MDedge Neurology

The presence of antiphospholipid antibodies is associated with an increased risk for future cardiovascular events, according to a new study.

The findings point to possible new approaches to risk stratification and the potential for new therapeutic targets in heart disease.

“In this study of the general population, we found that two antiphospholipid antibodies were associated with an increased risk of having a serious cardiovascular event over a follow-up of 8 years,” coauthor Jason Knight, MD, University of Michigan, Ann Arbor, said in an interview.

“If confirmed in further studies, these findings could be used to identify a subgroup of patients who need more careful monitoring and more aggressive risk-factor modification, and if the increased risk linked to these antibodies is high enough, it may also justify preemptive treatments such as the anticoagulants that are routinely used in antiphospholipid syndrome,” Dr. Knight said.

“The long-term vision is that we may identify some people in the general population who would benefit from treating the immune system for the prevention and treatment of cardiovascular disease instead of, or in addition to, using typical cardiovascular medications,” he added.

The study was published online in JAMA Network Open.

Individuals with autoimmune and inflammatory diseases have a greater risk for cardiovascular events than expected based on traditional cardiovascular risk factors, with mechanisms proposed to explain this risk including inflammation-mediated disruption of vascular integrity and activation of platelets and coagulation pathways, the authors explained. However, the role of autoantibodies remains unclear.

They noted that antiphospholipid antibodies can activate endothelial cells, platelets, and neutrophils, and some patients with persistently circulating antiphospholipid antibodies can develop antiphospholipid syndrome – an acquired thromboinflammatory disease characterized by arterial, venous, and microvascular thrombotic events and obstetric complications.

Cross-sectional studies have shown that antiphospholipid antibodies are acutely present in up to 17.4% of patients with stroke or transient ischemic attack, and small cohort studies have suggested that such antibodies may be present in 1%-12% of seemingly healthy individuals. However, the impact of sex, race, and ethnicity on the prevalence of antiphospholipid antibodies and their association with atherosclerotic cardiovascular disease is not known.

The researchers conducted the current study to look at the association between antiphospholipid antibodies and future risk for atherosclerotic cardiovascular events.

They analyzed data from 2,427 participants in the population-based Dallas Heart Study who had no history of atherosclerotic cardiovascular disease or autoimmune diseases requiring immunosuppressive medications at the time of blood sampling at study entry in 2007-2009.

Eight different types of antiphospholipid antibodies were measured, and data on cardiovascular events over the next 8 years was recorded.

Results showed that 14.5% of the cohort tested positive for one of these antiphospholipid antibodies at the start of the study, with approximately one-third of those detected at a moderate or high titer.

The researchers also found that the IgA isotypes of two antiphospholipid antibodies – anticardiolipin and anti-beta-2 glycoprotein – were associated with future atherosclerotic cardiovascular events.

After adjustment for other known risk factors, individuals testing positive for the IgA isotype of anticardiolipin had an almost five times increased risk (hazard ratio, 4.92) of the primary endpoint (myocardial infarction, stroke, coronary revascularization, or cardiovascular death); while those testing positive for anti–beta₂-glycoprotein had an almost three times increased risk (HR, 2.91).

Furthermore, there was what appeared to be a dose effect. People with the highest levels of these antibodies also had the highest risk for cardiovascular events, with up to an almost 10-fold increased risk with the higher level of anticardiolipin. 

Dr. Knight said that more research into the IgA isotypes of these antiphospholipid antibodies is needed.

“Most of the mechanistic work in the antiphospholipid syndrome field has focused on IgG antiphospholipid antibodies. While we commonly find these IgA antibodies in patients with APS, the extent to which they contribute to disease has not been firmly established,” he said. “The fact that IgA was the primary hit in our unbiased screen suggests that there is more to the story and we need to better understand the implications of having these antibodies in circulation, and what specific problems they may be causing.”

Noting that antiphospholipid antibodies can form transiently after certain situations, such as infections, Dr. Knight said that further studies were needed with repeat blood testing to detect the chronic presence of the antibodies.

He added that information of venous thromboses was not available in this study and “perhaps some of the other antibodies might have stood out if we were able to analyze for different outcomes.”

This study was supported by a Pfizer Aspire Award. Dr. Knight reported receiving research funding and consulting fees from Jazz Pharmaceuticals outside the submitted work.

A version of this article first appeared on Medscape.com.

The presence of antiphospholipid antibodies is associated with an increased risk for future cardiovascular events, according to a new study.

The findings point to possible new approaches to risk stratification and the potential for new therapeutic targets in heart disease.

“In this study of the general population, we found that two antiphospholipid antibodies were associated with an increased risk of having a serious cardiovascular event over a follow-up of 8 years,” coauthor Jason Knight, MD, University of Michigan, Ann Arbor, said in an interview.

“If confirmed in further studies, these findings could be used to identify a subgroup of patients who need more careful monitoring and more aggressive risk-factor modification, and if the increased risk linked to these antibodies is high enough, it may also justify preemptive treatments such as the anticoagulants that are routinely used in antiphospholipid syndrome,” Dr. Knight said.

“The long-term vision is that we may identify some people in the general population who would benefit from treating the immune system for the prevention and treatment of cardiovascular disease instead of, or in addition to, using typical cardiovascular medications,” he added.

The study was published online in JAMA Network Open.

Individuals with autoimmune and inflammatory diseases have a greater risk for cardiovascular events than expected based on traditional cardiovascular risk factors, with mechanisms proposed to explain this risk including inflammation-mediated disruption of vascular integrity and activation of platelets and coagulation pathways, the authors explained. However, the role of autoantibodies remains unclear.

They noted that antiphospholipid antibodies can activate endothelial cells, platelets, and neutrophils, and some patients with persistently circulating antiphospholipid antibodies can develop antiphospholipid syndrome – an acquired thromboinflammatory disease characterized by arterial, venous, and microvascular thrombotic events and obstetric complications.

Cross-sectional studies have shown that antiphospholipid antibodies are acutely present in up to 17.4% of patients with stroke or transient ischemic attack, and small cohort studies have suggested that such antibodies may be present in 1%-12% of seemingly healthy individuals. However, the impact of sex, race, and ethnicity on the prevalence of antiphospholipid antibodies and their association with atherosclerotic cardiovascular disease is not known.

The researchers conducted the current study to look at the association between antiphospholipid antibodies and future risk for atherosclerotic cardiovascular events.

They analyzed data from 2,427 participants in the population-based Dallas Heart Study who had no history of atherosclerotic cardiovascular disease or autoimmune diseases requiring immunosuppressive medications at the time of blood sampling at study entry in 2007-2009.

Eight different types of antiphospholipid antibodies were measured, and data on cardiovascular events over the next 8 years was recorded.

Results showed that 14.5% of the cohort tested positive for one of these antiphospholipid antibodies at the start of the study, with approximately one-third of those detected at a moderate or high titer.

The researchers also found that the IgA isotypes of two antiphospholipid antibodies – anticardiolipin and anti-beta-2 glycoprotein – were associated with future atherosclerotic cardiovascular events.

After adjustment for other known risk factors, individuals testing positive for the IgA isotype of anticardiolipin had an almost five times increased risk (hazard ratio, 4.92) of the primary endpoint (myocardial infarction, stroke, coronary revascularization, or cardiovascular death); while those testing positive for anti–beta₂-glycoprotein had an almost three times increased risk (HR, 2.91).

Furthermore, there was what appeared to be a dose effect. People with the highest levels of these antibodies also had the highest risk for cardiovascular events, with up to an almost 10-fold increased risk with the higher level of anticardiolipin. 

Dr. Knight said that more research into the IgA isotypes of these antiphospholipid antibodies is needed.

“Most of the mechanistic work in the antiphospholipid syndrome field has focused on IgG antiphospholipid antibodies. While we commonly find these IgA antibodies in patients with APS, the extent to which they contribute to disease has not been firmly established,” he said. “The fact that IgA was the primary hit in our unbiased screen suggests that there is more to the story and we need to better understand the implications of having these antibodies in circulation, and what specific problems they may be causing.”

Noting that antiphospholipid antibodies can form transiently after certain situations, such as infections, Dr. Knight said that further studies were needed with repeat blood testing to detect the chronic presence of the antibodies.

He added that information of venous thromboses was not available in this study and “perhaps some of the other antibodies might have stood out if we were able to analyze for different outcomes.”

This study was supported by a Pfizer Aspire Award. Dr. Knight reported receiving research funding and consulting fees from Jazz Pharmaceuticals outside the submitted work.

A version of this article first appeared on Medscape.com.

The presence of antiphospholipid antibodies is associated with an increased risk for future cardiovascular events, according to a new study.

The findings point to possible new approaches to risk stratification and the potential for new therapeutic targets in heart disease.

“In this study of the general population, we found that two antiphospholipid antibodies were associated with an increased risk of having a serious cardiovascular event over a follow-up of 8 years,” coauthor Jason Knight, MD, University of Michigan, Ann Arbor, said in an interview.

“If confirmed in further studies, these findings could be used to identify a subgroup of patients who need more careful monitoring and more aggressive risk-factor modification, and if the increased risk linked to these antibodies is high enough, it may also justify preemptive treatments such as the anticoagulants that are routinely used in antiphospholipid syndrome,” Dr. Knight said.

“The long-term vision is that we may identify some people in the general population who would benefit from treating the immune system for the prevention and treatment of cardiovascular disease instead of, or in addition to, using typical cardiovascular medications,” he added.

The study was published online in JAMA Network Open.

Individuals with autoimmune and inflammatory diseases have a greater risk for cardiovascular events than expected based on traditional cardiovascular risk factors, with mechanisms proposed to explain this risk including inflammation-mediated disruption of vascular integrity and activation of platelets and coagulation pathways, the authors explained. However, the role of autoantibodies remains unclear.

They noted that antiphospholipid antibodies can activate endothelial cells, platelets, and neutrophils, and some patients with persistently circulating antiphospholipid antibodies can develop antiphospholipid syndrome – an acquired thromboinflammatory disease characterized by arterial, venous, and microvascular thrombotic events and obstetric complications.

Cross-sectional studies have shown that antiphospholipid antibodies are acutely present in up to 17.4% of patients with stroke or transient ischemic attack, and small cohort studies have suggested that such antibodies may be present in 1%-12% of seemingly healthy individuals. However, the impact of sex, race, and ethnicity on the prevalence of antiphospholipid antibodies and their association with atherosclerotic cardiovascular disease is not known.

The researchers conducted the current study to look at the association between antiphospholipid antibodies and future risk for atherosclerotic cardiovascular events.

They analyzed data from 2,427 participants in the population-based Dallas Heart Study who had no history of atherosclerotic cardiovascular disease or autoimmune diseases requiring immunosuppressive medications at the time of blood sampling at study entry in 2007-2009.

Eight different types of antiphospholipid antibodies were measured, and data on cardiovascular events over the next 8 years was recorded.

Results showed that 14.5% of the cohort tested positive for one of these antiphospholipid antibodies at the start of the study, with approximately one-third of those detected at a moderate or high titer.

The researchers also found that the IgA isotypes of two antiphospholipid antibodies – anticardiolipin and anti-beta-2 glycoprotein – were associated with future atherosclerotic cardiovascular events.

After adjustment for other known risk factors, individuals testing positive for the IgA isotype of anticardiolipin had an almost five times increased risk (hazard ratio, 4.92) of the primary endpoint (myocardial infarction, stroke, coronary revascularization, or cardiovascular death); while those testing positive for anti–beta₂-glycoprotein had an almost three times increased risk (HR, 2.91).

Furthermore, there was what appeared to be a dose effect. People with the highest levels of these antibodies also had the highest risk for cardiovascular events, with up to an almost 10-fold increased risk with the higher level of anticardiolipin. 

Dr. Knight said that more research into the IgA isotypes of these antiphospholipid antibodies is needed.

“Most of the mechanistic work in the antiphospholipid syndrome field has focused on IgG antiphospholipid antibodies. While we commonly find these IgA antibodies in patients with APS, the extent to which they contribute to disease has not been firmly established,” he said. “The fact that IgA was the primary hit in our unbiased screen suggests that there is more to the story and we need to better understand the implications of having these antibodies in circulation, and what specific problems they may be causing.”

Noting that antiphospholipid antibodies can form transiently after certain situations, such as infections, Dr. Knight said that further studies were needed with repeat blood testing to detect the chronic presence of the antibodies.

He added that information of venous thromboses was not available in this study and “perhaps some of the other antibodies might have stood out if we were able to analyze for different outcomes.”

This study was supported by a Pfizer Aspire Award. Dr. Knight reported receiving research funding and consulting fees from Jazz Pharmaceuticals outside the submitted work.

A version of this article first appeared on Medscape.com.

Phototherapy is a safe, effective, noninvasive, and inexpensive way of boosting cognition for patients with dementia, new research suggests. It may be “one of the most promising interventions for improving core symptoms” of the disease.

A new meta-analysis shows that patients with dementia who received phototherapy experienced significant cognitive improvement, compared with those who received usual treatment. However, there were no differences between study groups in terms of improved depression, agitation, or sleep problems.

“Our meta-analysis indicates that phototherapy improved cognitive function in patients with dementia. ... This suggests that phototherapy may be one of the most promising non-pharmacological interventions for improving core symptoms of dementia,” wrote the investigators, led by Xinlian Lu, Peking University, Beijing.

The study was published online in Brain and Behavior.
 

A new treatment option?

“As drug treatment for dementia has limitations such as medical contraindications, limited efficacy, and adverse effects, nonpharmacological therapy has been increasingly regarded as a critical part of comprehensive dementia care,” the investigators noted.

Phototherapy, which utilizes full-spectrum bright light (usually > 600 lux) or wavelength-specific light (for example, blue-enriched or blue-green), is a “promising nonpharmacological therapy” that is noninvasive, inexpensive, and safe.

Most studies of phototherapy have focused on sleep. Findings have shown “high heterogeneity” among the interventions and the populations in the studies, and results have been “inconsistent.” In addition, the effect of phototherapy on cognitive function and behavioral and psychological symptoms of dementia (BPSD) “still need to be clarified.”

In the systematic review and meta-analysis, the investigators examined the effects of phototherapy on cognitive function, BPSD, and sleep in older adults with dementia.

They searched several databases for randomized controlled trials that investigated phototherapy interventions for elderly patients. The primary outcome was cognitive function, which was assessed via the Mini-Mental State Examination (MMSE).

Secondary outcomes included BPSD, including agitation, anxiety, irritability, depression, anxiety, and sleep disturbances, as assessed by the Cornell Scale for Depression in Dementia (CSDD), the Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI), and measures of sleep, including total sleep time (TST), sleep efficiency (SE), and sleep disorders, as assessed by the Sleep Disorder Inventory (SDI).

To be included in the analysis, individual studies had to focus on elderly adults who had some form of dementia. In addition, a group receiving a phototherapy intervention had to be compared with a nonintervention group, and the study had to specify one of the above-defined outcomes.

The review included phototherapy interventions of all forms, frequencies, and durations, including use of bright light, LED light, and blue or blue-green light.
 

Regulating circadian rhythm

Twelve studies met the researchers’ criteria. They included a total of 766 patients with dementia – 426 in the intervention group and 340 in the control group. The mean ages ranged from 73.73 to 85.9 years, and there was a greater number of female than male participants.

Of the studies, seven employed routine daily light in the control group, while the others used either dim light (≤ 50 lux) or devices without light.

The researchers found “significant positive intervention effects” for global cognitive function. Improvements in postintervention MMSE scores differed significantly between the experimental groups and control groups (mean difference, 2.68; 95% confidence interval, 1.38-3.98; I2 = 0%).

No significant differences were found in the effects of intervention on depression symptoms, as evidenced in CSDD scores (MD, −0.70; 95% CI, −3.10 to 1.70; I² = 81%).

Among patients with higher CMAI scores, which indicate more severe agitation behaviors, there was a “trend of decreasing CMAI scores” after phototherapy (MD, −3.12; 95% CI, −8.05 to 1.82; I² = 0%). No significant difference in NPI scores was observed between the two groups.

Similarly, no significant difference was found between the two groups in TST, SE, or SDI scores.

Adverse effects were infrequent and were not severe. Two of the 426 patients in the intervention group experienced mild ocular irritation, and one experienced slight transient redness of the forehead.

Light “may compensate for the reduction in the visual sensory input of patients with dementia and stimulate specific neurons in the suprachiasmatic nucleus of the hypothalamus to regulate circadian rhythm,” the researchers suggested.

“As circadian rhythms are involved in optimal brain function, light supplementation may act on the synchronizing/phase-shifting effects of circadian rhythms to improve cognitive function,” they added.

They note that the light box is the “most commonly used device in phototherapy.” Light boxes provide full-spectrum bright light, usually greater than 2,500 lux. The duration is 30 minutes in the daytime, and treatment lasts 4-8 weeks.

The investigators cautioned that the light box should be placed 60 cm away from the patient or above the patient’s eye level. They said that a ceiling-mounted light is a “good choice” for providing whole-day phototherapy, since such lights do not interfere with the patient’s daily routine, reduce the demand on staff, and contribute to better adherence.

Phototherapy helmets and glasses are also available. These portable devices “allow for better control of light intensity and are ergonomic without interfering with patients’ normal activities.”

The researchers noted that “further well-designed studies are needed to explore the most effective clinical implementation conditions, including device type, duration, frequency, and time.”
 

Easy to use

Mariana Figueiro, PhD, professor and director of the Light and Health Research Center, department of population health medicine, Icahn School of Medicine at Mount Sinai, New York, said light is the “major stimulus for the circadian system, and a robust light-dark pattern daily (which can be given by light therapy during the day) improves sleep and behavior and reduces depression and agitation.”

Dr. Figueiro, who was not involved with the current study, noted that patients with dementia “have sleep issues, which can further affect their cognition; improvement in sleep leads to improvement in cognition,” and this may be an underlying mechanism associated with these results.

The clinical significance of the study “is that this is a nonpharmacological intervention and can be easily applied in the homes or controlled facilities, and it can be used with any other medication,” she pointed out.

“More importantly, sleep medications have negative side effects, so the use of nonpharmacological interventions improving sleep and cognition is great for clinical practice,” she added.

However, she took issue with the finding that phototherapy was not effective for depression and agitation, noting that there were “too few studies to say for sure that light therapy is ineffective at improving these outcomes.”

The research received no external funding. The authors and Dr. Figueiro disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Phototherapy is a safe, effective, noninvasive, and inexpensive way of boosting cognition for patients with dementia, new research suggests. It may be “one of the most promising interventions for improving core symptoms” of the disease.

A new meta-analysis shows that patients with dementia who received phototherapy experienced significant cognitive improvement, compared with those who received usual treatment. However, there were no differences between study groups in terms of improved depression, agitation, or sleep problems.

“Our meta-analysis indicates that phototherapy improved cognitive function in patients with dementia. ... This suggests that phototherapy may be one of the most promising non-pharmacological interventions for improving core symptoms of dementia,” wrote the investigators, led by Xinlian Lu, Peking University, Beijing.

The study was published online in Brain and Behavior.
 

A new treatment option?

“As drug treatment for dementia has limitations such as medical contraindications, limited efficacy, and adverse effects, nonpharmacological therapy has been increasingly regarded as a critical part of comprehensive dementia care,” the investigators noted.

Phototherapy, which utilizes full-spectrum bright light (usually > 600 lux) or wavelength-specific light (for example, blue-enriched or blue-green), is a “promising nonpharmacological therapy” that is noninvasive, inexpensive, and safe.

Most studies of phototherapy have focused on sleep. Findings have shown “high heterogeneity” among the interventions and the populations in the studies, and results have been “inconsistent.” In addition, the effect of phototherapy on cognitive function and behavioral and psychological symptoms of dementia (BPSD) “still need to be clarified.”

In the systematic review and meta-analysis, the investigators examined the effects of phototherapy on cognitive function, BPSD, and sleep in older adults with dementia.

They searched several databases for randomized controlled trials that investigated phototherapy interventions for elderly patients. The primary outcome was cognitive function, which was assessed via the Mini-Mental State Examination (MMSE).

Secondary outcomes included BPSD, including agitation, anxiety, irritability, depression, anxiety, and sleep disturbances, as assessed by the Cornell Scale for Depression in Dementia (CSDD), the Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI), and measures of sleep, including total sleep time (TST), sleep efficiency (SE), and sleep disorders, as assessed by the Sleep Disorder Inventory (SDI).

To be included in the analysis, individual studies had to focus on elderly adults who had some form of dementia. In addition, a group receiving a phototherapy intervention had to be compared with a nonintervention group, and the study had to specify one of the above-defined outcomes.

The review included phototherapy interventions of all forms, frequencies, and durations, including use of bright light, LED light, and blue or blue-green light.
 

Regulating circadian rhythm

Twelve studies met the researchers’ criteria. They included a total of 766 patients with dementia – 426 in the intervention group and 340 in the control group. The mean ages ranged from 73.73 to 85.9 years, and there was a greater number of female than male participants.

Of the studies, seven employed routine daily light in the control group, while the others used either dim light (≤ 50 lux) or devices without light.

The researchers found “significant positive intervention effects” for global cognitive function. Improvements in postintervention MMSE scores differed significantly between the experimental groups and control groups (mean difference, 2.68; 95% confidence interval, 1.38-3.98; I2 = 0%).

No significant differences were found in the effects of intervention on depression symptoms, as evidenced in CSDD scores (MD, −0.70; 95% CI, −3.10 to 1.70; I² = 81%).

Among patients with higher CMAI scores, which indicate more severe agitation behaviors, there was a “trend of decreasing CMAI scores” after phototherapy (MD, −3.12; 95% CI, −8.05 to 1.82; I² = 0%). No significant difference in NPI scores was observed between the two groups.

Similarly, no significant difference was found between the two groups in TST, SE, or SDI scores.

Adverse effects were infrequent and were not severe. Two of the 426 patients in the intervention group experienced mild ocular irritation, and one experienced slight transient redness of the forehead.

Light “may compensate for the reduction in the visual sensory input of patients with dementia and stimulate specific neurons in the suprachiasmatic nucleus of the hypothalamus to regulate circadian rhythm,” the researchers suggested.

“As circadian rhythms are involved in optimal brain function, light supplementation may act on the synchronizing/phase-shifting effects of circadian rhythms to improve cognitive function,” they added.

They note that the light box is the “most commonly used device in phototherapy.” Light boxes provide full-spectrum bright light, usually greater than 2,500 lux. The duration is 30 minutes in the daytime, and treatment lasts 4-8 weeks.

The investigators cautioned that the light box should be placed 60 cm away from the patient or above the patient’s eye level. They said that a ceiling-mounted light is a “good choice” for providing whole-day phototherapy, since such lights do not interfere with the patient’s daily routine, reduce the demand on staff, and contribute to better adherence.

Phototherapy helmets and glasses are also available. These portable devices “allow for better control of light intensity and are ergonomic without interfering with patients’ normal activities.”

The researchers noted that “further well-designed studies are needed to explore the most effective clinical implementation conditions, including device type, duration, frequency, and time.”
 

Easy to use

Mariana Figueiro, PhD, professor and director of the Light and Health Research Center, department of population health medicine, Icahn School of Medicine at Mount Sinai, New York, said light is the “major stimulus for the circadian system, and a robust light-dark pattern daily (which can be given by light therapy during the day) improves sleep and behavior and reduces depression and agitation.”

Dr. Figueiro, who was not involved with the current study, noted that patients with dementia “have sleep issues, which can further affect their cognition; improvement in sleep leads to improvement in cognition,” and this may be an underlying mechanism associated with these results.

The clinical significance of the study “is that this is a nonpharmacological intervention and can be easily applied in the homes or controlled facilities, and it can be used with any other medication,” she pointed out.

“More importantly, sleep medications have negative side effects, so the use of nonpharmacological interventions improving sleep and cognition is great for clinical practice,” she added.

However, she took issue with the finding that phototherapy was not effective for depression and agitation, noting that there were “too few studies to say for sure that light therapy is ineffective at improving these outcomes.”

The research received no external funding. The authors and Dr. Figueiro disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Phototherapy is a safe, effective, noninvasive, and inexpensive way of boosting cognition for patients with dementia, new research suggests. It may be “one of the most promising interventions for improving core symptoms” of the disease.

A new meta-analysis shows that patients with dementia who received phototherapy experienced significant cognitive improvement, compared with those who received usual treatment. However, there were no differences between study groups in terms of improved depression, agitation, or sleep problems.

“Our meta-analysis indicates that phototherapy improved cognitive function in patients with dementia. ... This suggests that phototherapy may be one of the most promising non-pharmacological interventions for improving core symptoms of dementia,” wrote the investigators, led by Xinlian Lu, Peking University, Beijing.

The study was published online in Brain and Behavior.
 

A new treatment option?

“As drug treatment for dementia has limitations such as medical contraindications, limited efficacy, and adverse effects, nonpharmacological therapy has been increasingly regarded as a critical part of comprehensive dementia care,” the investigators noted.

Phototherapy, which utilizes full-spectrum bright light (usually > 600 lux) or wavelength-specific light (for example, blue-enriched or blue-green), is a “promising nonpharmacological therapy” that is noninvasive, inexpensive, and safe.

Most studies of phototherapy have focused on sleep. Findings have shown “high heterogeneity” among the interventions and the populations in the studies, and results have been “inconsistent.” In addition, the effect of phototherapy on cognitive function and behavioral and psychological symptoms of dementia (BPSD) “still need to be clarified.”

In the systematic review and meta-analysis, the investigators examined the effects of phototherapy on cognitive function, BPSD, and sleep in older adults with dementia.

They searched several databases for randomized controlled trials that investigated phototherapy interventions for elderly patients. The primary outcome was cognitive function, which was assessed via the Mini-Mental State Examination (MMSE).

Secondary outcomes included BPSD, including agitation, anxiety, irritability, depression, anxiety, and sleep disturbances, as assessed by the Cornell Scale for Depression in Dementia (CSDD), the Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI), and measures of sleep, including total sleep time (TST), sleep efficiency (SE), and sleep disorders, as assessed by the Sleep Disorder Inventory (SDI).

To be included in the analysis, individual studies had to focus on elderly adults who had some form of dementia. In addition, a group receiving a phototherapy intervention had to be compared with a nonintervention group, and the study had to specify one of the above-defined outcomes.

The review included phototherapy interventions of all forms, frequencies, and durations, including use of bright light, LED light, and blue or blue-green light.
 

Regulating circadian rhythm

Twelve studies met the researchers’ criteria. They included a total of 766 patients with dementia – 426 in the intervention group and 340 in the control group. The mean ages ranged from 73.73 to 85.9 years, and there was a greater number of female than male participants.

Of the studies, seven employed routine daily light in the control group, while the others used either dim light (≤ 50 lux) or devices without light.

The researchers found “significant positive intervention effects” for global cognitive function. Improvements in postintervention MMSE scores differed significantly between the experimental groups and control groups (mean difference, 2.68; 95% confidence interval, 1.38-3.98; I2 = 0%).

No significant differences were found in the effects of intervention on depression symptoms, as evidenced in CSDD scores (MD, −0.70; 95% CI, −3.10 to 1.70; I² = 81%).

Among patients with higher CMAI scores, which indicate more severe agitation behaviors, there was a “trend of decreasing CMAI scores” after phototherapy (MD, −3.12; 95% CI, −8.05 to 1.82; I² = 0%). No significant difference in NPI scores was observed between the two groups.

Similarly, no significant difference was found between the two groups in TST, SE, or SDI scores.

Adverse effects were infrequent and were not severe. Two of the 426 patients in the intervention group experienced mild ocular irritation, and one experienced slight transient redness of the forehead.

Light “may compensate for the reduction in the visual sensory input of patients with dementia and stimulate specific neurons in the suprachiasmatic nucleus of the hypothalamus to regulate circadian rhythm,” the researchers suggested.

“As circadian rhythms are involved in optimal brain function, light supplementation may act on the synchronizing/phase-shifting effects of circadian rhythms to improve cognitive function,” they added.

They note that the light box is the “most commonly used device in phototherapy.” Light boxes provide full-spectrum bright light, usually greater than 2,500 lux. The duration is 30 minutes in the daytime, and treatment lasts 4-8 weeks.

The investigators cautioned that the light box should be placed 60 cm away from the patient or above the patient’s eye level. They said that a ceiling-mounted light is a “good choice” for providing whole-day phototherapy, since such lights do not interfere with the patient’s daily routine, reduce the demand on staff, and contribute to better adherence.

Phototherapy helmets and glasses are also available. These portable devices “allow for better control of light intensity and are ergonomic without interfering with patients’ normal activities.”

The researchers noted that “further well-designed studies are needed to explore the most effective clinical implementation conditions, including device type, duration, frequency, and time.”
 

Easy to use

Mariana Figueiro, PhD, professor and director of the Light and Health Research Center, department of population health medicine, Icahn School of Medicine at Mount Sinai, New York, said light is the “major stimulus for the circadian system, and a robust light-dark pattern daily (which can be given by light therapy during the day) improves sleep and behavior and reduces depression and agitation.”

Dr. Figueiro, who was not involved with the current study, noted that patients with dementia “have sleep issues, which can further affect their cognition; improvement in sleep leads to improvement in cognition,” and this may be an underlying mechanism associated with these results.

The clinical significance of the study “is that this is a nonpharmacological intervention and can be easily applied in the homes or controlled facilities, and it can be used with any other medication,” she pointed out.

“More importantly, sleep medications have negative side effects, so the use of nonpharmacological interventions improving sleep and cognition is great for clinical practice,” she added.

However, she took issue with the finding that phototherapy was not effective for depression and agitation, noting that there were “too few studies to say for sure that light therapy is ineffective at improving these outcomes.”

The research received no external funding. The authors and Dr. Figueiro disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Disordered sleep is associated with a significantly increased risk for stroke, new research shows.

Results of a large international study show stroke risk was more than three times higher in those who slept too little, more than twice as high in those who sleep too much, and two to three times higher in those with symptoms of severe obstructive sleep apnea.

The study also showed that the greater the number of sleep disorder symptoms, the greater the stroke risk. The 11% of study participants with five or more symptoms of disordered sleep had a fivefold increased risk for stroke.

Jupiterimages/Thinkstock

More symptoms, more risk

Previous research shows severe OSA doubles the risk of stroke and increases the chance of recurrent stroke. A 2019 study showed that people with insomnia had a small increased risk of stroke.

“Both snoring and extremes of sleep duration have been previously associated with an increased risk of stroke in observational research, but less is known about other symptoms of sleep impairment, with less consistent findings,” Dr. McCarthy said.

Prior studies have also generally come from a single geographic region, which Dr. McCarthy noted could limit their generalizability.

For this effort, investigators used data from 4,496 participants in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. About half of the participants had a history of stroke.

Using information collected from a survey of sleep habits, researchers found an elevated stroke risk in those who received less than 5 hours of sleep per night (odds ratio, 3.15; 95% confidence interval, 2.09-4.76) or more than 9 hours of sleep per night (OR, 2.67; 95% CI, 1.89-3.78), compared with those who slept 7 hours a night.

Participants who took unplanned naps or naps lasting an hour or more (OR, 2.46; 95% CI, 1.69-3.57) and participants who reported poor quality sleep (OR,1.52; 95% CI, 1.32-1.75) were also at an increased risk for stroke.

Symptoms of OSA were also strongly associated with increased stroke risk, including snoring (OR, 1.91; 95% CI, 1.62-2.24), snorting (OR, 2.64; 95% CI, 2.17-3.20), and breathing cessation (OR, 2.87; 95% CI, 2.28-2.60).

Stroke risk increased as the number of sleep disturbance symptoms rose, with the greatest risk in the 11% of participants who had five or more symptoms (OR, 5.38; 95% CI, 4.03-7.18).

“This study finds an association between a broad range of sleep impairment symptoms and stroke, and a graded association with increasing symptoms, in an international setting,” Dr. McCarthy said.

Researchers aren’t sure what’s driving the higher stroke risk among people with sleep disturbances. Although the study did control for potential confounders, it wasn’t designed to get at what’s driving the association.

“Sleep disturbance may also have a bi-directional relationship with many stroke risk factors; for example, sleep disturbance may be a symptom of disease and exacerbate disease,” Dr. McCarthy said. “Future interventional studies are required to determine the true direction of the relationship.”
 

A marker of stroke risk

Daniel Lackland, DrPH, professor of neurology at the Medical University of South Carolina, Charleston, said the findings provide additional evidence of the link between sleep and stroke risk.

“The results confirm sleep disorders as a potential marker and part of the risk profile,” he said.

Collecting information about sleep using a validated assessment tool is an important piece of clinical care, Dr. Lackland said, especially among patients with other stroke risk factors.

One limitation of the study was that data on sleep was collected only at one point, and participants were not followed over time to see if changes in sleep affected stroke risk.

“This is an important point and should be a focus for future studies, as it is critical in the design of interventions,” Dr. Lackland said.

The INTERSTROKE study is funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, U.K. Chest, and U.K. Heart and Stroke. Dr. McCarthy and Lackland report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Disordered sleep is associated with a significantly increased risk for stroke, new research shows.

Results of a large international study show stroke risk was more than three times higher in those who slept too little, more than twice as high in those who sleep too much, and two to three times higher in those with symptoms of severe obstructive sleep apnea.

The study also showed that the greater the number of sleep disorder symptoms, the greater the stroke risk. The 11% of study participants with five or more symptoms of disordered sleep had a fivefold increased risk for stroke.

Jupiterimages/Thinkstock

More symptoms, more risk

Previous research shows severe OSA doubles the risk of stroke and increases the chance of recurrent stroke. A 2019 study showed that people with insomnia had a small increased risk of stroke.

“Both snoring and extremes of sleep duration have been previously associated with an increased risk of stroke in observational research, but less is known about other symptoms of sleep impairment, with less consistent findings,” Dr. McCarthy said.

Prior studies have also generally come from a single geographic region, which Dr. McCarthy noted could limit their generalizability.

For this effort, investigators used data from 4,496 participants in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. About half of the participants had a history of stroke.

Using information collected from a survey of sleep habits, researchers found an elevated stroke risk in those who received less than 5 hours of sleep per night (odds ratio, 3.15; 95% confidence interval, 2.09-4.76) or more than 9 hours of sleep per night (OR, 2.67; 95% CI, 1.89-3.78), compared with those who slept 7 hours a night.

Participants who took unplanned naps or naps lasting an hour or more (OR, 2.46; 95% CI, 1.69-3.57) and participants who reported poor quality sleep (OR,1.52; 95% CI, 1.32-1.75) were also at an increased risk for stroke.

Symptoms of OSA were also strongly associated with increased stroke risk, including snoring (OR, 1.91; 95% CI, 1.62-2.24), snorting (OR, 2.64; 95% CI, 2.17-3.20), and breathing cessation (OR, 2.87; 95% CI, 2.28-2.60).

Stroke risk increased as the number of sleep disturbance symptoms rose, with the greatest risk in the 11% of participants who had five or more symptoms (OR, 5.38; 95% CI, 4.03-7.18).

“This study finds an association between a broad range of sleep impairment symptoms and stroke, and a graded association with increasing symptoms, in an international setting,” Dr. McCarthy said.

Researchers aren’t sure what’s driving the higher stroke risk among people with sleep disturbances. Although the study did control for potential confounders, it wasn’t designed to get at what’s driving the association.

“Sleep disturbance may also have a bi-directional relationship with many stroke risk factors; for example, sleep disturbance may be a symptom of disease and exacerbate disease,” Dr. McCarthy said. “Future interventional studies are required to determine the true direction of the relationship.”
 

A marker of stroke risk

Daniel Lackland, DrPH, professor of neurology at the Medical University of South Carolina, Charleston, said the findings provide additional evidence of the link between sleep and stroke risk.

“The results confirm sleep disorders as a potential marker and part of the risk profile,” he said.

Collecting information about sleep using a validated assessment tool is an important piece of clinical care, Dr. Lackland said, especially among patients with other stroke risk factors.

One limitation of the study was that data on sleep was collected only at one point, and participants were not followed over time to see if changes in sleep affected stroke risk.

“This is an important point and should be a focus for future studies, as it is critical in the design of interventions,” Dr. Lackland said.

The INTERSTROKE study is funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, U.K. Chest, and U.K. Heart and Stroke. Dr. McCarthy and Lackland report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Disordered sleep is associated with a significantly increased risk for stroke, new research shows.

Results of a large international study show stroke risk was more than three times higher in those who slept too little, more than twice as high in those who sleep too much, and two to three times higher in those with symptoms of severe obstructive sleep apnea.

The study also showed that the greater the number of sleep disorder symptoms, the greater the stroke risk. The 11% of study participants with five or more symptoms of disordered sleep had a fivefold increased risk for stroke.

Jupiterimages/Thinkstock

More symptoms, more risk

Previous research shows severe OSA doubles the risk of stroke and increases the chance of recurrent stroke. A 2019 study showed that people with insomnia had a small increased risk of stroke.

“Both snoring and extremes of sleep duration have been previously associated with an increased risk of stroke in observational research, but less is known about other symptoms of sleep impairment, with less consistent findings,” Dr. McCarthy said.

Prior studies have also generally come from a single geographic region, which Dr. McCarthy noted could limit their generalizability.

For this effort, investigators used data from 4,496 participants in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. About half of the participants had a history of stroke.

Using information collected from a survey of sleep habits, researchers found an elevated stroke risk in those who received less than 5 hours of sleep per night (odds ratio, 3.15; 95% confidence interval, 2.09-4.76) or more than 9 hours of sleep per night (OR, 2.67; 95% CI, 1.89-3.78), compared with those who slept 7 hours a night.

Participants who took unplanned naps or naps lasting an hour or more (OR, 2.46; 95% CI, 1.69-3.57) and participants who reported poor quality sleep (OR,1.52; 95% CI, 1.32-1.75) were also at an increased risk for stroke.

Symptoms of OSA were also strongly associated with increased stroke risk, including snoring (OR, 1.91; 95% CI, 1.62-2.24), snorting (OR, 2.64; 95% CI, 2.17-3.20), and breathing cessation (OR, 2.87; 95% CI, 2.28-2.60).

Stroke risk increased as the number of sleep disturbance symptoms rose, with the greatest risk in the 11% of participants who had five or more symptoms (OR, 5.38; 95% CI, 4.03-7.18).

“This study finds an association between a broad range of sleep impairment symptoms and stroke, and a graded association with increasing symptoms, in an international setting,” Dr. McCarthy said.

Researchers aren’t sure what’s driving the higher stroke risk among people with sleep disturbances. Although the study did control for potential confounders, it wasn’t designed to get at what’s driving the association.

“Sleep disturbance may also have a bi-directional relationship with many stroke risk factors; for example, sleep disturbance may be a symptom of disease and exacerbate disease,” Dr. McCarthy said. “Future interventional studies are required to determine the true direction of the relationship.”
 

A marker of stroke risk

Daniel Lackland, DrPH, professor of neurology at the Medical University of South Carolina, Charleston, said the findings provide additional evidence of the link between sleep and stroke risk.

“The results confirm sleep disorders as a potential marker and part of the risk profile,” he said.

Collecting information about sleep using a validated assessment tool is an important piece of clinical care, Dr. Lackland said, especially among patients with other stroke risk factors.

One limitation of the study was that data on sleep was collected only at one point, and participants were not followed over time to see if changes in sleep affected stroke risk.

“This is an important point and should be a focus for future studies, as it is critical in the design of interventions,” Dr. Lackland said.

The INTERSTROKE study is funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, U.K. Chest, and U.K. Heart and Stroke. Dr. McCarthy and Lackland report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Medicare beneficiaries living in the Mississippi–Ohio River valley had a higher risk of developing Parkinson’s disease, compared with other regions of the United States, according to findings from a study that was released ahead of its scheduled presentation at the annual meeting of the American Academy of Neurology.

The association was attributed to concentrations of particulate matter (PM) _2.5 in the Mississippi–Ohio River valley, which was on average higher than in other areas, but that didn’t entirely explain the increase in Parkinson’s disease in that region, Brittany Krzyzanowski, PhD, a postdoctoral research fellow in the neuroepidemiology research program of the department of neurology at Barrow Neurological Institute, Dignity Health St. Joseph’s Hospital and Medical Center, Phoenix, said in an interview.

Barrow Neurological Institute

“This study revealed Parkinson’s disease hot spots in the Mississippi–Ohio River valley, a region that has some of the highest levels of air pollution in the nation,” she said, “but we also still find a relationship between air pollution and Parkinson’s risk in the regions in the western half of the United States where Parkinson’s disease and air pollution levels are relatively low.”

Dr. Krzyzanowski and colleagues evaluated 22,546,965 Medicare beneficiaries in 2009, using a multimethod approach that included geospatial analytical techniques to categorize their exposure to PM_2.5 based on age, sex, race, smoking status, and health care usage. The researchers also performed individual-level case-control analysis to assess PM_2.5 results at the county level. The Medicare beneficiaries were grouped according to average exposure, with the lowest group having an average annual exposure of 5 mcg/m³ and the group with the highest exposure having an average annual exposure of 19 mcg/m³.

In total, researchers identified 83,674 Medicare beneficiaries with incident Parkinson’s disease, with 434 new cases per 100,000 people in the highest exposure group, compared with 359 new cases per 100,000 people in the lowest-exposure group. The relative risk for Parkinson’s disease increased in the highest quartile of PM_2.5 by 25%, compared with the lowest quartile after adjusting for factors such as age, smoking status, and health care usage (95% confidence interval, 20%–29%).

The results showed the nationwide average annual PM_2.5 was associated with incident Parkinson’s disease, and the Rocky Mountain region carried a strong association between PM_2.5 and Parkson’s disease with a 16% increase in risk per level of exposure to PM_2.5. While the Mississippi-Ohio River valley was also associated with Parkinson’s disease, there was a weaker association between PM_2.5 and Parkinson’s disease, which the researchers attributed to a “ceiling effect” of PM_2.5 between approximately 12-19 mcg/m³.

Dr. Krzyzanowski said that use of a large-population-based dataset and high-resolution location data were major strengths of the study. “Having this level of information leaves less room for uncertainty in our measures and analyses,” she said. “Our study also leveraged innovative geographic information systems which allowed us to refine local patterns of disease by using population behavior and demographic information (such as smoking and age) to ensure that we could provide the most accurate map representation available to date.”
 

A focus on air pollution

Existing research in examining the etiology of Parkinson’s mainly focused on exposure to pesticides,* Dr. Krzyzanowski explained, and “consists of studies using relatively small populations and low-resolution air pollution data.” Genetics is another possible cause, she noted, but only explains some Parkinson’s disease cases.

“Our work suggests that we should also be looking at air pollution as a contributor in the development of Parkinson’s disease,” she said.

Ray Dorsey, MD, professor of neurology at the University of Rochester (N.Y.), who was not involved with the study, said that evidence is mounting that “air pollution may be an important causal factor in Parkinson’s and especially Alzheimer’s disease.”

“This study by a well-regarded group of researchers adds epidemiological evidence for that association,” he said. Another strength is that the study was conducted in the United States, as many epidemiological studies evaluating air pollution and Parkinson’s disease have been performed outside the country because of “a dearth of reliable data sources.”

“This study, along with others, suggest that some of the important environmental toxicants tied to brain disease may be inhaled,” Dr. Dorsey said. “The nose may be the front door to the brain.”

Dr. Krzyzanowski said the next step in their research is further examination of different types of air pollution. “Air pollution contains a variety of toxic components which vary from region to region. Understanding the different components in air pollution and how they interact with climate, temperature, and topography could help explain the regional differences we observed.”

One potential limitation in the study is a lag between air pollution exposure and development of Parkinson’s disease, Dr. Dorsey noted.

“Here, it looks like (but I am not certain) that the investigators looked at current air pollution levels and new cases of Parkinson’s. Ideally, for incident cases of Parkinson’s disease, we would want to know historical data on exposure to air pollution,” he said.

Future studies should include prospective evaluation of adults as well as babies and children who have been exposed to both high and low levels of air pollution. That kind of study “would be incredibly valuable for determining the role of an important environmental toxicant in many brain diseases, including stroke, Alzheimer’s, and Parkinson’s,” he said.

Dr. Krzyzanowski and Dr. Dorsey reported no relevant financial disclosures. This study was supported by grants from the Department of Defense, the National Institute of Environmental Health Sciences, and The Michael J. Fox Foundation for Parkinson’s Research.

*Correction, 4/14/23: An earlier version of this article mischaracterized the disease that was the subject of this research.

Medicare beneficiaries living in the Mississippi–Ohio River valley had a higher risk of developing Parkinson’s disease, compared with other regions of the United States, according to findings from a study that was released ahead of its scheduled presentation at the annual meeting of the American Academy of Neurology.

The association was attributed to concentrations of particulate matter (PM) _2.5 in the Mississippi–Ohio River valley, which was on average higher than in other areas, but that didn’t entirely explain the increase in Parkinson’s disease in that region, Brittany Krzyzanowski, PhD, a postdoctoral research fellow in the neuroepidemiology research program of the department of neurology at Barrow Neurological Institute, Dignity Health St. Joseph’s Hospital and Medical Center, Phoenix, said in an interview.

Barrow Neurological Institute

“This study revealed Parkinson’s disease hot spots in the Mississippi–Ohio River valley, a region that has some of the highest levels of air pollution in the nation,” she said, “but we also still find a relationship between air pollution and Parkinson’s risk in the regions in the western half of the United States where Parkinson’s disease and air pollution levels are relatively low.”

Dr. Krzyzanowski and colleagues evaluated 22,546,965 Medicare beneficiaries in 2009, using a multimethod approach that included geospatial analytical techniques to categorize their exposure to PM_2.5 based on age, sex, race, smoking status, and health care usage. The researchers also performed individual-level case-control analysis to assess PM_2.5 results at the county level. The Medicare beneficiaries were grouped according to average exposure, with the lowest group having an average annual exposure of 5 mcg/m³ and the group with the highest exposure having an average annual exposure of 19 mcg/m³.

In total, researchers identified 83,674 Medicare beneficiaries with incident Parkinson’s disease, with 434 new cases per 100,000 people in the highest exposure group, compared with 359 new cases per 100,000 people in the lowest-exposure group. The relative risk for Parkinson’s disease increased in the highest quartile of PM_2.5 by 25%, compared with the lowest quartile after adjusting for factors such as age, smoking status, and health care usage (95% confidence interval, 20%–29%).

The results showed the nationwide average annual PM_2.5 was associated with incident Parkinson’s disease, and the Rocky Mountain region carried a strong association between PM_2.5 and Parkson’s disease with a 16% increase in risk per level of exposure to PM_2.5. While the Mississippi-Ohio River valley was also associated with Parkinson’s disease, there was a weaker association between PM_2.5 and Parkinson’s disease, which the researchers attributed to a “ceiling effect” of PM_2.5 between approximately 12-19 mcg/m³.

Dr. Krzyzanowski said that use of a large-population-based dataset and high-resolution location data were major strengths of the study. “Having this level of information leaves less room for uncertainty in our measures and analyses,” she said. “Our study also leveraged innovative geographic information systems which allowed us to refine local patterns of disease by using population behavior and demographic information (such as smoking and age) to ensure that we could provide the most accurate map representation available to date.”
 

A focus on air pollution

Existing research in examining the etiology of Parkinson’s mainly focused on exposure to pesticides,* Dr. Krzyzanowski explained, and “consists of studies using relatively small populations and low-resolution air pollution data.” Genetics is another possible cause, she noted, but only explains some Parkinson’s disease cases.

“Our work suggests that we should also be looking at air pollution as a contributor in the development of Parkinson’s disease,” she said.

Ray Dorsey, MD, professor of neurology at the University of Rochester (N.Y.), who was not involved with the study, said that evidence is mounting that “air pollution may be an important causal factor in Parkinson’s and especially Alzheimer’s disease.”

“This study by a well-regarded group of researchers adds epidemiological evidence for that association,” he said. Another strength is that the study was conducted in the United States, as many epidemiological studies evaluating air pollution and Parkinson’s disease have been performed outside the country because of “a dearth of reliable data sources.”

“This study, along with others, suggest that some of the important environmental toxicants tied to brain disease may be inhaled,” Dr. Dorsey said. “The nose may be the front door to the brain.”

Dr. Krzyzanowski said the next step in their research is further examination of different types of air pollution. “Air pollution contains a variety of toxic components which vary from region to region. Understanding the different components in air pollution and how they interact with climate, temperature, and topography could help explain the regional differences we observed.”

One potential limitation in the study is a lag between air pollution exposure and development of Parkinson’s disease, Dr. Dorsey noted.

“Here, it looks like (but I am not certain) that the investigators looked at current air pollution levels and new cases of Parkinson’s. Ideally, for incident cases of Parkinson’s disease, we would want to know historical data on exposure to air pollution,” he said.

Future studies should include prospective evaluation of adults as well as babies and children who have been exposed to both high and low levels of air pollution. That kind of study “would be incredibly valuable for determining the role of an important environmental toxicant in many brain diseases, including stroke, Alzheimer’s, and Parkinson’s,” he said.

Dr. Krzyzanowski and Dr. Dorsey reported no relevant financial disclosures. This study was supported by grants from the Department of Defense, the National Institute of Environmental Health Sciences, and The Michael J. Fox Foundation for Parkinson’s Research.

*Correction, 4/14/23: An earlier version of this article mischaracterized the disease that was the subject of this research.

Medicare beneficiaries living in the Mississippi–Ohio River valley had a higher risk of developing Parkinson’s disease, compared with other regions of the United States, according to findings from a study that was released ahead of its scheduled presentation at the annual meeting of the American Academy of Neurology.

The association was attributed to concentrations of particulate matter (PM) _2.5 in the Mississippi–Ohio River valley, which was on average higher than in other areas, but that didn’t entirely explain the increase in Parkinson’s disease in that region, Brittany Krzyzanowski, PhD, a postdoctoral research fellow in the neuroepidemiology research program of the department of neurology at Barrow Neurological Institute, Dignity Health St. Joseph’s Hospital and Medical Center, Phoenix, said in an interview.

Barrow Neurological Institute

“This study revealed Parkinson’s disease hot spots in the Mississippi–Ohio River valley, a region that has some of the highest levels of air pollution in the nation,” she said, “but we also still find a relationship between air pollution and Parkinson’s risk in the regions in the western half of the United States where Parkinson’s disease and air pollution levels are relatively low.”

Dr. Krzyzanowski and colleagues evaluated 22,546,965 Medicare beneficiaries in 2009, using a multimethod approach that included geospatial analytical techniques to categorize their exposure to PM_2.5 based on age, sex, race, smoking status, and health care usage. The researchers also performed individual-level case-control analysis to assess PM_2.5 results at the county level. The Medicare beneficiaries were grouped according to average exposure, with the lowest group having an average annual exposure of 5 mcg/m³ and the group with the highest exposure having an average annual exposure of 19 mcg/m³.

In total, researchers identified 83,674 Medicare beneficiaries with incident Parkinson’s disease, with 434 new cases per 100,000 people in the highest exposure group, compared with 359 new cases per 100,000 people in the lowest-exposure group. The relative risk for Parkinson’s disease increased in the highest quartile of PM_2.5 by 25%, compared with the lowest quartile after adjusting for factors such as age, smoking status, and health care usage (95% confidence interval, 20%–29%).

The results showed the nationwide average annual PM_2.5 was associated with incident Parkinson’s disease, and the Rocky Mountain region carried a strong association between PM_2.5 and Parkson’s disease with a 16% increase in risk per level of exposure to PM_2.5. While the Mississippi-Ohio River valley was also associated with Parkinson’s disease, there was a weaker association between PM_2.5 and Parkinson’s disease, which the researchers attributed to a “ceiling effect” of PM_2.5 between approximately 12-19 mcg/m³.

Dr. Krzyzanowski said that use of a large-population-based dataset and high-resolution location data were major strengths of the study. “Having this level of information leaves less room for uncertainty in our measures and analyses,” she said. “Our study also leveraged innovative geographic information systems which allowed us to refine local patterns of disease by using population behavior and demographic information (such as smoking and age) to ensure that we could provide the most accurate map representation available to date.”
 

A focus on air pollution

Existing research in examining the etiology of Parkinson’s mainly focused on exposure to pesticides,* Dr. Krzyzanowski explained, and “consists of studies using relatively small populations and low-resolution air pollution data.” Genetics is another possible cause, she noted, but only explains some Parkinson’s disease cases.

“Our work suggests that we should also be looking at air pollution as a contributor in the development of Parkinson’s disease,” she said.

Ray Dorsey, MD, professor of neurology at the University of Rochester (N.Y.), who was not involved with the study, said that evidence is mounting that “air pollution may be an important causal factor in Parkinson’s and especially Alzheimer’s disease.”

“This study by a well-regarded group of researchers adds epidemiological evidence for that association,” he said. Another strength is that the study was conducted in the United States, as many epidemiological studies evaluating air pollution and Parkinson’s disease have been performed outside the country because of “a dearth of reliable data sources.”

“This study, along with others, suggest that some of the important environmental toxicants tied to brain disease may be inhaled,” Dr. Dorsey said. “The nose may be the front door to the brain.”

Dr. Krzyzanowski said the next step in their research is further examination of different types of air pollution. “Air pollution contains a variety of toxic components which vary from region to region. Understanding the different components in air pollution and how they interact with climate, temperature, and topography could help explain the regional differences we observed.”

One potential limitation in the study is a lag between air pollution exposure and development of Parkinson’s disease, Dr. Dorsey noted.

“Here, it looks like (but I am not certain) that the investigators looked at current air pollution levels and new cases of Parkinson’s. Ideally, for incident cases of Parkinson’s disease, we would want to know historical data on exposure to air pollution,” he said.

Future studies should include prospective evaluation of adults as well as babies and children who have been exposed to both high and low levels of air pollution. That kind of study “would be incredibly valuable for determining the role of an important environmental toxicant in many brain diseases, including stroke, Alzheimer’s, and Parkinson’s,” he said.

Dr. Krzyzanowski and Dr. Dorsey reported no relevant financial disclosures. This study was supported by grants from the Department of Defense, the National Institute of Environmental Health Sciences, and The Michael J. Fox Foundation for Parkinson’s Research.

*Correction, 4/14/23: An earlier version of this article mischaracterized the disease that was the subject of this research.

Women with better indicators of cardiovascular health at midlife saw reduced risk of later dementia, according to results of a study that was released early, ahead of its scheduled presentation at the annual meeting of the American Academy of Neurology.

Epidemiologist Pamela M. Rist, ScD, assistant professor of medicine at Harvard Medical School and associate epidemiologist at Brigham and Women’s Hospital, both in Boston, and colleagues, used data from 13,720 women whose mean age was 54 when they enrolled in the Harvard-based Women’s Health Study between 1992 and 1995. Subjects in that study were followed up in 2004.

Brigham and Women's Hospital

Putting ‘Life’s Simple 7’ to the test

Dr. Rist and colleagues used the Harvard data to discern how well closely women conformed, during the initial study period and at 10-year follow up, to what the American Heart Association describes as “Life’s Simple 7,” a list of behavioral and biometric measures that indicate and predict cardiovascular health. The measures include four modifiable behaviors – not smoking, healthy weight, a healthy diet, and being physically active – along with three biometric measures of blood pressure, cholesterol, and blood sugar (AHA has since added a sleep component).

Researchers assigned women one point for each desirable habit or measure on the list, with subjects’ average Simple 7 score at baseline 4.3, and 4.2 at 10 years’ follow-up.

The investigators then looked at Medicare data for the study subjects from 2011 to 2018 – approximately 20 years after their enrollment in the Women’s Health Study – seeking dementia diagnoses. Some 13% of the study cohort (n = 1,771) had gone on to develop dementia.

Each point on the Simple 7 score at baseline corresponded with a 6% reduction in later dementia risk, Dr. Rist and her colleagues found after adjusting for variables including age and education (odds ratio per one unit change in score, 0.94; 95% CI, 0.90-0.98). This effect was similar for Simple 7 scores measured at 10 years of follow-up (OR, 0.95; 95% CI, 0.91-1.00).

“It can be empowering for people to know that by taking steps such as exercising for a half an hour a day or keeping their blood pressure under control, they can reduce their risk of dementia,” Dr. Rist said in a statement on the findings.
 

‘A simple take-home message’

Reached for comment, Andrew E. Budson, MD, chief of cognitive-behavioral neurology at the VA Boston Healthcare System, praised Dr. Rist and colleagues’ study as one that “builds on existing knowledge to provide a simple take-home message that empowers women to take control of their dementia risk.”

VA Boston Healthcare System

Each of the seven known risk factors – being active, eating better, maintaining a healthy weight, not smoking, maintaining a healthy blood pressure, controlling cholesterol, and having low blood sugar – “was associated with a 6% reduced risk of dementia,” Dr. Budson continued. “So, women who work to address all seven risk factors can reduce their risk of developing dementia by 42%: a huge amount. Moreover, although this study only looked at women, I am confident that if men follow this same advice they will also be able to reduce their risk of dementia, although we don’t know if the size of the effect will be the same.”

Dr. Rist and colleagues’ study was supported by the National Institutes of Health. None of the study authors reported conflicts of interest. Dr. Budson has reported receiving past compensation as a speaker for Eli Lilly.

Women with better indicators of cardiovascular health at midlife saw reduced risk of later dementia, according to results of a study that was released early, ahead of its scheduled presentation at the annual meeting of the American Academy of Neurology.

Epidemiologist Pamela M. Rist, ScD, assistant professor of medicine at Harvard Medical School and associate epidemiologist at Brigham and Women’s Hospital, both in Boston, and colleagues, used data from 13,720 women whose mean age was 54 when they enrolled in the Harvard-based Women’s Health Study between 1992 and 1995. Subjects in that study were followed up in 2004.

Brigham and Women's Hospital

Putting ‘Life’s Simple 7’ to the test

Dr. Rist and colleagues used the Harvard data to discern how well closely women conformed, during the initial study period and at 10-year follow up, to what the American Heart Association describes as “Life’s Simple 7,” a list of behavioral and biometric measures that indicate and predict cardiovascular health. The measures include four modifiable behaviors – not smoking, healthy weight, a healthy diet, and being physically active – along with three biometric measures of blood pressure, cholesterol, and blood sugar (AHA has since added a sleep component).

Researchers assigned women one point for each desirable habit or measure on the list, with subjects’ average Simple 7 score at baseline 4.3, and 4.2 at 10 years’ follow-up.

The investigators then looked at Medicare data for the study subjects from 2011 to 2018 – approximately 20 years after their enrollment in the Women’s Health Study – seeking dementia diagnoses. Some 13% of the study cohort (n = 1,771) had gone on to develop dementia.

Each point on the Simple 7 score at baseline corresponded with a 6% reduction in later dementia risk, Dr. Rist and her colleagues found after adjusting for variables including age and education (odds ratio per one unit change in score, 0.94; 95% CI, 0.90-0.98). This effect was similar for Simple 7 scores measured at 10 years of follow-up (OR, 0.95; 95% CI, 0.91-1.00).

“It can be empowering for people to know that by taking steps such as exercising for a half an hour a day or keeping their blood pressure under control, they can reduce their risk of dementia,” Dr. Rist said in a statement on the findings.
 

‘A simple take-home message’

Reached for comment, Andrew E. Budson, MD, chief of cognitive-behavioral neurology at the VA Boston Healthcare System, praised Dr. Rist and colleagues’ study as one that “builds on existing knowledge to provide a simple take-home message that empowers women to take control of their dementia risk.”

VA Boston Healthcare System

Each of the seven known risk factors – being active, eating better, maintaining a healthy weight, not smoking, maintaining a healthy blood pressure, controlling cholesterol, and having low blood sugar – “was associated with a 6% reduced risk of dementia,” Dr. Budson continued. “So, women who work to address all seven risk factors can reduce their risk of developing dementia by 42%: a huge amount. Moreover, although this study only looked at women, I am confident that if men follow this same advice they will also be able to reduce their risk of dementia, although we don’t know if the size of the effect will be the same.”

Dr. Rist and colleagues’ study was supported by the National Institutes of Health. None of the study authors reported conflicts of interest. Dr. Budson has reported receiving past compensation as a speaker for Eli Lilly.

Women with better indicators of cardiovascular health at midlife saw reduced risk of later dementia, according to results of a study that was released early, ahead of its scheduled presentation at the annual meeting of the American Academy of Neurology.

Epidemiologist Pamela M. Rist, ScD, assistant professor of medicine at Harvard Medical School and associate epidemiologist at Brigham and Women’s Hospital, both in Boston, and colleagues, used data from 13,720 women whose mean age was 54 when they enrolled in the Harvard-based Women’s Health Study between 1992 and 1995. Subjects in that study were followed up in 2004.

Brigham and Women's Hospital

Putting ‘Life’s Simple 7’ to the test

Dr. Rist and colleagues used the Harvard data to discern how well closely women conformed, during the initial study period and at 10-year follow up, to what the American Heart Association describes as “Life’s Simple 7,” a list of behavioral and biometric measures that indicate and predict cardiovascular health. The measures include four modifiable behaviors – not smoking, healthy weight, a healthy diet, and being physically active – along with three biometric measures of blood pressure, cholesterol, and blood sugar (AHA has since added a sleep component).

Researchers assigned women one point for each desirable habit or measure on the list, with subjects’ average Simple 7 score at baseline 4.3, and 4.2 at 10 years’ follow-up.

The investigators then looked at Medicare data for the study subjects from 2011 to 2018 – approximately 20 years after their enrollment in the Women’s Health Study – seeking dementia diagnoses. Some 13% of the study cohort (n = 1,771) had gone on to develop dementia.

Each point on the Simple 7 score at baseline corresponded with a 6% reduction in later dementia risk, Dr. Rist and her colleagues found after adjusting for variables including age and education (odds ratio per one unit change in score, 0.94; 95% CI, 0.90-0.98). This effect was similar for Simple 7 scores measured at 10 years of follow-up (OR, 0.95; 95% CI, 0.91-1.00).

“It can be empowering for people to know that by taking steps such as exercising for a half an hour a day or keeping their blood pressure under control, they can reduce their risk of dementia,” Dr. Rist said in a statement on the findings.
 

‘A simple take-home message’

Reached for comment, Andrew E. Budson, MD, chief of cognitive-behavioral neurology at the VA Boston Healthcare System, praised Dr. Rist and colleagues’ study as one that “builds on existing knowledge to provide a simple take-home message that empowers women to take control of their dementia risk.”

VA Boston Healthcare System

Each of the seven known risk factors – being active, eating better, maintaining a healthy weight, not smoking, maintaining a healthy blood pressure, controlling cholesterol, and having low blood sugar – “was associated with a 6% reduced risk of dementia,” Dr. Budson continued. “So, women who work to address all seven risk factors can reduce their risk of developing dementia by 42%: a huge amount. Moreover, although this study only looked at women, I am confident that if men follow this same advice they will also be able to reduce their risk of dementia, although we don’t know if the size of the effect will be the same.”

Dr. Rist and colleagues’ study was supported by the National Institutes of Health. None of the study authors reported conflicts of interest. Dr. Budson has reported receiving past compensation as a speaker for Eli Lilly.

I’m not going to get rich off Mike.

Of course, I’m not going to get rich off anyone, nor do I want to. I’m not here to rip anyone off.

Mike goes back with me, roughly 23 years.

He was born with cerebral palsy and refractory seizures. His birth mother gave him up quickly, and he was adopted by a couple who knew what they were getting into (to me that constitutes sainthood).

Over the years Mike has done his best to buck the odds. He’s tried to stay employed, in spite of his physical limitations, working variously as a janitor, grocery courtesy clerk, and store greeter. He tells me that he can still work and wants to, even with having to rely on public transportation.

By the time he came to me he’d been through several neurologists and even more failed epilepsy drugs. His brain MRI and EEGs showed multifocal seizures from numerous inoperable cortical heterotopias.

I dabbled with a few newer drugs at the time for him, without success. Finally, I reached for the neurological equivalent of unstable dynamite – Felbatol (felbamate).

As it often does, it worked. One of my attendings in training (you, Bob) told me it was the home-run drug. When nothing else worked, it might – but you had to handle it carefully.

Fortunately, after 23 years, that hasn’t happened. Mike’s labs have looked good. His seizures have dropped from several a week to a few per year.

Ten years ago Mike had to change insurance to one I don’t take, and had me forward his records to another neurologist. That office told him they don’t handle Felbatol. As did another. And another.

Mike, understandably, doesn’t want to change meds. This is the only drug that’s given him a decent quality of life, and let him have a job. That’s pretty important to him.

So, I see him for free now, once or twice a year. Sometimes he offers me a token payment of $5-$10, but I turn it down. He needs it more than I do, for bus fair to my office if nothing else.

I’m sure some would be critical of me, saying that I should be more open to new drugs and treatments. I am, believe me. But Mike can’t afford many of them, or the loss of work they’d entail if his seizures worsen. He doesn’t want to take that chance, and I don’t blame him.

Of course, none of us can see everyone for free. In fact, he’s the only one I do. I’m not greedy, but I also have to pay my rent, staff, and mortgage.

But taking money from Mike, who’s come up on the short end of the stick in so many ways, doesn’t seem right. I can’t do it, and really don’t want to.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I’m not going to get rich off Mike.

Of course, I’m not going to get rich off anyone, nor do I want to. I’m not here to rip anyone off.

Mike goes back with me, roughly 23 years.

He was born with cerebral palsy and refractory seizures. His birth mother gave him up quickly, and he was adopted by a couple who knew what they were getting into (to me that constitutes sainthood).

Over the years Mike has done his best to buck the odds. He’s tried to stay employed, in spite of his physical limitations, working variously as a janitor, grocery courtesy clerk, and store greeter. He tells me that he can still work and wants to, even with having to rely on public transportation.

By the time he came to me he’d been through several neurologists and even more failed epilepsy drugs. His brain MRI and EEGs showed multifocal seizures from numerous inoperable cortical heterotopias.

I dabbled with a few newer drugs at the time for him, without success. Finally, I reached for the neurological equivalent of unstable dynamite – Felbatol (felbamate).

As it often does, it worked. One of my attendings in training (you, Bob) told me it was the home-run drug. When nothing else worked, it might – but you had to handle it carefully.

Fortunately, after 23 years, that hasn’t happened. Mike’s labs have looked good. His seizures have dropped from several a week to a few per year.

Ten years ago Mike had to change insurance to one I don’t take, and had me forward his records to another neurologist. That office told him they don’t handle Felbatol. As did another. And another.

Mike, understandably, doesn’t want to change meds. This is the only drug that’s given him a decent quality of life, and let him have a job. That’s pretty important to him.

So, I see him for free now, once or twice a year. Sometimes he offers me a token payment of $5-$10, but I turn it down. He needs it more than I do, for bus fair to my office if nothing else.

I’m sure some would be critical of me, saying that I should be more open to new drugs and treatments. I am, believe me. But Mike can’t afford many of them, or the loss of work they’d entail if his seizures worsen. He doesn’t want to take that chance, and I don’t blame him.

Of course, none of us can see everyone for free. In fact, he’s the only one I do. I’m not greedy, but I also have to pay my rent, staff, and mortgage.

But taking money from Mike, who’s come up on the short end of the stick in so many ways, doesn’t seem right. I can’t do it, and really don’t want to.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I’m not going to get rich off Mike.

Of course, I’m not going to get rich off anyone, nor do I want to. I’m not here to rip anyone off.

Mike goes back with me, roughly 23 years.

He was born with cerebral palsy and refractory seizures. His birth mother gave him up quickly, and he was adopted by a couple who knew what they were getting into (to me that constitutes sainthood).

Over the years Mike has done his best to buck the odds. He’s tried to stay employed, in spite of his physical limitations, working variously as a janitor, grocery courtesy clerk, and store greeter. He tells me that he can still work and wants to, even with having to rely on public transportation.

By the time he came to me he’d been through several neurologists and even more failed epilepsy drugs. His brain MRI and EEGs showed multifocal seizures from numerous inoperable cortical heterotopias.

I dabbled with a few newer drugs at the time for him, without success. Finally, I reached for the neurological equivalent of unstable dynamite – Felbatol (felbamate).

As it often does, it worked. One of my attendings in training (you, Bob) told me it was the home-run drug. When nothing else worked, it might – but you had to handle it carefully.

Fortunately, after 23 years, that hasn’t happened. Mike’s labs have looked good. His seizures have dropped from several a week to a few per year.

Ten years ago Mike had to change insurance to one I don’t take, and had me forward his records to another neurologist. That office told him they don’t handle Felbatol. As did another. And another.

Mike, understandably, doesn’t want to change meds. This is the only drug that’s given him a decent quality of life, and let him have a job. That’s pretty important to him.

So, I see him for free now, once or twice a year. Sometimes he offers me a token payment of $5-$10, but I turn it down. He needs it more than I do, for bus fair to my office if nothing else.

I’m sure some would be critical of me, saying that I should be more open to new drugs and treatments. I am, believe me. But Mike can’t afford many of them, or the loss of work they’d entail if his seizures worsen. He doesn’t want to take that chance, and I don’t blame him.

Of course, none of us can see everyone for free. In fact, he’s the only one I do. I’m not greedy, but I also have to pay my rent, staff, and mortgage.

But taking money from Mike, who’s come up on the short end of the stick in so many ways, doesn’t seem right. I can’t do it, and really don’t want to.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Radiotherapy followed by immunotherapy within 1-12 months – but not sooner or later – may boost progression-free survival in patients with metastatic non–small cell lung cancer, according to a new study. However, patients still fared poorly on average since overall survival remained low and didn’t change significantly.

While not conclusive, the new research – released at European Lung Cancer Congress 2023 – offers early insight into the best timing for the experimental combination treatment, study coauthor Yanyan Lou, MD, PhD, an oncologist at Mayo Clinic in Jacksonville, Fla., said in an interview.

The wide availability of radiation therapy could also allow the therapy to be administered even in regions with poor access to sophisticated medical care, she said. “Radiation is a very feasible approach that pretty much everybody in your community can get.”

Radiotherapy is typically not added to immunotherapy in patients with non–small cell lung cancer. But “there has been recent interest in the combination: Would tumor necrosis from radiation enhance the immunogenicity of the tumor and thus enhance the effect of immunotherapy?” oncologist Toby Campbell, MD, of University of Wisconsin–Madison, said in an interview.

Research has indeed suggested that the treatments may have a synergistic effect, he said, and it’s clear that “strategies to try and increase immunogenicity are an important area to investigate.”

But he cautioned that “we have a long way to go to understanding how immunogenicity works and how the gut microbiome, tumor, immunotherapy, and the immune system interact with one another.”

For the new study, researchers retrospectively analyzed cases of 225 patients with metastatic non–small cell lung cancer (male = 56%, median age = 68, 79% adenocarcinoma) who were treated with immunotherapy at Mayo Clinic–Jacksonville from 2011 to 2022. The study excluded those who received targeted therapy or prior concurrent chemoradiotherapy and durvalumab.

The most common metastases were bone and central nervous system types (41% and 25%, respectively). Fifty-six percent of patients received radiotherapy before or during immunotherapy. Another 27% never received radiotherapy, and 17% received it after immunotherapy was discontinued.

Common types of immunotherapy included pembrolizumab (78%), nivolumab (14%), and atezolizumab (12%).

Overall, the researchers found no statistically significant differences in various outcomes between patients who received radiotherapy before or during immunotherapy compared with those who didn’t get radiotherapy (progression-free survival: 5.9 vs. 5.5 months, P = .66; overall survival: 16.9 vs. 13.1 months, P = .84; immune-related adverse events: 26.2% vs. 34.4%, P = .24).

However, the researchers found that progression-free survival was significantly higher in one group: Those who received radiotherapy 1-12 months before immunotherapy vs. those who received it less than 1 month before (12.6 vs. 4.2 months, hazard ratio [HR], 0.46, 95% confidence interval [CI], 0.26-0.83, P = .005,) and those who never received radiotherapy (12.6 vs. 5.5 months, HR, 0.56, 95% CI, 0.36-0.89, P = .0197).

There wasn’t a statistically significant difference in overall survival.

The small number of subjects and the variation in treatment protocols may have prevented the study from revealing a survival benefit, Dr. Lou said.

As for adverse effects, she said a preliminary analysis didn’t turn up any.

It’s not clear why a 1- to 12-month gap between radiotherapy and immunotherapy may be most effective, she said. Moving forward, “we need validate this in a large cohort,” she noted.

In regard to cost, immunotherapy is notoriously expensive. Pembrolizumab, for example, has a list price of $10,897 per 200-mg dose given every 3 weeks, and patients may take the drug for a year or two.

Dr. Campbell, who didn’t take part in the new study, said it suggests that research into radiation-immunotherapy combination treatment may be worthwhile.

No funding was reported. The study authors and Dr. Campbell reported no disclosures.

Radiotherapy followed by immunotherapy within 1-12 months – but not sooner or later – may boost progression-free survival in patients with metastatic non–small cell lung cancer, according to a new study. However, patients still fared poorly on average since overall survival remained low and didn’t change significantly.

While not conclusive, the new research – released at European Lung Cancer Congress 2023 – offers early insight into the best timing for the experimental combination treatment, study coauthor Yanyan Lou, MD, PhD, an oncologist at Mayo Clinic in Jacksonville, Fla., said in an interview.

The wide availability of radiation therapy could also allow the therapy to be administered even in regions with poor access to sophisticated medical care, she said. “Radiation is a very feasible approach that pretty much everybody in your community can get.”

Radiotherapy is typically not added to immunotherapy in patients with non–small cell lung cancer. But “there has been recent interest in the combination: Would tumor necrosis from radiation enhance the immunogenicity of the tumor and thus enhance the effect of immunotherapy?” oncologist Toby Campbell, MD, of University of Wisconsin–Madison, said in an interview.

Research has indeed suggested that the treatments may have a synergistic effect, he said, and it’s clear that “strategies to try and increase immunogenicity are an important area to investigate.”

But he cautioned that “we have a long way to go to understanding how immunogenicity works and how the gut microbiome, tumor, immunotherapy, and the immune system interact with one another.”

For the new study, researchers retrospectively analyzed cases of 225 patients with metastatic non–small cell lung cancer (male = 56%, median age = 68, 79% adenocarcinoma) who were treated with immunotherapy at Mayo Clinic–Jacksonville from 2011 to 2022. The study excluded those who received targeted therapy or prior concurrent chemoradiotherapy and durvalumab.

The most common metastases were bone and central nervous system types (41% and 25%, respectively). Fifty-six percent of patients received radiotherapy before or during immunotherapy. Another 27% never received radiotherapy, and 17% received it after immunotherapy was discontinued.

Common types of immunotherapy included pembrolizumab (78%), nivolumab (14%), and atezolizumab (12%).

Overall, the researchers found no statistically significant differences in various outcomes between patients who received radiotherapy before or during immunotherapy compared with those who didn’t get radiotherapy (progression-free survival: 5.9 vs. 5.5 months, P = .66; overall survival: 16.9 vs. 13.1 months, P = .84; immune-related adverse events: 26.2% vs. 34.4%, P = .24).

However, the researchers found that progression-free survival was significantly higher in one group: Those who received radiotherapy 1-12 months before immunotherapy vs. those who received it less than 1 month before (12.6 vs. 4.2 months, hazard ratio [HR], 0.46, 95% confidence interval [CI], 0.26-0.83, P = .005,) and those who never received radiotherapy (12.6 vs. 5.5 months, HR, 0.56, 95% CI, 0.36-0.89, P = .0197).

There wasn’t a statistically significant difference in overall survival.

The small number of subjects and the variation in treatment protocols may have prevented the study from revealing a survival benefit, Dr. Lou said.

As for adverse effects, she said a preliminary analysis didn’t turn up any.

It’s not clear why a 1- to 12-month gap between radiotherapy and immunotherapy may be most effective, she said. Moving forward, “we need validate this in a large cohort,” she noted.

In regard to cost, immunotherapy is notoriously expensive. Pembrolizumab, for example, has a list price of $10,897 per 200-mg dose given every 3 weeks, and patients may take the drug for a year or two.

Dr. Campbell, who didn’t take part in the new study, said it suggests that research into radiation-immunotherapy combination treatment may be worthwhile.

No funding was reported. The study authors and Dr. Campbell reported no disclosures.

Radiotherapy followed by immunotherapy within 1-12 months – but not sooner or later – may boost progression-free survival in patients with metastatic non–small cell lung cancer, according to a new study. However, patients still fared poorly on average since overall survival remained low and didn’t change significantly.

While not conclusive, the new research – released at European Lung Cancer Congress 2023 – offers early insight into the best timing for the experimental combination treatment, study coauthor Yanyan Lou, MD, PhD, an oncologist at Mayo Clinic in Jacksonville, Fla., said in an interview.

The wide availability of radiation therapy could also allow the therapy to be administered even in regions with poor access to sophisticated medical care, she said. “Radiation is a very feasible approach that pretty much everybody in your community can get.”

Radiotherapy is typically not added to immunotherapy in patients with non–small cell lung cancer. But “there has been recent interest in the combination: Would tumor necrosis from radiation enhance the immunogenicity of the tumor and thus enhance the effect of immunotherapy?” oncologist Toby Campbell, MD, of University of Wisconsin–Madison, said in an interview.

Research has indeed suggested that the treatments may have a synergistic effect, he said, and it’s clear that “strategies to try and increase immunogenicity are an important area to investigate.”

But he cautioned that “we have a long way to go to understanding how immunogenicity works and how the gut microbiome, tumor, immunotherapy, and the immune system interact with one another.”

For the new study, researchers retrospectively analyzed cases of 225 patients with metastatic non–small cell lung cancer (male = 56%, median age = 68, 79% adenocarcinoma) who were treated with immunotherapy at Mayo Clinic–Jacksonville from 2011 to 2022. The study excluded those who received targeted therapy or prior concurrent chemoradiotherapy and durvalumab.

The most common metastases were bone and central nervous system types (41% and 25%, respectively). Fifty-six percent of patients received radiotherapy before or during immunotherapy. Another 27% never received radiotherapy, and 17% received it after immunotherapy was discontinued.

Common types of immunotherapy included pembrolizumab (78%), nivolumab (14%), and atezolizumab (12%).

Overall, the researchers found no statistically significant differences in various outcomes between patients who received radiotherapy before or during immunotherapy compared with those who didn’t get radiotherapy (progression-free survival: 5.9 vs. 5.5 months, P = .66; overall survival: 16.9 vs. 13.1 months, P = .84; immune-related adverse events: 26.2% vs. 34.4%, P = .24).

However, the researchers found that progression-free survival was significantly higher in one group: Those who received radiotherapy 1-12 months before immunotherapy vs. those who received it less than 1 month before (12.6 vs. 4.2 months, hazard ratio [HR], 0.46, 95% confidence interval [CI], 0.26-0.83, P = .005,) and those who never received radiotherapy (12.6 vs. 5.5 months, HR, 0.56, 95% CI, 0.36-0.89, P = .0197).

There wasn’t a statistically significant difference in overall survival.

The small number of subjects and the variation in treatment protocols may have prevented the study from revealing a survival benefit, Dr. Lou said.

As for adverse effects, she said a preliminary analysis didn’t turn up any.

It’s not clear why a 1- to 12-month gap between radiotherapy and immunotherapy may be most effective, she said. Moving forward, “we need validate this in a large cohort,” she noted.

In regard to cost, immunotherapy is notoriously expensive. Pembrolizumab, for example, has a list price of $10,897 per 200-mg dose given every 3 weeks, and patients may take the drug for a year or two.

Dr. Campbell, who didn’t take part in the new study, said it suggests that research into radiation-immunotherapy combination treatment may be worthwhile.

No funding was reported. The study authors and Dr. Campbell reported no disclosures.

A new analysis suggests that the initial target of therapy – lung or brain – doesn’t affect overall survival rates in patients with non–small cell lung cancer that has spread to the brain.

“The findings of our study highlight the importance of adopting a personalized, case-based approach when treating each patient” instead of always treating the brain or lung first, lead author Arvind Kumar, a medical student at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The study was released at European Lung Cancer Congress 2023.

According to the author, current guidelines recommend treating the brain first in patients with non–small cell lung cancer and a tumor that has spread to the brain.

“Determining whether the brain or body gets treated first depends on where the symptoms are coming from, how severe the symptoms are, how bulky the disease is, and how long the treatment to each is expected to take,” radiation oncologist Henry S. Park, MD, MPH, chief of the thoracic radiotherapy program at Yale University, New Haven, Conn., said in an interview. “Often the brain is treated first since surgery is used for both diagnosis of metastatic disease as well as removal of the brain metastasis, especially if it is causing symptoms. The radiosurgery that follows tends to occur within a day or a few days.”

However, he said, “if the brain disease is small and not causing symptoms, and the lung disease is more problematic, then we will often treat the body first and fit in the brain treatment later.”

For the new study, researchers identified 1,044 patients in the National Cancer Database with non–small cell lung cancer and brain metastases who received systemic therapy plus surgery, brain stereotactic radiosurgery, or lung radiation. All were treated from 2010 to 2019; 79.0% received brain treatment first, and the other 21.0% received lung treatment first.

There was no statistically significant difference in overall survival between those whose brains were treated first and those whose lungs were treated first (hazard ratio, 1.24, 95% confidence interval [CI], 0.91-1.70, P = .17). A propensity score–matched analysis turned up no difference in 5-year survival (38.2% of those whose brains were treated first, 95% CI, 27.5-34.4, vs. 38.0% of those whose lungs were treated first, 95% CI, 29.9-44.7, P = .32.)

“These results were consistent regardless of which combination of treatment modalities the patient received – neurosurgery versus brain stereotactic radiosurgery, thoracic surgery versus thoracic radiation,” the author said.

He cautioned that “our study only included patients who were considered candidates for either surgery or radiation to both the brain and lung. The results of our study should therefore be cautiously interpreted for patients who may have contraindications to such treatment.”

Dr. Park, who didn’t take part in the study, said “the results are consistent with what I would generally expect.”

He added: “The take-home message for clinicians should be that there is no one correct answer in how to manage non–small cell lung cancer with synchronous limited metastatic disease in only the brain. If the brain disease is bulky and/or causes symptoms while the body disease isn’t – or if a biopsy or surgery is required to prove that the patient in fact has metastatic disease – then the brain disease should be treated first. On the other hand, if the body disease is bulky and/or causing symptoms while the brain disease isn’t – and there is no need for surgery but rather only a biopsy of the brain – then the body disease can be treated first.”

No funding was reported. The study authors and Dr. Park reported no financial conflicts or other disclosures.

A new analysis suggests that the initial target of therapy – lung or brain – doesn’t affect overall survival rates in patients with non–small cell lung cancer that has spread to the brain.

“The findings of our study highlight the importance of adopting a personalized, case-based approach when treating each patient” instead of always treating the brain or lung first, lead author Arvind Kumar, a medical student at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The study was released at European Lung Cancer Congress 2023.

According to the author, current guidelines recommend treating the brain first in patients with non–small cell lung cancer and a tumor that has spread to the brain.

“Determining whether the brain or body gets treated first depends on where the symptoms are coming from, how severe the symptoms are, how bulky the disease is, and how long the treatment to each is expected to take,” radiation oncologist Henry S. Park, MD, MPH, chief of the thoracic radiotherapy program at Yale University, New Haven, Conn., said in an interview. “Often the brain is treated first since surgery is used for both diagnosis of metastatic disease as well as removal of the brain metastasis, especially if it is causing symptoms. The radiosurgery that follows tends to occur within a day or a few days.”

However, he said, “if the brain disease is small and not causing symptoms, and the lung disease is more problematic, then we will often treat the body first and fit in the brain treatment later.”

For the new study, researchers identified 1,044 patients in the National Cancer Database with non–small cell lung cancer and brain metastases who received systemic therapy plus surgery, brain stereotactic radiosurgery, or lung radiation. All were treated from 2010 to 2019; 79.0% received brain treatment first, and the other 21.0% received lung treatment first.

There was no statistically significant difference in overall survival between those whose brains were treated first and those whose lungs were treated first (hazard ratio, 1.24, 95% confidence interval [CI], 0.91-1.70, P = .17). A propensity score–matched analysis turned up no difference in 5-year survival (38.2% of those whose brains were treated first, 95% CI, 27.5-34.4, vs. 38.0% of those whose lungs were treated first, 95% CI, 29.9-44.7, P = .32.)

“These results were consistent regardless of which combination of treatment modalities the patient received – neurosurgery versus brain stereotactic radiosurgery, thoracic surgery versus thoracic radiation,” the author said.

He cautioned that “our study only included patients who were considered candidates for either surgery or radiation to both the brain and lung. The results of our study should therefore be cautiously interpreted for patients who may have contraindications to such treatment.”

Dr. Park, who didn’t take part in the study, said “the results are consistent with what I would generally expect.”

He added: “The take-home message for clinicians should be that there is no one correct answer in how to manage non–small cell lung cancer with synchronous limited metastatic disease in only the brain. If the brain disease is bulky and/or causes symptoms while the body disease isn’t – or if a biopsy or surgery is required to prove that the patient in fact has metastatic disease – then the brain disease should be treated first. On the other hand, if the body disease is bulky and/or causing symptoms while the brain disease isn’t – and there is no need for surgery but rather only a biopsy of the brain – then the body disease can be treated first.”

No funding was reported. The study authors and Dr. Park reported no financial conflicts or other disclosures.

A new analysis suggests that the initial target of therapy – lung or brain – doesn’t affect overall survival rates in patients with non–small cell lung cancer that has spread to the brain.

“The findings of our study highlight the importance of adopting a personalized, case-based approach when treating each patient” instead of always treating the brain or lung first, lead author Arvind Kumar, a medical student at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The study was released at European Lung Cancer Congress 2023.

According to the author, current guidelines recommend treating the brain first in patients with non–small cell lung cancer and a tumor that has spread to the brain.

“Determining whether the brain or body gets treated first depends on where the symptoms are coming from, how severe the symptoms are, how bulky the disease is, and how long the treatment to each is expected to take,” radiation oncologist Henry S. Park, MD, MPH, chief of the thoracic radiotherapy program at Yale University, New Haven, Conn., said in an interview. “Often the brain is treated first since surgery is used for both diagnosis of metastatic disease as well as removal of the brain metastasis, especially if it is causing symptoms. The radiosurgery that follows tends to occur within a day or a few days.”

However, he said, “if the brain disease is small and not causing symptoms, and the lung disease is more problematic, then we will often treat the body first and fit in the brain treatment later.”

For the new study, researchers identified 1,044 patients in the National Cancer Database with non–small cell lung cancer and brain metastases who received systemic therapy plus surgery, brain stereotactic radiosurgery, or lung radiation. All were treated from 2010 to 2019; 79.0% received brain treatment first, and the other 21.0% received lung treatment first.

There was no statistically significant difference in overall survival between those whose brains were treated first and those whose lungs were treated first (hazard ratio, 1.24, 95% confidence interval [CI], 0.91-1.70, P = .17). A propensity score–matched analysis turned up no difference in 5-year survival (38.2% of those whose brains were treated first, 95% CI, 27.5-34.4, vs. 38.0% of those whose lungs were treated first, 95% CI, 29.9-44.7, P = .32.)

“These results were consistent regardless of which combination of treatment modalities the patient received – neurosurgery versus brain stereotactic radiosurgery, thoracic surgery versus thoracic radiation,” the author said.

He cautioned that “our study only included patients who were considered candidates for either surgery or radiation to both the brain and lung. The results of our study should therefore be cautiously interpreted for patients who may have contraindications to such treatment.”

Dr. Park, who didn’t take part in the study, said “the results are consistent with what I would generally expect.”

He added: “The take-home message for clinicians should be that there is no one correct answer in how to manage non–small cell lung cancer with synchronous limited metastatic disease in only the brain. If the brain disease is bulky and/or causes symptoms while the body disease isn’t – or if a biopsy or surgery is required to prove that the patient in fact has metastatic disease – then the brain disease should be treated first. On the other hand, if the body disease is bulky and/or causing symptoms while the brain disease isn’t – and there is no need for surgery but rather only a biopsy of the brain – then the body disease can be treated first.”

No funding was reported. The study authors and Dr. Park reported no financial conflicts or other disclosures.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. We had a great discussion on Parkinson’s Disease for Primary Care with Dr. Albert Hung. Paul, this was something that really made me nervous. I didn’t have a lot of comfort with it. But he taught us a lot of tips about how to recognize Parkinson’s.

I hadn’t been as aware of the premotor symptoms: constipation, hyposmia (loss of sense of smell), and rapid eye movement sleep behavior disorder. If patients have those early on and they aren’t explained by other things (especially the REM sleep behavior disorder), you should really key in because those patients are at risk of developing Parkinson’s years down the line. Those symptoms could present first, which just kind of blew my mind.

What tips do you have about how to recognize Parkinson’s? Do you want to talk about the physical exam?

Paul N. Williams, MD: You know I love the physical exam stuff, so I’m happy to talk about that.

Dr. Watto: He also told us about some red flags.

Dr. Williams: This was a really fascinating point because we typically think if a patient’s symptoms are related to a drug exposure – in this case, drug-induced parkinsonism – we can just stop the medication and the symptoms will disappear in a couple of days as the drug leaves the system. But as it turns out, it might take much longer. A mistake that Dr Hung often sees is that the clinician stops the possibly offending agent, but when they don’t see an immediate relief of symptoms, they assume the drug wasn’t causing them. You really have to give the patient a fair shot off the medication to experience recovery because those symptoms can last weeks or even months after the drug is discontinued.

Dr. Watto: Dr Hung looks at the patient’s problem list and asks whether is there any reason this patient might have been exposed to one of these medications?

We’re not going to get too much into specific Parkinson’s treatment, but I was glad to hear that exercise actually improves mobility and may even have some neuroprotective effects. He mentioned ongoing trials looking at that. We always love an excuse to tell patients that they should be moving around more and being physically active.

Dr. Williams: That was one of the more shocking things I learned, that exercise might actually be good for you. That will deeply inform my practice. Many of the treatments that we use for Parkinson’s only address symptoms. They don’t address progression or fix anything, but exercise can help with that.

Dr. Watto: Paul, the last question I wanted to ask you is about our role in primary care. Patients with Parkinson’s have autonomic symptoms. They have neurocognitive symptoms. What is our role in that as primary care physicians?

Dr. Williams: Myriad symptoms can accompany Parkinson’s, and we have experience with most of them. We should all feel fairly comfortable dealing with constipation, which can be a very bothersome symptom. And we can use our full arsenal for symptoms such as depression, anxiety, and even apathy – the anhedonia, which apparently can be the predominant feature. We do have the tools to address these problems.

This might be a situation where we might reach for bupropion or a tricyclic antidepressant, which might not be your initial choice for a patient with a possibly annoying mood disorder. But for someone with Parkinson’s disease, this actually may be very helpful. We know how to manage a lot of the symptoms that come along with Parkinson’s that are not just the motor symptoms, and we should take ownership of those things.

Dr. Watto: You can hear the rest of this podcast here. This has been another episode of The Curbsiders bringing you a little knowledge food for your brain hole. Until next time, I’ve been Dr Matthew Frank Watto.

Dr. Williams: And I’m Dr Paul Nelson Williams.

Dr. Watto is a clinical assistant professor, department of medicine, at the University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, at Temple University, Philadelphia. Neither Dr. Watto nor Dr. Williams reported any relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. We had a great discussion on Parkinson’s Disease for Primary Care with Dr. Albert Hung. Paul, this was something that really made me nervous. I didn’t have a lot of comfort with it. But he taught us a lot of tips about how to recognize Parkinson’s.

I hadn’t been as aware of the premotor symptoms: constipation, hyposmia (loss of sense of smell), and rapid eye movement sleep behavior disorder. If patients have those early on and they aren’t explained by other things (especially the REM sleep behavior disorder), you should really key in because those patients are at risk of developing Parkinson’s years down the line. Those symptoms could present first, which just kind of blew my mind.

What tips do you have about how to recognize Parkinson’s? Do you want to talk about the physical exam?

Paul N. Williams, MD: You know I love the physical exam stuff, so I’m happy to talk about that.

Dr. Watto: He also told us about some red flags.

Dr. Williams: This was a really fascinating point because we typically think if a patient’s symptoms are related to a drug exposure – in this case, drug-induced parkinsonism – we can just stop the medication and the symptoms will disappear in a couple of days as the drug leaves the system. But as it turns out, it might take much longer. A mistake that Dr Hung often sees is that the clinician stops the possibly offending agent, but when they don’t see an immediate relief of symptoms, they assume the drug wasn’t causing them. You really have to give the patient a fair shot off the medication to experience recovery because those symptoms can last weeks or even months after the drug is discontinued.

Dr. Watto: Dr Hung looks at the patient’s problem list and asks whether is there any reason this patient might have been exposed to one of these medications?

We’re not going to get too much into specific Parkinson’s treatment, but I was glad to hear that exercise actually improves mobility and may even have some neuroprotective effects. He mentioned ongoing trials looking at that. We always love an excuse to tell patients that they should be moving around more and being physically active.

Dr. Williams: That was one of the more shocking things I learned, that exercise might actually be good for you. That will deeply inform my practice. Many of the treatments that we use for Parkinson’s only address symptoms. They don’t address progression or fix anything, but exercise can help with that.

Dr. Watto: Paul, the last question I wanted to ask you is about our role in primary care. Patients with Parkinson’s have autonomic symptoms. They have neurocognitive symptoms. What is our role in that as primary care physicians?

Dr. Williams: Myriad symptoms can accompany Parkinson’s, and we have experience with most of them. We should all feel fairly comfortable dealing with constipation, which can be a very bothersome symptom. And we can use our full arsenal for symptoms such as depression, anxiety, and even apathy – the anhedonia, which apparently can be the predominant feature. We do have the tools to address these problems.

This might be a situation where we might reach for bupropion or a tricyclic antidepressant, which might not be your initial choice for a patient with a possibly annoying mood disorder. But for someone with Parkinson’s disease, this actually may be very helpful. We know how to manage a lot of the symptoms that come along with Parkinson’s that are not just the motor symptoms, and we should take ownership of those things.

Dr. Watto: You can hear the rest of this podcast here. This has been another episode of The Curbsiders bringing you a little knowledge food for your brain hole. Until next time, I’ve been Dr Matthew Frank Watto.

Dr. Williams: And I’m Dr Paul Nelson Williams.

Dr. Watto is a clinical assistant professor, department of medicine, at the University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, at Temple University, Philadelphia. Neither Dr. Watto nor Dr. Williams reported any relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome back to The Curbsiders. We had a great discussion on Parkinson’s Disease for Primary Care with Dr. Albert Hung. Paul, this was something that really made me nervous. I didn’t have a lot of comfort with it. But he taught us a lot of tips about how to recognize Parkinson’s.

I hadn’t been as aware of the premotor symptoms: constipation, hyposmia (loss of sense of smell), and rapid eye movement sleep behavior disorder. If patients have those early on and they aren’t explained by other things (especially the REM sleep behavior disorder), you should really key in because those patients are at risk of developing Parkinson’s years down the line. Those symptoms could present first, which just kind of blew my mind.

What tips do you have about how to recognize Parkinson’s? Do you want to talk about the physical exam?

Paul N. Williams, MD: You know I love the physical exam stuff, so I’m happy to talk about that.

Dr. Watto: He also told us about some red flags.

Dr. Williams: This was a really fascinating point because we typically think if a patient’s symptoms are related to a drug exposure – in this case, drug-induced parkinsonism – we can just stop the medication and the symptoms will disappear in a couple of days as the drug leaves the system. But as it turns out, it might take much longer. A mistake that Dr Hung often sees is that the clinician stops the possibly offending agent, but when they don’t see an immediate relief of symptoms, they assume the drug wasn’t causing them. You really have to give the patient a fair shot off the medication to experience recovery because those symptoms can last weeks or even months after the drug is discontinued.

Dr. Watto: Dr Hung looks at the patient’s problem list and asks whether is there any reason this patient might have been exposed to one of these medications?

We’re not going to get too much into specific Parkinson’s treatment, but I was glad to hear that exercise actually improves mobility and may even have some neuroprotective effects. He mentioned ongoing trials looking at that. We always love an excuse to tell patients that they should be moving around more and being physically active.

Dr. Williams: That was one of the more shocking things I learned, that exercise might actually be good for you. That will deeply inform my practice. Many of the treatments that we use for Parkinson’s only address symptoms. They don’t address progression or fix anything, but exercise can help with that.

Dr. Watto: Paul, the last question I wanted to ask you is about our role in primary care. Patients with Parkinson’s have autonomic symptoms. They have neurocognitive symptoms. What is our role in that as primary care physicians?

Dr. Williams: Myriad symptoms can accompany Parkinson’s, and we have experience with most of them. We should all feel fairly comfortable dealing with constipation, which can be a very bothersome symptom. And we can use our full arsenal for symptoms such as depression, anxiety, and even apathy – the anhedonia, which apparently can be the predominant feature. We do have the tools to address these problems.

This might be a situation where we might reach for bupropion or a tricyclic antidepressant, which might not be your initial choice for a patient with a possibly annoying mood disorder. But for someone with Parkinson’s disease, this actually may be very helpful. We know how to manage a lot of the symptoms that come along with Parkinson’s that are not just the motor symptoms, and we should take ownership of those things.

Dr. Watto: You can hear the rest of this podcast here. This has been another episode of The Curbsiders bringing you a little knowledge food for your brain hole. Until next time, I’ve been Dr Matthew Frank Watto.

Dr. Williams: And I’m Dr Paul Nelson Williams.

Dr. Watto is a clinical assistant professor, department of medicine, at the University of Pennsylvania, Philadelphia. Dr. Williams is Associate Professor of Clinical Medicine, Department of General Internal Medicine, at Temple University, Philadelphia. Neither Dr. Watto nor Dr. Williams reported any relevant conflicts of interest.

A version of this article first appeared on Medscape.com.