diego, and colleagues reported that two different neuronal subpopulations within the external globus pallidus, an important nucleus within the basal ganglia, are associated, respectively, with movement and with reversal learning (having to adapt to a reward pattern that is the reverse of a previous pattern). This is the first time, the investigators said, that the contributions of specific microcircuits in the basal ganglia have been linked to different behaviors.
Using electrophysiology, viral tracing, and other approaches, Dr. Lilascharoen and colleagues demonstrated that two microcircuits or populations of parvalbumin-expressing neurons could be manipulated to exacerbate or alleviate the motor or cognitive deficits in the dopamine-depleted mice.
One of these microcircuits, made up of substantia nigra pars reticulata-projecting GPe-PV neurons, could be manipulated in ways that promoted or inhibited the mice’s movement. The other, which comprises parafascicular thalamus-projecting GPe-PV neurons, could be manipulated to affect reversal learning, the researchers found. Activation or inhibition of either circuit was not seen affecting function in the other.
The results shed light on the functional organization of the different basal ganglia nuclei at the circuit level, and suggest, the authors argued, that differences in how different neuronal subpopulations adapt to dopamine loss could explain some of the patterns of progression seen in Parkinson’s disease.
The findings “establish the differential contributions from two distinct GPe-PV microcircuits in specific Parkinsonian-like behaviors linked to early and late stages of the disease,” Dr. Lilascharoen and colleagues wrote in their analysis. “[F]urther elucidation of the detailed connectivity of GPe subpopulations to their downstream targets … is needed to fully define the function of each microcircuit and design better therapeutic strategies for the various behavioral impairments of Parkinson’s disease.”
Commenting on the research, Stefan Lang, MD, PhD, of the University of Calgary in Alberta said, “While Parkinson’s disease is often referred to as a movement disorder, it is well known that nonmotor symptoms, including cognitive and behavioral impairment, are common and debilitating. Impairment of basal ganglia function is known to contribute to these different symptom domains, though the specific circuits have never been elucidated. [Dr.] Lilascharoen et al. tease apart specific basal ganglia circuits associated with motor and behavioral symptoms, thereby providing evidence that distinct microcircuits might contribute to unique behaviours. As technological advances in neuromodulatory therapies continue to improve the spatial and temporal resolution of stimulation, future treatments may allow for specific targeting of behavioral impairment symptoms in Parkinson’s disease.”
Dr. Lilascharoen and Dr. Lang did not report outside funding or conflicts of interest.
FROM NATURE NEUROSCIENCE
NfL beats T-tau as a prognostic marker of cognitive decline
, new research suggests. In certain contexts, T-tau improves cross-sectional analyses of these outcomes, but adding T-tau measurements to NfL measurements does not improve the predictive power of NfL, results of a longitudinal analysis show.
“The major distinction, for cognition at least, was that NfL cross-sectionally was associated with most cognitive outcomes, and longitudinally, higher NfL at baseline was associated with cognitive decline in every domain,” said study investigator Jordan Marks, an MD/PhD student at the Mayo Medical School, Rochester, Minn.
The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
New tool for dementia diagnosis?
In recent years, researchers have studied NfL and T-tau as potential blood-based biomarkers of neurodegeneration. In cross-sectional and longitudinal studies, NfL and T-tau have been associated with worse cognition and with neuroimaging measures of cortical thickness, cortical atrophy, white-matter hyperintensity, and white-matter integrity. However, no previous research has directly compared the prognostic ability of these two biomarkers.
The study included 995 participants without dementia in the Mayo Clinic Study on Aging. All participants underwent measurement of NfL and T-tau and assessment of cognitive status, as well as neuroimaging. The investigators measured NfL and T-tau on the Simoa HD-1 platform. They reexamined patients approximately every 15 months. The median follow-up time was 6.2 years.
To examine associations between baseline plasma NfL or T-tau and cognitive or neuroimaging outcomes, the researchers conducted data analyses using linear mixed effects models and adjusted the data for age, sex, and education. They replicated these analyses using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). For these analyses, they selected 387 participants without dementia who had been followed for a median of 3.0 years.
In all analyses, baseline plasma NfL was more strongly associated with cognitive and neuroimaging outcomes than T-tau. “Baseline plasma NfL was associated with cognitive decline in all domains measured, while T-tau was not associated with cognitive decline,” said Mr. Marks.
Plasma NfL was more strongly associated with decreases in cortical thickness over time than T-tau was. NfL was also more strongly associated with declining hippocampal volume and white-matter changes.
However, in cross-sectional analysis, the combination of elevated NfL levels and elevated T-tau levels at baseline was more strongly associated with decreased global cognition and memory, compared with elevated NfL levels alone. The combination also was more strongly associated with neuroimaging measures, such as temporal cortex thickness and increased number of infarcts. However, in longitudinal analyses, T-tau did not add to the predictive value of NfL.
The analyses using ADNI data yielded similar results. Overall, the results suggest that NfL is a better prognostic marker of neurodegeneration in general, said Mr. Marks.
These findings, he said, may have implications for screening and diagnosis. “I’m definitely hopeful that NfL will be useful in a clinical setting to screen for those at risk of dementia and will be helpful, along with other modalities, like cognitive testing, for dementia diagnosis,” said Mr. Marks.
Future research should examine how changes in these biomarkers are associated with cognitive and neuroimaging outcomes over time.
“We used plasma levels at one point in time in this study, but we need a better sense of how to interpret, for example, what a rise in plasma NfL over a certain time period means for someone’s risk of developing neurodegenerative disease,” Mr. Marks added.
An ‘exciting’ prospect
Commenting on the study, Glen R. Finney, MD, director of the Memory and Cognition Program for Geisinger Health in Wilkes-Barre, Pa., said the findings add to neurologists’ ability to screen for brain diseases. “Evidence of neurodegeneration is part of the modern diagnosis of several disorders. While brain imaging can also provide that and may be needed for other reasons, this could provide an easy, potentially inexpensive way to screen for damage to the brain, giving us an added tool,” said Dr. Finney.
The prospect of using blood plasma markers to explore disease of the brain is exciting, Dr. Finney added. “I would like to see ongoing refinement of this approach and would like to see if there’s other markers in blood that could be used to find what specifically may be causing the damage,” he said.
The study was funded by the National Institutes of Health, the National Institute on Aging, and the GHR Foundation. Mr. Marks and Dr. Finney have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In certain contexts, T-tau improves cross-sectional analyses of these outcomes, but adding T-tau measurements to NfL measurements does not improve the predictive power of NfL, results of a longitudinal analysis show.
“The major distinction, for cognition at least, was that NfL cross-sectionally was associated with most cognitive outcomes, and longitudinally, higher NfL at baseline was associated with cognitive decline in every domain,” said study investigator Jordan Marks, an MD/PhD student at the Mayo Medical School, Rochester, Minn.
The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
New tool for dementia diagnosis?
In recent years, researchers have studied NfL and T-tau as potential blood-based biomarkers of neurodegeneration. In cross-sectional and longitudinal studies, NfL and T-tau have been associated with worse cognition and with neuroimaging measures of cortical thickness, cortical atrophy, white-matter hyperintensity, and white-matter integrity. However, no previous research has directly compared the prognostic ability of these two biomarkers.
The study included 995 participants without dementia in the Mayo Clinic Study on Aging. All participants underwent measurement of NfL and T-tau and assessment of cognitive status, as well as neuroimaging. The investigators measured NfL and T-tau on the Simoa HD-1 platform. They reexamined patients approximately every 15 months. The median follow-up time was 6.2 years.
To examine associations between baseline plasma NfL or T-tau and cognitive or neuroimaging outcomes, the researchers conducted data analyses using linear mixed effects models and adjusted the data for age, sex, and education. They replicated these analyses using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). For these analyses, they selected 387 participants without dementia who had been followed for a median of 3.0 years.
In all analyses, baseline plasma NfL was more strongly associated with cognitive and neuroimaging outcomes than T-tau. “Baseline plasma NfL was associated with cognitive decline in all domains measured, while T-tau was not associated with cognitive decline,” said Mr. Marks.
Plasma NfL was more strongly associated with decreases in cortical thickness over time than T-tau was. NfL was also more strongly associated with declining hippocampal volume and white-matter changes.
However, in cross-sectional analysis, the combination of elevated NfL levels and elevated T-tau levels at baseline was more strongly associated with decreased global cognition and memory, compared with elevated NfL levels alone. The combination also was more strongly associated with neuroimaging measures, such as temporal cortex thickness and increased number of infarcts. However, in longitudinal analyses, T-tau did not add to the predictive value of NfL.
The analyses using ADNI data yielded similar results. Overall, the results suggest that NfL is a better prognostic marker of neurodegeneration in general, said Mr. Marks.
These findings, he said, may have implications for screening and diagnosis. “I’m definitely hopeful that NfL will be useful in a clinical setting to screen for those at risk of dementia and will be helpful, along with other modalities, like cognitive testing, for dementia diagnosis,” said Mr. Marks.
Future research should examine how changes in these biomarkers are associated with cognitive and neuroimaging outcomes over time.
“We used plasma levels at one point in time in this study, but we need a better sense of how to interpret, for example, what a rise in plasma NfL over a certain time period means for someone’s risk of developing neurodegenerative disease,” Mr. Marks added.
An ‘exciting’ prospect
Commenting on the study, Glen R. Finney, MD, director of the Memory and Cognition Program for Geisinger Health in Wilkes-Barre, Pa., said the findings add to neurologists’ ability to screen for brain diseases. “Evidence of neurodegeneration is part of the modern diagnosis of several disorders. While brain imaging can also provide that and may be needed for other reasons, this could provide an easy, potentially inexpensive way to screen for damage to the brain, giving us an added tool,” said Dr. Finney.
The prospect of using blood plasma markers to explore disease of the brain is exciting, Dr. Finney added. “I would like to see ongoing refinement of this approach and would like to see if there’s other markers in blood that could be used to find what specifically may be causing the damage,” he said.
The study was funded by the National Institutes of Health, the National Institute on Aging, and the GHR Foundation. Mr. Marks and Dr. Finney have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In certain contexts, T-tau improves cross-sectional analyses of these outcomes, but adding T-tau measurements to NfL measurements does not improve the predictive power of NfL, results of a longitudinal analysis show.
“The major distinction, for cognition at least, was that NfL cross-sectionally was associated with most cognitive outcomes, and longitudinally, higher NfL at baseline was associated with cognitive decline in every domain,” said study investigator Jordan Marks, an MD/PhD student at the Mayo Medical School, Rochester, Minn.
The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
New tool for dementia diagnosis?
In recent years, researchers have studied NfL and T-tau as potential blood-based biomarkers of neurodegeneration. In cross-sectional and longitudinal studies, NfL and T-tau have been associated with worse cognition and with neuroimaging measures of cortical thickness, cortical atrophy, white-matter hyperintensity, and white-matter integrity. However, no previous research has directly compared the prognostic ability of these two biomarkers.
The study included 995 participants without dementia in the Mayo Clinic Study on Aging. All participants underwent measurement of NfL and T-tau and assessment of cognitive status, as well as neuroimaging. The investigators measured NfL and T-tau on the Simoa HD-1 platform. They reexamined patients approximately every 15 months. The median follow-up time was 6.2 years.
To examine associations between baseline plasma NfL or T-tau and cognitive or neuroimaging outcomes, the researchers conducted data analyses using linear mixed effects models and adjusted the data for age, sex, and education. They replicated these analyses using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). For these analyses, they selected 387 participants without dementia who had been followed for a median of 3.0 years.
In all analyses, baseline plasma NfL was more strongly associated with cognitive and neuroimaging outcomes than T-tau. “Baseline plasma NfL was associated with cognitive decline in all domains measured, while T-tau was not associated with cognitive decline,” said Mr. Marks.
Plasma NfL was more strongly associated with decreases in cortical thickness over time than T-tau was. NfL was also more strongly associated with declining hippocampal volume and white-matter changes.
However, in cross-sectional analysis, the combination of elevated NfL levels and elevated T-tau levels at baseline was more strongly associated with decreased global cognition and memory, compared with elevated NfL levels alone. The combination also was more strongly associated with neuroimaging measures, such as temporal cortex thickness and increased number of infarcts. However, in longitudinal analyses, T-tau did not add to the predictive value of NfL.
The analyses using ADNI data yielded similar results. Overall, the results suggest that NfL is a better prognostic marker of neurodegeneration in general, said Mr. Marks.
These findings, he said, may have implications for screening and diagnosis. “I’m definitely hopeful that NfL will be useful in a clinical setting to screen for those at risk of dementia and will be helpful, along with other modalities, like cognitive testing, for dementia diagnosis,” said Mr. Marks.
Future research should examine how changes in these biomarkers are associated with cognitive and neuroimaging outcomes over time.
“We used plasma levels at one point in time in this study, but we need a better sense of how to interpret, for example, what a rise in plasma NfL over a certain time period means for someone’s risk of developing neurodegenerative disease,” Mr. Marks added.
An ‘exciting’ prospect
Commenting on the study, Glen R. Finney, MD, director of the Memory and Cognition Program for Geisinger Health in Wilkes-Barre, Pa., said the findings add to neurologists’ ability to screen for brain diseases. “Evidence of neurodegeneration is part of the modern diagnosis of several disorders. While brain imaging can also provide that and may be needed for other reasons, this could provide an easy, potentially inexpensive way to screen for damage to the brain, giving us an added tool,” said Dr. Finney.
The prospect of using blood plasma markers to explore disease of the brain is exciting, Dr. Finney added. “I would like to see ongoing refinement of this approach and would like to see if there’s other markers in blood that could be used to find what specifically may be causing the damage,” he said.
The study was funded by the National Institutes of Health, the National Institute on Aging, and the GHR Foundation. Mr. Marks and Dr. Finney have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From AAN 2021
Investigational drug reduces brain lesions in highly active MS
new research suggests. After 12 weeks of treatment, MRI revealed the drug, a Bruton tyrosine kinase inhibitor, was associated with a 93% reduction in new gadolinium-enhancing lesions and an 89% reduction in new and enlarging T2 lesions, compared with placebo.
The analysis supports that tolebrutinib is as effective in this group of patients with highly active relapsing remitting MS as it is in the overall patient population, study investigator said Anthony Traboulsee, MD, professor and research chair of the MS Society of Canada at the University of British Columbia, Vancouver.
“What is additionally exciting is that this effect was seen within a relatively short period of time – within 3 months. This will be important for patients and physicians to know how soon to expect a treatment to work if they have high-risk baseline features,” he added.
The findings were presented at the 2021 annual meeting of the American Academy of Neurology.
New drug class
BTK inhibitors are a new class of oral therapies, and phase 2 trials in patients with relapsing remitting MS show they are safe and effective. BTK inhibitors modulate B lymphocytes without causing depletion, thus reducing the risk for lymphopenia or immunoglobulin depletion.
Tolebrutinib is a covalent, irreversible BTK inhibitor that penetrates the central nervous system well. In a previous randomized, double-blind, phase 2b trial, it was well tolerated and was associated with a dose-dependent reduction in new or enlarging MRI lesions. Of the four doses studied, the 60-mg dose was the most effective.
Because highly active MS is associated with a more aggressive disease course, the investigators examined tolebrutinib’s efficacy and safety in patients with highly active disease who were participants in the phase 2b trial. This subgroup analysis had been predefined in the study’s statistical analysis plan.
The investigators defined highly active disease as one relapse in the year before screening and one or more gadolinium-enhancing lesions on MRI performed within 6 months before screening, or nine or more T2 lesions at baseline, or two or more relapses in the year before screening.
Of the 130 participants enrolled in the study, 61 (47%) met criteria for highly active disease at baseline. These patients represented 44% of the placebo group (29 of 66 participants) who later crossed over to tolebrutinib treatment.
At baseline, demographics in patients with highly active disease were similar to those of the overall study population, although it was slightly younger with slightly shorter disease duration, slightly less disability, and a greater likelihood of gadolinium-enhancing lesions at baseline versus the overall study population.
The proportion of patients with highly active disease was 36% in the 5-mg group, 59% in the 15-mg group, 48% in the 30-mg group, and 44% in the 60-mg group.
The study’s primary objective was to examine the dose-response relationship after 12 weeks of treatment with tolebrutinib.
Good safety, tolerability
After 12 weeks, the mean number of new gadolinium-enhancing lesions in patients with highly active disease was 0.82 in the 5-mg group, 0.50 in the 15-mg group, 0.38 in the 30-mg group, and 0.08 in the 60-mg group. The corresponding measurements in the overall study population were 1.39 in the 5-mg group, 0.77 in the 15-mg group, 0.76 in the 30-mg group, and 0.13 in the 60-mg group.
After 12 weeks, numbers of new or enlarging T2 lesions among patients with highly active disease were 1.09 (5 mg), 0.89 (15 mg), 0.75 (30 mg) and 0.15 (60 mg). The corresponding measurements in the overall population were 1.90 (5 mg), 1.32 (15 mg) 1.30 (30 mg) and 0.23 (60 mg).
Tolebrutinib had excellent safety and tolerability in patients with highly active disease and in the overall population, said Dr. Traboulsee.
No adverse events were linked to the study drug. One patient with highly active disease who received 60 mg of tolebrutinib had transient elevated ALT levels greater than three times the upper limit of normal. This patient also previously had elevated ALT at baseline.
One serious adverse event occurred during the study. One patient was hospitalized for MS relapse. The patient had been assigned to the 60-mg dose of tolebrutinib. The patient recovered and remained on study treatment.
Two independent studies have indicated that BTK inhibition is an effective treatment approach for relapsing remitting MS. The main advantage of tolebrutinib is its ability to penetrate the CNS.
“Most, if not all, MS therapies mostly affect the peripheral immune system, preventing autoreactive lymphocytes crossing the blood-brain barrier and causing damage,” said Dr. Traboulsee.
Therapies that enter the CNS can target abnormal immune cells, including microglia that are believed to promote disease progression. “If this is an important target, then we now have a highly CNS-penetrant drug that could potentially change the course of progression,” said Dr. Traboulsee.
Serum biomarkers and advanced imaging data collected during the phase 2 trial could help clarify the mechanisms of disease progression and the effects of tolebrutinib, he added. “Ultimately though, it is the clinical outcomes in the phase 3 programs that are essential to know where to place tolebrutinib in the future care of relapsing and progressive forms of MS.”
Not an unmet need
Commenting on the findings, Joseph R. Berger, MD, professor of neurology and associate chief of the MS division at the University of Pennsylvania, Philadelphia, said there are several available treatments that effectively suppress clinical and radiologic evidence of acute inflammation in relapsing remitting MS.
“Any new drug that is to be added to that pharmacological armamentarium should have distinct advantages over what is currently available. Treating relapsing remitting MS is not, in my opinion, an unmet need in MS; treating progressive disease is,” he said.
Dr. Berger said that tolebrutinib appears to be better than placebo in suppressing disease activity, particularly at higher doses. “However, the study is small – only 61 patients,” noted Dr. Berger, who was not involved in the study.
In addition, disease activity was assessed after 4 weeks with placebo and at 12 weeks with tolebrutinib treatment.
“As there is a regression to the mean with respect to disease activity, the interpretation of the apparent response to tolebrutinib needs to be tempered with that in mind,” said Dr. Berger.
Evaluating how tolebrutinib compares with other BTK inhibitors will require a head-to-head trial. “I’d be more interested in whether the drug has an effect on progressive disease,” Dr. Berger concluded.
The study was supported by Sanofi Genzyme, which is developing tolebrutinib. Dr. Traboulsee has received research grant support, honoraria for consulting, and honoraria for participating in a speakers’ bureau from Sanofi Genzyme. Dr. Berger disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests. After 12 weeks of treatment, MRI revealed the drug, a Bruton tyrosine kinase inhibitor, was associated with a 93% reduction in new gadolinium-enhancing lesions and an 89% reduction in new and enlarging T2 lesions, compared with placebo.
The analysis supports that tolebrutinib is as effective in this group of patients with highly active relapsing remitting MS as it is in the overall patient population, study investigator said Anthony Traboulsee, MD, professor and research chair of the MS Society of Canada at the University of British Columbia, Vancouver.
“What is additionally exciting is that this effect was seen within a relatively short period of time – within 3 months. This will be important for patients and physicians to know how soon to expect a treatment to work if they have high-risk baseline features,” he added.
The findings were presented at the 2021 annual meeting of the American Academy of Neurology.
New drug class
BTK inhibitors are a new class of oral therapies, and phase 2 trials in patients with relapsing remitting MS show they are safe and effective. BTK inhibitors modulate B lymphocytes without causing depletion, thus reducing the risk for lymphopenia or immunoglobulin depletion.
Tolebrutinib is a covalent, irreversible BTK inhibitor that penetrates the central nervous system well. In a previous randomized, double-blind, phase 2b trial, it was well tolerated and was associated with a dose-dependent reduction in new or enlarging MRI lesions. Of the four doses studied, the 60-mg dose was the most effective.
Because highly active MS is associated with a more aggressive disease course, the investigators examined tolebrutinib’s efficacy and safety in patients with highly active disease who were participants in the phase 2b trial. This subgroup analysis had been predefined in the study’s statistical analysis plan.
The investigators defined highly active disease as one relapse in the year before screening and one or more gadolinium-enhancing lesions on MRI performed within 6 months before screening, or nine or more T2 lesions at baseline, or two or more relapses in the year before screening.
Of the 130 participants enrolled in the study, 61 (47%) met criteria for highly active disease at baseline. These patients represented 44% of the placebo group (29 of 66 participants) who later crossed over to tolebrutinib treatment.
At baseline, demographics in patients with highly active disease were similar to those of the overall study population, although it was slightly younger with slightly shorter disease duration, slightly less disability, and a greater likelihood of gadolinium-enhancing lesions at baseline versus the overall study population.
The proportion of patients with highly active disease was 36% in the 5-mg group, 59% in the 15-mg group, 48% in the 30-mg group, and 44% in the 60-mg group.
The study’s primary objective was to examine the dose-response relationship after 12 weeks of treatment with tolebrutinib.
Good safety, tolerability
After 12 weeks, the mean number of new gadolinium-enhancing lesions in patients with highly active disease was 0.82 in the 5-mg group, 0.50 in the 15-mg group, 0.38 in the 30-mg group, and 0.08 in the 60-mg group. The corresponding measurements in the overall study population were 1.39 in the 5-mg group, 0.77 in the 15-mg group, 0.76 in the 30-mg group, and 0.13 in the 60-mg group.
After 12 weeks, numbers of new or enlarging T2 lesions among patients with highly active disease were 1.09 (5 mg), 0.89 (15 mg), 0.75 (30 mg) and 0.15 (60 mg). The corresponding measurements in the overall population were 1.90 (5 mg), 1.32 (15 mg) 1.30 (30 mg) and 0.23 (60 mg).
Tolebrutinib had excellent safety and tolerability in patients with highly active disease and in the overall population, said Dr. Traboulsee.
No adverse events were linked to the study drug. One patient with highly active disease who received 60 mg of tolebrutinib had transient elevated ALT levels greater than three times the upper limit of normal. This patient also previously had elevated ALT at baseline.
One serious adverse event occurred during the study. One patient was hospitalized for MS relapse. The patient had been assigned to the 60-mg dose of tolebrutinib. The patient recovered and remained on study treatment.
Two independent studies have indicated that BTK inhibition is an effective treatment approach for relapsing remitting MS. The main advantage of tolebrutinib is its ability to penetrate the CNS.
“Most, if not all, MS therapies mostly affect the peripheral immune system, preventing autoreactive lymphocytes crossing the blood-brain barrier and causing damage,” said Dr. Traboulsee.
Therapies that enter the CNS can target abnormal immune cells, including microglia that are believed to promote disease progression. “If this is an important target, then we now have a highly CNS-penetrant drug that could potentially change the course of progression,” said Dr. Traboulsee.
Serum biomarkers and advanced imaging data collected during the phase 2 trial could help clarify the mechanisms of disease progression and the effects of tolebrutinib, he added. “Ultimately though, it is the clinical outcomes in the phase 3 programs that are essential to know where to place tolebrutinib in the future care of relapsing and progressive forms of MS.”
Not an unmet need
Commenting on the findings, Joseph R. Berger, MD, professor of neurology and associate chief of the MS division at the University of Pennsylvania, Philadelphia, said there are several available treatments that effectively suppress clinical and radiologic evidence of acute inflammation in relapsing remitting MS.
“Any new drug that is to be added to that pharmacological armamentarium should have distinct advantages over what is currently available. Treating relapsing remitting MS is not, in my opinion, an unmet need in MS; treating progressive disease is,” he said.
Dr. Berger said that tolebrutinib appears to be better than placebo in suppressing disease activity, particularly at higher doses. “However, the study is small – only 61 patients,” noted Dr. Berger, who was not involved in the study.
In addition, disease activity was assessed after 4 weeks with placebo and at 12 weeks with tolebrutinib treatment.
“As there is a regression to the mean with respect to disease activity, the interpretation of the apparent response to tolebrutinib needs to be tempered with that in mind,” said Dr. Berger.
Evaluating how tolebrutinib compares with other BTK inhibitors will require a head-to-head trial. “I’d be more interested in whether the drug has an effect on progressive disease,” Dr. Berger concluded.
The study was supported by Sanofi Genzyme, which is developing tolebrutinib. Dr. Traboulsee has received research grant support, honoraria for consulting, and honoraria for participating in a speakers’ bureau from Sanofi Genzyme. Dr. Berger disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests. After 12 weeks of treatment, MRI revealed the drug, a Bruton tyrosine kinase inhibitor, was associated with a 93% reduction in new gadolinium-enhancing lesions and an 89% reduction in new and enlarging T2 lesions, compared with placebo.
The analysis supports that tolebrutinib is as effective in this group of patients with highly active relapsing remitting MS as it is in the overall patient population, study investigator said Anthony Traboulsee, MD, professor and research chair of the MS Society of Canada at the University of British Columbia, Vancouver.
“What is additionally exciting is that this effect was seen within a relatively short period of time – within 3 months. This will be important for patients and physicians to know how soon to expect a treatment to work if they have high-risk baseline features,” he added.
The findings were presented at the 2021 annual meeting of the American Academy of Neurology.
New drug class
BTK inhibitors are a new class of oral therapies, and phase 2 trials in patients with relapsing remitting MS show they are safe and effective. BTK inhibitors modulate B lymphocytes without causing depletion, thus reducing the risk for lymphopenia or immunoglobulin depletion.
Tolebrutinib is a covalent, irreversible BTK inhibitor that penetrates the central nervous system well. In a previous randomized, double-blind, phase 2b trial, it was well tolerated and was associated with a dose-dependent reduction in new or enlarging MRI lesions. Of the four doses studied, the 60-mg dose was the most effective.
Because highly active MS is associated with a more aggressive disease course, the investigators examined tolebrutinib’s efficacy and safety in patients with highly active disease who were participants in the phase 2b trial. This subgroup analysis had been predefined in the study’s statistical analysis plan.
The investigators defined highly active disease as one relapse in the year before screening and one or more gadolinium-enhancing lesions on MRI performed within 6 months before screening, or nine or more T2 lesions at baseline, or two or more relapses in the year before screening.
Of the 130 participants enrolled in the study, 61 (47%) met criteria for highly active disease at baseline. These patients represented 44% of the placebo group (29 of 66 participants) who later crossed over to tolebrutinib treatment.
At baseline, demographics in patients with highly active disease were similar to those of the overall study population, although it was slightly younger with slightly shorter disease duration, slightly less disability, and a greater likelihood of gadolinium-enhancing lesions at baseline versus the overall study population.
The proportion of patients with highly active disease was 36% in the 5-mg group, 59% in the 15-mg group, 48% in the 30-mg group, and 44% in the 60-mg group.
The study’s primary objective was to examine the dose-response relationship after 12 weeks of treatment with tolebrutinib.
Good safety, tolerability
After 12 weeks, the mean number of new gadolinium-enhancing lesions in patients with highly active disease was 0.82 in the 5-mg group, 0.50 in the 15-mg group, 0.38 in the 30-mg group, and 0.08 in the 60-mg group. The corresponding measurements in the overall study population were 1.39 in the 5-mg group, 0.77 in the 15-mg group, 0.76 in the 30-mg group, and 0.13 in the 60-mg group.
After 12 weeks, numbers of new or enlarging T2 lesions among patients with highly active disease were 1.09 (5 mg), 0.89 (15 mg), 0.75 (30 mg) and 0.15 (60 mg). The corresponding measurements in the overall population were 1.90 (5 mg), 1.32 (15 mg) 1.30 (30 mg) and 0.23 (60 mg).
Tolebrutinib had excellent safety and tolerability in patients with highly active disease and in the overall population, said Dr. Traboulsee.
No adverse events were linked to the study drug. One patient with highly active disease who received 60 mg of tolebrutinib had transient elevated ALT levels greater than three times the upper limit of normal. This patient also previously had elevated ALT at baseline.
One serious adverse event occurred during the study. One patient was hospitalized for MS relapse. The patient had been assigned to the 60-mg dose of tolebrutinib. The patient recovered and remained on study treatment.
Two independent studies have indicated that BTK inhibition is an effective treatment approach for relapsing remitting MS. The main advantage of tolebrutinib is its ability to penetrate the CNS.
“Most, if not all, MS therapies mostly affect the peripheral immune system, preventing autoreactive lymphocytes crossing the blood-brain barrier and causing damage,” said Dr. Traboulsee.
Therapies that enter the CNS can target abnormal immune cells, including microglia that are believed to promote disease progression. “If this is an important target, then we now have a highly CNS-penetrant drug that could potentially change the course of progression,” said Dr. Traboulsee.
Serum biomarkers and advanced imaging data collected during the phase 2 trial could help clarify the mechanisms of disease progression and the effects of tolebrutinib, he added. “Ultimately though, it is the clinical outcomes in the phase 3 programs that are essential to know where to place tolebrutinib in the future care of relapsing and progressive forms of MS.”
Not an unmet need
Commenting on the findings, Joseph R. Berger, MD, professor of neurology and associate chief of the MS division at the University of Pennsylvania, Philadelphia, said there are several available treatments that effectively suppress clinical and radiologic evidence of acute inflammation in relapsing remitting MS.
“Any new drug that is to be added to that pharmacological armamentarium should have distinct advantages over what is currently available. Treating relapsing remitting MS is not, in my opinion, an unmet need in MS; treating progressive disease is,” he said.
Dr. Berger said that tolebrutinib appears to be better than placebo in suppressing disease activity, particularly at higher doses. “However, the study is small – only 61 patients,” noted Dr. Berger, who was not involved in the study.
In addition, disease activity was assessed after 4 weeks with placebo and at 12 weeks with tolebrutinib treatment.
“As there is a regression to the mean with respect to disease activity, the interpretation of the apparent response to tolebrutinib needs to be tempered with that in mind,” said Dr. Berger.
Evaluating how tolebrutinib compares with other BTK inhibitors will require a head-to-head trial. “I’d be more interested in whether the drug has an effect on progressive disease,” Dr. Berger concluded.
The study was supported by Sanofi Genzyme, which is developing tolebrutinib. Dr. Traboulsee has received research grant support, honoraria for consulting, and honoraria for participating in a speakers’ bureau from Sanofi Genzyme. Dr. Berger disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAN 2021
Doctors more likely to prescribe opioids to COVID ‘long-haulers,’ raising addiction fears
COVID-19 survivors are at risk from a possible second pandemic, this time of opioid addiction, given the high rate of painkillers being prescribed to these patients, health experts say.
A new study in Nature found alarmingly high rates of opioid use among COVID survivors with lingering symptoms at Veterans Affairs facilities. About 10% of COVID survivors develop “long COVID,” struggling with often disabling health problems even 6 months or longer after a diagnosis.
For every 1,000 long-COVID patients, known as “long-haulers,” who were treated at a VA facility, doctors wrote nine more prescriptions for opioids than they otherwise would have, along with 22 additional prescriptions for benzodiazepines, which include Xanax and other addictive pills used to treat anxiety.
Although previous studies have found many COVID survivors experience persistent health problems, the new article is the first to show they’re using more addictive medications, said Ziyad Al-Aly, MD, the paper’s lead author.
He’s concerned that even an apparently small increase in the inappropriate use of addictive pain pills will lead to a resurgence of the prescription opioid crisis, given the large number of COVID survivors. More than 3 million of the 31 million Americans infected with COVID develop long-term symptoms, which can include fatigue, shortness of breath, depression, anxiety, and memory problems known as “brain fog.”
The new study also found many patients have significant muscle and bone pain.
The frequent use of opioids was surprising, given concerns about their potential for addiction, said Dr. Al-Aly, chief of research and education service at the VA St. Louis Health Care System.
“Physicians now are supposed to shy away from prescribing opioids,” said Dr. Al-Aly, who studied more than 73,000 patients in the VA system. When Dr. Al-Aly saw the number of opioids prescriptions, he said, he thought to himself: “Is this really happening all over again?”
Doctors need to act now, before “it’s too late to do something,” Dr. Al-Aly said. “We must act now and ensure that people are getting the care they need. We do not want this to balloon into a suicide crisis or another opioid epidemic.”
As more doctors became aware of their addictive potential, new opioid prescriptions fell, by more than half since 2012. But said Andrew Kolodny, MD, medical director of opioid policy research at Brandeis University, Waltham, Mass.
Some patients who became addicted to prescription painkillers switched to heroin, either because it was cheaper or because they could no longer obtain opioids from their doctors. Overdose deaths surged in recent years as drug dealers began spiking heroin with a powerful synthetic opioid called fentanyl.
More than 88,000 Americans died from overdoses during the 12 months ending in August 2020, according to the Centers for Disease Control and Prevention. Health experts now advise doctors to avoid prescribing opioids for long periods.
The new study “suggests to me that many clinicians still don’t get it,” Dr. Kolodny said. “Many clinicians are under the false impression that opioids are appropriate for chronic pain patients.”
Hospitalized COVID patients often receive a lot of medication to control pain and anxiety, especially in ICUs, said Greg Martin, MD, president of the Society of Critical Care Medicine. Patients placed on ventilators, for example, are often sedated to make them more comfortable.
Martin said he’s concerned by the study’s findings, which suggest patients are unnecessarily continuing medications after leaving the hospital.
“I worry that COVID-19 patients, especially those who are severely and critically ill, receive a lot of medications during the hospitalization, and because they have persistent symptoms, the medications are continued after hospital discharge,” Dr. Martin said.
While some COVID patients are experiencing muscle and bone pain for the first time, others say the illness has intensified their preexisting pain.
Rachael Sunshine Burnett has suffered from chronic pain in her back and feet for 20 years, ever since an accident at a warehouse where she once worked. But Ms. Burnett, who first was diagnosed with COVID in April 2020, said the pain soon became 10 times worse and spread to the area between her shoulders and spine. Although she was already taking long-acting OxyContin twice a day, her doctor prescribed an additional opioid called oxycodone, which relieves pain immediately. She was reinfected with COVID in December.
“It’s been a horrible, horrible year,” said Ms. Burnett, 43, of Coxsackie, N.Y.
Doctors should recognize that pain can be a part of long COVID, Dr. Martin said. “We need to find the proper nonnarcotic treatment for it, just like we do with other forms of chronic pain,” he said.
The CDC recommends a number of alternatives to opioids – from physical therapy to biofeedback, over-the-counter anti-inflammatories, antidepressants, and antiseizure drugs that also relieve nerve pain.
The country also needs an overall strategy to cope with the wave of post-COVID complications, Dr. Al-Aly said.
“It’s better to be prepared than to be caught off guard years from now, when doctors realize: ‘Oh, we have a resurgence in opioids,’ ” Dr. Al-Aly said.
Dr. Al-Aly noted that his study may not capture the full complexity of post-COVID patient needs. Although women make up the majority of long-COVID patients in most studies, most patients in the VA system are men.
The study of VA patients makes it “abundantly clear that we are not prepared to meet the needs of 3 million Americans with long COVID,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute in San Diego. “We desperately need an intervention that will effectively treat these individuals.”
Dr. Al-Aly said COVID survivors may need care for years.
“That’s going to be a huge, significant burden on the health care system,” Dr. Al-Aly said. “Long COVID will reverberate in the health system for years or even decades to come.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
COVID-19 survivors are at risk from a possible second pandemic, this time of opioid addiction, given the high rate of painkillers being prescribed to these patients, health experts say.
A new study in Nature found alarmingly high rates of opioid use among COVID survivors with lingering symptoms at Veterans Affairs facilities. About 10% of COVID survivors develop “long COVID,” struggling with often disabling health problems even 6 months or longer after a diagnosis.
For every 1,000 long-COVID patients, known as “long-haulers,” who were treated at a VA facility, doctors wrote nine more prescriptions for opioids than they otherwise would have, along with 22 additional prescriptions for benzodiazepines, which include Xanax and other addictive pills used to treat anxiety.
Although previous studies have found many COVID survivors experience persistent health problems, the new article is the first to show they’re using more addictive medications, said Ziyad Al-Aly, MD, the paper’s lead author.
He’s concerned that even an apparently small increase in the inappropriate use of addictive pain pills will lead to a resurgence of the prescription opioid crisis, given the large number of COVID survivors. More than 3 million of the 31 million Americans infected with COVID develop long-term symptoms, which can include fatigue, shortness of breath, depression, anxiety, and memory problems known as “brain fog.”
The new study also found many patients have significant muscle and bone pain.
The frequent use of opioids was surprising, given concerns about their potential for addiction, said Dr. Al-Aly, chief of research and education service at the VA St. Louis Health Care System.
“Physicians now are supposed to shy away from prescribing opioids,” said Dr. Al-Aly, who studied more than 73,000 patients in the VA system. When Dr. Al-Aly saw the number of opioids prescriptions, he said, he thought to himself: “Is this really happening all over again?”
Doctors need to act now, before “it’s too late to do something,” Dr. Al-Aly said. “We must act now and ensure that people are getting the care they need. We do not want this to balloon into a suicide crisis or another opioid epidemic.”
As more doctors became aware of their addictive potential, new opioid prescriptions fell, by more than half since 2012. But said Andrew Kolodny, MD, medical director of opioid policy research at Brandeis University, Waltham, Mass.
Some patients who became addicted to prescription painkillers switched to heroin, either because it was cheaper or because they could no longer obtain opioids from their doctors. Overdose deaths surged in recent years as drug dealers began spiking heroin with a powerful synthetic opioid called fentanyl.
More than 88,000 Americans died from overdoses during the 12 months ending in August 2020, according to the Centers for Disease Control and Prevention. Health experts now advise doctors to avoid prescribing opioids for long periods.
The new study “suggests to me that many clinicians still don’t get it,” Dr. Kolodny said. “Many clinicians are under the false impression that opioids are appropriate for chronic pain patients.”
Hospitalized COVID patients often receive a lot of medication to control pain and anxiety, especially in ICUs, said Greg Martin, MD, president of the Society of Critical Care Medicine. Patients placed on ventilators, for example, are often sedated to make them more comfortable.
Martin said he’s concerned by the study’s findings, which suggest patients are unnecessarily continuing medications after leaving the hospital.
“I worry that COVID-19 patients, especially those who are severely and critically ill, receive a lot of medications during the hospitalization, and because they have persistent symptoms, the medications are continued after hospital discharge,” Dr. Martin said.
While some COVID patients are experiencing muscle and bone pain for the first time, others say the illness has intensified their preexisting pain.
Rachael Sunshine Burnett has suffered from chronic pain in her back and feet for 20 years, ever since an accident at a warehouse where she once worked. But Ms. Burnett, who first was diagnosed with COVID in April 2020, said the pain soon became 10 times worse and spread to the area between her shoulders and spine. Although she was already taking long-acting OxyContin twice a day, her doctor prescribed an additional opioid called oxycodone, which relieves pain immediately. She was reinfected with COVID in December.
“It’s been a horrible, horrible year,” said Ms. Burnett, 43, of Coxsackie, N.Y.
Doctors should recognize that pain can be a part of long COVID, Dr. Martin said. “We need to find the proper nonnarcotic treatment for it, just like we do with other forms of chronic pain,” he said.
The CDC recommends a number of alternatives to opioids – from physical therapy to biofeedback, over-the-counter anti-inflammatories, antidepressants, and antiseizure drugs that also relieve nerve pain.
The country also needs an overall strategy to cope with the wave of post-COVID complications, Dr. Al-Aly said.
“It’s better to be prepared than to be caught off guard years from now, when doctors realize: ‘Oh, we have a resurgence in opioids,’ ” Dr. Al-Aly said.
Dr. Al-Aly noted that his study may not capture the full complexity of post-COVID patient needs. Although women make up the majority of long-COVID patients in most studies, most patients in the VA system are men.
The study of VA patients makes it “abundantly clear that we are not prepared to meet the needs of 3 million Americans with long COVID,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute in San Diego. “We desperately need an intervention that will effectively treat these individuals.”
Dr. Al-Aly said COVID survivors may need care for years.
“That’s going to be a huge, significant burden on the health care system,” Dr. Al-Aly said. “Long COVID will reverberate in the health system for years or even decades to come.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
COVID-19 survivors are at risk from a possible second pandemic, this time of opioid addiction, given the high rate of painkillers being prescribed to these patients, health experts say.
A new study in Nature found alarmingly high rates of opioid use among COVID survivors with lingering symptoms at Veterans Affairs facilities. About 10% of COVID survivors develop “long COVID,” struggling with often disabling health problems even 6 months or longer after a diagnosis.
For every 1,000 long-COVID patients, known as “long-haulers,” who were treated at a VA facility, doctors wrote nine more prescriptions for opioids than they otherwise would have, along with 22 additional prescriptions for benzodiazepines, which include Xanax and other addictive pills used to treat anxiety.
Although previous studies have found many COVID survivors experience persistent health problems, the new article is the first to show they’re using more addictive medications, said Ziyad Al-Aly, MD, the paper’s lead author.
He’s concerned that even an apparently small increase in the inappropriate use of addictive pain pills will lead to a resurgence of the prescription opioid crisis, given the large number of COVID survivors. More than 3 million of the 31 million Americans infected with COVID develop long-term symptoms, which can include fatigue, shortness of breath, depression, anxiety, and memory problems known as “brain fog.”
The new study also found many patients have significant muscle and bone pain.
The frequent use of opioids was surprising, given concerns about their potential for addiction, said Dr. Al-Aly, chief of research and education service at the VA St. Louis Health Care System.
“Physicians now are supposed to shy away from prescribing opioids,” said Dr. Al-Aly, who studied more than 73,000 patients in the VA system. When Dr. Al-Aly saw the number of opioids prescriptions, he said, he thought to himself: “Is this really happening all over again?”
Doctors need to act now, before “it’s too late to do something,” Dr. Al-Aly said. “We must act now and ensure that people are getting the care they need. We do not want this to balloon into a suicide crisis or another opioid epidemic.”
As more doctors became aware of their addictive potential, new opioid prescriptions fell, by more than half since 2012. But said Andrew Kolodny, MD, medical director of opioid policy research at Brandeis University, Waltham, Mass.
Some patients who became addicted to prescription painkillers switched to heroin, either because it was cheaper or because they could no longer obtain opioids from their doctors. Overdose deaths surged in recent years as drug dealers began spiking heroin with a powerful synthetic opioid called fentanyl.
More than 88,000 Americans died from overdoses during the 12 months ending in August 2020, according to the Centers for Disease Control and Prevention. Health experts now advise doctors to avoid prescribing opioids for long periods.
The new study “suggests to me that many clinicians still don’t get it,” Dr. Kolodny said. “Many clinicians are under the false impression that opioids are appropriate for chronic pain patients.”
Hospitalized COVID patients often receive a lot of medication to control pain and anxiety, especially in ICUs, said Greg Martin, MD, president of the Society of Critical Care Medicine. Patients placed on ventilators, for example, are often sedated to make them more comfortable.
Martin said he’s concerned by the study’s findings, which suggest patients are unnecessarily continuing medications after leaving the hospital.
“I worry that COVID-19 patients, especially those who are severely and critically ill, receive a lot of medications during the hospitalization, and because they have persistent symptoms, the medications are continued after hospital discharge,” Dr. Martin said.
While some COVID patients are experiencing muscle and bone pain for the first time, others say the illness has intensified their preexisting pain.
Rachael Sunshine Burnett has suffered from chronic pain in her back and feet for 20 years, ever since an accident at a warehouse where she once worked. But Ms. Burnett, who first was diagnosed with COVID in April 2020, said the pain soon became 10 times worse and spread to the area between her shoulders and spine. Although she was already taking long-acting OxyContin twice a day, her doctor prescribed an additional opioid called oxycodone, which relieves pain immediately. She was reinfected with COVID in December.
“It’s been a horrible, horrible year,” said Ms. Burnett, 43, of Coxsackie, N.Y.
Doctors should recognize that pain can be a part of long COVID, Dr. Martin said. “We need to find the proper nonnarcotic treatment for it, just like we do with other forms of chronic pain,” he said.
The CDC recommends a number of alternatives to opioids – from physical therapy to biofeedback, over-the-counter anti-inflammatories, antidepressants, and antiseizure drugs that also relieve nerve pain.
The country also needs an overall strategy to cope with the wave of post-COVID complications, Dr. Al-Aly said.
“It’s better to be prepared than to be caught off guard years from now, when doctors realize: ‘Oh, we have a resurgence in opioids,’ ” Dr. Al-Aly said.
Dr. Al-Aly noted that his study may not capture the full complexity of post-COVID patient needs. Although women make up the majority of long-COVID patients in most studies, most patients in the VA system are men.
The study of VA patients makes it “abundantly clear that we are not prepared to meet the needs of 3 million Americans with long COVID,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute in San Diego. “We desperately need an intervention that will effectively treat these individuals.”
Dr. Al-Aly said COVID survivors may need care for years.
“That’s going to be a huge, significant burden on the health care system,” Dr. Al-Aly said. “Long COVID will reverberate in the health system for years or even decades to come.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
Rituximab benefits seen in neuropsychiatric lupus
Patients with neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) seem to benefit from rituximab (Rituxan) therapy, according to data from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR).
Indeed, the percentage of patients with active disease, as scored by the BILAG-2004 index or SLEDAI-2K (SLE Disease Activity Index 2000), fell significantly (P < .0001) when comparing pre- and postrituximab treatment scores. There was also a reduction in the dose of oral steroids used.
Interestingly, the use of concomitant cyclophosphamide might enhance the level of improvement seen in some patients, Trixy David, MBBS, reported during an abstract session at the British Society for Rheumatology annual conference.
“Larger-scale studies are warranted to establish the effectiveness of rituximab alone, or in combination with cyclophosphamide, in the treatment neuropsychiatric lupus,” said Dr. David, a clinical research fellow at the University of Manchester (England) and specialist registrar in rheumatology at the Manchester University National Health Service Foundation Trust.
Neil Basu, MBChB, PhD, who chaired the virtual session, called the findings “enlightening” and “descriptive.”
The study “provides some interesting data, which should be tested in a robust, randomized clinical trial,” he agreed, and not that clinicians should now start using rituximab for their NPSLE cases.
Dr. Basu, who is a clinical senior lecturer in rheumatology and honorary consultant rheumatologist at the Institute of Infection, Immunity and Inflammation at the University of Glasgow, added: “It is really important that we do these studies to help support a rationale for such a trial, which are obviously very expensive and require strong evidence before we go down that track. I think these data have really been quite enlightening in that respect.”
Rationale for rituximab in neuropsychiatric lupus
Managing patients with NPSLE remains an area of substantial unmet need. According to a recent review in Rheumatology, “there is a dearth of controlled clinical trials to guide management” and “therapeutic options include symptomatic, antithrombotic, and immunosuppressive agents that are supported by observational cohort studies.”
Despite being seen in at least half of all patients with SLE, neuropsychiatric disease “is not very well studied in patients with lupus, as a lot of large-scale trials tend to exclude patients with active neurological disease,” Dr. David said.
Although it is unclear why neuropsychiatric disease occurs in SLE, it could be “as a result of vascular injury or disruption of the blood brain barrier, thereby allowing the passive diffusion of autoantibodies and cytokines across through the cerebral spinal fluid, thereby generating a proinflammatory response,” Dr. David suggested.
“We know B cells are involved in the pathogenesis of lupus, and rituximab is a chimeric monoclonal antibody that selectively targets CD20-positive B cells and mediates transient B-cell depletion,” she said. Notably, there have been some small studies suggesting that rituximab may be effective in neuropsychiatric lupus, and it is currently widely used to treat refractory lupus in the United Kingdom.
About the BILAG-BR and results
“Our aim was to describe the baseline characteristics and short-term effectiveness of rituximab in patients treated for neuropsychiatric lupus within the BILAG-BR,” Dr. David explained.
Started in 2009, the BILAG-BR now contains information on more than 1,400 individuals with SLE who have been recruited at 62 centers in the United Kingdom. Its purpose is to evaluate the long-term safety and effectiveness of biologic drugs versus standard immunosuppressive therapy such as azathioprine, mycophenolate mofetil, cyclophosphamide, and cyclosporine. To date, 1,229 patients have been treated with biologics, of whom 1,056 have received rituximab.
A total of 74 rituximab-treated patients were identified as having active neuropsychiatric disease, making this “the largest prospective observational cohort to date, to our knowledge,” Dr. David said.
The median age of patients was 45.5 years, the majority was female (82%) and White (74%). The median disease duration was 11.5 years.
A total of 96% had multiple organ involvement and not just neuropsychiatric disease, and 91% were positive for antineutrophil antibodies.
The top six neuropsychiatric manifestations were cognitive dysfunction and lupus headache (both affecting 27.5% of patients); acute confessional state or mononeuropathy (each seen in 10% of patients); and seizure disorder and polyneuropathy, seen in a respective 8.6% and 8.7% of patients. These findings are in line with a 2011 meta-analysis, Dr. David pointed out.
BILAG-2004 scores before and after rituximab treatment were available for 50 patients. The number of patients with a BILAG A score dropped from 24 (48%) at baseline to 7 (14%) after treatment with rituximab, and the number with a BILAG B score declined from 26 (52%) at baseline to 4 (8%) after rituximab (both P < .0001).
There was also a reduction following rituximab treatment in the percentage of patients categorized as having mainly central nervous system disease (70% vs. 11%), peripheral nervous system disease (19% vs. 6%), or both (11% vs. 8%).
Total SLEDAI-2K scores were also reduced following rituximab treatment, from a median of 12 at baseline to 2 (P < .0001).
Pre- and postrituximab oral prednisolone doses were a median of 15 mg and 10 mg (P = .009).
Limitations
“Our data are from a real-world setting of patients who had active neuropsychiatric disease and were treated with rituximab,” Dr. David said. There are of course many limitations that go hand in hand with observational studies.
“There was the issue of missing data,” Dr. David said. It was difficult or not possible to determine what doses of steroids patients were taking after rituximab therapy, particularly in terms of intravenous steroids, and what doses of any other concomitant disease-modifying therapy might have been around the time that patients initiated or stopped rituximab treatment.
“These could have acted as potential confounders,” she acknowledged.
Dr. Basu noted: “My major haziness from it is the uncertainty of knowing why these patients improved. Yes, they had rituximab, but I’m sure also that they probably received high doses of steroids if they had quite severe CNS lupus which was categorized as a BILAG-A or a B.”
Patients may also be given methylprednisolone when clinicians are really concerned, he continued, and “as was quite clearly pointed out,” there was quite a lot of missing data from a steroid perspective.
Dr. David and coinvestigators reported having no conflicts of interest. The BILAG-BR is supported by funding from Lupus UK, GlaxoSmithKline, and Roche. Dr. Basu did not state having any disclosures.
Patients with neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) seem to benefit from rituximab (Rituxan) therapy, according to data from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR).
Indeed, the percentage of patients with active disease, as scored by the BILAG-2004 index or SLEDAI-2K (SLE Disease Activity Index 2000), fell significantly (P < .0001) when comparing pre- and postrituximab treatment scores. There was also a reduction in the dose of oral steroids used.
Interestingly, the use of concomitant cyclophosphamide might enhance the level of improvement seen in some patients, Trixy David, MBBS, reported during an abstract session at the British Society for Rheumatology annual conference.
“Larger-scale studies are warranted to establish the effectiveness of rituximab alone, or in combination with cyclophosphamide, in the treatment neuropsychiatric lupus,” said Dr. David, a clinical research fellow at the University of Manchester (England) and specialist registrar in rheumatology at the Manchester University National Health Service Foundation Trust.
Neil Basu, MBChB, PhD, who chaired the virtual session, called the findings “enlightening” and “descriptive.”
The study “provides some interesting data, which should be tested in a robust, randomized clinical trial,” he agreed, and not that clinicians should now start using rituximab for their NPSLE cases.
Dr. Basu, who is a clinical senior lecturer in rheumatology and honorary consultant rheumatologist at the Institute of Infection, Immunity and Inflammation at the University of Glasgow, added: “It is really important that we do these studies to help support a rationale for such a trial, which are obviously very expensive and require strong evidence before we go down that track. I think these data have really been quite enlightening in that respect.”
Rationale for rituximab in neuropsychiatric lupus
Managing patients with NPSLE remains an area of substantial unmet need. According to a recent review in Rheumatology, “there is a dearth of controlled clinical trials to guide management” and “therapeutic options include symptomatic, antithrombotic, and immunosuppressive agents that are supported by observational cohort studies.”
Despite being seen in at least half of all patients with SLE, neuropsychiatric disease “is not very well studied in patients with lupus, as a lot of large-scale trials tend to exclude patients with active neurological disease,” Dr. David said.
Although it is unclear why neuropsychiatric disease occurs in SLE, it could be “as a result of vascular injury or disruption of the blood brain barrier, thereby allowing the passive diffusion of autoantibodies and cytokines across through the cerebral spinal fluid, thereby generating a proinflammatory response,” Dr. David suggested.
“We know B cells are involved in the pathogenesis of lupus, and rituximab is a chimeric monoclonal antibody that selectively targets CD20-positive B cells and mediates transient B-cell depletion,” she said. Notably, there have been some small studies suggesting that rituximab may be effective in neuropsychiatric lupus, and it is currently widely used to treat refractory lupus in the United Kingdom.
About the BILAG-BR and results
“Our aim was to describe the baseline characteristics and short-term effectiveness of rituximab in patients treated for neuropsychiatric lupus within the BILAG-BR,” Dr. David explained.
Started in 2009, the BILAG-BR now contains information on more than 1,400 individuals with SLE who have been recruited at 62 centers in the United Kingdom. Its purpose is to evaluate the long-term safety and effectiveness of biologic drugs versus standard immunosuppressive therapy such as azathioprine, mycophenolate mofetil, cyclophosphamide, and cyclosporine. To date, 1,229 patients have been treated with biologics, of whom 1,056 have received rituximab.
A total of 74 rituximab-treated patients were identified as having active neuropsychiatric disease, making this “the largest prospective observational cohort to date, to our knowledge,” Dr. David said.
The median age of patients was 45.5 years, the majority was female (82%) and White (74%). The median disease duration was 11.5 years.
A total of 96% had multiple organ involvement and not just neuropsychiatric disease, and 91% were positive for antineutrophil antibodies.
The top six neuropsychiatric manifestations were cognitive dysfunction and lupus headache (both affecting 27.5% of patients); acute confessional state or mononeuropathy (each seen in 10% of patients); and seizure disorder and polyneuropathy, seen in a respective 8.6% and 8.7% of patients. These findings are in line with a 2011 meta-analysis, Dr. David pointed out.
BILAG-2004 scores before and after rituximab treatment were available for 50 patients. The number of patients with a BILAG A score dropped from 24 (48%) at baseline to 7 (14%) after treatment with rituximab, and the number with a BILAG B score declined from 26 (52%) at baseline to 4 (8%) after rituximab (both P < .0001).
There was also a reduction following rituximab treatment in the percentage of patients categorized as having mainly central nervous system disease (70% vs. 11%), peripheral nervous system disease (19% vs. 6%), or both (11% vs. 8%).
Total SLEDAI-2K scores were also reduced following rituximab treatment, from a median of 12 at baseline to 2 (P < .0001).
Pre- and postrituximab oral prednisolone doses were a median of 15 mg and 10 mg (P = .009).
Limitations
“Our data are from a real-world setting of patients who had active neuropsychiatric disease and were treated with rituximab,” Dr. David said. There are of course many limitations that go hand in hand with observational studies.
“There was the issue of missing data,” Dr. David said. It was difficult or not possible to determine what doses of steroids patients were taking after rituximab therapy, particularly in terms of intravenous steroids, and what doses of any other concomitant disease-modifying therapy might have been around the time that patients initiated or stopped rituximab treatment.
“These could have acted as potential confounders,” she acknowledged.
Dr. Basu noted: “My major haziness from it is the uncertainty of knowing why these patients improved. Yes, they had rituximab, but I’m sure also that they probably received high doses of steroids if they had quite severe CNS lupus which was categorized as a BILAG-A or a B.”
Patients may also be given methylprednisolone when clinicians are really concerned, he continued, and “as was quite clearly pointed out,” there was quite a lot of missing data from a steroid perspective.
Dr. David and coinvestigators reported having no conflicts of interest. The BILAG-BR is supported by funding from Lupus UK, GlaxoSmithKline, and Roche. Dr. Basu did not state having any disclosures.
Patients with neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) seem to benefit from rituximab (Rituxan) therapy, according to data from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR).
Indeed, the percentage of patients with active disease, as scored by the BILAG-2004 index or SLEDAI-2K (SLE Disease Activity Index 2000), fell significantly (P < .0001) when comparing pre- and postrituximab treatment scores. There was also a reduction in the dose of oral steroids used.
Interestingly, the use of concomitant cyclophosphamide might enhance the level of improvement seen in some patients, Trixy David, MBBS, reported during an abstract session at the British Society for Rheumatology annual conference.
“Larger-scale studies are warranted to establish the effectiveness of rituximab alone, or in combination with cyclophosphamide, in the treatment neuropsychiatric lupus,” said Dr. David, a clinical research fellow at the University of Manchester (England) and specialist registrar in rheumatology at the Manchester University National Health Service Foundation Trust.
Neil Basu, MBChB, PhD, who chaired the virtual session, called the findings “enlightening” and “descriptive.”
The study “provides some interesting data, which should be tested in a robust, randomized clinical trial,” he agreed, and not that clinicians should now start using rituximab for their NPSLE cases.
Dr. Basu, who is a clinical senior lecturer in rheumatology and honorary consultant rheumatologist at the Institute of Infection, Immunity and Inflammation at the University of Glasgow, added: “It is really important that we do these studies to help support a rationale for such a trial, which are obviously very expensive and require strong evidence before we go down that track. I think these data have really been quite enlightening in that respect.”
Rationale for rituximab in neuropsychiatric lupus
Managing patients with NPSLE remains an area of substantial unmet need. According to a recent review in Rheumatology, “there is a dearth of controlled clinical trials to guide management” and “therapeutic options include symptomatic, antithrombotic, and immunosuppressive agents that are supported by observational cohort studies.”
Despite being seen in at least half of all patients with SLE, neuropsychiatric disease “is not very well studied in patients with lupus, as a lot of large-scale trials tend to exclude patients with active neurological disease,” Dr. David said.
Although it is unclear why neuropsychiatric disease occurs in SLE, it could be “as a result of vascular injury or disruption of the blood brain barrier, thereby allowing the passive diffusion of autoantibodies and cytokines across through the cerebral spinal fluid, thereby generating a proinflammatory response,” Dr. David suggested.
“We know B cells are involved in the pathogenesis of lupus, and rituximab is a chimeric monoclonal antibody that selectively targets CD20-positive B cells and mediates transient B-cell depletion,” she said. Notably, there have been some small studies suggesting that rituximab may be effective in neuropsychiatric lupus, and it is currently widely used to treat refractory lupus in the United Kingdom.
About the BILAG-BR and results
“Our aim was to describe the baseline characteristics and short-term effectiveness of rituximab in patients treated for neuropsychiatric lupus within the BILAG-BR,” Dr. David explained.
Started in 2009, the BILAG-BR now contains information on more than 1,400 individuals with SLE who have been recruited at 62 centers in the United Kingdom. Its purpose is to evaluate the long-term safety and effectiveness of biologic drugs versus standard immunosuppressive therapy such as azathioprine, mycophenolate mofetil, cyclophosphamide, and cyclosporine. To date, 1,229 patients have been treated with biologics, of whom 1,056 have received rituximab.
A total of 74 rituximab-treated patients were identified as having active neuropsychiatric disease, making this “the largest prospective observational cohort to date, to our knowledge,” Dr. David said.
The median age of patients was 45.5 years, the majority was female (82%) and White (74%). The median disease duration was 11.5 years.
A total of 96% had multiple organ involvement and not just neuropsychiatric disease, and 91% were positive for antineutrophil antibodies.
The top six neuropsychiatric manifestations were cognitive dysfunction and lupus headache (both affecting 27.5% of patients); acute confessional state or mononeuropathy (each seen in 10% of patients); and seizure disorder and polyneuropathy, seen in a respective 8.6% and 8.7% of patients. These findings are in line with a 2011 meta-analysis, Dr. David pointed out.
BILAG-2004 scores before and after rituximab treatment were available for 50 patients. The number of patients with a BILAG A score dropped from 24 (48%) at baseline to 7 (14%) after treatment with rituximab, and the number with a BILAG B score declined from 26 (52%) at baseline to 4 (8%) after rituximab (both P < .0001).
There was also a reduction following rituximab treatment in the percentage of patients categorized as having mainly central nervous system disease (70% vs. 11%), peripheral nervous system disease (19% vs. 6%), or both (11% vs. 8%).
Total SLEDAI-2K scores were also reduced following rituximab treatment, from a median of 12 at baseline to 2 (P < .0001).
Pre- and postrituximab oral prednisolone doses were a median of 15 mg and 10 mg (P = .009).
Limitations
“Our data are from a real-world setting of patients who had active neuropsychiatric disease and were treated with rituximab,” Dr. David said. There are of course many limitations that go hand in hand with observational studies.
“There was the issue of missing data,” Dr. David said. It was difficult or not possible to determine what doses of steroids patients were taking after rituximab therapy, particularly in terms of intravenous steroids, and what doses of any other concomitant disease-modifying therapy might have been around the time that patients initiated or stopped rituximab treatment.
“These could have acted as potential confounders,” she acknowledged.
Dr. Basu noted: “My major haziness from it is the uncertainty of knowing why these patients improved. Yes, they had rituximab, but I’m sure also that they probably received high doses of steroids if they had quite severe CNS lupus which was categorized as a BILAG-A or a B.”
Patients may also be given methylprednisolone when clinicians are really concerned, he continued, and “as was quite clearly pointed out,” there was quite a lot of missing data from a steroid perspective.
Dr. David and coinvestigators reported having no conflicts of interest. The BILAG-BR is supported by funding from Lupus UK, GlaxoSmithKline, and Roche. Dr. Basu did not state having any disclosures.
FROM BSR 2021
CDC guidelines coming on long COVID
The Centers for Disease Control and Prevention is finalizing new guidelines to help clinicians diagnose and manage long COVID, or postacute sequelae of SARS-CoV-2 infection.
In a day-long congressional hearing on April 28, John Brooks, MD, a medical epidemiologist at the CDC’s division of HIV/AIDS prevention, testified that the guidelines were going through the clearance process at the agency, but would be forthcoming.
“They should be coming out very shortly,” Dr. Brooks said.
The guidelines, which were developed in collaboration with newly established long-COVID clinics and patient advocacy groups, will “illustrate how to diagnose and begin to pull together what we know about management,” of the complex condition, he said.
For many doctors and patients who are struggling to understand symptoms that persist for months after the initial viral infection, the guidelines can’t come soon enough.
National Institutes of Health Director Francis Collins, MD, PhD, who also testified at the hearing, estimated that as many as 3 million people could be left with chronic health problems after even mild COVID infections.
“I can’t overstate how serious this issue is for the health of our nation,” he said.
Dr. Collins said his estimate was based on studies showing that roughly 10% of people who get COVID could be affected by this and whose “long-term course is uncertain,” he said. So far, more than 32 million Americans are known to have been infected with the new coronavirus.
“We need to make sure we put our arms around them and bring answers and care to them,” said Rep. Anna Eshoo (D-Calif.), chairwoman of the Subcommittee on Health.
Jennifer Possick, MD, who directs the post-COVID recovery program at Yale New Haven (Conn.) Hospital, testified that the tidal wave of patients she and her colleagues were seeing was overwhelming.
“We are a well-resourced program at an academic medical center, but we are swamped by the need in our community. This year, we have seen more patients with post COVID-19 conditions in our clinic alone than we have new cases of asthma and COPD combined,” she said. “The magnitude of the challenge is daunting.”
Dr. Possick estimated that there are “over 60” clinics in the United States that have started to treat long-COVID patients, but said they are grassroots efforts and all very different from each other.
“Whoever had the resources, had the time, [and] was able to take the initiative and forge to the relationships because most of them are multidisciplinary, did so,” she said.
Patients testify
Several representatives shared moving personal stories of loved ones or staffers who remained ill months after a COVID diagnosis.
Rep. Ann Kuster, from New Hampshire, talked about her 34-year-old niece, a member of the U.S. Ski Team, who had COVID just over a year ago and “continues to struggle with everything, even the simplest activities of daily living” she said. “She has to choose between taking a shower or making dinner. I’m so proud of her for hanging in there.”
Long-COVID patients invited to testify by the subcommittee described months of disability that left them with soaring medical bills and no ability to work to pay them.
“I am now a poor, Black, disabled woman, living with long COVID,” said Chimere Smith, who said she had been a school teacher in Baltimore. “Saying it aloud makes it no more easy to accept.”
She said COVID had affected her ability to think clearly and caused debilitating fatigue, which prevented her from working. She said she lost her vision for almost 5 months because doctors misdiagnosed a cataract caused by long COVID as dry eye.
“If I did not have a loving family, I [would] be speaking to you today [from] my car, the only property I now own.”
Ms. Smith said that long-COVID clinics, which are mostly housed within academic medical centers, were not going to be accessible for all long-haulers, who are disproportionately women of color. She has started a clinic, based out of her church, to help other patients from her community.
“No one wants to hear that long COVID has decimated my life or the lives of other black women in less than a year,” Ms. Smith said. “We’ve just been waiting and hoping for compassionate doctors and politicians who would acknowledge us.”
A version of this article first appeared on Medscape.com.
The Centers for Disease Control and Prevention is finalizing new guidelines to help clinicians diagnose and manage long COVID, or postacute sequelae of SARS-CoV-2 infection.
In a day-long congressional hearing on April 28, John Brooks, MD, a medical epidemiologist at the CDC’s division of HIV/AIDS prevention, testified that the guidelines were going through the clearance process at the agency, but would be forthcoming.
“They should be coming out very shortly,” Dr. Brooks said.
The guidelines, which were developed in collaboration with newly established long-COVID clinics and patient advocacy groups, will “illustrate how to diagnose and begin to pull together what we know about management,” of the complex condition, he said.
For many doctors and patients who are struggling to understand symptoms that persist for months after the initial viral infection, the guidelines can’t come soon enough.
National Institutes of Health Director Francis Collins, MD, PhD, who also testified at the hearing, estimated that as many as 3 million people could be left with chronic health problems after even mild COVID infections.
“I can’t overstate how serious this issue is for the health of our nation,” he said.
Dr. Collins said his estimate was based on studies showing that roughly 10% of people who get COVID could be affected by this and whose “long-term course is uncertain,” he said. So far, more than 32 million Americans are known to have been infected with the new coronavirus.
“We need to make sure we put our arms around them and bring answers and care to them,” said Rep. Anna Eshoo (D-Calif.), chairwoman of the Subcommittee on Health.
Jennifer Possick, MD, who directs the post-COVID recovery program at Yale New Haven (Conn.) Hospital, testified that the tidal wave of patients she and her colleagues were seeing was overwhelming.
“We are a well-resourced program at an academic medical center, but we are swamped by the need in our community. This year, we have seen more patients with post COVID-19 conditions in our clinic alone than we have new cases of asthma and COPD combined,” she said. “The magnitude of the challenge is daunting.”
Dr. Possick estimated that there are “over 60” clinics in the United States that have started to treat long-COVID patients, but said they are grassroots efforts and all very different from each other.
“Whoever had the resources, had the time, [and] was able to take the initiative and forge to the relationships because most of them are multidisciplinary, did so,” she said.
Patients testify
Several representatives shared moving personal stories of loved ones or staffers who remained ill months after a COVID diagnosis.
Rep. Ann Kuster, from New Hampshire, talked about her 34-year-old niece, a member of the U.S. Ski Team, who had COVID just over a year ago and “continues to struggle with everything, even the simplest activities of daily living” she said. “She has to choose between taking a shower or making dinner. I’m so proud of her for hanging in there.”
Long-COVID patients invited to testify by the subcommittee described months of disability that left them with soaring medical bills and no ability to work to pay them.
“I am now a poor, Black, disabled woman, living with long COVID,” said Chimere Smith, who said she had been a school teacher in Baltimore. “Saying it aloud makes it no more easy to accept.”
She said COVID had affected her ability to think clearly and caused debilitating fatigue, which prevented her from working. She said she lost her vision for almost 5 months because doctors misdiagnosed a cataract caused by long COVID as dry eye.
“If I did not have a loving family, I [would] be speaking to you today [from] my car, the only property I now own.”
Ms. Smith said that long-COVID clinics, which are mostly housed within academic medical centers, were not going to be accessible for all long-haulers, who are disproportionately women of color. She has started a clinic, based out of her church, to help other patients from her community.
“No one wants to hear that long COVID has decimated my life or the lives of other black women in less than a year,” Ms. Smith said. “We’ve just been waiting and hoping for compassionate doctors and politicians who would acknowledge us.”
A version of this article first appeared on Medscape.com.
The Centers for Disease Control and Prevention is finalizing new guidelines to help clinicians diagnose and manage long COVID, or postacute sequelae of SARS-CoV-2 infection.
In a day-long congressional hearing on April 28, John Brooks, MD, a medical epidemiologist at the CDC’s division of HIV/AIDS prevention, testified that the guidelines were going through the clearance process at the agency, but would be forthcoming.
“They should be coming out very shortly,” Dr. Brooks said.
The guidelines, which were developed in collaboration with newly established long-COVID clinics and patient advocacy groups, will “illustrate how to diagnose and begin to pull together what we know about management,” of the complex condition, he said.
For many doctors and patients who are struggling to understand symptoms that persist for months after the initial viral infection, the guidelines can’t come soon enough.
National Institutes of Health Director Francis Collins, MD, PhD, who also testified at the hearing, estimated that as many as 3 million people could be left with chronic health problems after even mild COVID infections.
“I can’t overstate how serious this issue is for the health of our nation,” he said.
Dr. Collins said his estimate was based on studies showing that roughly 10% of people who get COVID could be affected by this and whose “long-term course is uncertain,” he said. So far, more than 32 million Americans are known to have been infected with the new coronavirus.
“We need to make sure we put our arms around them and bring answers and care to them,” said Rep. Anna Eshoo (D-Calif.), chairwoman of the Subcommittee on Health.
Jennifer Possick, MD, who directs the post-COVID recovery program at Yale New Haven (Conn.) Hospital, testified that the tidal wave of patients she and her colleagues were seeing was overwhelming.
“We are a well-resourced program at an academic medical center, but we are swamped by the need in our community. This year, we have seen more patients with post COVID-19 conditions in our clinic alone than we have new cases of asthma and COPD combined,” she said. “The magnitude of the challenge is daunting.”
Dr. Possick estimated that there are “over 60” clinics in the United States that have started to treat long-COVID patients, but said they are grassroots efforts and all very different from each other.
“Whoever had the resources, had the time, [and] was able to take the initiative and forge to the relationships because most of them are multidisciplinary, did so,” she said.
Patients testify
Several representatives shared moving personal stories of loved ones or staffers who remained ill months after a COVID diagnosis.
Rep. Ann Kuster, from New Hampshire, talked about her 34-year-old niece, a member of the U.S. Ski Team, who had COVID just over a year ago and “continues to struggle with everything, even the simplest activities of daily living” she said. “She has to choose between taking a shower or making dinner. I’m so proud of her for hanging in there.”
Long-COVID patients invited to testify by the subcommittee described months of disability that left them with soaring medical bills and no ability to work to pay them.
“I am now a poor, Black, disabled woman, living with long COVID,” said Chimere Smith, who said she had been a school teacher in Baltimore. “Saying it aloud makes it no more easy to accept.”
She said COVID had affected her ability to think clearly and caused debilitating fatigue, which prevented her from working. She said she lost her vision for almost 5 months because doctors misdiagnosed a cataract caused by long COVID as dry eye.
“If I did not have a loving family, I [would] be speaking to you today [from] my car, the only property I now own.”
Ms. Smith said that long-COVID clinics, which are mostly housed within academic medical centers, were not going to be accessible for all long-haulers, who are disproportionately women of color. She has started a clinic, based out of her church, to help other patients from her community.
“No one wants to hear that long COVID has decimated my life or the lives of other black women in less than a year,” Ms. Smith said. “We’ve just been waiting and hoping for compassionate doctors and politicians who would acknowledge us.”
A version of this article first appeared on Medscape.com.
Being overweight ups risk of severe COVID-19 in hospital
In a global meta-analysis of more than 7,000 patients who were hospitalized with COVID-19, individuals with overweight or obesity were more likely to need respiratory support but were not more likely to die in the hospital, compared to individuals of normal weight.
Compared to patients without diabetes, those with diabetes had higher odds of needing invasive respiratory support (with intubation) but not for needing noninvasive respiratory support or of dying in the hospital.
“Surprisingly,” among patients with diabetes, being overweight or having obesity did not further increase the odds of any of these outcomes, the researchers wrote. The finding needs to be confirmed in larger studies, they said, because the sample sizes in these subanalyses were small and the confidence intervals were large.
The study by Danielle K. Longmore, PhD, of Murdoch Children’s Research Institute (MCRI), Melbourne, and colleagues from the International BMI-COVID consortium, was published online April 15 in Diabetes Care.
This new research “adds to the known data on the associations between obesity and severe COVID-19 disease and extends these findings” to patients who are overweight and/or have diabetes, Dr. Longmore, a pediatric endocrinologist with a clinical and research interest in childhood and youth obesity, said in an interview.
Immunologist Siroon Bekkering, PhD, of Radboud University Medical Center, Nijmegen, the Netherlands, explained that never before have so much data of different types regarding obesity been combined in one large study. Dr. Bekkering is a coauthor of the article and was a principal investigator.
“Several national and international observations already showed the important role of overweight and obesity in a more severe COVID-19 course. This study adds to those observations by combining data from several countries with the possibility to look at the risk factors separately,” she said in a statement from her institution.
“Regardless of other risk factors (such as heart disease or diabetes), we now see that too high a BMI [body mass index] can actually lead to a more severe course in [coronavirus] infection,” she said.
Study implications: Data show that overweight, obesity add to risk
These latest findings highlight the urgent need to develop public health policies to address socioeconomic and psychological drivers of obesity, Dr. Longmore said.
“Although taking steps to address obesity in the short term is unlikely to have an immediate impact in the COVID-19 pandemic, it will likely reduce the disease burden in future viral pandemics and reduce risks of complications like heart disease and stroke,” she observed in a statement issued by MCRI.
Coauthor Kirsty R. Short, PhD, a research fellow at the University of Queensland, Brisbane, Australia, noted that “obesity is associated with numerous poor health outcomes, including increased risk of cardiometabolic and respiratory disease and more severe viral disease including influenza, dengue, and SARS-CoV-1.
“Given the large scale of this study,” she said, “we have conclusively shown that being overweight or obese are independent risk factors for worse outcomes in adults hospitalized with COVID-19.”
“At the moment, the World Health Organization has not had enough high-quality data to include being overweight or obese as a risk factor for severe COVID-19 disease,” added another author, David P. Burgner, PhD, a pediatric infectious diseases clinician scientist from MCRI.
“Our study should help inform decisions about which higher-risk groups should be vaccinated as a priority,” he observed.
Does being overweight up risk of worse COVID-19 outcomes?
About 13% of the world’s population are overweight, and 40% have obesity. There are wide between-country variations in these data, and about 90% of patients with type 2 diabetes are overweight or obese, the researchers noted.
The Organisation for Economic Co-operation and Development reported that the prevalence of obesity in 2016-2017 was 5.7% to 8.9% in Asia, 9.8% to 16.8% in Europe, 26.5% in South Africa, and 40.0% in the United States, they added.
Obesity is common and has emerged as an important risk factor for severe COVID-19. However, most previous studies of COVID-19 and elevated BMI were conducted in single centers and did not focus on patients with overweight.
To investigate, the researchers identified 7,244 patients (two-thirds were overweight or obese) who were hospitalized with COVID-19 in 69 hospitals (18 sites) in 11 countries from Jan. 17, 2020, to June 2, 2020.
Most patients were hospitalized with COVID-19 in the Netherlands (2,260), followed by New York City (1,682), Switzerland (920), St. Louis (805), Norway, Italy, China, South Africa, Indonesia, Denmark, Los Angeles, Austria, and Singapore.
Just over half (60%) of the individuals were male, and 52% were older than 65.
Overall, 34.8% were overweight, and 30.8% had obesity, but the average weight varied considerably between countries and sites.
Increased need for respiratory support, same mortality risk
Compared with patients with normal weight, patients who were overweight had a 44% increased risk of needing supplemental oxygen/noninvasive ventilation, and those with obesity had a 75% increased risk of this, after adjustment for age (< 65, ≥ 65), sex, hypertension, diabetes, or preexisting cardiovascular disease or respiratory conditions.
Patients who were overweight had a 22% increased risk of needing invasive (mechanical) ventilation, and those with obesity had a 73% increased risk of this, after multivariable adjustment.
Being overweight or having obesity was not associated with a significantly increased risk of dying in the hospital, however.
“In other viral respiratory infections, such as influenza, there is a similar pattern of increased requirement for ventilatory support but lower in-hospital mortality among individuals with obesity, when compared to those with normal range BMI,” Dr. Longmore noted. She said that larger studies are needed to further explore this finding regarding COVID-19.
Compared to patients without diabetes, those with diabetes had a 21% increased risk of requiring invasive ventilation, but they did not have an increased risk of needing noninvasive ventilation or of dying in the hospital.
As in previous studies, individuals who had cardiovascular and preexisting respiratory diseases were not at greater risk of needing oxygen or mechanical ventilation but were at increased risk for in-hospital death. Men had a greater risk of needing invasive mechanical ventilation, and individuals who were older than 65 had an increased risk of requiring oxygen or of dying in the hospital.
A living meta-analysis, call for more collaborators
“We consider this a ‘living meta-analysis’ and invite other centers to join us,” Dr. Longmore said. “We hope to update the analyses as more data are contributed.”
No specific project funded the study. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a global meta-analysis of more than 7,000 patients who were hospitalized with COVID-19, individuals with overweight or obesity were more likely to need respiratory support but were not more likely to die in the hospital, compared to individuals of normal weight.
Compared to patients without diabetes, those with diabetes had higher odds of needing invasive respiratory support (with intubation) but not for needing noninvasive respiratory support or of dying in the hospital.
“Surprisingly,” among patients with diabetes, being overweight or having obesity did not further increase the odds of any of these outcomes, the researchers wrote. The finding needs to be confirmed in larger studies, they said, because the sample sizes in these subanalyses were small and the confidence intervals were large.
The study by Danielle K. Longmore, PhD, of Murdoch Children’s Research Institute (MCRI), Melbourne, and colleagues from the International BMI-COVID consortium, was published online April 15 in Diabetes Care.
This new research “adds to the known data on the associations between obesity and severe COVID-19 disease and extends these findings” to patients who are overweight and/or have diabetes, Dr. Longmore, a pediatric endocrinologist with a clinical and research interest in childhood and youth obesity, said in an interview.
Immunologist Siroon Bekkering, PhD, of Radboud University Medical Center, Nijmegen, the Netherlands, explained that never before have so much data of different types regarding obesity been combined in one large study. Dr. Bekkering is a coauthor of the article and was a principal investigator.
“Several national and international observations already showed the important role of overweight and obesity in a more severe COVID-19 course. This study adds to those observations by combining data from several countries with the possibility to look at the risk factors separately,” she said in a statement from her institution.
“Regardless of other risk factors (such as heart disease or diabetes), we now see that too high a BMI [body mass index] can actually lead to a more severe course in [coronavirus] infection,” she said.
Study implications: Data show that overweight, obesity add to risk
These latest findings highlight the urgent need to develop public health policies to address socioeconomic and psychological drivers of obesity, Dr. Longmore said.
“Although taking steps to address obesity in the short term is unlikely to have an immediate impact in the COVID-19 pandemic, it will likely reduce the disease burden in future viral pandemics and reduce risks of complications like heart disease and stroke,” she observed in a statement issued by MCRI.
Coauthor Kirsty R. Short, PhD, a research fellow at the University of Queensland, Brisbane, Australia, noted that “obesity is associated with numerous poor health outcomes, including increased risk of cardiometabolic and respiratory disease and more severe viral disease including influenza, dengue, and SARS-CoV-1.
“Given the large scale of this study,” she said, “we have conclusively shown that being overweight or obese are independent risk factors for worse outcomes in adults hospitalized with COVID-19.”
“At the moment, the World Health Organization has not had enough high-quality data to include being overweight or obese as a risk factor for severe COVID-19 disease,” added another author, David P. Burgner, PhD, a pediatric infectious diseases clinician scientist from MCRI.
“Our study should help inform decisions about which higher-risk groups should be vaccinated as a priority,” he observed.
Does being overweight up risk of worse COVID-19 outcomes?
About 13% of the world’s population are overweight, and 40% have obesity. There are wide between-country variations in these data, and about 90% of patients with type 2 diabetes are overweight or obese, the researchers noted.
The Organisation for Economic Co-operation and Development reported that the prevalence of obesity in 2016-2017 was 5.7% to 8.9% in Asia, 9.8% to 16.8% in Europe, 26.5% in South Africa, and 40.0% in the United States, they added.
Obesity is common and has emerged as an important risk factor for severe COVID-19. However, most previous studies of COVID-19 and elevated BMI were conducted in single centers and did not focus on patients with overweight.
To investigate, the researchers identified 7,244 patients (two-thirds were overweight or obese) who were hospitalized with COVID-19 in 69 hospitals (18 sites) in 11 countries from Jan. 17, 2020, to June 2, 2020.
Most patients were hospitalized with COVID-19 in the Netherlands (2,260), followed by New York City (1,682), Switzerland (920), St. Louis (805), Norway, Italy, China, South Africa, Indonesia, Denmark, Los Angeles, Austria, and Singapore.
Just over half (60%) of the individuals were male, and 52% were older than 65.
Overall, 34.8% were overweight, and 30.8% had obesity, but the average weight varied considerably between countries and sites.
Increased need for respiratory support, same mortality risk
Compared with patients with normal weight, patients who were overweight had a 44% increased risk of needing supplemental oxygen/noninvasive ventilation, and those with obesity had a 75% increased risk of this, after adjustment for age (< 65, ≥ 65), sex, hypertension, diabetes, or preexisting cardiovascular disease or respiratory conditions.
Patients who were overweight had a 22% increased risk of needing invasive (mechanical) ventilation, and those with obesity had a 73% increased risk of this, after multivariable adjustment.
Being overweight or having obesity was not associated with a significantly increased risk of dying in the hospital, however.
“In other viral respiratory infections, such as influenza, there is a similar pattern of increased requirement for ventilatory support but lower in-hospital mortality among individuals with obesity, when compared to those with normal range BMI,” Dr. Longmore noted. She said that larger studies are needed to further explore this finding regarding COVID-19.
Compared to patients without diabetes, those with diabetes had a 21% increased risk of requiring invasive ventilation, but they did not have an increased risk of needing noninvasive ventilation or of dying in the hospital.
As in previous studies, individuals who had cardiovascular and preexisting respiratory diseases were not at greater risk of needing oxygen or mechanical ventilation but were at increased risk for in-hospital death. Men had a greater risk of needing invasive mechanical ventilation, and individuals who were older than 65 had an increased risk of requiring oxygen or of dying in the hospital.
A living meta-analysis, call for more collaborators
“We consider this a ‘living meta-analysis’ and invite other centers to join us,” Dr. Longmore said. “We hope to update the analyses as more data are contributed.”
No specific project funded the study. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a global meta-analysis of more than 7,000 patients who were hospitalized with COVID-19, individuals with overweight or obesity were more likely to need respiratory support but were not more likely to die in the hospital, compared to individuals of normal weight.
Compared to patients without diabetes, those with diabetes had higher odds of needing invasive respiratory support (with intubation) but not for needing noninvasive respiratory support or of dying in the hospital.
“Surprisingly,” among patients with diabetes, being overweight or having obesity did not further increase the odds of any of these outcomes, the researchers wrote. The finding needs to be confirmed in larger studies, they said, because the sample sizes in these subanalyses were small and the confidence intervals were large.
The study by Danielle K. Longmore, PhD, of Murdoch Children’s Research Institute (MCRI), Melbourne, and colleagues from the International BMI-COVID consortium, was published online April 15 in Diabetes Care.
This new research “adds to the known data on the associations between obesity and severe COVID-19 disease and extends these findings” to patients who are overweight and/or have diabetes, Dr. Longmore, a pediatric endocrinologist with a clinical and research interest in childhood and youth obesity, said in an interview.
Immunologist Siroon Bekkering, PhD, of Radboud University Medical Center, Nijmegen, the Netherlands, explained that never before have so much data of different types regarding obesity been combined in one large study. Dr. Bekkering is a coauthor of the article and was a principal investigator.
“Several national and international observations already showed the important role of overweight and obesity in a more severe COVID-19 course. This study adds to those observations by combining data from several countries with the possibility to look at the risk factors separately,” she said in a statement from her institution.
“Regardless of other risk factors (such as heart disease or diabetes), we now see that too high a BMI [body mass index] can actually lead to a more severe course in [coronavirus] infection,” she said.
Study implications: Data show that overweight, obesity add to risk
These latest findings highlight the urgent need to develop public health policies to address socioeconomic and psychological drivers of obesity, Dr. Longmore said.
“Although taking steps to address obesity in the short term is unlikely to have an immediate impact in the COVID-19 pandemic, it will likely reduce the disease burden in future viral pandemics and reduce risks of complications like heart disease and stroke,” she observed in a statement issued by MCRI.
Coauthor Kirsty R. Short, PhD, a research fellow at the University of Queensland, Brisbane, Australia, noted that “obesity is associated with numerous poor health outcomes, including increased risk of cardiometabolic and respiratory disease and more severe viral disease including influenza, dengue, and SARS-CoV-1.
“Given the large scale of this study,” she said, “we have conclusively shown that being overweight or obese are independent risk factors for worse outcomes in adults hospitalized with COVID-19.”
“At the moment, the World Health Organization has not had enough high-quality data to include being overweight or obese as a risk factor for severe COVID-19 disease,” added another author, David P. Burgner, PhD, a pediatric infectious diseases clinician scientist from MCRI.
“Our study should help inform decisions about which higher-risk groups should be vaccinated as a priority,” he observed.
Does being overweight up risk of worse COVID-19 outcomes?
About 13% of the world’s population are overweight, and 40% have obesity. There are wide between-country variations in these data, and about 90% of patients with type 2 diabetes are overweight or obese, the researchers noted.
The Organisation for Economic Co-operation and Development reported that the prevalence of obesity in 2016-2017 was 5.7% to 8.9% in Asia, 9.8% to 16.8% in Europe, 26.5% in South Africa, and 40.0% in the United States, they added.
Obesity is common and has emerged as an important risk factor for severe COVID-19. However, most previous studies of COVID-19 and elevated BMI were conducted in single centers and did not focus on patients with overweight.
To investigate, the researchers identified 7,244 patients (two-thirds were overweight or obese) who were hospitalized with COVID-19 in 69 hospitals (18 sites) in 11 countries from Jan. 17, 2020, to June 2, 2020.
Most patients were hospitalized with COVID-19 in the Netherlands (2,260), followed by New York City (1,682), Switzerland (920), St. Louis (805), Norway, Italy, China, South Africa, Indonesia, Denmark, Los Angeles, Austria, and Singapore.
Just over half (60%) of the individuals were male, and 52% were older than 65.
Overall, 34.8% were overweight, and 30.8% had obesity, but the average weight varied considerably between countries and sites.
Increased need for respiratory support, same mortality risk
Compared with patients with normal weight, patients who were overweight had a 44% increased risk of needing supplemental oxygen/noninvasive ventilation, and those with obesity had a 75% increased risk of this, after adjustment for age (< 65, ≥ 65), sex, hypertension, diabetes, or preexisting cardiovascular disease or respiratory conditions.
Patients who were overweight had a 22% increased risk of needing invasive (mechanical) ventilation, and those with obesity had a 73% increased risk of this, after multivariable adjustment.
Being overweight or having obesity was not associated with a significantly increased risk of dying in the hospital, however.
“In other viral respiratory infections, such as influenza, there is a similar pattern of increased requirement for ventilatory support but lower in-hospital mortality among individuals with obesity, when compared to those with normal range BMI,” Dr. Longmore noted. She said that larger studies are needed to further explore this finding regarding COVID-19.
Compared to patients without diabetes, those with diabetes had a 21% increased risk of requiring invasive ventilation, but they did not have an increased risk of needing noninvasive ventilation or of dying in the hospital.
As in previous studies, individuals who had cardiovascular and preexisting respiratory diseases were not at greater risk of needing oxygen or mechanical ventilation but were at increased risk for in-hospital death. Men had a greater risk of needing invasive mechanical ventilation, and individuals who were older than 65 had an increased risk of requiring oxygen or of dying in the hospital.
A living meta-analysis, call for more collaborators
“We consider this a ‘living meta-analysis’ and invite other centers to join us,” Dr. Longmore said. “We hope to update the analyses as more data are contributed.”
No specific project funded the study. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
HIV patients show accelerated aging related to altered sleep
Accelerated brain aging among HIV-infected adults might be caused in part by altered deep sleep patterns, new research suggests.
Using a measure known as the brain age index (BAI) – a machine-learning model that measures deviations in brain activity during sleep relative to healthy individuals – investigators identified 34 sleep electroencephalogram features that were significantly altered by HIV infection. The most notable of these was the decline in slow-wave activity during non-REM sleep, which has been previously associated with MRI markers of brain aging in healthy adults.
“One of the functions of slow-wave sleep appears to be its association with the glymphatic system, which clears [metabolic] waste products and supports memory consolidation,” study coauthor Brandon Westover, MD, PhD, associate professor of neurology at Massachusetts General Hospital/Harvard Medical School, Boston, said in an interview. “It’s also believed to be associated with an accelerated risk for dementia and other cognitive issues.”
Previous work conducted at Johns Hopkins and other institutions confirm Dr. Westerson’s hypothesis. Charlene Gamaldo, MD, medical director of Johns Hopkins Sleep Disorders Center in Baltimore, pointed to other study findings in patients with neurodegenerative disease that have shown a link between predominant habitual sleep positions and dementia, potentially driven by inefficient glymphatic transport. Dr. Gamaldo was not involved in the current study.
Threefold acceleration vs. healthy volunteers
“We’ve been grappling with whether people with HIV on ART experience accelerated aging or accentuated aging,” coauthor Shibani Mukerji, MD, PhD, associate director of the neuroinfectious diseases unit at Massachusetts General, said in an interview. “We have yet to have biomarkers to address this question, and most of the tools are limited to invasive or expensive diagnostics. “In general, sleep and its influence on health have been understudied in the HIV population.”
To address this question, the researchers retrospectively examined a Massachusetts General Hospital database of diagnostic sleep study participants from 2008 to 2018, identifying 3,155 healthy, HIV-negative control subjects and 43 HIV-positive participants. Thirty-four (79%) of the HIV-positive participants were men, 30 (70%) were White, and 38 (93%) were virally suppressed at the time of their sleep study. Four patients were taking efavirenz, 13 were taking an integrase strand transfer inhibitor, and all were adherent to antiretroviral therapy (ART) at the time of their sleep study.
None of the HIV-positive participants had a history of secondary brain infection or brain tumor, although one patient had recovered fully from a previous HIV-associated encephalitis.
The study findings, which were published online March 30, 2021, in Sleep, first showed that HIV-positive participants had an average BAI of 3.19 years (standard error of the mean,1.43 years), compared with the control participants, who had an average BAI of –0.16 (SEM, 0.18 years).
These findings held after adjustment for potential confounders (age, sex, race, tobacco use disorder, and alcohol use disorder), yielding a total effect of HIV on BAI of 3.35 years (P < .01).
“Despite being well controlled on ART, HIV-positive individuals who had participated in the sleep studies still had elevated brain age,” said Dr. Westover. “We didn’t have enough information to determine the pathways by which HIV increases the BAI, but chronic inflammation appears to be an important factor.”
The findings also demonstrated that comorbidities accounted for roughly a quarter of the effect of HIV on BAI. However, the lack of statistical significance (in part because of the limited sample size) precluded the ability to determine if treating or preventing them might influence the degree to which HIV affects BAI and, in turn, cognitive decline.
HIV, sleep EEG, and brain aging
To estimate the effect of HIV on specific EEG features, the investigators again evaluated the total effect, this time replacing BAI with individual sleep EEG as the primary outcome. Among the 34 EEG features significantly altered by HIV, none were observed in the wake state and three were altered in REM (each associated with reduced delta band power). The rest were distributed in non-REM sleep, most notably in the deepest phase, corresponding to relative reductions in delta wave power.
The study findings build on the investigators’ previous research, which demonstrated an association between greater mean BAI and dementia, psychotic disorders, and anxiety/mood disorders in HIV-negative subjects, all of which correlated to attenuated slow-wave sleep.
More research is needed to determine if BAI, as it relates to sleep EEG, can effectively track the risk for cognitive decline among HIV-positive people, and if certain confounders might attenuate or accelerate this risk.
“While our team has not specifically looked at BAI, the findings in this study seem perfectly in line with what we have found with our own research,” Dr. Gamaldo said in an interview. “Not only have we observed a robust association between minimal cognitive deficits and patients’ sleep complaints (despite being virally controlled), but also, the potential value of measuring the architectural sleep features by ambulatory EEG to identify HIV patients’ vulnerability to cognitive decline.”
“BAI is a physiologic, easily repeatable measurement that can be used to track if an intervention is having a good effect,” Dr. Westover said.
Dr. Mukerji concurred, adding that “having a tool that can be used in resource-challenged settings and also be incorporated into longitudinal studies in a patient population with substantial age-related comorbidities, like HIV, would be really helpful.”
Dr. Westover and Dr. Mukerji disclosed no relevant financial relationships. Dr. Gamaldo is a consultant for Jazz Pharmaceuticals, and has received author royalties from UpToDate and honoraria from Medscape CME for content contribution.
A version of this article first appeared on Medscape.com.
Accelerated brain aging among HIV-infected adults might be caused in part by altered deep sleep patterns, new research suggests.
Using a measure known as the brain age index (BAI) – a machine-learning model that measures deviations in brain activity during sleep relative to healthy individuals – investigators identified 34 sleep electroencephalogram features that were significantly altered by HIV infection. The most notable of these was the decline in slow-wave activity during non-REM sleep, which has been previously associated with MRI markers of brain aging in healthy adults.
“One of the functions of slow-wave sleep appears to be its association with the glymphatic system, which clears [metabolic] waste products and supports memory consolidation,” study coauthor Brandon Westover, MD, PhD, associate professor of neurology at Massachusetts General Hospital/Harvard Medical School, Boston, said in an interview. “It’s also believed to be associated with an accelerated risk for dementia and other cognitive issues.”
Previous work conducted at Johns Hopkins and other institutions confirm Dr. Westerson’s hypothesis. Charlene Gamaldo, MD, medical director of Johns Hopkins Sleep Disorders Center in Baltimore, pointed to other study findings in patients with neurodegenerative disease that have shown a link between predominant habitual sleep positions and dementia, potentially driven by inefficient glymphatic transport. Dr. Gamaldo was not involved in the current study.
Threefold acceleration vs. healthy volunteers
“We’ve been grappling with whether people with HIV on ART experience accelerated aging or accentuated aging,” coauthor Shibani Mukerji, MD, PhD, associate director of the neuroinfectious diseases unit at Massachusetts General, said in an interview. “We have yet to have biomarkers to address this question, and most of the tools are limited to invasive or expensive diagnostics. “In general, sleep and its influence on health have been understudied in the HIV population.”
To address this question, the researchers retrospectively examined a Massachusetts General Hospital database of diagnostic sleep study participants from 2008 to 2018, identifying 3,155 healthy, HIV-negative control subjects and 43 HIV-positive participants. Thirty-four (79%) of the HIV-positive participants were men, 30 (70%) were White, and 38 (93%) were virally suppressed at the time of their sleep study. Four patients were taking efavirenz, 13 were taking an integrase strand transfer inhibitor, and all were adherent to antiretroviral therapy (ART) at the time of their sleep study.
None of the HIV-positive participants had a history of secondary brain infection or brain tumor, although one patient had recovered fully from a previous HIV-associated encephalitis.
The study findings, which were published online March 30, 2021, in Sleep, first showed that HIV-positive participants had an average BAI of 3.19 years (standard error of the mean,1.43 years), compared with the control participants, who had an average BAI of –0.16 (SEM, 0.18 years).
These findings held after adjustment for potential confounders (age, sex, race, tobacco use disorder, and alcohol use disorder), yielding a total effect of HIV on BAI of 3.35 years (P < .01).
“Despite being well controlled on ART, HIV-positive individuals who had participated in the sleep studies still had elevated brain age,” said Dr. Westover. “We didn’t have enough information to determine the pathways by which HIV increases the BAI, but chronic inflammation appears to be an important factor.”
The findings also demonstrated that comorbidities accounted for roughly a quarter of the effect of HIV on BAI. However, the lack of statistical significance (in part because of the limited sample size) precluded the ability to determine if treating or preventing them might influence the degree to which HIV affects BAI and, in turn, cognitive decline.
HIV, sleep EEG, and brain aging
To estimate the effect of HIV on specific EEG features, the investigators again evaluated the total effect, this time replacing BAI with individual sleep EEG as the primary outcome. Among the 34 EEG features significantly altered by HIV, none were observed in the wake state and three were altered in REM (each associated with reduced delta band power). The rest were distributed in non-REM sleep, most notably in the deepest phase, corresponding to relative reductions in delta wave power.
The study findings build on the investigators’ previous research, which demonstrated an association between greater mean BAI and dementia, psychotic disorders, and anxiety/mood disorders in HIV-negative subjects, all of which correlated to attenuated slow-wave sleep.
More research is needed to determine if BAI, as it relates to sleep EEG, can effectively track the risk for cognitive decline among HIV-positive people, and if certain confounders might attenuate or accelerate this risk.
“While our team has not specifically looked at BAI, the findings in this study seem perfectly in line with what we have found with our own research,” Dr. Gamaldo said in an interview. “Not only have we observed a robust association between minimal cognitive deficits and patients’ sleep complaints (despite being virally controlled), but also, the potential value of measuring the architectural sleep features by ambulatory EEG to identify HIV patients’ vulnerability to cognitive decline.”
“BAI is a physiologic, easily repeatable measurement that can be used to track if an intervention is having a good effect,” Dr. Westover said.
Dr. Mukerji concurred, adding that “having a tool that can be used in resource-challenged settings and also be incorporated into longitudinal studies in a patient population with substantial age-related comorbidities, like HIV, would be really helpful.”
Dr. Westover and Dr. Mukerji disclosed no relevant financial relationships. Dr. Gamaldo is a consultant for Jazz Pharmaceuticals, and has received author royalties from UpToDate and honoraria from Medscape CME for content contribution.
A version of this article first appeared on Medscape.com.
Accelerated brain aging among HIV-infected adults might be caused in part by altered deep sleep patterns, new research suggests.
Using a measure known as the brain age index (BAI) – a machine-learning model that measures deviations in brain activity during sleep relative to healthy individuals – investigators identified 34 sleep electroencephalogram features that were significantly altered by HIV infection. The most notable of these was the decline in slow-wave activity during non-REM sleep, which has been previously associated with MRI markers of brain aging in healthy adults.
“One of the functions of slow-wave sleep appears to be its association with the glymphatic system, which clears [metabolic] waste products and supports memory consolidation,” study coauthor Brandon Westover, MD, PhD, associate professor of neurology at Massachusetts General Hospital/Harvard Medical School, Boston, said in an interview. “It’s also believed to be associated with an accelerated risk for dementia and other cognitive issues.”
Previous work conducted at Johns Hopkins and other institutions confirm Dr. Westerson’s hypothesis. Charlene Gamaldo, MD, medical director of Johns Hopkins Sleep Disorders Center in Baltimore, pointed to other study findings in patients with neurodegenerative disease that have shown a link between predominant habitual sleep positions and dementia, potentially driven by inefficient glymphatic transport. Dr. Gamaldo was not involved in the current study.
Threefold acceleration vs. healthy volunteers
“We’ve been grappling with whether people with HIV on ART experience accelerated aging or accentuated aging,” coauthor Shibani Mukerji, MD, PhD, associate director of the neuroinfectious diseases unit at Massachusetts General, said in an interview. “We have yet to have biomarkers to address this question, and most of the tools are limited to invasive or expensive diagnostics. “In general, sleep and its influence on health have been understudied in the HIV population.”
To address this question, the researchers retrospectively examined a Massachusetts General Hospital database of diagnostic sleep study participants from 2008 to 2018, identifying 3,155 healthy, HIV-negative control subjects and 43 HIV-positive participants. Thirty-four (79%) of the HIV-positive participants were men, 30 (70%) were White, and 38 (93%) were virally suppressed at the time of their sleep study. Four patients were taking efavirenz, 13 were taking an integrase strand transfer inhibitor, and all were adherent to antiretroviral therapy (ART) at the time of their sleep study.
None of the HIV-positive participants had a history of secondary brain infection or brain tumor, although one patient had recovered fully from a previous HIV-associated encephalitis.
The study findings, which were published online March 30, 2021, in Sleep, first showed that HIV-positive participants had an average BAI of 3.19 years (standard error of the mean,1.43 years), compared with the control participants, who had an average BAI of –0.16 (SEM, 0.18 years).
These findings held after adjustment for potential confounders (age, sex, race, tobacco use disorder, and alcohol use disorder), yielding a total effect of HIV on BAI of 3.35 years (P < .01).
“Despite being well controlled on ART, HIV-positive individuals who had participated in the sleep studies still had elevated brain age,” said Dr. Westover. “We didn’t have enough information to determine the pathways by which HIV increases the BAI, but chronic inflammation appears to be an important factor.”
The findings also demonstrated that comorbidities accounted for roughly a quarter of the effect of HIV on BAI. However, the lack of statistical significance (in part because of the limited sample size) precluded the ability to determine if treating or preventing them might influence the degree to which HIV affects BAI and, in turn, cognitive decline.
HIV, sleep EEG, and brain aging
To estimate the effect of HIV on specific EEG features, the investigators again evaluated the total effect, this time replacing BAI with individual sleep EEG as the primary outcome. Among the 34 EEG features significantly altered by HIV, none were observed in the wake state and three were altered in REM (each associated with reduced delta band power). The rest were distributed in non-REM sleep, most notably in the deepest phase, corresponding to relative reductions in delta wave power.
The study findings build on the investigators’ previous research, which demonstrated an association between greater mean BAI and dementia, psychotic disorders, and anxiety/mood disorders in HIV-negative subjects, all of which correlated to attenuated slow-wave sleep.
More research is needed to determine if BAI, as it relates to sleep EEG, can effectively track the risk for cognitive decline among HIV-positive people, and if certain confounders might attenuate or accelerate this risk.
“While our team has not specifically looked at BAI, the findings in this study seem perfectly in line with what we have found with our own research,” Dr. Gamaldo said in an interview. “Not only have we observed a robust association between minimal cognitive deficits and patients’ sleep complaints (despite being virally controlled), but also, the potential value of measuring the architectural sleep features by ambulatory EEG to identify HIV patients’ vulnerability to cognitive decline.”
“BAI is a physiologic, easily repeatable measurement that can be used to track if an intervention is having a good effect,” Dr. Westover said.
Dr. Mukerji concurred, adding that “having a tool that can be used in resource-challenged settings and also be incorporated into longitudinal studies in a patient population with substantial age-related comorbidities, like HIV, would be really helpful.”
Dr. Westover and Dr. Mukerji disclosed no relevant financial relationships. Dr. Gamaldo is a consultant for Jazz Pharmaceuticals, and has received author royalties from UpToDate and honoraria from Medscape CME for content contribution.
A version of this article first appeared on Medscape.com.
Is common courtesy no longer contagious?
The other day, in a fairly common occurrence, I needed to fax a records request over to another office.
Not having memorized all the fax numbers in my area, I turned to the internet and quickly had their website and the needed information in front of me.
But at the top of the page, before you got to phone numbers and directions, was this statement in bold print (caps as seen):
“NOTICE TO ALL PATIENTS:
“Please show RESPECT AND KINDNESS to other patients and staff.
“We have a ZERO TOLERANCE policy for aggressive behavior, vulgar language, and violence, whether in person, on the phone, or online.”
A veterinarian I know recently put something similar up, saying: “We DO NOT TOLERATE physically or verbally abusive behavior by clients. We are compassionate and understand you are under stress, but we are also human and deserve respect. Thank you.”
I absolutely agree with this. Hell, I’m the same way.
But what is wrong with people that we actually need to have notices like that up?
Realistically, the vast majority of patients don’t need the reminder. They treat each other, and my staff, with politeness and respect, and we do the same. To me that’s part of the whole sandbox thing. Personally, I prefer my office to have the same atmosphere as a library, and am known to “shhhh” people who are too loud.
But the real point here is that we shouldn’t have to remind anyone else to behave with common courtesy. If you’re an adult, I’m going to assume your parents and teachers taught you the importance of manners and the Golden Rule.
I’ve been in practice for 23 years now, and I’ve never had to deal with this sort of behavior, this frequently, before. Is it that the pandemic, and its economic and social consequences, has gotten on everyone’s nerves? If so, hopefully it will gradually fade away as the crisis does. I’m vaccinated. My family and the majority of my patients are vaccinated. I encourage pretty much everyone who asks me about it to get vaccinated.
But I’m more concerned that isn’t really the issue. Maybe our polarized, divided society is moving in that direction. Common good is now often reduced to us against them, and the conditions of the times have just aggravated a problem that was festering.
The majority of people, of all beliefs, remain decent people. But
Decency and manners, unfortunately, can’t be legislated. If you’ve forgotten yours, though, don’t think others will put up with you.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
The other day, in a fairly common occurrence, I needed to fax a records request over to another office.
Not having memorized all the fax numbers in my area, I turned to the internet and quickly had their website and the needed information in front of me.
But at the top of the page, before you got to phone numbers and directions, was this statement in bold print (caps as seen):
“NOTICE TO ALL PATIENTS:
“Please show RESPECT AND KINDNESS to other patients and staff.
“We have a ZERO TOLERANCE policy for aggressive behavior, vulgar language, and violence, whether in person, on the phone, or online.”
A veterinarian I know recently put something similar up, saying: “We DO NOT TOLERATE physically or verbally abusive behavior by clients. We are compassionate and understand you are under stress, but we are also human and deserve respect. Thank you.”
I absolutely agree with this. Hell, I’m the same way.
But what is wrong with people that we actually need to have notices like that up?
Realistically, the vast majority of patients don’t need the reminder. They treat each other, and my staff, with politeness and respect, and we do the same. To me that’s part of the whole sandbox thing. Personally, I prefer my office to have the same atmosphere as a library, and am known to “shhhh” people who are too loud.
But the real point here is that we shouldn’t have to remind anyone else to behave with common courtesy. If you’re an adult, I’m going to assume your parents and teachers taught you the importance of manners and the Golden Rule.
I’ve been in practice for 23 years now, and I’ve never had to deal with this sort of behavior, this frequently, before. Is it that the pandemic, and its economic and social consequences, has gotten on everyone’s nerves? If so, hopefully it will gradually fade away as the crisis does. I’m vaccinated. My family and the majority of my patients are vaccinated. I encourage pretty much everyone who asks me about it to get vaccinated.
But I’m more concerned that isn’t really the issue. Maybe our polarized, divided society is moving in that direction. Common good is now often reduced to us against them, and the conditions of the times have just aggravated a problem that was festering.
The majority of people, of all beliefs, remain decent people. But
Decency and manners, unfortunately, can’t be legislated. If you’ve forgotten yours, though, don’t think others will put up with you.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
The other day, in a fairly common occurrence, I needed to fax a records request over to another office.
Not having memorized all the fax numbers in my area, I turned to the internet and quickly had their website and the needed information in front of me.
But at the top of the page, before you got to phone numbers and directions, was this statement in bold print (caps as seen):
“NOTICE TO ALL PATIENTS:
“Please show RESPECT AND KINDNESS to other patients and staff.
“We have a ZERO TOLERANCE policy for aggressive behavior, vulgar language, and violence, whether in person, on the phone, or online.”
A veterinarian I know recently put something similar up, saying: “We DO NOT TOLERATE physically or verbally abusive behavior by clients. We are compassionate and understand you are under stress, but we are also human and deserve respect. Thank you.”
I absolutely agree with this. Hell, I’m the same way.
But what is wrong with people that we actually need to have notices like that up?
Realistically, the vast majority of patients don’t need the reminder. They treat each other, and my staff, with politeness and respect, and we do the same. To me that’s part of the whole sandbox thing. Personally, I prefer my office to have the same atmosphere as a library, and am known to “shhhh” people who are too loud.
But the real point here is that we shouldn’t have to remind anyone else to behave with common courtesy. If you’re an adult, I’m going to assume your parents and teachers taught you the importance of manners and the Golden Rule.
I’ve been in practice for 23 years now, and I’ve never had to deal with this sort of behavior, this frequently, before. Is it that the pandemic, and its economic and social consequences, has gotten on everyone’s nerves? If so, hopefully it will gradually fade away as the crisis does. I’m vaccinated. My family and the majority of my patients are vaccinated. I encourage pretty much everyone who asks me about it to get vaccinated.
But I’m more concerned that isn’t really the issue. Maybe our polarized, divided society is moving in that direction. Common good is now often reduced to us against them, and the conditions of the times have just aggravated a problem that was festering.
The majority of people, of all beliefs, remain decent people. But
Decency and manners, unfortunately, can’t be legislated. If you’ve forgotten yours, though, don’t think others will put up with you.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Drinking your way to heart failure, and the fringe benefits of COVID-19 vaccination
Energy drink doom
Who doesn’t need some caffeine to get going in the morning and keep moving throughout the day? Whether it’s tea, coffee, or energy drinks, people can get addicted to caffeinated beverages when there are only so many hours in a day and way too much work to get done.
That’s what happened to a 21-year-old college student who powered down four 16-ounce cans of energy drink – each with double the amount of caffeine in an ordinary cup of coffee – every day for 2 years. Now, if you’ve ever overdone it with caffeine, you know there are some uncomfortable side effects, like shaking and anxiety. In this case, the student reported migraines, tremors, and heart palpitations. Instead of being able to focus better on his work, he had trouble concentrating.
Over time, after these side effects took a turn for the worse and became shortness of breath and weight loss, he visited St. Thomas’ Hospital in London, where physicians diagnosed him with both heart and renal failure.
Excessive consumption of energy drinks is known to cause issues such as high blood pressure and irregular heart beat, so if that’s your fuel of choice, it might be worth cutting down. Maybe take a morning run to get the blood pumping – in a good way – instead?
Loneliness may be hazardous to your health
Sometimes loneliness can feel like it affects your physical health, but according to a study there’s a possibility that it actually does.
Back in the 1980s, researchers from the University of Eastern Finland started monitoring almost 3,000 middle-aged men. They’ve kept up with the participants until the present day, and the results have been staggering. After an average follow-up of over 20 years, 25% of participants developed cancer and 11% died from cancer, and the increase in risk from loneliness was about 10%, regardless of age, lifestyle, and BMI.
What does that say about preventive care? The researchers think these data are cause enough to pay attention to loneliness as a health issue along with smoking and weight.
Social interactions and relationships play important roles in human mental health, of course, but this is pretty solid evidence that they play a role in physical health too. As the researchers said, “Awareness of the health effects of loneliness is constantly increasing. Therefore, it is important to examine, in more detail, the mechanisms by which loneliness causes adverse health effects.”
So, as we progress through this pandemic, maybe you should join that social group on Facebook? Who knows what kind of effect it could have on your health?
An ounce of prevention is worth 12 ounces of lager
COVID-19 vaccine refusal is now a thing, and there’s no law that says people have to be immunized against our newest, bestest buddy, SARS-CoV-2, but the folks who skip it are missing out. And no, we’re not talking about immunity against disease.
We’re talking … FREE STUFF!
Corporate America has stepped up and is now rewarding those who get the COVID-19 vaccine:
- Budweiser will give a free beer to anyone – anyone over age 21, that is – with proof of vaccination until May 16.
- Show a vaccination card at a Krispy Kreme and you can get a free glazed doughnut, every day. You don’t even need to buy anything.
- White Castle will give you a free dessert-on-a-stick just for showing proof of vaccination. No purchase is required, but the offer ends May 31.
But wait, there’s more!
Even the public sector is getting in on the giveaway action. Gov. Jim Justice announced April 26 that West Virginia will give a $100 savings bond to any resident aged 16-35 years who receives a COVID-19 vaccine. It must make sense, because the governor broke out a white board to show residents he’s done the math.
One closing thought: How cool would it be if he was named to the Supreme Court, so he could be Justice Justice?
Where no shirt has gone before
Space. The final frontier, for both humanity and for shirts. Specifically, it’s a new frontier for the Bio-Monitor smart shirt, a tank-top filled with sensors that monitor the wearer’s stats, such as heart and breathing rate, oxygen saturation, skin temperature, and blood pressure. And you thought space was just for finding a new human habitat and growing steak.
This shirt is already used by athletes to assess performance and by people with limited mobility to monitor health, so its potential impending usage by astronauts makes sense. Space is a pretty extreme environment, to put it mildly, and there’s a lot we still don’t know about how the human body reacts to it. Traditionally, astronauts hook themselves up to separate devices so their stats can be measured, a method which captures only snapshots of their bodies. By wearing the shirt constantly, the astronauts can be measured constantly, so scientists and doctors can see how the body deals with microgravity during normal activities and sleep. It also reduces stress, as there is no psychological impact of having to report in for constant health checks.
For the test, astronauts wore the shirt for 72 hours before flight and for 72 hours during flight. The shirts passed this first test with flying colors; in addition to providing accurate and more consistent stats monitoring than traditional methods, scientists on the ground determined that the astronauts recorded far less physical activity during flight than preflight, a finding in line with previous studies.
And before you question whether or not a tank top is really appropriate for space, just remember, Picard pulled it off at the end of “First Contact,” and that’s arguably the best Star Trek movie. So there’s certainly precedent.
Energy drink doom
Who doesn’t need some caffeine to get going in the morning and keep moving throughout the day? Whether it’s tea, coffee, or energy drinks, people can get addicted to caffeinated beverages when there are only so many hours in a day and way too much work to get done.
That’s what happened to a 21-year-old college student who powered down four 16-ounce cans of energy drink – each with double the amount of caffeine in an ordinary cup of coffee – every day for 2 years. Now, if you’ve ever overdone it with caffeine, you know there are some uncomfortable side effects, like shaking and anxiety. In this case, the student reported migraines, tremors, and heart palpitations. Instead of being able to focus better on his work, he had trouble concentrating.
Over time, after these side effects took a turn for the worse and became shortness of breath and weight loss, he visited St. Thomas’ Hospital in London, where physicians diagnosed him with both heart and renal failure.
Excessive consumption of energy drinks is known to cause issues such as high blood pressure and irregular heart beat, so if that’s your fuel of choice, it might be worth cutting down. Maybe take a morning run to get the blood pumping – in a good way – instead?
Loneliness may be hazardous to your health
Sometimes loneliness can feel like it affects your physical health, but according to a study there’s a possibility that it actually does.
Back in the 1980s, researchers from the University of Eastern Finland started monitoring almost 3,000 middle-aged men. They’ve kept up with the participants until the present day, and the results have been staggering. After an average follow-up of over 20 years, 25% of participants developed cancer and 11% died from cancer, and the increase in risk from loneliness was about 10%, regardless of age, lifestyle, and BMI.
What does that say about preventive care? The researchers think these data are cause enough to pay attention to loneliness as a health issue along with smoking and weight.
Social interactions and relationships play important roles in human mental health, of course, but this is pretty solid evidence that they play a role in physical health too. As the researchers said, “Awareness of the health effects of loneliness is constantly increasing. Therefore, it is important to examine, in more detail, the mechanisms by which loneliness causes adverse health effects.”
So, as we progress through this pandemic, maybe you should join that social group on Facebook? Who knows what kind of effect it could have on your health?
An ounce of prevention is worth 12 ounces of lager
COVID-19 vaccine refusal is now a thing, and there’s no law that says people have to be immunized against our newest, bestest buddy, SARS-CoV-2, but the folks who skip it are missing out. And no, we’re not talking about immunity against disease.
We’re talking … FREE STUFF!
Corporate America has stepped up and is now rewarding those who get the COVID-19 vaccine:
- Budweiser will give a free beer to anyone – anyone over age 21, that is – with proof of vaccination until May 16.
- Show a vaccination card at a Krispy Kreme and you can get a free glazed doughnut, every day. You don’t even need to buy anything.
- White Castle will give you a free dessert-on-a-stick just for showing proof of vaccination. No purchase is required, but the offer ends May 31.
But wait, there’s more!
Even the public sector is getting in on the giveaway action. Gov. Jim Justice announced April 26 that West Virginia will give a $100 savings bond to any resident aged 16-35 years who receives a COVID-19 vaccine. It must make sense, because the governor broke out a white board to show residents he’s done the math.
One closing thought: How cool would it be if he was named to the Supreme Court, so he could be Justice Justice?
Where no shirt has gone before
Space. The final frontier, for both humanity and for shirts. Specifically, it’s a new frontier for the Bio-Monitor smart shirt, a tank-top filled with sensors that monitor the wearer’s stats, such as heart and breathing rate, oxygen saturation, skin temperature, and blood pressure. And you thought space was just for finding a new human habitat and growing steak.
This shirt is already used by athletes to assess performance and by people with limited mobility to monitor health, so its potential impending usage by astronauts makes sense. Space is a pretty extreme environment, to put it mildly, and there’s a lot we still don’t know about how the human body reacts to it. Traditionally, astronauts hook themselves up to separate devices so their stats can be measured, a method which captures only snapshots of their bodies. By wearing the shirt constantly, the astronauts can be measured constantly, so scientists and doctors can see how the body deals with microgravity during normal activities and sleep. It also reduces stress, as there is no psychological impact of having to report in for constant health checks.
For the test, astronauts wore the shirt for 72 hours before flight and for 72 hours during flight. The shirts passed this first test with flying colors; in addition to providing accurate and more consistent stats monitoring than traditional methods, scientists on the ground determined that the astronauts recorded far less physical activity during flight than preflight, a finding in line with previous studies.
And before you question whether or not a tank top is really appropriate for space, just remember, Picard pulled it off at the end of “First Contact,” and that’s arguably the best Star Trek movie. So there’s certainly precedent.
Energy drink doom
Who doesn’t need some caffeine to get going in the morning and keep moving throughout the day? Whether it’s tea, coffee, or energy drinks, people can get addicted to caffeinated beverages when there are only so many hours in a day and way too much work to get done.
That’s what happened to a 21-year-old college student who powered down four 16-ounce cans of energy drink – each with double the amount of caffeine in an ordinary cup of coffee – every day for 2 years. Now, if you’ve ever overdone it with caffeine, you know there are some uncomfortable side effects, like shaking and anxiety. In this case, the student reported migraines, tremors, and heart palpitations. Instead of being able to focus better on his work, he had trouble concentrating.
Over time, after these side effects took a turn for the worse and became shortness of breath and weight loss, he visited St. Thomas’ Hospital in London, where physicians diagnosed him with both heart and renal failure.
Excessive consumption of energy drinks is known to cause issues such as high blood pressure and irregular heart beat, so if that’s your fuel of choice, it might be worth cutting down. Maybe take a morning run to get the blood pumping – in a good way – instead?
Loneliness may be hazardous to your health
Sometimes loneliness can feel like it affects your physical health, but according to a study there’s a possibility that it actually does.
Back in the 1980s, researchers from the University of Eastern Finland started monitoring almost 3,000 middle-aged men. They’ve kept up with the participants until the present day, and the results have been staggering. After an average follow-up of over 20 years, 25% of participants developed cancer and 11% died from cancer, and the increase in risk from loneliness was about 10%, regardless of age, lifestyle, and BMI.
What does that say about preventive care? The researchers think these data are cause enough to pay attention to loneliness as a health issue along with smoking and weight.
Social interactions and relationships play important roles in human mental health, of course, but this is pretty solid evidence that they play a role in physical health too. As the researchers said, “Awareness of the health effects of loneliness is constantly increasing. Therefore, it is important to examine, in more detail, the mechanisms by which loneliness causes adverse health effects.”
So, as we progress through this pandemic, maybe you should join that social group on Facebook? Who knows what kind of effect it could have on your health?
An ounce of prevention is worth 12 ounces of lager
COVID-19 vaccine refusal is now a thing, and there’s no law that says people have to be immunized against our newest, bestest buddy, SARS-CoV-2, but the folks who skip it are missing out. And no, we’re not talking about immunity against disease.
We’re talking … FREE STUFF!
Corporate America has stepped up and is now rewarding those who get the COVID-19 vaccine:
- Budweiser will give a free beer to anyone – anyone over age 21, that is – with proof of vaccination until May 16.
- Show a vaccination card at a Krispy Kreme and you can get a free glazed doughnut, every day. You don’t even need to buy anything.
- White Castle will give you a free dessert-on-a-stick just for showing proof of vaccination. No purchase is required, but the offer ends May 31.
But wait, there’s more!
Even the public sector is getting in on the giveaway action. Gov. Jim Justice announced April 26 that West Virginia will give a $100 savings bond to any resident aged 16-35 years who receives a COVID-19 vaccine. It must make sense, because the governor broke out a white board to show residents he’s done the math.
One closing thought: How cool would it be if he was named to the Supreme Court, so he could be Justice Justice?
Where no shirt has gone before
Space. The final frontier, for both humanity and for shirts. Specifically, it’s a new frontier for the Bio-Monitor smart shirt, a tank-top filled with sensors that monitor the wearer’s stats, such as heart and breathing rate, oxygen saturation, skin temperature, and blood pressure. And you thought space was just for finding a new human habitat and growing steak.
This shirt is already used by athletes to assess performance and by people with limited mobility to monitor health, so its potential impending usage by astronauts makes sense. Space is a pretty extreme environment, to put it mildly, and there’s a lot we still don’t know about how the human body reacts to it. Traditionally, astronauts hook themselves up to separate devices so their stats can be measured, a method which captures only snapshots of their bodies. By wearing the shirt constantly, the astronauts can be measured constantly, so scientists and doctors can see how the body deals with microgravity during normal activities and sleep. It also reduces stress, as there is no psychological impact of having to report in for constant health checks.
For the test, astronauts wore the shirt for 72 hours before flight and for 72 hours during flight. The shirts passed this first test with flying colors; in addition to providing accurate and more consistent stats monitoring than traditional methods, scientists on the ground determined that the astronauts recorded far less physical activity during flight than preflight, a finding in line with previous studies.
And before you question whether or not a tank top is really appropriate for space, just remember, Picard pulled it off at the end of “First Contact,” and that’s arguably the best Star Trek movie. So there’s certainly precedent.