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Daily aspirin for stroke prevention in healthy elderly should be avoided
according to results from a large randomized trial.
The findings, published in JAMA Network Open, bolster recommendations published in 2022 by the U.S. Preventive Services Task Force against daily aspirin for primary prevention of stroke in older adults and add to a mounting consensus that it should be avoided in the healthy elderly, for whom bleeding risks outweigh potential benefits.
Stroke was a preplanned secondary outcome of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which randomized 19,114 community-living people in Australia and the United States (56% women, 91% White) to 100 mg. daily aspirin or placebo. Participants were aged 70 and older, with the exception of U.S. Black and Hispanic individuals, who could be as young as 65. Participants did not have disability or known cardiovascular disease at baseline, and blood pressure was adequately controlled.
ASPEE findings
In 2018 the ASPREE authors, led by John McNeil, PhD, of Monash University, Melbourne, published their findings that aspirin did not reduce mortality or cardiovascular events (including stroke) in the same large cohort.
The new analysis, led by Geoffrey Cloud, MB, BS, of Monash University, focuses on stroke and intracranial bleeding outcomes. At 5 years’ follow up, the ASPREE investigators saw no significant reduction in ischemic stroke incidence associated with aspirin (hazard ratio, 0.89; 95% confidence interval, 0.71-1.11), while incidence of all types of intracranial bleeding, including hemorrhagic stroke, was significantly increased (HR, 1.38; 95% CI, 1.03-1.84).
Altogether 108 of participants taking aspirin (1.1%) experienced some form of intracranial bleeding (subdural, extradural, and/or subarachnoid), compared with 79 (0.8%) in the placebo group. Aspirin-treated patients also saw more hemorrhagic stroke (0.5% vs. 0.4%). As the ASPREE investigators had reported in an earlier paper, upper gastrointestinal bleeding occurred in significantly more aspirin-treated patients than those on placebo (HR, 1.87; 95% CI, 1.32-2.66).
“These outcomes may alter the balance of risks and benefits of an antiplatelet drug, especially if given to individuals at low risk in a primary prevention setting. This concern is relevant given the high stroke risk in older individuals, worldwide increases in populations of older individuals, and the importance of evaluating preventive strategies in this age group,” the investigators wrote.
The investigators cited the study’s large size as a strength while noting among its weaknesses that fewer stroke and bleeding events occurred during follow-up than expected, and that not all ischemic stroke events among older participants were thoroughly investigated.
Patients need to know their risk
In an interview, Shlee Song, MD, director of the stroke center at Cedars-Sinai, Los Angeles, said that the new ASPREE findings underscore the importance of careful communication with patients and their families, who may be confused about which risk group they belong to and either cease taking aspirin when it is in fact indicated, or take it when it could harm them.
“We need to be clear for our patients whether these results are relevant to them or not,” Dr. Song said. “People with a history of ischemic stroke need to know aspirin therapy is helpful in reducing risk of another stroke.”
Some patients may come to believe that because their stroke occurred a long time ago, they are in a lower-risk group. “But people need to understand that with a history of a heart attack or stroke, you’re always a separate group,” Dr. Song said. “Our job is also surveillance screening – have you had a fall this past year? Have you had a change in bowel movements? The bleeding events seen in ASPREE include bleeding in the head and bleeding in the gut.”
A key issue to stress with patients, Dr. Song said, is blood pressure management. “Patients might take aspirin because a family member had a stroke, without controlling blood pressure first. That could be the perfect storm for a head bleed: uncontrolled hypertension and an antiplatelet agent.”
The ASPREE study was funded by the National Institutes of Health in the United States and Monash University and the Victorian Cancer Agency in Australia. Three coauthors reported receiving funding or fees from drug manufacturers. Dr. Song disclosed no financial conflicts related to her comments.
according to results from a large randomized trial.
The findings, published in JAMA Network Open, bolster recommendations published in 2022 by the U.S. Preventive Services Task Force against daily aspirin for primary prevention of stroke in older adults and add to a mounting consensus that it should be avoided in the healthy elderly, for whom bleeding risks outweigh potential benefits.
Stroke was a preplanned secondary outcome of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which randomized 19,114 community-living people in Australia and the United States (56% women, 91% White) to 100 mg. daily aspirin or placebo. Participants were aged 70 and older, with the exception of U.S. Black and Hispanic individuals, who could be as young as 65. Participants did not have disability or known cardiovascular disease at baseline, and blood pressure was adequately controlled.
ASPEE findings
In 2018 the ASPREE authors, led by John McNeil, PhD, of Monash University, Melbourne, published their findings that aspirin did not reduce mortality or cardiovascular events (including stroke) in the same large cohort.
The new analysis, led by Geoffrey Cloud, MB, BS, of Monash University, focuses on stroke and intracranial bleeding outcomes. At 5 years’ follow up, the ASPREE investigators saw no significant reduction in ischemic stroke incidence associated with aspirin (hazard ratio, 0.89; 95% confidence interval, 0.71-1.11), while incidence of all types of intracranial bleeding, including hemorrhagic stroke, was significantly increased (HR, 1.38; 95% CI, 1.03-1.84).
Altogether 108 of participants taking aspirin (1.1%) experienced some form of intracranial bleeding (subdural, extradural, and/or subarachnoid), compared with 79 (0.8%) in the placebo group. Aspirin-treated patients also saw more hemorrhagic stroke (0.5% vs. 0.4%). As the ASPREE investigators had reported in an earlier paper, upper gastrointestinal bleeding occurred in significantly more aspirin-treated patients than those on placebo (HR, 1.87; 95% CI, 1.32-2.66).
“These outcomes may alter the balance of risks and benefits of an antiplatelet drug, especially if given to individuals at low risk in a primary prevention setting. This concern is relevant given the high stroke risk in older individuals, worldwide increases in populations of older individuals, and the importance of evaluating preventive strategies in this age group,” the investigators wrote.
The investigators cited the study’s large size as a strength while noting among its weaknesses that fewer stroke and bleeding events occurred during follow-up than expected, and that not all ischemic stroke events among older participants were thoroughly investigated.
Patients need to know their risk
In an interview, Shlee Song, MD, director of the stroke center at Cedars-Sinai, Los Angeles, said that the new ASPREE findings underscore the importance of careful communication with patients and their families, who may be confused about which risk group they belong to and either cease taking aspirin when it is in fact indicated, or take it when it could harm them.
“We need to be clear for our patients whether these results are relevant to them or not,” Dr. Song said. “People with a history of ischemic stroke need to know aspirin therapy is helpful in reducing risk of another stroke.”
Some patients may come to believe that because their stroke occurred a long time ago, they are in a lower-risk group. “But people need to understand that with a history of a heart attack or stroke, you’re always a separate group,” Dr. Song said. “Our job is also surveillance screening – have you had a fall this past year? Have you had a change in bowel movements? The bleeding events seen in ASPREE include bleeding in the head and bleeding in the gut.”
A key issue to stress with patients, Dr. Song said, is blood pressure management. “Patients might take aspirin because a family member had a stroke, without controlling blood pressure first. That could be the perfect storm for a head bleed: uncontrolled hypertension and an antiplatelet agent.”
The ASPREE study was funded by the National Institutes of Health in the United States and Monash University and the Victorian Cancer Agency in Australia. Three coauthors reported receiving funding or fees from drug manufacturers. Dr. Song disclosed no financial conflicts related to her comments.
according to results from a large randomized trial.
The findings, published in JAMA Network Open, bolster recommendations published in 2022 by the U.S. Preventive Services Task Force against daily aspirin for primary prevention of stroke in older adults and add to a mounting consensus that it should be avoided in the healthy elderly, for whom bleeding risks outweigh potential benefits.
Stroke was a preplanned secondary outcome of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which randomized 19,114 community-living people in Australia and the United States (56% women, 91% White) to 100 mg. daily aspirin or placebo. Participants were aged 70 and older, with the exception of U.S. Black and Hispanic individuals, who could be as young as 65. Participants did not have disability or known cardiovascular disease at baseline, and blood pressure was adequately controlled.
ASPEE findings
In 2018 the ASPREE authors, led by John McNeil, PhD, of Monash University, Melbourne, published their findings that aspirin did not reduce mortality or cardiovascular events (including stroke) in the same large cohort.
The new analysis, led by Geoffrey Cloud, MB, BS, of Monash University, focuses on stroke and intracranial bleeding outcomes. At 5 years’ follow up, the ASPREE investigators saw no significant reduction in ischemic stroke incidence associated with aspirin (hazard ratio, 0.89; 95% confidence interval, 0.71-1.11), while incidence of all types of intracranial bleeding, including hemorrhagic stroke, was significantly increased (HR, 1.38; 95% CI, 1.03-1.84).
Altogether 108 of participants taking aspirin (1.1%) experienced some form of intracranial bleeding (subdural, extradural, and/or subarachnoid), compared with 79 (0.8%) in the placebo group. Aspirin-treated patients also saw more hemorrhagic stroke (0.5% vs. 0.4%). As the ASPREE investigators had reported in an earlier paper, upper gastrointestinal bleeding occurred in significantly more aspirin-treated patients than those on placebo (HR, 1.87; 95% CI, 1.32-2.66).
“These outcomes may alter the balance of risks and benefits of an antiplatelet drug, especially if given to individuals at low risk in a primary prevention setting. This concern is relevant given the high stroke risk in older individuals, worldwide increases in populations of older individuals, and the importance of evaluating preventive strategies in this age group,” the investigators wrote.
The investigators cited the study’s large size as a strength while noting among its weaknesses that fewer stroke and bleeding events occurred during follow-up than expected, and that not all ischemic stroke events among older participants were thoroughly investigated.
Patients need to know their risk
In an interview, Shlee Song, MD, director of the stroke center at Cedars-Sinai, Los Angeles, said that the new ASPREE findings underscore the importance of careful communication with patients and their families, who may be confused about which risk group they belong to and either cease taking aspirin when it is in fact indicated, or take it when it could harm them.
“We need to be clear for our patients whether these results are relevant to them or not,” Dr. Song said. “People with a history of ischemic stroke need to know aspirin therapy is helpful in reducing risk of another stroke.”
Some patients may come to believe that because their stroke occurred a long time ago, they are in a lower-risk group. “But people need to understand that with a history of a heart attack or stroke, you’re always a separate group,” Dr. Song said. “Our job is also surveillance screening – have you had a fall this past year? Have you had a change in bowel movements? The bleeding events seen in ASPREE include bleeding in the head and bleeding in the gut.”
A key issue to stress with patients, Dr. Song said, is blood pressure management. “Patients might take aspirin because a family member had a stroke, without controlling blood pressure first. That could be the perfect storm for a head bleed: uncontrolled hypertension and an antiplatelet agent.”
The ASPREE study was funded by the National Institutes of Health in the United States and Monash University and the Victorian Cancer Agency in Australia. Three coauthors reported receiving funding or fees from drug manufacturers. Dr. Song disclosed no financial conflicts related to her comments.
FROM JAMA NETWORK OPEN
New approaches for diabetic keratopathy in the eye?
Vision loss caused by diabetes arises primarily from retinopathy, but up to 70% of people with diabetes also experience corneal problems, including keratopathy and neuropathy. Diabetic keratopathy involves impairments in epithelial wound healing, barrier function, and tear production, along with epithelial erosions and keratitis. As a result, the cornea may heal more slowly and less completely following an injury or procedures such as cataract surgery or laser therapy for diabetic retinopathy.
The abnormal wound healing is caused by impaired limbal epithelial stem cells, and the new research, published online in Diabetologia, involved isolation of those cells from 30 donor eyes of humans with and 23 without diabetes. Significant differences were found in DNA methylation between the cells of those two groups. Specifically, the WNT5A gene was hypermethylated at the promotor region in the diabetic cells and its protein markedly repressed.
However, treatment with various approaches, including exogenous WNT5A methylation inhibitors and a nanoconjugate that inhibits WNT5A suppression, improved corneal epithelial wound healing as well as expression of the limbic epithelial stem cells.
“Overall, [the] Wnt-5a [protein] is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea,” wrote Ruchi Shah, PhD, of the Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, and colleagues.
The finding represents more cellular changes than researchers had previously been aware of, study senior author Alexander Ljubimov, PhD, DSc, director of the eye program at the Institute, said in a statement.
“The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression – what are known as epigenetic alterations,” he said.
In the experiments, treatment of the impaired diabetic limbal epithelial cells with the exogenous Wnt-5a accelerated wound healing by 1.4-fold (P < .05), compared with untreated cells and reduced healing time in diabetic organ-ultured corneas by 37% (P < .05).
Treatment with the DNA methylation inhibitor zebularine also increased levels of Wnt-5a in the diabetic limbic epithelial cells by 37% (P < .01), dose-dependently stimulated wound healing by 60% at 24 hours (P < .01), and improved wound healing by 30% in diabetic organ-cultured corneas.
The finding of Wnt-5a as a new diabetic corneal marker regulating wound healing and stem cell function may have implications for other diabetes complications involving impaired wound healing, including diabetic foot ulcers, as they share similar neurovascular, sensory, and immunological compromise with diabetic eye disease, Dr. Shah and colleagues wrote.
“Novel therapies to reverse both types of epigenetic silencing could benefit corneal function and may also prove to be beneficial in other wound healing–related diabetic complications,” they wrote.
The investigators are now working on combination therapies that target both mRNA and DNA methylation in hopes of obtaining even better wound healing.
“Our goal is to develop topical, sustained-release drugs for corneal wound healing,” said Dr. Ljubimov. “Drugs that are [Food and Drug Administration] approved and could be easily applied may be one of the most promising approaches for effective future therapies.”
This work was funded by the National Institutes of Health and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. The authors reported no further disclosures.
A version of this article appeared on Medscape.com.
Vision loss caused by diabetes arises primarily from retinopathy, but up to 70% of people with diabetes also experience corneal problems, including keratopathy and neuropathy. Diabetic keratopathy involves impairments in epithelial wound healing, barrier function, and tear production, along with epithelial erosions and keratitis. As a result, the cornea may heal more slowly and less completely following an injury or procedures such as cataract surgery or laser therapy for diabetic retinopathy.
The abnormal wound healing is caused by impaired limbal epithelial stem cells, and the new research, published online in Diabetologia, involved isolation of those cells from 30 donor eyes of humans with and 23 without diabetes. Significant differences were found in DNA methylation between the cells of those two groups. Specifically, the WNT5A gene was hypermethylated at the promotor region in the diabetic cells and its protein markedly repressed.
However, treatment with various approaches, including exogenous WNT5A methylation inhibitors and a nanoconjugate that inhibits WNT5A suppression, improved corneal epithelial wound healing as well as expression of the limbic epithelial stem cells.
“Overall, [the] Wnt-5a [protein] is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea,” wrote Ruchi Shah, PhD, of the Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, and colleagues.
The finding represents more cellular changes than researchers had previously been aware of, study senior author Alexander Ljubimov, PhD, DSc, director of the eye program at the Institute, said in a statement.
“The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression – what are known as epigenetic alterations,” he said.
In the experiments, treatment of the impaired diabetic limbal epithelial cells with the exogenous Wnt-5a accelerated wound healing by 1.4-fold (P < .05), compared with untreated cells and reduced healing time in diabetic organ-ultured corneas by 37% (P < .05).
Treatment with the DNA methylation inhibitor zebularine also increased levels of Wnt-5a in the diabetic limbic epithelial cells by 37% (P < .01), dose-dependently stimulated wound healing by 60% at 24 hours (P < .01), and improved wound healing by 30% in diabetic organ-cultured corneas.
The finding of Wnt-5a as a new diabetic corneal marker regulating wound healing and stem cell function may have implications for other diabetes complications involving impaired wound healing, including diabetic foot ulcers, as they share similar neurovascular, sensory, and immunological compromise with diabetic eye disease, Dr. Shah and colleagues wrote.
“Novel therapies to reverse both types of epigenetic silencing could benefit corneal function and may also prove to be beneficial in other wound healing–related diabetic complications,” they wrote.
The investigators are now working on combination therapies that target both mRNA and DNA methylation in hopes of obtaining even better wound healing.
“Our goal is to develop topical, sustained-release drugs for corneal wound healing,” said Dr. Ljubimov. “Drugs that are [Food and Drug Administration] approved and could be easily applied may be one of the most promising approaches for effective future therapies.”
This work was funded by the National Institutes of Health and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. The authors reported no further disclosures.
A version of this article appeared on Medscape.com.
Vision loss caused by diabetes arises primarily from retinopathy, but up to 70% of people with diabetes also experience corneal problems, including keratopathy and neuropathy. Diabetic keratopathy involves impairments in epithelial wound healing, barrier function, and tear production, along with epithelial erosions and keratitis. As a result, the cornea may heal more slowly and less completely following an injury or procedures such as cataract surgery or laser therapy for diabetic retinopathy.
The abnormal wound healing is caused by impaired limbal epithelial stem cells, and the new research, published online in Diabetologia, involved isolation of those cells from 30 donor eyes of humans with and 23 without diabetes. Significant differences were found in DNA methylation between the cells of those two groups. Specifically, the WNT5A gene was hypermethylated at the promotor region in the diabetic cells and its protein markedly repressed.
However, treatment with various approaches, including exogenous WNT5A methylation inhibitors and a nanoconjugate that inhibits WNT5A suppression, improved corneal epithelial wound healing as well as expression of the limbic epithelial stem cells.
“Overall, [the] Wnt-5a [protein] is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea,” wrote Ruchi Shah, PhD, of the Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, and colleagues.
The finding represents more cellular changes than researchers had previously been aware of, study senior author Alexander Ljubimov, PhD, DSc, director of the eye program at the Institute, said in a statement.
“The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression – what are known as epigenetic alterations,” he said.
In the experiments, treatment of the impaired diabetic limbal epithelial cells with the exogenous Wnt-5a accelerated wound healing by 1.4-fold (P < .05), compared with untreated cells and reduced healing time in diabetic organ-ultured corneas by 37% (P < .05).
Treatment with the DNA methylation inhibitor zebularine also increased levels of Wnt-5a in the diabetic limbic epithelial cells by 37% (P < .01), dose-dependently stimulated wound healing by 60% at 24 hours (P < .01), and improved wound healing by 30% in diabetic organ-cultured corneas.
The finding of Wnt-5a as a new diabetic corneal marker regulating wound healing and stem cell function may have implications for other diabetes complications involving impaired wound healing, including diabetic foot ulcers, as they share similar neurovascular, sensory, and immunological compromise with diabetic eye disease, Dr. Shah and colleagues wrote.
“Novel therapies to reverse both types of epigenetic silencing could benefit corneal function and may also prove to be beneficial in other wound healing–related diabetic complications,” they wrote.
The investigators are now working on combination therapies that target both mRNA and DNA methylation in hopes of obtaining even better wound healing.
“Our goal is to develop topical, sustained-release drugs for corneal wound healing,” said Dr. Ljubimov. “Drugs that are [Food and Drug Administration] approved and could be easily applied may be one of the most promising approaches for effective future therapies.”
This work was funded by the National Institutes of Health and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. The authors reported no further disclosures.
A version of this article appeared on Medscape.com.
FROM DIABETOLOGIA
Social isolation linked to lower brain volume
Further, the association between social isolation and reduced brain volume appears to be at least partly mediated by depressive symptoms.
“We believe that efforts should be made to reduce social isolation among the elderly as much as possible,” investigator Toshiharu Ninomiya, MD, PhD, professor of epidemiology and public health at Kyushu University in Fukuoka, Japan, said in an interview.
The study was published online in Neurology.
A dementia prevention strategy
Dr. Ninomiya noted there have been several studies suggesting that social interaction is beneficial in preventing cognitive decline and the onset of dementia.
In addition, recent epidemiological studies have shown social isolation is associated with a risk for cognitive decline and dementia.
Although the investigators note that very little is known about the link between the two, some studies have shown that social isolation is linked with depressive symptoms in older adults, and late-life depression has been associated with brain atrophy.
To explore the potential link between social isolation and brain atrophy, as well as the role of depression as a potential mediator, the investigators studied nearly 9,000 citizens aged 65 and older as part of the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD), an ongoing, community-based nationwide cohort study of dementia in Japan.
Participants were recruited from eight research sites across Japan, and each had a baseline MRI scan between 2016 and 2018. The investigators excluded those with a dementia diagnosis at baseline. Self-reported frequency of social contact was categorized as every day, several times a week, several times a month, or seldom.
Participants also answered questions about medical history and treatment, antihypertensive or antidiabetic medications, exercise, current alcohol intake, and smoking habits. Depressive symptoms were assessed with the Geriatric Depression Scale. Of the participants, 57% were women, and the mean age was 73 years.
Lower brain volume
Total brain volume was lower in those with the lowest frequency of social contact vs. those with the highest frequency (67.3% vs. 67.8%). Less social contact was also linked to smaller temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala volumes.
White matter lesion volume increased with fewer social interactions, from 0.26% in the most social group to 0.30% in the least.
Cognitive function was higher in participants who had daily social contact, compared with those who had the least contact (28 vs. 27 on the Mini-Mental State Examination; P < .001). Scores between 25 and 30 are considered normal.
Depressive symptoms were lower in the daily contact group, compared with the seldom-contact group (P < .001).
The team also found that lower frequency of social contact was significantly associated with the smaller superior, middle, or inferior temporal gyrus; and a smaller fusiform gyrus, transverse temporal gyrus, temporal pole, and entorhinal cortex, among other subregions.
Mediation analyses indicated that depressive symptoms accounted for only 15%-29% of the associations of lower frequency of social contact with each regional volume.
Worse physical health
The results also showed that socially isolated participants were more likely to have diabetes, to have hypertension, to smoke, and to be physically inactive.
“Cardiovascular risk factors have been reported to cause endothelial dysfunction in the brain, which could in turn lead to problems in maintaining microcirculation and blood-brain barrier function,” the investigators write.
Some epidemiological studies have associated cardiovascular risk factors with brain atrophy, they noted, which could have been one of the underlying mechanisms.
Another possibility is that reduced cognitive stimulation due to social isolation may cause brain atrophy, they add.
“Ultimately,” Dr. Ninomiya said, “the detailed mechanism of the relationship between social isolation and brain volume is not yet clear.”
He also said more research is needed to know whether the findings would apply to people in other countries.
In an accompanying editorial, Alexa Walter, PhD, and Danielle Sandsmark, MD, PhD, from the University of Pennsylvania, Philadelphia, note that isolation has been associated with many adverse health outcomes, including increased risk of heart disease, stroke, and premature death.
“Given these findings, future work considering social health factors in the context of neurological disease is an important area of research to consider. Additionally, leveraging other existing longitudinal studies could provide us with an opportunity to better understand these relationships within populations and inform public policy to address these issues,” Dr. Walter and Dr. Sandsmark write.
The study was funded by the Japan Agency for Medical Research and Development and Suntory Holdings Limited. Dr. Ninomiya reports receiving grants from Suntory Holdings Limited.
A version of this article first appeared on Medscape.com.
Further, the association between social isolation and reduced brain volume appears to be at least partly mediated by depressive symptoms.
“We believe that efforts should be made to reduce social isolation among the elderly as much as possible,” investigator Toshiharu Ninomiya, MD, PhD, professor of epidemiology and public health at Kyushu University in Fukuoka, Japan, said in an interview.
The study was published online in Neurology.
A dementia prevention strategy
Dr. Ninomiya noted there have been several studies suggesting that social interaction is beneficial in preventing cognitive decline and the onset of dementia.
In addition, recent epidemiological studies have shown social isolation is associated with a risk for cognitive decline and dementia.
Although the investigators note that very little is known about the link between the two, some studies have shown that social isolation is linked with depressive symptoms in older adults, and late-life depression has been associated with brain atrophy.
To explore the potential link between social isolation and brain atrophy, as well as the role of depression as a potential mediator, the investigators studied nearly 9,000 citizens aged 65 and older as part of the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD), an ongoing, community-based nationwide cohort study of dementia in Japan.
Participants were recruited from eight research sites across Japan, and each had a baseline MRI scan between 2016 and 2018. The investigators excluded those with a dementia diagnosis at baseline. Self-reported frequency of social contact was categorized as every day, several times a week, several times a month, or seldom.
Participants also answered questions about medical history and treatment, antihypertensive or antidiabetic medications, exercise, current alcohol intake, and smoking habits. Depressive symptoms were assessed with the Geriatric Depression Scale. Of the participants, 57% were women, and the mean age was 73 years.
Lower brain volume
Total brain volume was lower in those with the lowest frequency of social contact vs. those with the highest frequency (67.3% vs. 67.8%). Less social contact was also linked to smaller temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala volumes.
White matter lesion volume increased with fewer social interactions, from 0.26% in the most social group to 0.30% in the least.
Cognitive function was higher in participants who had daily social contact, compared with those who had the least contact (28 vs. 27 on the Mini-Mental State Examination; P < .001). Scores between 25 and 30 are considered normal.
Depressive symptoms were lower in the daily contact group, compared with the seldom-contact group (P < .001).
The team also found that lower frequency of social contact was significantly associated with the smaller superior, middle, or inferior temporal gyrus; and a smaller fusiform gyrus, transverse temporal gyrus, temporal pole, and entorhinal cortex, among other subregions.
Mediation analyses indicated that depressive symptoms accounted for only 15%-29% of the associations of lower frequency of social contact with each regional volume.
Worse physical health
The results also showed that socially isolated participants were more likely to have diabetes, to have hypertension, to smoke, and to be physically inactive.
“Cardiovascular risk factors have been reported to cause endothelial dysfunction in the brain, which could in turn lead to problems in maintaining microcirculation and blood-brain barrier function,” the investigators write.
Some epidemiological studies have associated cardiovascular risk factors with brain atrophy, they noted, which could have been one of the underlying mechanisms.
Another possibility is that reduced cognitive stimulation due to social isolation may cause brain atrophy, they add.
“Ultimately,” Dr. Ninomiya said, “the detailed mechanism of the relationship between social isolation and brain volume is not yet clear.”
He also said more research is needed to know whether the findings would apply to people in other countries.
In an accompanying editorial, Alexa Walter, PhD, and Danielle Sandsmark, MD, PhD, from the University of Pennsylvania, Philadelphia, note that isolation has been associated with many adverse health outcomes, including increased risk of heart disease, stroke, and premature death.
“Given these findings, future work considering social health factors in the context of neurological disease is an important area of research to consider. Additionally, leveraging other existing longitudinal studies could provide us with an opportunity to better understand these relationships within populations and inform public policy to address these issues,” Dr. Walter and Dr. Sandsmark write.
The study was funded by the Japan Agency for Medical Research and Development and Suntory Holdings Limited. Dr. Ninomiya reports receiving grants from Suntory Holdings Limited.
A version of this article first appeared on Medscape.com.
Further, the association between social isolation and reduced brain volume appears to be at least partly mediated by depressive symptoms.
“We believe that efforts should be made to reduce social isolation among the elderly as much as possible,” investigator Toshiharu Ninomiya, MD, PhD, professor of epidemiology and public health at Kyushu University in Fukuoka, Japan, said in an interview.
The study was published online in Neurology.
A dementia prevention strategy
Dr. Ninomiya noted there have been several studies suggesting that social interaction is beneficial in preventing cognitive decline and the onset of dementia.
In addition, recent epidemiological studies have shown social isolation is associated with a risk for cognitive decline and dementia.
Although the investigators note that very little is known about the link between the two, some studies have shown that social isolation is linked with depressive symptoms in older adults, and late-life depression has been associated with brain atrophy.
To explore the potential link between social isolation and brain atrophy, as well as the role of depression as a potential mediator, the investigators studied nearly 9,000 citizens aged 65 and older as part of the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD), an ongoing, community-based nationwide cohort study of dementia in Japan.
Participants were recruited from eight research sites across Japan, and each had a baseline MRI scan between 2016 and 2018. The investigators excluded those with a dementia diagnosis at baseline. Self-reported frequency of social contact was categorized as every day, several times a week, several times a month, or seldom.
Participants also answered questions about medical history and treatment, antihypertensive or antidiabetic medications, exercise, current alcohol intake, and smoking habits. Depressive symptoms were assessed with the Geriatric Depression Scale. Of the participants, 57% were women, and the mean age was 73 years.
Lower brain volume
Total brain volume was lower in those with the lowest frequency of social contact vs. those with the highest frequency (67.3% vs. 67.8%). Less social contact was also linked to smaller temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala volumes.
White matter lesion volume increased with fewer social interactions, from 0.26% in the most social group to 0.30% in the least.
Cognitive function was higher in participants who had daily social contact, compared with those who had the least contact (28 vs. 27 on the Mini-Mental State Examination; P < .001). Scores between 25 and 30 are considered normal.
Depressive symptoms were lower in the daily contact group, compared with the seldom-contact group (P < .001).
The team also found that lower frequency of social contact was significantly associated with the smaller superior, middle, or inferior temporal gyrus; and a smaller fusiform gyrus, transverse temporal gyrus, temporal pole, and entorhinal cortex, among other subregions.
Mediation analyses indicated that depressive symptoms accounted for only 15%-29% of the associations of lower frequency of social contact with each regional volume.
Worse physical health
The results also showed that socially isolated participants were more likely to have diabetes, to have hypertension, to smoke, and to be physically inactive.
“Cardiovascular risk factors have been reported to cause endothelial dysfunction in the brain, which could in turn lead to problems in maintaining microcirculation and blood-brain barrier function,” the investigators write.
Some epidemiological studies have associated cardiovascular risk factors with brain atrophy, they noted, which could have been one of the underlying mechanisms.
Another possibility is that reduced cognitive stimulation due to social isolation may cause brain atrophy, they add.
“Ultimately,” Dr. Ninomiya said, “the detailed mechanism of the relationship between social isolation and brain volume is not yet clear.”
He also said more research is needed to know whether the findings would apply to people in other countries.
In an accompanying editorial, Alexa Walter, PhD, and Danielle Sandsmark, MD, PhD, from the University of Pennsylvania, Philadelphia, note that isolation has been associated with many adverse health outcomes, including increased risk of heart disease, stroke, and premature death.
“Given these findings, future work considering social health factors in the context of neurological disease is an important area of research to consider. Additionally, leveraging other existing longitudinal studies could provide us with an opportunity to better understand these relationships within populations and inform public policy to address these issues,” Dr. Walter and Dr. Sandsmark write.
The study was funded by the Japan Agency for Medical Research and Development and Suntory Holdings Limited. Dr. Ninomiya reports receiving grants from Suntory Holdings Limited.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Early MS treatment tied to a major reduction in severe disability
a new study suggests.
Patients who received early treatment had a 45% lower risk of reaching a disability score of 3 and a 60% lower risk of advancing to secondary progressive MS compared with those who began treatment 18 months or more after symptoms presented.
Those with a score of 3 can still walk unassisted but have moderate disability in one of eight areas, such as motor function, vision or thinking skills, or mild disability in three or four areas.
“With a very early treatment, within 6 months from the first symptoms and even before the MS diagnosis, we are now able to decrease long-term disability. This means the earlier the better – time is brain,” lead author Alvaro Cobo-Calvo, MD, PhD, clinical neurologists and researcher with the Multiple Sclerosis Center of Catalonia in Barcelona and the Universitat Autonoma de Barcelona, said in an interview.
The findings were published online in Neurology.
Measuring disability
The observational, retrospective study included people aged 50 years or younger who received MS treatment within 6 months of their first clinical demyelinating event (n = 194), 6-16 months later (n = 192), or more than 16 months after the initial symptoms presented (n = 194).
The investigators noted that this cohort is one of the few that is considered “deeply phenotyped,” meaning it is followed prospectively over time with strict quality controls and systematic data collection methods.
MRIs were done within 3-5 months of the first symptoms, again at 12 months after the first event, and every 5 years over a median 11.2-year follow-up.
Disability levels were measured using the Expanded Disability Status Scale, with scores ranging from 0-10 and higher scores indicating more disability.
Patients who received treatment within 6 months of first symptoms were 45% less likely to have a disability score of 3 by the end of the study than did those who received treatment more than 16 months after that first event (hazard ratio, 0.55; 95% confidence interval, 0.32-0.97).
The earliest-treatment group also had a 60% lower risk of advancing to secondary progressive MS than did people in the latest-treatment group (HR, 0.40; 95% CI, 0.19-0.85).
Better disease stability
The researchers also found that earlier treatment was associated with a 53% better chance of disease stability 1 year after initial treatment (HR, 0.47; 95% CI, 0.28-0.80).
The early-treatment group also had a lower disability progression rate and lower severe disability in a self-reported test, compared with those who were treated later.
The investigators also found that patients who received early treatment were at lower risk for disability, even those with a higher baseline radiologic burden.
Current guidelines recommend early treatment of MS, but it is unclear whether disease-modifying treatments (DMTs) should be prescribed after the first MS symptoms or after a definitive MS diagnosis.
Earlier studies often evaluated treatment efficacy after MS diagnosis. This study began tracking efficacy when therapy began after the first symptoms. In some cases, that was before a diagnosis was given.
“It is important to be cautious when starting treatment and we need to know if the patient will evolve to MS or if the patient is diagnosed with MS based on current McDonald criteria.
“In our study, 70% of patients had MS at the time of the first symptoms according to McDonald 201, but the remainder started treatment without an ‘official’ diagnosis but with an event highly suggestive of MS,” Dr. Cobo-Calvo said.
He added that very early treatment after first symptoms is key to preserving neurologic functionality.
Controversy remains
Adding MRI results as a clinical variable is a novel approach, but the MRI risk score used in the study is a new tool that has not yet been validated, the authors of an accompanying editorial noted.
“The results of this study show that in order to achieve a balance between compared groups, matching on MRI has little to add to good-quality balancing on patients’ clinical and demographic features,” wrote Erin Longbrake, MD, PhD, of the department of neurology, Yale University, New Haven, Conn., and Tomas Kalincik, MD, PhD, of the Neuroimmunology Centre, department of neurology, Royal Melbourne Hospital and the CORe unit, department of medicine, University of Melbourne.
Despite growing evidence pointing to improved outcomes from administering DMTs soon after diagnosis, the timing and sequence of therapy remains an area of controversy, they added.
“While these uncertain diagnostic scenarios may tempt neurologists to ‘wait and see,’ the data presented here remind us that these patients remain at risk of accumulating disability,” the authors wrote. “Neurologists must therefore remain vigilant to ensure that diagnosis is made promptly, that patients are followed up effectively and that effective treatments are used liberally.”
The study was funded by the European Regional Development Fund, Instituto de Salud Carlos III. Dr. Cobo-Calvo has received a grant from Instituto de Salud Carlos III. Dr. Longbrake has consulted for Genentech and NGM Bio and received research support from Biogen & Genentech. Dr. Kalincik has received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi Genzyme, Teva, BioCSL, and Merck, and has received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck.
A version of this article first appeared on Medscape.com.
a new study suggests.
Patients who received early treatment had a 45% lower risk of reaching a disability score of 3 and a 60% lower risk of advancing to secondary progressive MS compared with those who began treatment 18 months or more after symptoms presented.
Those with a score of 3 can still walk unassisted but have moderate disability in one of eight areas, such as motor function, vision or thinking skills, or mild disability in three or four areas.
“With a very early treatment, within 6 months from the first symptoms and even before the MS diagnosis, we are now able to decrease long-term disability. This means the earlier the better – time is brain,” lead author Alvaro Cobo-Calvo, MD, PhD, clinical neurologists and researcher with the Multiple Sclerosis Center of Catalonia in Barcelona and the Universitat Autonoma de Barcelona, said in an interview.
The findings were published online in Neurology.
Measuring disability
The observational, retrospective study included people aged 50 years or younger who received MS treatment within 6 months of their first clinical demyelinating event (n = 194), 6-16 months later (n = 192), or more than 16 months after the initial symptoms presented (n = 194).
The investigators noted that this cohort is one of the few that is considered “deeply phenotyped,” meaning it is followed prospectively over time with strict quality controls and systematic data collection methods.
MRIs were done within 3-5 months of the first symptoms, again at 12 months after the first event, and every 5 years over a median 11.2-year follow-up.
Disability levels were measured using the Expanded Disability Status Scale, with scores ranging from 0-10 and higher scores indicating more disability.
Patients who received treatment within 6 months of first symptoms were 45% less likely to have a disability score of 3 by the end of the study than did those who received treatment more than 16 months after that first event (hazard ratio, 0.55; 95% confidence interval, 0.32-0.97).
The earliest-treatment group also had a 60% lower risk of advancing to secondary progressive MS than did people in the latest-treatment group (HR, 0.40; 95% CI, 0.19-0.85).
Better disease stability
The researchers also found that earlier treatment was associated with a 53% better chance of disease stability 1 year after initial treatment (HR, 0.47; 95% CI, 0.28-0.80).
The early-treatment group also had a lower disability progression rate and lower severe disability in a self-reported test, compared with those who were treated later.
The investigators also found that patients who received early treatment were at lower risk for disability, even those with a higher baseline radiologic burden.
Current guidelines recommend early treatment of MS, but it is unclear whether disease-modifying treatments (DMTs) should be prescribed after the first MS symptoms or after a definitive MS diagnosis.
Earlier studies often evaluated treatment efficacy after MS diagnosis. This study began tracking efficacy when therapy began after the first symptoms. In some cases, that was before a diagnosis was given.
“It is important to be cautious when starting treatment and we need to know if the patient will evolve to MS or if the patient is diagnosed with MS based on current McDonald criteria.
“In our study, 70% of patients had MS at the time of the first symptoms according to McDonald 201, but the remainder started treatment without an ‘official’ diagnosis but with an event highly suggestive of MS,” Dr. Cobo-Calvo said.
He added that very early treatment after first symptoms is key to preserving neurologic functionality.
Controversy remains
Adding MRI results as a clinical variable is a novel approach, but the MRI risk score used in the study is a new tool that has not yet been validated, the authors of an accompanying editorial noted.
“The results of this study show that in order to achieve a balance between compared groups, matching on MRI has little to add to good-quality balancing on patients’ clinical and demographic features,” wrote Erin Longbrake, MD, PhD, of the department of neurology, Yale University, New Haven, Conn., and Tomas Kalincik, MD, PhD, of the Neuroimmunology Centre, department of neurology, Royal Melbourne Hospital and the CORe unit, department of medicine, University of Melbourne.
Despite growing evidence pointing to improved outcomes from administering DMTs soon after diagnosis, the timing and sequence of therapy remains an area of controversy, they added.
“While these uncertain diagnostic scenarios may tempt neurologists to ‘wait and see,’ the data presented here remind us that these patients remain at risk of accumulating disability,” the authors wrote. “Neurologists must therefore remain vigilant to ensure that diagnosis is made promptly, that patients are followed up effectively and that effective treatments are used liberally.”
The study was funded by the European Regional Development Fund, Instituto de Salud Carlos III. Dr. Cobo-Calvo has received a grant from Instituto de Salud Carlos III. Dr. Longbrake has consulted for Genentech and NGM Bio and received research support from Biogen & Genentech. Dr. Kalincik has received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi Genzyme, Teva, BioCSL, and Merck, and has received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck.
A version of this article first appeared on Medscape.com.
a new study suggests.
Patients who received early treatment had a 45% lower risk of reaching a disability score of 3 and a 60% lower risk of advancing to secondary progressive MS compared with those who began treatment 18 months or more after symptoms presented.
Those with a score of 3 can still walk unassisted but have moderate disability in one of eight areas, such as motor function, vision or thinking skills, or mild disability in three or four areas.
“With a very early treatment, within 6 months from the first symptoms and even before the MS diagnosis, we are now able to decrease long-term disability. This means the earlier the better – time is brain,” lead author Alvaro Cobo-Calvo, MD, PhD, clinical neurologists and researcher with the Multiple Sclerosis Center of Catalonia in Barcelona and the Universitat Autonoma de Barcelona, said in an interview.
The findings were published online in Neurology.
Measuring disability
The observational, retrospective study included people aged 50 years or younger who received MS treatment within 6 months of their first clinical demyelinating event (n = 194), 6-16 months later (n = 192), or more than 16 months after the initial symptoms presented (n = 194).
The investigators noted that this cohort is one of the few that is considered “deeply phenotyped,” meaning it is followed prospectively over time with strict quality controls and systematic data collection methods.
MRIs were done within 3-5 months of the first symptoms, again at 12 months after the first event, and every 5 years over a median 11.2-year follow-up.
Disability levels were measured using the Expanded Disability Status Scale, with scores ranging from 0-10 and higher scores indicating more disability.
Patients who received treatment within 6 months of first symptoms were 45% less likely to have a disability score of 3 by the end of the study than did those who received treatment more than 16 months after that first event (hazard ratio, 0.55; 95% confidence interval, 0.32-0.97).
The earliest-treatment group also had a 60% lower risk of advancing to secondary progressive MS than did people in the latest-treatment group (HR, 0.40; 95% CI, 0.19-0.85).
Better disease stability
The researchers also found that earlier treatment was associated with a 53% better chance of disease stability 1 year after initial treatment (HR, 0.47; 95% CI, 0.28-0.80).
The early-treatment group also had a lower disability progression rate and lower severe disability in a self-reported test, compared with those who were treated later.
The investigators also found that patients who received early treatment were at lower risk for disability, even those with a higher baseline radiologic burden.
Current guidelines recommend early treatment of MS, but it is unclear whether disease-modifying treatments (DMTs) should be prescribed after the first MS symptoms or after a definitive MS diagnosis.
Earlier studies often evaluated treatment efficacy after MS diagnosis. This study began tracking efficacy when therapy began after the first symptoms. In some cases, that was before a diagnosis was given.
“It is important to be cautious when starting treatment and we need to know if the patient will evolve to MS or if the patient is diagnosed with MS based on current McDonald criteria.
“In our study, 70% of patients had MS at the time of the first symptoms according to McDonald 201, but the remainder started treatment without an ‘official’ diagnosis but with an event highly suggestive of MS,” Dr. Cobo-Calvo said.
He added that very early treatment after first symptoms is key to preserving neurologic functionality.
Controversy remains
Adding MRI results as a clinical variable is a novel approach, but the MRI risk score used in the study is a new tool that has not yet been validated, the authors of an accompanying editorial noted.
“The results of this study show that in order to achieve a balance between compared groups, matching on MRI has little to add to good-quality balancing on patients’ clinical and demographic features,” wrote Erin Longbrake, MD, PhD, of the department of neurology, Yale University, New Haven, Conn., and Tomas Kalincik, MD, PhD, of the Neuroimmunology Centre, department of neurology, Royal Melbourne Hospital and the CORe unit, department of medicine, University of Melbourne.
Despite growing evidence pointing to improved outcomes from administering DMTs soon after diagnosis, the timing and sequence of therapy remains an area of controversy, they added.
“While these uncertain diagnostic scenarios may tempt neurologists to ‘wait and see,’ the data presented here remind us that these patients remain at risk of accumulating disability,” the authors wrote. “Neurologists must therefore remain vigilant to ensure that diagnosis is made promptly, that patients are followed up effectively and that effective treatments are used liberally.”
The study was funded by the European Regional Development Fund, Instituto de Salud Carlos III. Dr. Cobo-Calvo has received a grant from Instituto de Salud Carlos III. Dr. Longbrake has consulted for Genentech and NGM Bio and received research support from Biogen & Genentech. Dr. Kalincik has received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi Genzyme, Teva, BioCSL, and Merck, and has received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Vegetarian diets can improve high-risk cardiovascular disease
, a meta-analysis of randomized controlled trials shows.
“To the best of our knowledge, this meta-analysis is the first that generates evidence from randomized controlled trials to assess the association of vegetarian diets with outcomes in people affected by cardiovascular diseases,” report the authors. The study was published online in JAMA Network Open.
“The greatest improvements in hemoglobin A1c and low-density lipoprotein cholesterol (LDL-C) were observed in individuals with type 2 diabetes and people at high risk of cardiovascular disease, highlighting the potential protective and synergistic effects of vegetarian diets for the primary prevention of cardiovascular disease,” they say.
Poor diet is well-established as increasing the morbidity and mortality associated with cardiovascular disease; however, although data has linked vegetarian diets to cardiovascular disease prevention in the general population, research on the effectiveness of such diets in people at high risk of cardiovascular disease is lacking.
“To the best of our knowledge, no meta-analysis of randomized controlled trials has been conducted to investigate the association of vegetarian diets with outcomes among people with CVD – indeed, research here has primarily focused on observational studies,” writes Tian Wang, RD, and colleagues at the University of Sydney.
Greater decreases in LDL-C, A1c, and body weight with vegetarian diets
For the meta-analysis, researchers identified 20 randomized controlled trials involving vegetarian diets that included 1,878 adults with or at a high risk of cardiovascular disease and included measurements of LDL-C, A1c, or systolic blood pressure.
The studies were conducted in the United States, Asia, Europe, and New Zealand between 1990 and 2021. Sample sizes ranged from 12 to 291 participants.
The mean range age of participants was 28-64 years. Studies included patients with cardiovascular disease (four studies), diabetes (seven studies), and those with at least two cardiovascular risk factors (nine studies).
The mean duration of the dietary intervention was 25.4 weeks (range 2-24 months). The most commonly prescribed diets were vegan (plant-based foods only), lacto-ovo-vegetarian (excluded meat, poultry, seafood, and dairy products, but allowed eggs), and lacto-vegetarian (same as previous but allowed dairy products).
Overall, those who consumed a vegetarian diet for an average of 6 months, versus comparison diets, had significantly greater decreases in LDL-C (6.6 mg/dL beyond the reduction achieved with standard therapy); A1c (0.24%); and body weight (3.4 kg), but the reduction in systolic blood pressure (0.1 mmHg) was not significantly greater.
Assessment of the overall certainty of evidence evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool showed a moderate level of evidence for reductions in LDL-C and A1c with the vegetarian diet.
Lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (14.1 mg/dL); however, four out of the five trials restricted energy intake.
Of note, vegetarian diets were most effective for achieving glycemic control among people with type 2 diabetes and leading to improvements in weight among those at high risk of cardiovascular disease as well as those with type 2 diabetes.
The effects “suggest that vegetarian diets might have a synergistic [or at least nonantagonistic] use in potentiating the effects of optimal drug therapy in the prevention and treatment of a range of cardiometabolic diseases,” the authors write.
Although previous studies have shown similar improvements associated with a vegetarian diet, most studies did not stratify populations based on disease status, type of vegetarian diet, or comparison diet, the authors note.
The lack of improvement in systolic blood pressure is consistent with previous meta-analyses of vegetarian diets in general and suggests that salt intake may be the more important factor for those measures.
“[The meta-analysis] suggests that diet quality plays a major role in lowering blood pressure independent of animal food consumption, as the DASH [Dietary Approaches to Stop Hypertension] ... trial demonstrated,” the authors note.
Decreases in medication dose with vegetarian diet
Although most patients were taking medications to manage hypertension, hyperglycemia, and/or dyslipidemia at trial enrollment in as many as eight of the studies, the vegetarian diet intervention resulted in a decrease in medication dose.
In fact, medication use could obscure the favorable effects of vegetarian diets, which could have a larger effect size, the authors speculate.
“This hypothesis is supported by two randomized controlled trials in our meta-analysis that required patients not to take medication that could influence cardiometabolic outcomes, [and] these studies significantly improved systolic blood pressure and LDL-C,” they write.
Not all vegetarian diets are healthy
Although there are numerous variations in vegetarian diets, ranging from vegan diets that eliminate all animal food to pesco-vegetarian diets that allow fish or seafood, most that are well-balanced can provide health benefits including lower saturated fat, L-carnitine, and choline (precursors of the atherogenic TMAO), and other benefits that might explain the improvements seen in the meta-analysis.
The diets may also be high in dietary fiber, mono- and polyunsaturated fatty acids, potassium, magnesium, and phytochemical, and have lower glycemic index scores.
Of note, 12 studies in the meta-analysis emphasized low-fat content, which the authors speculate may have contributed to the improvements observed in LDC-C.
Specifically, lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (–14.1 mg/dL); however, four out of five of the trials restricted energy intake, which could have also played a role in improvements.
Importantly, not all vegetarian diets are healthy, and the authors caution about some that allow, for instance, deep-fried foods rich in trans-fatty acids and salt, such as tempura vegetables, potentially increasing the risk of type 2 diabetes and coronary heart disease.
They note that “more than one-third of the studies included in our meta-analysis did not emphasize the importance of consuming minimally processed plant-based whole foods.”
Overall, however, the fact that the greatest improvements in A1c and LDL-C were seen in patients with type 2 diabetes and those at high risk of CVD “highlight[s] the potential protective and synergistic effects of vegetarian diets for the primary prevention of CVD.”
A version of this article first appeared on Medscape.com.
, a meta-analysis of randomized controlled trials shows.
“To the best of our knowledge, this meta-analysis is the first that generates evidence from randomized controlled trials to assess the association of vegetarian diets with outcomes in people affected by cardiovascular diseases,” report the authors. The study was published online in JAMA Network Open.
“The greatest improvements in hemoglobin A1c and low-density lipoprotein cholesterol (LDL-C) were observed in individuals with type 2 diabetes and people at high risk of cardiovascular disease, highlighting the potential protective and synergistic effects of vegetarian diets for the primary prevention of cardiovascular disease,” they say.
Poor diet is well-established as increasing the morbidity and mortality associated with cardiovascular disease; however, although data has linked vegetarian diets to cardiovascular disease prevention in the general population, research on the effectiveness of such diets in people at high risk of cardiovascular disease is lacking.
“To the best of our knowledge, no meta-analysis of randomized controlled trials has been conducted to investigate the association of vegetarian diets with outcomes among people with CVD – indeed, research here has primarily focused on observational studies,” writes Tian Wang, RD, and colleagues at the University of Sydney.
Greater decreases in LDL-C, A1c, and body weight with vegetarian diets
For the meta-analysis, researchers identified 20 randomized controlled trials involving vegetarian diets that included 1,878 adults with or at a high risk of cardiovascular disease and included measurements of LDL-C, A1c, or systolic blood pressure.
The studies were conducted in the United States, Asia, Europe, and New Zealand between 1990 and 2021. Sample sizes ranged from 12 to 291 participants.
The mean range age of participants was 28-64 years. Studies included patients with cardiovascular disease (four studies), diabetes (seven studies), and those with at least two cardiovascular risk factors (nine studies).
The mean duration of the dietary intervention was 25.4 weeks (range 2-24 months). The most commonly prescribed diets were vegan (plant-based foods only), lacto-ovo-vegetarian (excluded meat, poultry, seafood, and dairy products, but allowed eggs), and lacto-vegetarian (same as previous but allowed dairy products).
Overall, those who consumed a vegetarian diet for an average of 6 months, versus comparison diets, had significantly greater decreases in LDL-C (6.6 mg/dL beyond the reduction achieved with standard therapy); A1c (0.24%); and body weight (3.4 kg), but the reduction in systolic blood pressure (0.1 mmHg) was not significantly greater.
Assessment of the overall certainty of evidence evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool showed a moderate level of evidence for reductions in LDL-C and A1c with the vegetarian diet.
Lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (14.1 mg/dL); however, four out of the five trials restricted energy intake.
Of note, vegetarian diets were most effective for achieving glycemic control among people with type 2 diabetes and leading to improvements in weight among those at high risk of cardiovascular disease as well as those with type 2 diabetes.
The effects “suggest that vegetarian diets might have a synergistic [or at least nonantagonistic] use in potentiating the effects of optimal drug therapy in the prevention and treatment of a range of cardiometabolic diseases,” the authors write.
Although previous studies have shown similar improvements associated with a vegetarian diet, most studies did not stratify populations based on disease status, type of vegetarian diet, or comparison diet, the authors note.
The lack of improvement in systolic blood pressure is consistent with previous meta-analyses of vegetarian diets in general and suggests that salt intake may be the more important factor for those measures.
“[The meta-analysis] suggests that diet quality plays a major role in lowering blood pressure independent of animal food consumption, as the DASH [Dietary Approaches to Stop Hypertension] ... trial demonstrated,” the authors note.
Decreases in medication dose with vegetarian diet
Although most patients were taking medications to manage hypertension, hyperglycemia, and/or dyslipidemia at trial enrollment in as many as eight of the studies, the vegetarian diet intervention resulted in a decrease in medication dose.
In fact, medication use could obscure the favorable effects of vegetarian diets, which could have a larger effect size, the authors speculate.
“This hypothesis is supported by two randomized controlled trials in our meta-analysis that required patients not to take medication that could influence cardiometabolic outcomes, [and] these studies significantly improved systolic blood pressure and LDL-C,” they write.
Not all vegetarian diets are healthy
Although there are numerous variations in vegetarian diets, ranging from vegan diets that eliminate all animal food to pesco-vegetarian diets that allow fish or seafood, most that are well-balanced can provide health benefits including lower saturated fat, L-carnitine, and choline (precursors of the atherogenic TMAO), and other benefits that might explain the improvements seen in the meta-analysis.
The diets may also be high in dietary fiber, mono- and polyunsaturated fatty acids, potassium, magnesium, and phytochemical, and have lower glycemic index scores.
Of note, 12 studies in the meta-analysis emphasized low-fat content, which the authors speculate may have contributed to the improvements observed in LDC-C.
Specifically, lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (–14.1 mg/dL); however, four out of five of the trials restricted energy intake, which could have also played a role in improvements.
Importantly, not all vegetarian diets are healthy, and the authors caution about some that allow, for instance, deep-fried foods rich in trans-fatty acids and salt, such as tempura vegetables, potentially increasing the risk of type 2 diabetes and coronary heart disease.
They note that “more than one-third of the studies included in our meta-analysis did not emphasize the importance of consuming minimally processed plant-based whole foods.”
Overall, however, the fact that the greatest improvements in A1c and LDL-C were seen in patients with type 2 diabetes and those at high risk of CVD “highlight[s] the potential protective and synergistic effects of vegetarian diets for the primary prevention of CVD.”
A version of this article first appeared on Medscape.com.
, a meta-analysis of randomized controlled trials shows.
“To the best of our knowledge, this meta-analysis is the first that generates evidence from randomized controlled trials to assess the association of vegetarian diets with outcomes in people affected by cardiovascular diseases,” report the authors. The study was published online in JAMA Network Open.
“The greatest improvements in hemoglobin A1c and low-density lipoprotein cholesterol (LDL-C) were observed in individuals with type 2 diabetes and people at high risk of cardiovascular disease, highlighting the potential protective and synergistic effects of vegetarian diets for the primary prevention of cardiovascular disease,” they say.
Poor diet is well-established as increasing the morbidity and mortality associated with cardiovascular disease; however, although data has linked vegetarian diets to cardiovascular disease prevention in the general population, research on the effectiveness of such diets in people at high risk of cardiovascular disease is lacking.
“To the best of our knowledge, no meta-analysis of randomized controlled trials has been conducted to investigate the association of vegetarian diets with outcomes among people with CVD – indeed, research here has primarily focused on observational studies,” writes Tian Wang, RD, and colleagues at the University of Sydney.
Greater decreases in LDL-C, A1c, and body weight with vegetarian diets
For the meta-analysis, researchers identified 20 randomized controlled trials involving vegetarian diets that included 1,878 adults with or at a high risk of cardiovascular disease and included measurements of LDL-C, A1c, or systolic blood pressure.
The studies were conducted in the United States, Asia, Europe, and New Zealand between 1990 and 2021. Sample sizes ranged from 12 to 291 participants.
The mean range age of participants was 28-64 years. Studies included patients with cardiovascular disease (four studies), diabetes (seven studies), and those with at least two cardiovascular risk factors (nine studies).
The mean duration of the dietary intervention was 25.4 weeks (range 2-24 months). The most commonly prescribed diets were vegan (plant-based foods only), lacto-ovo-vegetarian (excluded meat, poultry, seafood, and dairy products, but allowed eggs), and lacto-vegetarian (same as previous but allowed dairy products).
Overall, those who consumed a vegetarian diet for an average of 6 months, versus comparison diets, had significantly greater decreases in LDL-C (6.6 mg/dL beyond the reduction achieved with standard therapy); A1c (0.24%); and body weight (3.4 kg), but the reduction in systolic blood pressure (0.1 mmHg) was not significantly greater.
Assessment of the overall certainty of evidence evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool showed a moderate level of evidence for reductions in LDL-C and A1c with the vegetarian diet.
Lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (14.1 mg/dL); however, four out of the five trials restricted energy intake.
Of note, vegetarian diets were most effective for achieving glycemic control among people with type 2 diabetes and leading to improvements in weight among those at high risk of cardiovascular disease as well as those with type 2 diabetes.
The effects “suggest that vegetarian diets might have a synergistic [or at least nonantagonistic] use in potentiating the effects of optimal drug therapy in the prevention and treatment of a range of cardiometabolic diseases,” the authors write.
Although previous studies have shown similar improvements associated with a vegetarian diet, most studies did not stratify populations based on disease status, type of vegetarian diet, or comparison diet, the authors note.
The lack of improvement in systolic blood pressure is consistent with previous meta-analyses of vegetarian diets in general and suggests that salt intake may be the more important factor for those measures.
“[The meta-analysis] suggests that diet quality plays a major role in lowering blood pressure independent of animal food consumption, as the DASH [Dietary Approaches to Stop Hypertension] ... trial demonstrated,” the authors note.
Decreases in medication dose with vegetarian diet
Although most patients were taking medications to manage hypertension, hyperglycemia, and/or dyslipidemia at trial enrollment in as many as eight of the studies, the vegetarian diet intervention resulted in a decrease in medication dose.
In fact, medication use could obscure the favorable effects of vegetarian diets, which could have a larger effect size, the authors speculate.
“This hypothesis is supported by two randomized controlled trials in our meta-analysis that required patients not to take medication that could influence cardiometabolic outcomes, [and] these studies significantly improved systolic blood pressure and LDL-C,” they write.
Not all vegetarian diets are healthy
Although there are numerous variations in vegetarian diets, ranging from vegan diets that eliminate all animal food to pesco-vegetarian diets that allow fish or seafood, most that are well-balanced can provide health benefits including lower saturated fat, L-carnitine, and choline (precursors of the atherogenic TMAO), and other benefits that might explain the improvements seen in the meta-analysis.
The diets may also be high in dietary fiber, mono- and polyunsaturated fatty acids, potassium, magnesium, and phytochemical, and have lower glycemic index scores.
Of note, 12 studies in the meta-analysis emphasized low-fat content, which the authors speculate may have contributed to the improvements observed in LDC-C.
Specifically, lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (–14.1 mg/dL); however, four out of five of the trials restricted energy intake, which could have also played a role in improvements.
Importantly, not all vegetarian diets are healthy, and the authors caution about some that allow, for instance, deep-fried foods rich in trans-fatty acids and salt, such as tempura vegetables, potentially increasing the risk of type 2 diabetes and coronary heart disease.
They note that “more than one-third of the studies included in our meta-analysis did not emphasize the importance of consuming minimally processed plant-based whole foods.”
Overall, however, the fact that the greatest improvements in A1c and LDL-C were seen in patients with type 2 diabetes and those at high risk of CVD “highlight[s] the potential protective and synergistic effects of vegetarian diets for the primary prevention of CVD.”
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
SGLT2 inhibitors linked with fewer gout flares in diabetes
TOPLINE:
compared with matched patients treated with a dipeptidyl peptidase–4 (DPP-4) inhibitor.
METHODOLOGY:
- The study used observational data collected from the entire population of British Columbia that included 15,067 adults with both gout and type 2 diabetes in 2014-2020.
- The group included 8,318 patients who initiated an SGLT2 inhibitor and 6,749 patients who initiated a DPP-4 inhibitor during the study period after at least 1 year of continuous enrollment.
- Using propensity-score matching, 4,075 matched pairs were identified, where one person initiated an SGLT2 inhibitor and the other started a DPP-4 inhibitor.
- Primary outcome was recurrent gout flare counts during follow-up that required an ED visit, hospital admission, or an outpatient visit for a gout flare coupled with appropriate treatment, tallied from the first day of drug receipt until June 30, 2022, with an average follow-up of 1.6 years.
- Secondary endpoints included the incidence of myocardial infarction and stroke.
TAKEAWAY:
- Total gout-flare rates after SGLT2 inhibitor initiation were 52.4/1000 person-years and after DPP-4 inhibitor initiation were 79.7/1,000 person-years, an adjusted rate ratio of 0.66, a reduction significantly linked with SGLT2 inhibitor use.
- For flares that required an ED visit or hospitalization, initiation of an SGLT2 inhibitor was linked with a significant, reduced aRR of 0.52, compared with DPP-4 inhibitor initiation.
- The flare-rate reduction linked with SGLT2 inhibitor use was consistent regardless of sex, age, baseline diuretic use, prior treatment with a urate-lowering agent, and baseline gout intensity.
- SGLT2 inhibitor initiation was also significantly linked with an adjusted reduced hazard ratio of 0.69 in the incidence of myocardial infarction, compared with DPP-4 inhibitor initiation, but stroke incidence was not significantly different between the groups.
IN PRACTICE:
These findings suggest that SGLT2 inhibitors could have a much-needed ability to simultaneously reduce the burden of recurrent gout flares and coronary sequelae in patients with gout and type 2 diabetes, indicating that “SGLT2 inhibitors may offer distinct benefits,” making the drug class “a particularly attractive addition to current urate-lowering therapies,” the researchers write.
SOURCE:
The study was primarily conducted by researchers at Massachusetts General Hospital in Boston. The study was published online July 24 in Annals of Internal Medicine.
LIMITATIONS:
The data used in the study did not include gout flares that did not require medical attention and did not include laboratory findings for study participants. Because the data were observational the findings may be susceptible to unmeasured confounding.
DISCLOSURES:
The study received no commercial funding. One author has reported receiving consulting fees from ANI and LG Chem.
A version of this article first appeared on Medscape.com.
TOPLINE:
compared with matched patients treated with a dipeptidyl peptidase–4 (DPP-4) inhibitor.
METHODOLOGY:
- The study used observational data collected from the entire population of British Columbia that included 15,067 adults with both gout and type 2 diabetes in 2014-2020.
- The group included 8,318 patients who initiated an SGLT2 inhibitor and 6,749 patients who initiated a DPP-4 inhibitor during the study period after at least 1 year of continuous enrollment.
- Using propensity-score matching, 4,075 matched pairs were identified, where one person initiated an SGLT2 inhibitor and the other started a DPP-4 inhibitor.
- Primary outcome was recurrent gout flare counts during follow-up that required an ED visit, hospital admission, or an outpatient visit for a gout flare coupled with appropriate treatment, tallied from the first day of drug receipt until June 30, 2022, with an average follow-up of 1.6 years.
- Secondary endpoints included the incidence of myocardial infarction and stroke.
TAKEAWAY:
- Total gout-flare rates after SGLT2 inhibitor initiation were 52.4/1000 person-years and after DPP-4 inhibitor initiation were 79.7/1,000 person-years, an adjusted rate ratio of 0.66, a reduction significantly linked with SGLT2 inhibitor use.
- For flares that required an ED visit or hospitalization, initiation of an SGLT2 inhibitor was linked with a significant, reduced aRR of 0.52, compared with DPP-4 inhibitor initiation.
- The flare-rate reduction linked with SGLT2 inhibitor use was consistent regardless of sex, age, baseline diuretic use, prior treatment with a urate-lowering agent, and baseline gout intensity.
- SGLT2 inhibitor initiation was also significantly linked with an adjusted reduced hazard ratio of 0.69 in the incidence of myocardial infarction, compared with DPP-4 inhibitor initiation, but stroke incidence was not significantly different between the groups.
IN PRACTICE:
These findings suggest that SGLT2 inhibitors could have a much-needed ability to simultaneously reduce the burden of recurrent gout flares and coronary sequelae in patients with gout and type 2 diabetes, indicating that “SGLT2 inhibitors may offer distinct benefits,” making the drug class “a particularly attractive addition to current urate-lowering therapies,” the researchers write.
SOURCE:
The study was primarily conducted by researchers at Massachusetts General Hospital in Boston. The study was published online July 24 in Annals of Internal Medicine.
LIMITATIONS:
The data used in the study did not include gout flares that did not require medical attention and did not include laboratory findings for study participants. Because the data were observational the findings may be susceptible to unmeasured confounding.
DISCLOSURES:
The study received no commercial funding. One author has reported receiving consulting fees from ANI and LG Chem.
A version of this article first appeared on Medscape.com.
TOPLINE:
compared with matched patients treated with a dipeptidyl peptidase–4 (DPP-4) inhibitor.
METHODOLOGY:
- The study used observational data collected from the entire population of British Columbia that included 15,067 adults with both gout and type 2 diabetes in 2014-2020.
- The group included 8,318 patients who initiated an SGLT2 inhibitor and 6,749 patients who initiated a DPP-4 inhibitor during the study period after at least 1 year of continuous enrollment.
- Using propensity-score matching, 4,075 matched pairs were identified, where one person initiated an SGLT2 inhibitor and the other started a DPP-4 inhibitor.
- Primary outcome was recurrent gout flare counts during follow-up that required an ED visit, hospital admission, or an outpatient visit for a gout flare coupled with appropriate treatment, tallied from the first day of drug receipt until June 30, 2022, with an average follow-up of 1.6 years.
- Secondary endpoints included the incidence of myocardial infarction and stroke.
TAKEAWAY:
- Total gout-flare rates after SGLT2 inhibitor initiation were 52.4/1000 person-years and after DPP-4 inhibitor initiation were 79.7/1,000 person-years, an adjusted rate ratio of 0.66, a reduction significantly linked with SGLT2 inhibitor use.
- For flares that required an ED visit or hospitalization, initiation of an SGLT2 inhibitor was linked with a significant, reduced aRR of 0.52, compared with DPP-4 inhibitor initiation.
- The flare-rate reduction linked with SGLT2 inhibitor use was consistent regardless of sex, age, baseline diuretic use, prior treatment with a urate-lowering agent, and baseline gout intensity.
- SGLT2 inhibitor initiation was also significantly linked with an adjusted reduced hazard ratio of 0.69 in the incidence of myocardial infarction, compared with DPP-4 inhibitor initiation, but stroke incidence was not significantly different between the groups.
IN PRACTICE:
These findings suggest that SGLT2 inhibitors could have a much-needed ability to simultaneously reduce the burden of recurrent gout flares and coronary sequelae in patients with gout and type 2 diabetes, indicating that “SGLT2 inhibitors may offer distinct benefits,” making the drug class “a particularly attractive addition to current urate-lowering therapies,” the researchers write.
SOURCE:
The study was primarily conducted by researchers at Massachusetts General Hospital in Boston. The study was published online July 24 in Annals of Internal Medicine.
LIMITATIONS:
The data used in the study did not include gout flares that did not require medical attention and did not include laboratory findings for study participants. Because the data were observational the findings may be susceptible to unmeasured confounding.
DISCLOSURES:
The study received no commercial funding. One author has reported receiving consulting fees from ANI and LG Chem.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Functional MRI shows that empathetic remarks reduce pain
These are the results of a study, recently published in the Proceedings of the National Academy of Sciences, that was conducted by a team led by neuroscientist Dan-Mikael Ellingsen, PhD, from Oslo University Hospital.
The researchers used functional MRI to scan the brains of 20 patients with chronic pain to investigate how a physician’s demeanor may affect patients’ sensitivity to pain, including effects in the central nervous system. During the scans, which were conducted in two sessions, the patients’ legs were exposed to stimuli that ranged from painless to moderately painful. The patients recorded perceived pain intensity using a scale. The physicians also underwent fMRI.
Half of the patients were subjected to the pain stimuli while alone; the other half were subjected to pain while in the presence of a physician. The latter group of patients was divided into two subgroups. Half of the patients had spoken to the accompanying physician before the examination. They discussed the history of the patient’s condition to date, among other things. The other half underwent the brain scans without any prior interaction with a physician.
Worse when alone
Dr. Ellingsen and his colleagues found that patients who were alone during the examination reported greater pain than those who were in the presence of a physician, even though they were subjected to stimuli of the same intensity. In instances in which the physician and patient had already spoken before the brain scan, patients additionally felt that the physician was empathetic and understood their pain. Furthermore, the physicians were better able to estimate the pain that their patients experienced.
The patients who had a physician by their side consistently experienced pain that was milder than the pain experienced by those who were alone. For pairs that had spoken beforehand, the patients considered their physician to be better able to understand their pain, and the physicians estimated the perceived pain intensity of their patients more accurately.
Evidence of trust
There was greater activity in the dorsolateral and ventrolateral prefrontal cortex, as well as in the primary and secondary somatosensory areas, in patients in the subgroup that had spoken to a physician. For the physicians, compared with the comparison group, there was an increase in correspondence between activity in the dorsolateral prefrontal cortex and activity in the secondary somatosensory areas of patients, which is a brain region that is known to react to pain. The brain activity correlation increased in line with the self-reported mutual trust between the physician and patient.
“These results prove that empathy and support can decrease pain intensity,” the investigators write. The data shed light on the brain processes behind the social modulation of pain during the interaction between the physician and the patient. Concordances in the brain are increased by greater therapeutic alliance.
Beyond medication
Winfried Meissner, MD, head of the pain clinic at the department of anesthesiology and intensive care medicine at Jena University Hospital, Germany, and former president of the German Pain Society, said in an interview: “I view this as a vital study that impressively demonstrates that effective, intensive pain therapy is not just a case of administering the correct analgesic.”
“Instead, a focus should be placed on what common sense tells us, which is just how crucial an empathetic attitude from physicians and good communication with patients are when it comes to the success of any therapy,” Dr. Meissner added. Unfortunately, such an attitude and such communication often are not provided in clinical practice because of limitations on time.
“Now, with objectively collected data from patients and physicians, [Dr.] Ellingsen’s team has been able to demonstrate that human interaction has a decisive impact on the treatment of patients experiencing pain,” said Dr. Meissner. “The study should encourage practitioners to treat communication just as seriously as the pharmacology of analgesics.”
Perception and attitude
“The study shows remarkably well that empathetic conversation between the physician and patient represents a valuable therapeutic method and should be recognized as such,” emphasized Dr. Meissner. Of course, conversation cannot replace pharmacologic treatment, but it can supplement and reinforce it. Furthermore, a physician’s empathy presumably has an effect that is at least as great as a suitable analgesic.
“Pain is more than just sensory perception,” explained Dr. Meissner. “We all know that it has a strong affective component, and perception is greatly determined by context.” This can be seen, for example, in athletes, who often attribute less importance to their pain and can successfully perform competitively despite a painful injury.
Positive expectations
Dr. Meissner advised all physicians to treat patients with pain empathetically. He encourages them to ask patients about their pain, accompanying symptoms, possible fears, and other mental stress and to take these factors seriously.
Moreover, the findings accentuate the effect of prescribed analgesics. “Numerous studies have meanwhile shown that the more positive a patient’s expectations, the better the effect of a medication,” said Dr. Meissner. “We physicians must exploit this effect, too.”
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.
These are the results of a study, recently published in the Proceedings of the National Academy of Sciences, that was conducted by a team led by neuroscientist Dan-Mikael Ellingsen, PhD, from Oslo University Hospital.
The researchers used functional MRI to scan the brains of 20 patients with chronic pain to investigate how a physician’s demeanor may affect patients’ sensitivity to pain, including effects in the central nervous system. During the scans, which were conducted in two sessions, the patients’ legs were exposed to stimuli that ranged from painless to moderately painful. The patients recorded perceived pain intensity using a scale. The physicians also underwent fMRI.
Half of the patients were subjected to the pain stimuli while alone; the other half were subjected to pain while in the presence of a physician. The latter group of patients was divided into two subgroups. Half of the patients had spoken to the accompanying physician before the examination. They discussed the history of the patient’s condition to date, among other things. The other half underwent the brain scans without any prior interaction with a physician.
Worse when alone
Dr. Ellingsen and his colleagues found that patients who were alone during the examination reported greater pain than those who were in the presence of a physician, even though they were subjected to stimuli of the same intensity. In instances in which the physician and patient had already spoken before the brain scan, patients additionally felt that the physician was empathetic and understood their pain. Furthermore, the physicians were better able to estimate the pain that their patients experienced.
The patients who had a physician by their side consistently experienced pain that was milder than the pain experienced by those who were alone. For pairs that had spoken beforehand, the patients considered their physician to be better able to understand their pain, and the physicians estimated the perceived pain intensity of their patients more accurately.
Evidence of trust
There was greater activity in the dorsolateral and ventrolateral prefrontal cortex, as well as in the primary and secondary somatosensory areas, in patients in the subgroup that had spoken to a physician. For the physicians, compared with the comparison group, there was an increase in correspondence between activity in the dorsolateral prefrontal cortex and activity in the secondary somatosensory areas of patients, which is a brain region that is known to react to pain. The brain activity correlation increased in line with the self-reported mutual trust between the physician and patient.
“These results prove that empathy and support can decrease pain intensity,” the investigators write. The data shed light on the brain processes behind the social modulation of pain during the interaction between the physician and the patient. Concordances in the brain are increased by greater therapeutic alliance.
Beyond medication
Winfried Meissner, MD, head of the pain clinic at the department of anesthesiology and intensive care medicine at Jena University Hospital, Germany, and former president of the German Pain Society, said in an interview: “I view this as a vital study that impressively demonstrates that effective, intensive pain therapy is not just a case of administering the correct analgesic.”
“Instead, a focus should be placed on what common sense tells us, which is just how crucial an empathetic attitude from physicians and good communication with patients are when it comes to the success of any therapy,” Dr. Meissner added. Unfortunately, such an attitude and such communication often are not provided in clinical practice because of limitations on time.
“Now, with objectively collected data from patients and physicians, [Dr.] Ellingsen’s team has been able to demonstrate that human interaction has a decisive impact on the treatment of patients experiencing pain,” said Dr. Meissner. “The study should encourage practitioners to treat communication just as seriously as the pharmacology of analgesics.”
Perception and attitude
“The study shows remarkably well that empathetic conversation between the physician and patient represents a valuable therapeutic method and should be recognized as such,” emphasized Dr. Meissner. Of course, conversation cannot replace pharmacologic treatment, but it can supplement and reinforce it. Furthermore, a physician’s empathy presumably has an effect that is at least as great as a suitable analgesic.
“Pain is more than just sensory perception,” explained Dr. Meissner. “We all know that it has a strong affective component, and perception is greatly determined by context.” This can be seen, for example, in athletes, who often attribute less importance to their pain and can successfully perform competitively despite a painful injury.
Positive expectations
Dr. Meissner advised all physicians to treat patients with pain empathetically. He encourages them to ask patients about their pain, accompanying symptoms, possible fears, and other mental stress and to take these factors seriously.
Moreover, the findings accentuate the effect of prescribed analgesics. “Numerous studies have meanwhile shown that the more positive a patient’s expectations, the better the effect of a medication,” said Dr. Meissner. “We physicians must exploit this effect, too.”
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.
These are the results of a study, recently published in the Proceedings of the National Academy of Sciences, that was conducted by a team led by neuroscientist Dan-Mikael Ellingsen, PhD, from Oslo University Hospital.
The researchers used functional MRI to scan the brains of 20 patients with chronic pain to investigate how a physician’s demeanor may affect patients’ sensitivity to pain, including effects in the central nervous system. During the scans, which were conducted in two sessions, the patients’ legs were exposed to stimuli that ranged from painless to moderately painful. The patients recorded perceived pain intensity using a scale. The physicians also underwent fMRI.
Half of the patients were subjected to the pain stimuli while alone; the other half were subjected to pain while in the presence of a physician. The latter group of patients was divided into two subgroups. Half of the patients had spoken to the accompanying physician before the examination. They discussed the history of the patient’s condition to date, among other things. The other half underwent the brain scans without any prior interaction with a physician.
Worse when alone
Dr. Ellingsen and his colleagues found that patients who were alone during the examination reported greater pain than those who were in the presence of a physician, even though they were subjected to stimuli of the same intensity. In instances in which the physician and patient had already spoken before the brain scan, patients additionally felt that the physician was empathetic and understood their pain. Furthermore, the physicians were better able to estimate the pain that their patients experienced.
The patients who had a physician by their side consistently experienced pain that was milder than the pain experienced by those who were alone. For pairs that had spoken beforehand, the patients considered their physician to be better able to understand their pain, and the physicians estimated the perceived pain intensity of their patients more accurately.
Evidence of trust
There was greater activity in the dorsolateral and ventrolateral prefrontal cortex, as well as in the primary and secondary somatosensory areas, in patients in the subgroup that had spoken to a physician. For the physicians, compared with the comparison group, there was an increase in correspondence between activity in the dorsolateral prefrontal cortex and activity in the secondary somatosensory areas of patients, which is a brain region that is known to react to pain. The brain activity correlation increased in line with the self-reported mutual trust between the physician and patient.
“These results prove that empathy and support can decrease pain intensity,” the investigators write. The data shed light on the brain processes behind the social modulation of pain during the interaction between the physician and the patient. Concordances in the brain are increased by greater therapeutic alliance.
Beyond medication
Winfried Meissner, MD, head of the pain clinic at the department of anesthesiology and intensive care medicine at Jena University Hospital, Germany, and former president of the German Pain Society, said in an interview: “I view this as a vital study that impressively demonstrates that effective, intensive pain therapy is not just a case of administering the correct analgesic.”
“Instead, a focus should be placed on what common sense tells us, which is just how crucial an empathetic attitude from physicians and good communication with patients are when it comes to the success of any therapy,” Dr. Meissner added. Unfortunately, such an attitude and such communication often are not provided in clinical practice because of limitations on time.
“Now, with objectively collected data from patients and physicians, [Dr.] Ellingsen’s team has been able to demonstrate that human interaction has a decisive impact on the treatment of patients experiencing pain,” said Dr. Meissner. “The study should encourage practitioners to treat communication just as seriously as the pharmacology of analgesics.”
Perception and attitude
“The study shows remarkably well that empathetic conversation between the physician and patient represents a valuable therapeutic method and should be recognized as such,” emphasized Dr. Meissner. Of course, conversation cannot replace pharmacologic treatment, but it can supplement and reinforce it. Furthermore, a physician’s empathy presumably has an effect that is at least as great as a suitable analgesic.
“Pain is more than just sensory perception,” explained Dr. Meissner. “We all know that it has a strong affective component, and perception is greatly determined by context.” This can be seen, for example, in athletes, who often attribute less importance to their pain and can successfully perform competitively despite a painful injury.
Positive expectations
Dr. Meissner advised all physicians to treat patients with pain empathetically. He encourages them to ask patients about their pain, accompanying symptoms, possible fears, and other mental stress and to take these factors seriously.
Moreover, the findings accentuate the effect of prescribed analgesics. “Numerous studies have meanwhile shown that the more positive a patient’s expectations, the better the effect of a medication,” said Dr. Meissner. “We physicians must exploit this effect, too.”
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.
FROM THE PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES
‘Brain fitness program’ may aid memory loss, concussion, ADHD
new research shows.
The program, which consists of targeted cognitive training and EEG-based neurofeedback, coupled with meditation and diet/lifestyle coaching, led to improvements in memory, attention, mood, alertness, and sleep.
The program promotes “neuroplasticity and was equally effective for patients with all three conditions,” program creator Majid Fotuhi, MD, PhD, said in an interview.
Patients with mild to moderate cognitive symptoms often see “remarkable” results within 3 months of consistently following the program, said Dr. Fotuhi, adjunct professor of neuroscience at George Washington University, Washington, and medical director of NeuroGrow Brain Fitness Center, McLean, Va.
“It actually makes intuitive sense that a healthier and stronger brain would function better and that patients of all ages with various cognitive or emotional symptoms would all benefit from improving the biology of their brain,” Dr. Fotuhi added.
The study was published online in the Journal of Alzheimer’s Disease Reports.
Personalized program
The findings are based on 223 children and adults who completed the 12-week NeuroGrow Brain Fitness Program (NeuroGrow BFP), including 71 with ADHD, 88 with PCS, and 64 with memory loss, defined as diagnosed mild cognitive impairment or subjective cognitive decline.
As part of the program, participants undergo a complete neurocognitive evaluation, including tests for verbal memory, complex attention, processing speed, executive functioning, and the Neurocognitive Index.
They also complete questionnaires regarding sleep, mood, diet, exercise, and anxiety/depression, and they undergo quantitative EEG at the beginning and end of the program.
A comparison of before and after neurocognitive test scores showed that all three patient subgroups experienced statistically significant improvements on most measures, the study team reports.
After completing the program, 60%-90% of patients scored higher on cognitive tests and reported having fewer cognitive, sleep, and emotional symptoms.
In all subgroups, the most significant improvement was observed in executive functioning.
“These preliminary findings appear to show that multimodal interventions which are known to increase neuroplasticity in the brain, when personalized, can have benefits for patients with cognitive symptoms from a variety of neurological conditions,” the investigators wrote.
The study’s strengths include a large, community-based sample of patients of different ages who had disruptive symptoms and abnormalities as determined using objective cognitive tests whose progress was monitored by objective and subjective measures.
The chief limitation is the lack of a control or placebo group.
“Though it is difficult to find a comparable group of patients with the exact same profile of cognitive deficits and brain-related symptoms, studying a larger group of patients – and comparing them with a wait-list group – may make it possible to do a more definitive assessment of the NeuroGrow BFP,” the researchers noted.
Dr. Fotuhi said the “secret to the success” of the program is that it involves a full assessment of all cognitive and neurobehavioral symptoms for each patient. This allows for individualized and targeted interventions for specific concerns and symptoms.
He said there is a need to recognize that patients who present to a neurology practice with a single complaint, such as a problem with memory or attention, often have other problems, such as anxiety/depression, stress, insomnia, sedentary lifestyle, obesity, diabetes, sleep apnea, or alcohol overuse.
“Each of these factors can affect their cognitive abilities and need a multimodal set of interventions in order to see full resolution of their cognitive symptoms,” Dr. Fotuhi said.
He has created a series of educational videos to demonstrate the program’s benefits.
The self-pay cost for the NeuroGrow BFP assessment and treatment sessions is approximately $7,000.
Dr. Fotuhi said all of the interventions included in the program are readily available at low cost.
He suggested that health care professionals who lack time or staff for conducting a comprehensive neurocognitive assessment for their patients can provide them with a copy of the Brain Health Index.
“Patients can then be instructed to work on the individual components of their brain health on their own – and measure their brain health index on a weekly basis,” Dr. Fotuhi said. “Private practices or academic centers can use the detailed information I have provided in my paper to develop their own brain fitness program.”
Not ready for prime time
Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, noted that “nonpharmacologic interventions can help alleviate some of the symptoms associated with dementia.
“The current study investigates nonpharmacologic interventions in a small number of patients with ADHD, postconcussion syndrome, or memory loss. The researchers found improvements on most measures following the brain rehabilitation program.
“While this is interesting, more work is needed in larger, more diverse cohorts before these programs can be applied broadly. Nonpharmacologic interventions are a helpful tool that need to be studied further in future studies,” Dr. Griffin added.
Funding for the study was provided by the NeuroGrow Brain Fitness Center. Dr. Fotuhi, the owner of NeuroGrow, was involved in data analysis, writing, editing, approval, and decision to publish. Dr. Griffin reported no disclosures.
A version of this article appeared on Medscape.com.
new research shows.
The program, which consists of targeted cognitive training and EEG-based neurofeedback, coupled with meditation and diet/lifestyle coaching, led to improvements in memory, attention, mood, alertness, and sleep.
The program promotes “neuroplasticity and was equally effective for patients with all three conditions,” program creator Majid Fotuhi, MD, PhD, said in an interview.
Patients with mild to moderate cognitive symptoms often see “remarkable” results within 3 months of consistently following the program, said Dr. Fotuhi, adjunct professor of neuroscience at George Washington University, Washington, and medical director of NeuroGrow Brain Fitness Center, McLean, Va.
“It actually makes intuitive sense that a healthier and stronger brain would function better and that patients of all ages with various cognitive or emotional symptoms would all benefit from improving the biology of their brain,” Dr. Fotuhi added.
The study was published online in the Journal of Alzheimer’s Disease Reports.
Personalized program
The findings are based on 223 children and adults who completed the 12-week NeuroGrow Brain Fitness Program (NeuroGrow BFP), including 71 with ADHD, 88 with PCS, and 64 with memory loss, defined as diagnosed mild cognitive impairment or subjective cognitive decline.
As part of the program, participants undergo a complete neurocognitive evaluation, including tests for verbal memory, complex attention, processing speed, executive functioning, and the Neurocognitive Index.
They also complete questionnaires regarding sleep, mood, diet, exercise, and anxiety/depression, and they undergo quantitative EEG at the beginning and end of the program.
A comparison of before and after neurocognitive test scores showed that all three patient subgroups experienced statistically significant improvements on most measures, the study team reports.
After completing the program, 60%-90% of patients scored higher on cognitive tests and reported having fewer cognitive, sleep, and emotional symptoms.
In all subgroups, the most significant improvement was observed in executive functioning.
“These preliminary findings appear to show that multimodal interventions which are known to increase neuroplasticity in the brain, when personalized, can have benefits for patients with cognitive symptoms from a variety of neurological conditions,” the investigators wrote.
The study’s strengths include a large, community-based sample of patients of different ages who had disruptive symptoms and abnormalities as determined using objective cognitive tests whose progress was monitored by objective and subjective measures.
The chief limitation is the lack of a control or placebo group.
“Though it is difficult to find a comparable group of patients with the exact same profile of cognitive deficits and brain-related symptoms, studying a larger group of patients – and comparing them with a wait-list group – may make it possible to do a more definitive assessment of the NeuroGrow BFP,” the researchers noted.
Dr. Fotuhi said the “secret to the success” of the program is that it involves a full assessment of all cognitive and neurobehavioral symptoms for each patient. This allows for individualized and targeted interventions for specific concerns and symptoms.
He said there is a need to recognize that patients who present to a neurology practice with a single complaint, such as a problem with memory or attention, often have other problems, such as anxiety/depression, stress, insomnia, sedentary lifestyle, obesity, diabetes, sleep apnea, or alcohol overuse.
“Each of these factors can affect their cognitive abilities and need a multimodal set of interventions in order to see full resolution of their cognitive symptoms,” Dr. Fotuhi said.
He has created a series of educational videos to demonstrate the program’s benefits.
The self-pay cost for the NeuroGrow BFP assessment and treatment sessions is approximately $7,000.
Dr. Fotuhi said all of the interventions included in the program are readily available at low cost.
He suggested that health care professionals who lack time or staff for conducting a comprehensive neurocognitive assessment for their patients can provide them with a copy of the Brain Health Index.
“Patients can then be instructed to work on the individual components of their brain health on their own – and measure their brain health index on a weekly basis,” Dr. Fotuhi said. “Private practices or academic centers can use the detailed information I have provided in my paper to develop their own brain fitness program.”
Not ready for prime time
Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, noted that “nonpharmacologic interventions can help alleviate some of the symptoms associated with dementia.
“The current study investigates nonpharmacologic interventions in a small number of patients with ADHD, postconcussion syndrome, or memory loss. The researchers found improvements on most measures following the brain rehabilitation program.
“While this is interesting, more work is needed in larger, more diverse cohorts before these programs can be applied broadly. Nonpharmacologic interventions are a helpful tool that need to be studied further in future studies,” Dr. Griffin added.
Funding for the study was provided by the NeuroGrow Brain Fitness Center. Dr. Fotuhi, the owner of NeuroGrow, was involved in data analysis, writing, editing, approval, and decision to publish. Dr. Griffin reported no disclosures.
A version of this article appeared on Medscape.com.
new research shows.
The program, which consists of targeted cognitive training and EEG-based neurofeedback, coupled with meditation and diet/lifestyle coaching, led to improvements in memory, attention, mood, alertness, and sleep.
The program promotes “neuroplasticity and was equally effective for patients with all three conditions,” program creator Majid Fotuhi, MD, PhD, said in an interview.
Patients with mild to moderate cognitive symptoms often see “remarkable” results within 3 months of consistently following the program, said Dr. Fotuhi, adjunct professor of neuroscience at George Washington University, Washington, and medical director of NeuroGrow Brain Fitness Center, McLean, Va.
“It actually makes intuitive sense that a healthier and stronger brain would function better and that patients of all ages with various cognitive or emotional symptoms would all benefit from improving the biology of their brain,” Dr. Fotuhi added.
The study was published online in the Journal of Alzheimer’s Disease Reports.
Personalized program
The findings are based on 223 children and adults who completed the 12-week NeuroGrow Brain Fitness Program (NeuroGrow BFP), including 71 with ADHD, 88 with PCS, and 64 with memory loss, defined as diagnosed mild cognitive impairment or subjective cognitive decline.
As part of the program, participants undergo a complete neurocognitive evaluation, including tests for verbal memory, complex attention, processing speed, executive functioning, and the Neurocognitive Index.
They also complete questionnaires regarding sleep, mood, diet, exercise, and anxiety/depression, and they undergo quantitative EEG at the beginning and end of the program.
A comparison of before and after neurocognitive test scores showed that all three patient subgroups experienced statistically significant improvements on most measures, the study team reports.
After completing the program, 60%-90% of patients scored higher on cognitive tests and reported having fewer cognitive, sleep, and emotional symptoms.
In all subgroups, the most significant improvement was observed in executive functioning.
“These preliminary findings appear to show that multimodal interventions which are known to increase neuroplasticity in the brain, when personalized, can have benefits for patients with cognitive symptoms from a variety of neurological conditions,” the investigators wrote.
The study’s strengths include a large, community-based sample of patients of different ages who had disruptive symptoms and abnormalities as determined using objective cognitive tests whose progress was monitored by objective and subjective measures.
The chief limitation is the lack of a control or placebo group.
“Though it is difficult to find a comparable group of patients with the exact same profile of cognitive deficits and brain-related symptoms, studying a larger group of patients – and comparing them with a wait-list group – may make it possible to do a more definitive assessment of the NeuroGrow BFP,” the researchers noted.
Dr. Fotuhi said the “secret to the success” of the program is that it involves a full assessment of all cognitive and neurobehavioral symptoms for each patient. This allows for individualized and targeted interventions for specific concerns and symptoms.
He said there is a need to recognize that patients who present to a neurology practice with a single complaint, such as a problem with memory or attention, often have other problems, such as anxiety/depression, stress, insomnia, sedentary lifestyle, obesity, diabetes, sleep apnea, or alcohol overuse.
“Each of these factors can affect their cognitive abilities and need a multimodal set of interventions in order to see full resolution of their cognitive symptoms,” Dr. Fotuhi said.
He has created a series of educational videos to demonstrate the program’s benefits.
The self-pay cost for the NeuroGrow BFP assessment and treatment sessions is approximately $7,000.
Dr. Fotuhi said all of the interventions included in the program are readily available at low cost.
He suggested that health care professionals who lack time or staff for conducting a comprehensive neurocognitive assessment for their patients can provide them with a copy of the Brain Health Index.
“Patients can then be instructed to work on the individual components of their brain health on their own – and measure their brain health index on a weekly basis,” Dr. Fotuhi said. “Private practices or academic centers can use the detailed information I have provided in my paper to develop their own brain fitness program.”
Not ready for prime time
Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, noted that “nonpharmacologic interventions can help alleviate some of the symptoms associated with dementia.
“The current study investigates nonpharmacologic interventions in a small number of patients with ADHD, postconcussion syndrome, or memory loss. The researchers found improvements on most measures following the brain rehabilitation program.
“While this is interesting, more work is needed in larger, more diverse cohorts before these programs can be applied broadly. Nonpharmacologic interventions are a helpful tool that need to be studied further in future studies,” Dr. Griffin added.
Funding for the study was provided by the NeuroGrow Brain Fitness Center. Dr. Fotuhi, the owner of NeuroGrow, was involved in data analysis, writing, editing, approval, and decision to publish. Dr. Griffin reported no disclosures.
A version of this article appeared on Medscape.com.
FROM THE JOURNAL OF ALZHEIMER’S DISEASE REPORTS
Link between low co-pays for new diabetes drugs and patient adherence
Findings from a recent study indicate that the less U.S. patients pay out of pocket for drugs that often have high co-pays, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagonlike peptide-1 (GLP-1) agonists, the more they adhere to taking these medications.
The study, led by Utibe R. Essien, MD, from University of California, Los Angeles, and Balvindar Singh, MD, PhD, from University of Pittsburgh, was published online in JAMA Cardiology.
Patient data from Clinformatics Data Mart, a health insurance claims database, was analyzed for the study. The information for 90,041 adults from the United States who had commercial and Medicare health insurance, and who started taking a GLP-1 agonist or SGLT2 inhibitor between 2014 and 2020 was reviewed. Participants had type 2 diabetes, heart failure, or both.
The primary outcome showed patients with a lower drug co-pay had significantly higher odds of 12-month adherence to GLP-1 agonists and SGLT2 inhibitors, compared with those with a higher co-pay. These differences persisted after controlling for patient demographic, clinical, and socioeconomic covariates.
After full adjustments were made and after the 12 months, patients with a high co-pay of $50 per month or more were 53% less likely to adhere to an SGLT2 inhibitor and 32% less likely to adhere to a GLP-1 agonist, compared with patients with a co-pay of less than $10 per month for these agents.
“Lowering high out-of-pocket prescription costs may be key to improving adherence to guideline-recommended therapies and advancing overall quality of care in patients with type 2 diabetes and heart failure,” the authors conclude.
The authors acknowledge the study’s limitations, including the inability to exclude residual confounding, uncertain generalizability for those without health insurance or with public insurance and possible misclassifications of type 2 diabetes and heart failure diagnoses or medical comorbidities. Additionally, this study did not have information on patients’ preferences associated with medication use, including specific reasons for poor adherence, and could not assess how co-payments influenced initial prescription receipt or abandonment at the pharmacy, or other factors including possible price inflation.
The study received no commercial funding. One author (not a lead author) is an adviser to several drug companies including ones that market SGLT2 inhibitors or GLP-1 agonists.
Findings from a recent study indicate that the less U.S. patients pay out of pocket for drugs that often have high co-pays, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagonlike peptide-1 (GLP-1) agonists, the more they adhere to taking these medications.
The study, led by Utibe R. Essien, MD, from University of California, Los Angeles, and Balvindar Singh, MD, PhD, from University of Pittsburgh, was published online in JAMA Cardiology.
Patient data from Clinformatics Data Mart, a health insurance claims database, was analyzed for the study. The information for 90,041 adults from the United States who had commercial and Medicare health insurance, and who started taking a GLP-1 agonist or SGLT2 inhibitor between 2014 and 2020 was reviewed. Participants had type 2 diabetes, heart failure, or both.
The primary outcome showed patients with a lower drug co-pay had significantly higher odds of 12-month adherence to GLP-1 agonists and SGLT2 inhibitors, compared with those with a higher co-pay. These differences persisted after controlling for patient demographic, clinical, and socioeconomic covariates.
After full adjustments were made and after the 12 months, patients with a high co-pay of $50 per month or more were 53% less likely to adhere to an SGLT2 inhibitor and 32% less likely to adhere to a GLP-1 agonist, compared with patients with a co-pay of less than $10 per month for these agents.
“Lowering high out-of-pocket prescription costs may be key to improving adherence to guideline-recommended therapies and advancing overall quality of care in patients with type 2 diabetes and heart failure,” the authors conclude.
The authors acknowledge the study’s limitations, including the inability to exclude residual confounding, uncertain generalizability for those without health insurance or with public insurance and possible misclassifications of type 2 diabetes and heart failure diagnoses or medical comorbidities. Additionally, this study did not have information on patients’ preferences associated with medication use, including specific reasons for poor adherence, and could not assess how co-payments influenced initial prescription receipt or abandonment at the pharmacy, or other factors including possible price inflation.
The study received no commercial funding. One author (not a lead author) is an adviser to several drug companies including ones that market SGLT2 inhibitors or GLP-1 agonists.
Findings from a recent study indicate that the less U.S. patients pay out of pocket for drugs that often have high co-pays, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagonlike peptide-1 (GLP-1) agonists, the more they adhere to taking these medications.
The study, led by Utibe R. Essien, MD, from University of California, Los Angeles, and Balvindar Singh, MD, PhD, from University of Pittsburgh, was published online in JAMA Cardiology.
Patient data from Clinformatics Data Mart, a health insurance claims database, was analyzed for the study. The information for 90,041 adults from the United States who had commercial and Medicare health insurance, and who started taking a GLP-1 agonist or SGLT2 inhibitor between 2014 and 2020 was reviewed. Participants had type 2 diabetes, heart failure, or both.
The primary outcome showed patients with a lower drug co-pay had significantly higher odds of 12-month adherence to GLP-1 agonists and SGLT2 inhibitors, compared with those with a higher co-pay. These differences persisted after controlling for patient demographic, clinical, and socioeconomic covariates.
After full adjustments were made and after the 12 months, patients with a high co-pay of $50 per month or more were 53% less likely to adhere to an SGLT2 inhibitor and 32% less likely to adhere to a GLP-1 agonist, compared with patients with a co-pay of less than $10 per month for these agents.
“Lowering high out-of-pocket prescription costs may be key to improving adherence to guideline-recommended therapies and advancing overall quality of care in patients with type 2 diabetes and heart failure,” the authors conclude.
The authors acknowledge the study’s limitations, including the inability to exclude residual confounding, uncertain generalizability for those without health insurance or with public insurance and possible misclassifications of type 2 diabetes and heart failure diagnoses or medical comorbidities. Additionally, this study did not have information on patients’ preferences associated with medication use, including specific reasons for poor adherence, and could not assess how co-payments influenced initial prescription receipt or abandonment at the pharmacy, or other factors including possible price inflation.
The study received no commercial funding. One author (not a lead author) is an adviser to several drug companies including ones that market SGLT2 inhibitors or GLP-1 agonists.
FROM JAMA CARDIOLOGY
Can a biodegradable brain implant deliver lifesaving cancer meds?
It’s the latest advance in a rapidly growing field using ultrasound – high-frequency sound waves undetectable to humans – to fight cancer and other diseases.
The problem addressed by the researchers is the blood-brain barrier, a nearly impenetrable blood vessel lining that keeps harmful molecules from passing into the brain from the blood. But this lining can also block chemo drugs from reaching cancer cells.
So the scientists implanted 1-cm2 devices into the skulls of mice, directly behind the tumor site. The implants generate ultrasound waves, loosening the barrier and allowing the drugs to reach the tumor. The sound waves leave healthy tissue undamaged.
“You inject the drug into the body and turn on the ultrasound at the same time. You’re going to hit precisely at the tumor area every single time you use it,” said lead study author Thanh Nguyen, PhD, an associate professor of mechanical engineering at the University of Connecticut, Storrs.
The drug used in the study was paclitaxel, which normally struggles to get through the blood-brain barrier. The tumors shrank, and the mice doubled their lifetime, compared with untreated mice. The mice showed no bad health effects 6 months later.
Breaking through the blood-brain barrier
The biodegradable implant is made of glycine, an amino acid that’s also strongly piezoelectric, meaning it vibrates when subjected to an electrical current. To make it, researchers cultivated glycine crystals, shattered them into pieces, and finally used a process called electrospinning, which applies a high electrical voltage to the nanocrystals.
Voltage flows to the implant via an external device. The resulting ultrasound causes the tightly adhered cells of the blood-brain barrier to vibrate, stretching them out and creating space for pores to form.
“That allows in very tiny particles, including chemo drugs,” said Dr. Nguyen.
His earlier biodegradable implant broke apart from the force, but the new glycine implant is more flexible, stable, and highly piezoelectric. It could be implanted after a patient has surgery to remove a brain tumor, to continue treating residual cancer cells. The implant dissolves harmlessly in the body over time, and doctors can control its lifespan.
A new wave of uses for ultrasound
Dr. Nguyen’s study builds on similar efforts, including a recent clinical trial of a nonbiodegradable implant for treating brain tumors. Ultrasound can focus energy on precise targets in the body.
It’s like “using a magnifying glass to focus multiple beams of light on a point and burn a hole in a leaf,” said Neal Kassell, MD, founder and chairman of the Focused Ultrasound Foundation. This approach spares adjacent normal tissue.
Doctors now understand more than 30 ways that ultrasound interacts with tissue – from destroying abnormal tissue to delivering drugs more effectively to stimulating an immune response. A decade ago, only five such interactions were known.
This opens the door for treating “a wide spectrum of medical disorders,” from neurodegenerative diseases like Alzheimer’s and Parkinson’s to difficult-to-treat cancers of the prostate and pancreas, and even addiction, said Dr. Kassell.
Dr. Kassell envisions using focused ultrasound to treat brain tumors as an alternative (or complement) to surgery, chemotherapy, immunotherapy, or radiation therapy. In the meantime, implants have helped show “the effectiveness of opening the blood-brain barrier.”
Dr. Nguyen’s team plans on testing the safety and efficacy of their implant in pigs next. Eventually, Dr. Nguyen hopes to develop a patch with an array of implants to target different areas of the brain.
One study coauthor is cofounder of PiezoBioMembrane and SingleTimeMicroneedles. The other study authors reported no conflicts of interest.
A version of this article originally appeared on WebMD.com.
It’s the latest advance in a rapidly growing field using ultrasound – high-frequency sound waves undetectable to humans – to fight cancer and other diseases.
The problem addressed by the researchers is the blood-brain barrier, a nearly impenetrable blood vessel lining that keeps harmful molecules from passing into the brain from the blood. But this lining can also block chemo drugs from reaching cancer cells.
So the scientists implanted 1-cm2 devices into the skulls of mice, directly behind the tumor site. The implants generate ultrasound waves, loosening the barrier and allowing the drugs to reach the tumor. The sound waves leave healthy tissue undamaged.
“You inject the drug into the body and turn on the ultrasound at the same time. You’re going to hit precisely at the tumor area every single time you use it,” said lead study author Thanh Nguyen, PhD, an associate professor of mechanical engineering at the University of Connecticut, Storrs.
The drug used in the study was paclitaxel, which normally struggles to get through the blood-brain barrier. The tumors shrank, and the mice doubled their lifetime, compared with untreated mice. The mice showed no bad health effects 6 months later.
Breaking through the blood-brain barrier
The biodegradable implant is made of glycine, an amino acid that’s also strongly piezoelectric, meaning it vibrates when subjected to an electrical current. To make it, researchers cultivated glycine crystals, shattered them into pieces, and finally used a process called electrospinning, which applies a high electrical voltage to the nanocrystals.
Voltage flows to the implant via an external device. The resulting ultrasound causes the tightly adhered cells of the blood-brain barrier to vibrate, stretching them out and creating space for pores to form.
“That allows in very tiny particles, including chemo drugs,” said Dr. Nguyen.
His earlier biodegradable implant broke apart from the force, but the new glycine implant is more flexible, stable, and highly piezoelectric. It could be implanted after a patient has surgery to remove a brain tumor, to continue treating residual cancer cells. The implant dissolves harmlessly in the body over time, and doctors can control its lifespan.
A new wave of uses for ultrasound
Dr. Nguyen’s study builds on similar efforts, including a recent clinical trial of a nonbiodegradable implant for treating brain tumors. Ultrasound can focus energy on precise targets in the body.
It’s like “using a magnifying glass to focus multiple beams of light on a point and burn a hole in a leaf,” said Neal Kassell, MD, founder and chairman of the Focused Ultrasound Foundation. This approach spares adjacent normal tissue.
Doctors now understand more than 30 ways that ultrasound interacts with tissue – from destroying abnormal tissue to delivering drugs more effectively to stimulating an immune response. A decade ago, only five such interactions were known.
This opens the door for treating “a wide spectrum of medical disorders,” from neurodegenerative diseases like Alzheimer’s and Parkinson’s to difficult-to-treat cancers of the prostate and pancreas, and even addiction, said Dr. Kassell.
Dr. Kassell envisions using focused ultrasound to treat brain tumors as an alternative (or complement) to surgery, chemotherapy, immunotherapy, or radiation therapy. In the meantime, implants have helped show “the effectiveness of opening the blood-brain barrier.”
Dr. Nguyen’s team plans on testing the safety and efficacy of their implant in pigs next. Eventually, Dr. Nguyen hopes to develop a patch with an array of implants to target different areas of the brain.
One study coauthor is cofounder of PiezoBioMembrane and SingleTimeMicroneedles. The other study authors reported no conflicts of interest.
A version of this article originally appeared on WebMD.com.
It’s the latest advance in a rapidly growing field using ultrasound – high-frequency sound waves undetectable to humans – to fight cancer and other diseases.
The problem addressed by the researchers is the blood-brain barrier, a nearly impenetrable blood vessel lining that keeps harmful molecules from passing into the brain from the blood. But this lining can also block chemo drugs from reaching cancer cells.
So the scientists implanted 1-cm2 devices into the skulls of mice, directly behind the tumor site. The implants generate ultrasound waves, loosening the barrier and allowing the drugs to reach the tumor. The sound waves leave healthy tissue undamaged.
“You inject the drug into the body and turn on the ultrasound at the same time. You’re going to hit precisely at the tumor area every single time you use it,” said lead study author Thanh Nguyen, PhD, an associate professor of mechanical engineering at the University of Connecticut, Storrs.
The drug used in the study was paclitaxel, which normally struggles to get through the blood-brain barrier. The tumors shrank, and the mice doubled their lifetime, compared with untreated mice. The mice showed no bad health effects 6 months later.
Breaking through the blood-brain barrier
The biodegradable implant is made of glycine, an amino acid that’s also strongly piezoelectric, meaning it vibrates when subjected to an electrical current. To make it, researchers cultivated glycine crystals, shattered them into pieces, and finally used a process called electrospinning, which applies a high electrical voltage to the nanocrystals.
Voltage flows to the implant via an external device. The resulting ultrasound causes the tightly adhered cells of the blood-brain barrier to vibrate, stretching them out and creating space for pores to form.
“That allows in very tiny particles, including chemo drugs,” said Dr. Nguyen.
His earlier biodegradable implant broke apart from the force, but the new glycine implant is more flexible, stable, and highly piezoelectric. It could be implanted after a patient has surgery to remove a brain tumor, to continue treating residual cancer cells. The implant dissolves harmlessly in the body over time, and doctors can control its lifespan.
A new wave of uses for ultrasound
Dr. Nguyen’s study builds on similar efforts, including a recent clinical trial of a nonbiodegradable implant for treating brain tumors. Ultrasound can focus energy on precise targets in the body.
It’s like “using a magnifying glass to focus multiple beams of light on a point and burn a hole in a leaf,” said Neal Kassell, MD, founder and chairman of the Focused Ultrasound Foundation. This approach spares adjacent normal tissue.
Doctors now understand more than 30 ways that ultrasound interacts with tissue – from destroying abnormal tissue to delivering drugs more effectively to stimulating an immune response. A decade ago, only five such interactions were known.
This opens the door for treating “a wide spectrum of medical disorders,” from neurodegenerative diseases like Alzheimer’s and Parkinson’s to difficult-to-treat cancers of the prostate and pancreas, and even addiction, said Dr. Kassell.
Dr. Kassell envisions using focused ultrasound to treat brain tumors as an alternative (or complement) to surgery, chemotherapy, immunotherapy, or radiation therapy. In the meantime, implants have helped show “the effectiveness of opening the blood-brain barrier.”
Dr. Nguyen’s team plans on testing the safety and efficacy of their implant in pigs next. Eventually, Dr. Nguyen hopes to develop a patch with an array of implants to target different areas of the brain.
One study coauthor is cofounder of PiezoBioMembrane and SingleTimeMicroneedles. The other study authors reported no conflicts of interest.
A version of this article originally appeared on WebMD.com.
FROM SCIENCE ADVANCES