CPAP After Stroke May Improve Function

Treating sleep apnea after a stroke or transient ischemic attack (TIA) may improve speech impairment, neurologic symptoms, walking, and physical function, according to a study published August 15 in the Journal of the American Heart Association. To examine whether continuous positive airway pressure (CPAP) improves clinical outcomes among patients with stroke or TIA who have obstructive sleep apnea, researchers analyzed data from a trial that included 252 patients with stroke or TIA. Participants were randomized to intervention groups that received polysomnography soon after the stroke or TIA or to a control group. Among the 81 patients in the intervention groups with sleep apnea, more than 70% used CPAP during approximately one year of follow-up. In intention-to-treat analyses, changes in NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were similar across groups. In as-treated analyses among patients with sleep apnea, CPAP use was associated with improved NIHSS and mRS scores. In addition, 59% of intervention patients with sleep apnea had a final NIHSS score of 0 or 1 versus 38% of controls with sleep apnea.

Bravata DM, Sico J, Fragoso CAV, et al. Diagnosing and treating sleep apnea in patients with acute cerebrovascular disease. J Am Heart Assoc. 2018;7:e008841.

Intervention Reduces Cognitive Decline in Blacks With MCI

Among black patients with mild cognitive impairment (MCI), a behavioral intervention that aims to increase social, cognitive, and physical activity reduces the risk of memory decline, compared with supportive therapy, according to a study published online ahead of print September 10 in JAMA Neurology. Between June 2011 and October 2014, researchers enrolled 221 black participants with MCI (mean age, 75.8; 79% women) into a clinical trial. Participants were randomized to behavioral activation or supportive therapy (ie, an attention control treatment). The primary outcome was a decline of six or more recalled words on the total recall score of the Hopkins Verbal Learning Test-Revised at six, 12, 18, and 24 months. The two-year incidence of memory decline was lower in the behavioral activation group than in the supportive therapy group (1.2% vs 9.3%). Behavioral activation reduced the risk of cognitive decline by 88%, compared with supportive therapy.

Rovner BW, Casten RJ, Hegel MT, Leiby B. Preventing cognitive decline in black individuals with mild cognitive impairment: a randomized clinical trial. JAMA Neurol. 2018 Sep 10 [Epub ahead of print].

Medical Marijuana May Treat Nerve Pain

Among patients with neuropathic pain, sublingual tetrahydrocannabinol (THC) significantly reduces pain versus placebo, according to a randomized, double-blind study published online ahead of print September 5 in Neurology. The trial included 15 men with chronic radicular nerve pain (average age, 33). Before and one hour after treatment with THC or placebo oil, participants rated their pain levels on a scale from zero to 100. At least one week later, they received the other treatment. The average pain level before treatment was 53. After taking THC, participants’ average pain level was 35, compared with an average pain level of 43 after taking placebo. Functional MRI showed that the drug’s analgesic effect correlated with reduced functional connectivity between brain areas involved in emotion and pain processing.

Weizman L, Dayan L, Brill S, et al. Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity. Neurology. 2018 Sep 5 [Epub ahead of print].

For Which Clots Is t-PA Most Effective?

In patients with acute ischemic stroke, a more distal thrombus location, greater thrombus permeability, and longer time to assessment of recanalization are associated with recanalization of an arterial occlusion after administration of IV alteplase, according to a study published in the September 11 issue of JAMA. This multicenter prospective cohort study included 575 patients with acute ischemic stroke and intracranial arterial occlusion demonstrated on CT angiogram (CTA). In all, 275 participants received IV alteplase, 195 participants received IV alteplase plus endovascular thrombectomy, 48 participants received endovascular thrombectomy, and 57 participants received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes. Successful recanalization occurred at an unadjusted rate of 27.3%, including in 30.4% of patients who received IV alteplase and 13.3% who did not.

Menon BK, Al-Ajlan FS, Najm M, et al. Association of clinical, imaging, and thrombus characteristics with recanalization of visible intracranial occlusion in patients with acute ischemic stroke. JAMA. 2018;320(10):1017-1026.

FDA Approves Ajovy for Adults With Migraine

The FDA has approved Ajovy (fremanezumab-vfrm), a calcitonin gene-related peptide (CGRP) antagonist, for the preventive treatment of migraine in adults. Dosing options include 225 mg monthly administered as one subcutaneous injection or 675 mg quarterly administered as three subcutaneous injections. The injections can be administered by a healthcare professional or by a patient or caregiver. The treatment was evaluated in two phase III, placebo-controlled clinical trials that enrolled patients with migraine. The trials examined the therapy as a stand-alone preventive treatment and in combination with oral preventive treatments. Patients experienced a reduction in monthly migraine days during a 12-week period. The most common adverse reactions were injection site reactions. Ajovy is a humanized monoclonal antibody that binds to CGRP ligand and blocks its binding to the receptor. Teva Pharmaceutical Industries, which markets Ajovy, is headquartered in Jerusalem.

Is Daytime Sleepiness Associated With an Alzheimer’s Disease Biomarker?

Excessive daytime sleepiness (EDS) is associated with more than 2.5 times the odds of β-amyloid (Aβ) deposition an average of 15.7 years later, according to a study published online ahead of print September 5 in Sleep. Researchers studied 124 participants in the Baltimore Longitudinal Study of Aging Neuroimaging Substudy who completed self-reported measures of EDS and napping at baseline and underwent 11C-Pittsburgh compound B-PET scans of the brain an average of 15.7 years later. Participants’ mean age was 60.1 at baseline; 24.4% had EDS, and 28.5% napped. In unadjusted analyses, compared with participants without EDS, people with EDS had more than three times the odds of being Aβ+ (ie, having a cortical distribution volume ratio of greater than 1.06) at follow-up. After adjusting for age, sex, education, and BMI, the odds ratio was 2.75.

Spira AP, An Y, Wu MN, et al. Excessive daytime sleepiness and napping in cognitively normal adults: associations with subsequent amyloid deposition measured by PiB PET. Sleep. 2018 Sep 5 [Epub ahead of print].

Sepsis Heightens Risk of Stroke and Heart Attack

Patients recovering from sepsis have a greater risk of myocardial infarction or stroke in the first four weeks after hospital discharge, compared with population and hospital controls, according to a study published September 10 in the Canadian Medical Association Journal. This retrospective population-based cohort study included 42,316 patients with sepsis identified from the National Health Insurance Research Database in Taiwan. In all, 831 patients with sepsis had a stroke and 184 had a myocardial infarction within 180 days of discharge from the hospital. Compared with population controls, the risk was highest in the first seven days after discharge (hazard ratio, 4.78). Compared with hospital controls, the risk was attenuated but remained elevated before day 36 after discharge (hazard ratio, 1.32).

Lai CC, Lee MG, Lee WC, et al. Susceptible period for cardiovascular complications in patients recovering from sepsis. CMAJ. 2018;190(36):E1062-E1069.

Ten-Year Risk Factors for Dementia

Age, sex, and APOE genotype identify high-risk groups for Alzheimer’s disease and dementia, according to a study published September 4 in the Canadian Medical Association Journal. The study looked at data from 104,537 people in Copenhagen. Participants completed a questionnaire and underwent physical examination and blood sampling at baseline. The researchers obtained diagnoses of dementia and cerebrovascular disease from the Danish National Patient Registry through November 10, 2014. The absolute 10-year risk of Alzheimer’s disease among 3,017 people who were carriers of the APOE ε44 genotype was 7% for women and 6% for men ages 60 to 69, 16% for women and 12% for men ages 70 to 79, and 24% for women and 19% for men ages 80 and older.

Rasmussen KL, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study. CMAJ. 2018;190(35):E1033-E1041.

Is Job Stress Associated With Parkinson’s Disease Risk?

Occupational stress may increase Parkinson’s disease risk, according to a study published online ahead of print August 25 in Movement Disorders. Researchers conducted a population-based cohort study of 2,544,748 Swedes whose occupations had been reported in censuses. They identified incident Parkinson’s disease cases using Swedish national health registers and analyzed the data using Cox regression with age as the underlying time scale, adjusting for sex, education, and chronic obstructive pulmonary disease as a proxy for smoking. During a mean follow-up of 21.3 years, 21,544 incident Parkinson’s disease cases were identified. High job demands were associated with increased risk of Parkinson’s disease among men, most evidently in men with high levels of education. High levels of job control were associated with increased risk among people with low levels of education, and this association was stronger in women.

Sieurin J, Andel R, Tillander A, et al. Occupational stress and risk for Parkinson’s disease: a nationwide cohort study. Mov Disord. 2018 Aug 25 [Epub ahead of print].

FDA Approves Tiglutik for ALS

The FDA has approved Tiglutik (riluzole) oral suspension for the treatment of amyotrophic lateral sclerosis (ALS). Tiglutik is a thickened liquid taken twice daily by oral syringe. The approval of Tiglutik is based on bioavailability studies comparing oral riluzole tablets to Tiglutik oral suspension. The most common side effects of Tiglutik are consistent with the established clinical profile of riluzole and include oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, and abdominal pain. The recommended dosage is 50 mg/10 mL. The drug should be taken at least one hour before or two hours after a meal. In clinical studies, riluzole modulated glutamate neurotransmission by inhibiting glutamate release and postsynaptic glutamate receptor signaling. ITF Pharma, which markets the drug, is headquartered in Berwyn, Pennsylvania.

—Kimberly Williams

CPAP After Stroke May Improve Function

Treating sleep apnea after a stroke or transient ischemic attack (TIA) may improve speech impairment, neurologic symptoms, walking, and physical function, according to a study published August 15 in the Journal of the American Heart Association. To examine whether continuous positive airway pressure (CPAP) improves clinical outcomes among patients with stroke or TIA who have obstructive sleep apnea, researchers analyzed data from a trial that included 252 patients with stroke or TIA. Participants were randomized to intervention groups that received polysomnography soon after the stroke or TIA or to a control group. Among the 81 patients in the intervention groups with sleep apnea, more than 70% used CPAP during approximately one year of follow-up. In intention-to-treat analyses, changes in NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were similar across groups. In as-treated analyses among patients with sleep apnea, CPAP use was associated with improved NIHSS and mRS scores. In addition, 59% of intervention patients with sleep apnea had a final NIHSS score of 0 or 1 versus 38% of controls with sleep apnea.

Bravata DM, Sico J, Fragoso CAV, et al. Diagnosing and treating sleep apnea in patients with acute cerebrovascular disease. J Am Heart Assoc. 2018;7:e008841.

Intervention Reduces Cognitive Decline in Blacks With MCI

Among black patients with mild cognitive impairment (MCI), a behavioral intervention that aims to increase social, cognitive, and physical activity reduces the risk of memory decline, compared with supportive therapy, according to a study published online ahead of print September 10 in JAMA Neurology. Between June 2011 and October 2014, researchers enrolled 221 black participants with MCI (mean age, 75.8; 79% women) into a clinical trial. Participants were randomized to behavioral activation or supportive therapy (ie, an attention control treatment). The primary outcome was a decline of six or more recalled words on the total recall score of the Hopkins Verbal Learning Test-Revised at six, 12, 18, and 24 months. The two-year incidence of memory decline was lower in the behavioral activation group than in the supportive therapy group (1.2% vs 9.3%). Behavioral activation reduced the risk of cognitive decline by 88%, compared with supportive therapy.

Rovner BW, Casten RJ, Hegel MT, Leiby B. Preventing cognitive decline in black individuals with mild cognitive impairment: a randomized clinical trial. JAMA Neurol. 2018 Sep 10 [Epub ahead of print].

Medical Marijuana May Treat Nerve Pain

Among patients with neuropathic pain, sublingual tetrahydrocannabinol (THC) significantly reduces pain versus placebo, according to a randomized, double-blind study published online ahead of print September 5 in Neurology. The trial included 15 men with chronic radicular nerve pain (average age, 33). Before and one hour after treatment with THC or placebo oil, participants rated their pain levels on a scale from zero to 100. At least one week later, they received the other treatment. The average pain level before treatment was 53. After taking THC, participants’ average pain level was 35, compared with an average pain level of 43 after taking placebo. Functional MRI showed that the drug’s analgesic effect correlated with reduced functional connectivity between brain areas involved in emotion and pain processing.

Weizman L, Dayan L, Brill S, et al. Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity. Neurology. 2018 Sep 5 [Epub ahead of print].

For Which Clots Is t-PA Most Effective?

In patients with acute ischemic stroke, a more distal thrombus location, greater thrombus permeability, and longer time to assessment of recanalization are associated with recanalization of an arterial occlusion after administration of IV alteplase, according to a study published in the September 11 issue of JAMA. This multicenter prospective cohort study included 575 patients with acute ischemic stroke and intracranial arterial occlusion demonstrated on CT angiogram (CTA). In all, 275 participants received IV alteplase, 195 participants received IV alteplase plus endovascular thrombectomy, 48 participants received endovascular thrombectomy, and 57 participants received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes. Successful recanalization occurred at an unadjusted rate of 27.3%, including in 30.4% of patients who received IV alteplase and 13.3% who did not.

Menon BK, Al-Ajlan FS, Najm M, et al. Association of clinical, imaging, and thrombus characteristics with recanalization of visible intracranial occlusion in patients with acute ischemic stroke. JAMA. 2018;320(10):1017-1026.

FDA Approves Ajovy for Adults With Migraine

The FDA has approved Ajovy (fremanezumab-vfrm), a calcitonin gene-related peptide (CGRP) antagonist, for the preventive treatment of migraine in adults. Dosing options include 225 mg monthly administered as one subcutaneous injection or 675 mg quarterly administered as three subcutaneous injections. The injections can be administered by a healthcare professional or by a patient or caregiver. The treatment was evaluated in two phase III, placebo-controlled clinical trials that enrolled patients with migraine. The trials examined the therapy as a stand-alone preventive treatment and in combination with oral preventive treatments. Patients experienced a reduction in monthly migraine days during a 12-week period. The most common adverse reactions were injection site reactions. Ajovy is a humanized monoclonal antibody that binds to CGRP ligand and blocks its binding to the receptor. Teva Pharmaceutical Industries, which markets Ajovy, is headquartered in Jerusalem.

Is Daytime Sleepiness Associated With an Alzheimer’s Disease Biomarker?

Excessive daytime sleepiness (EDS) is associated with more than 2.5 times the odds of β-amyloid (Aβ) deposition an average of 15.7 years later, according to a study published online ahead of print September 5 in Sleep. Researchers studied 124 participants in the Baltimore Longitudinal Study of Aging Neuroimaging Substudy who completed self-reported measures of EDS and napping at baseline and underwent 11C-Pittsburgh compound B-PET scans of the brain an average of 15.7 years later. Participants’ mean age was 60.1 at baseline; 24.4% had EDS, and 28.5% napped. In unadjusted analyses, compared with participants without EDS, people with EDS had more than three times the odds of being Aβ+ (ie, having a cortical distribution volume ratio of greater than 1.06) at follow-up. After adjusting for age, sex, education, and BMI, the odds ratio was 2.75.

Spira AP, An Y, Wu MN, et al. Excessive daytime sleepiness and napping in cognitively normal adults: associations with subsequent amyloid deposition measured by PiB PET. Sleep. 2018 Sep 5 [Epub ahead of print].

Sepsis Heightens Risk of Stroke and Heart Attack

Patients recovering from sepsis have a greater risk of myocardial infarction or stroke in the first four weeks after hospital discharge, compared with population and hospital controls, according to a study published September 10 in the Canadian Medical Association Journal. This retrospective population-based cohort study included 42,316 patients with sepsis identified from the National Health Insurance Research Database in Taiwan. In all, 831 patients with sepsis had a stroke and 184 had a myocardial infarction within 180 days of discharge from the hospital. Compared with population controls, the risk was highest in the first seven days after discharge (hazard ratio, 4.78). Compared with hospital controls, the risk was attenuated but remained elevated before day 36 after discharge (hazard ratio, 1.32).

Lai CC, Lee MG, Lee WC, et al. Susceptible period for cardiovascular complications in patients recovering from sepsis. CMAJ. 2018;190(36):E1062-E1069.

Ten-Year Risk Factors for Dementia

Age, sex, and APOE genotype identify high-risk groups for Alzheimer’s disease and dementia, according to a study published September 4 in the Canadian Medical Association Journal. The study looked at data from 104,537 people in Copenhagen. Participants completed a questionnaire and underwent physical examination and blood sampling at baseline. The researchers obtained diagnoses of dementia and cerebrovascular disease from the Danish National Patient Registry through November 10, 2014. The absolute 10-year risk of Alzheimer’s disease among 3,017 people who were carriers of the APOE ε44 genotype was 7% for women and 6% for men ages 60 to 69, 16% for women and 12% for men ages 70 to 79, and 24% for women and 19% for men ages 80 and older.

Rasmussen KL, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study. CMAJ. 2018;190(35):E1033-E1041.

Is Job Stress Associated With Parkinson’s Disease Risk?

Occupational stress may increase Parkinson’s disease risk, according to a study published online ahead of print August 25 in Movement Disorders. Researchers conducted a population-based cohort study of 2,544,748 Swedes whose occupations had been reported in censuses. They identified incident Parkinson’s disease cases using Swedish national health registers and analyzed the data using Cox regression with age as the underlying time scale, adjusting for sex, education, and chronic obstructive pulmonary disease as a proxy for smoking. During a mean follow-up of 21.3 years, 21,544 incident Parkinson’s disease cases were identified. High job demands were associated with increased risk of Parkinson’s disease among men, most evidently in men with high levels of education. High levels of job control were associated with increased risk among people with low levels of education, and this association was stronger in women.

Sieurin J, Andel R, Tillander A, et al. Occupational stress and risk for Parkinson’s disease: a nationwide cohort study. Mov Disord. 2018 Aug 25 [Epub ahead of print].

FDA Approves Tiglutik for ALS

The FDA has approved Tiglutik (riluzole) oral suspension for the treatment of amyotrophic lateral sclerosis (ALS). Tiglutik is a thickened liquid taken twice daily by oral syringe. The approval of Tiglutik is based on bioavailability studies comparing oral riluzole tablets to Tiglutik oral suspension. The most common side effects of Tiglutik are consistent with the established clinical profile of riluzole and include oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, and abdominal pain. The recommended dosage is 50 mg/10 mL. The drug should be taken at least one hour before or two hours after a meal. In clinical studies, riluzole modulated glutamate neurotransmission by inhibiting glutamate release and postsynaptic glutamate receptor signaling. ITF Pharma, which markets the drug, is headquartered in Berwyn, Pennsylvania.

—Kimberly Williams

CPAP After Stroke May Improve Function

Treating sleep apnea after a stroke or transient ischemic attack (TIA) may improve speech impairment, neurologic symptoms, walking, and physical function, according to a study published August 15 in the Journal of the American Heart Association. To examine whether continuous positive airway pressure (CPAP) improves clinical outcomes among patients with stroke or TIA who have obstructive sleep apnea, researchers analyzed data from a trial that included 252 patients with stroke or TIA. Participants were randomized to intervention groups that received polysomnography soon after the stroke or TIA or to a control group. Among the 81 patients in the intervention groups with sleep apnea, more than 70% used CPAP during approximately one year of follow-up. In intention-to-treat analyses, changes in NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were similar across groups. In as-treated analyses among patients with sleep apnea, CPAP use was associated with improved NIHSS and mRS scores. In addition, 59% of intervention patients with sleep apnea had a final NIHSS score of 0 or 1 versus 38% of controls with sleep apnea.

Bravata DM, Sico J, Fragoso CAV, et al. Diagnosing and treating sleep apnea in patients with acute cerebrovascular disease. J Am Heart Assoc. 2018;7:e008841.

Intervention Reduces Cognitive Decline in Blacks With MCI

Among black patients with mild cognitive impairment (MCI), a behavioral intervention that aims to increase social, cognitive, and physical activity reduces the risk of memory decline, compared with supportive therapy, according to a study published online ahead of print September 10 in JAMA Neurology. Between June 2011 and October 2014, researchers enrolled 221 black participants with MCI (mean age, 75.8; 79% women) into a clinical trial. Participants were randomized to behavioral activation or supportive therapy (ie, an attention control treatment). The primary outcome was a decline of six or more recalled words on the total recall score of the Hopkins Verbal Learning Test-Revised at six, 12, 18, and 24 months. The two-year incidence of memory decline was lower in the behavioral activation group than in the supportive therapy group (1.2% vs 9.3%). Behavioral activation reduced the risk of cognitive decline by 88%, compared with supportive therapy.

Rovner BW, Casten RJ, Hegel MT, Leiby B. Preventing cognitive decline in black individuals with mild cognitive impairment: a randomized clinical trial. JAMA Neurol. 2018 Sep 10 [Epub ahead of print].

Medical Marijuana May Treat Nerve Pain

Among patients with neuropathic pain, sublingual tetrahydrocannabinol (THC) significantly reduces pain versus placebo, according to a randomized, double-blind study published online ahead of print September 5 in Neurology. The trial included 15 men with chronic radicular nerve pain (average age, 33). Before and one hour after treatment with THC or placebo oil, participants rated their pain levels on a scale from zero to 100. At least one week later, they received the other treatment. The average pain level before treatment was 53. After taking THC, participants’ average pain level was 35, compared with an average pain level of 43 after taking placebo. Functional MRI showed that the drug’s analgesic effect correlated with reduced functional connectivity between brain areas involved in emotion and pain processing.

Weizman L, Dayan L, Brill S, et al. Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity. Neurology. 2018 Sep 5 [Epub ahead of print].

For Which Clots Is t-PA Most Effective?

In patients with acute ischemic stroke, a more distal thrombus location, greater thrombus permeability, and longer time to assessment of recanalization are associated with recanalization of an arterial occlusion after administration of IV alteplase, according to a study published in the September 11 issue of JAMA. This multicenter prospective cohort study included 575 patients with acute ischemic stroke and intracranial arterial occlusion demonstrated on CT angiogram (CTA). In all, 275 participants received IV alteplase, 195 participants received IV alteplase plus endovascular thrombectomy, 48 participants received endovascular thrombectomy, and 57 participants received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes. Successful recanalization occurred at an unadjusted rate of 27.3%, including in 30.4% of patients who received IV alteplase and 13.3% who did not.

Menon BK, Al-Ajlan FS, Najm M, et al. Association of clinical, imaging, and thrombus characteristics with recanalization of visible intracranial occlusion in patients with acute ischemic stroke. JAMA. 2018;320(10):1017-1026.

FDA Approves Ajovy for Adults With Migraine

The FDA has approved Ajovy (fremanezumab-vfrm), a calcitonin gene-related peptide (CGRP) antagonist, for the preventive treatment of migraine in adults. Dosing options include 225 mg monthly administered as one subcutaneous injection or 675 mg quarterly administered as three subcutaneous injections. The injections can be administered by a healthcare professional or by a patient or caregiver. The treatment was evaluated in two phase III, placebo-controlled clinical trials that enrolled patients with migraine. The trials examined the therapy as a stand-alone preventive treatment and in combination with oral preventive treatments. Patients experienced a reduction in monthly migraine days during a 12-week period. The most common adverse reactions were injection site reactions. Ajovy is a humanized monoclonal antibody that binds to CGRP ligand and blocks its binding to the receptor. Teva Pharmaceutical Industries, which markets Ajovy, is headquartered in Jerusalem.

Is Daytime Sleepiness Associated With an Alzheimer’s Disease Biomarker?

Excessive daytime sleepiness (EDS) is associated with more than 2.5 times the odds of β-amyloid (Aβ) deposition an average of 15.7 years later, according to a study published online ahead of print September 5 in Sleep. Researchers studied 124 participants in the Baltimore Longitudinal Study of Aging Neuroimaging Substudy who completed self-reported measures of EDS and napping at baseline and underwent 11C-Pittsburgh compound B-PET scans of the brain an average of 15.7 years later. Participants’ mean age was 60.1 at baseline; 24.4% had EDS, and 28.5% napped. In unadjusted analyses, compared with participants without EDS, people with EDS had more than three times the odds of being Aβ+ (ie, having a cortical distribution volume ratio of greater than 1.06) at follow-up. After adjusting for age, sex, education, and BMI, the odds ratio was 2.75.

Spira AP, An Y, Wu MN, et al. Excessive daytime sleepiness and napping in cognitively normal adults: associations with subsequent amyloid deposition measured by PiB PET. Sleep. 2018 Sep 5 [Epub ahead of print].

Sepsis Heightens Risk of Stroke and Heart Attack

Patients recovering from sepsis have a greater risk of myocardial infarction or stroke in the first four weeks after hospital discharge, compared with population and hospital controls, according to a study published September 10 in the Canadian Medical Association Journal. This retrospective population-based cohort study included 42,316 patients with sepsis identified from the National Health Insurance Research Database in Taiwan. In all, 831 patients with sepsis had a stroke and 184 had a myocardial infarction within 180 days of discharge from the hospital. Compared with population controls, the risk was highest in the first seven days after discharge (hazard ratio, 4.78). Compared with hospital controls, the risk was attenuated but remained elevated before day 36 after discharge (hazard ratio, 1.32).

Lai CC, Lee MG, Lee WC, et al. Susceptible period for cardiovascular complications in patients recovering from sepsis. CMAJ. 2018;190(36):E1062-E1069.

Ten-Year Risk Factors for Dementia

Age, sex, and APOE genotype identify high-risk groups for Alzheimer’s disease and dementia, according to a study published September 4 in the Canadian Medical Association Journal. The study looked at data from 104,537 people in Copenhagen. Participants completed a questionnaire and underwent physical examination and blood sampling at baseline. The researchers obtained diagnoses of dementia and cerebrovascular disease from the Danish National Patient Registry through November 10, 2014. The absolute 10-year risk of Alzheimer’s disease among 3,017 people who were carriers of the APOE ε44 genotype was 7% for women and 6% for men ages 60 to 69, 16% for women and 12% for men ages 70 to 79, and 24% for women and 19% for men ages 80 and older.

Rasmussen KL, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study. CMAJ. 2018;190(35):E1033-E1041.

Is Job Stress Associated With Parkinson’s Disease Risk?

Occupational stress may increase Parkinson’s disease risk, according to a study published online ahead of print August 25 in Movement Disorders. Researchers conducted a population-based cohort study of 2,544,748 Swedes whose occupations had been reported in censuses. They identified incident Parkinson’s disease cases using Swedish national health registers and analyzed the data using Cox regression with age as the underlying time scale, adjusting for sex, education, and chronic obstructive pulmonary disease as a proxy for smoking. During a mean follow-up of 21.3 years, 21,544 incident Parkinson’s disease cases were identified. High job demands were associated with increased risk of Parkinson’s disease among men, most evidently in men with high levels of education. High levels of job control were associated with increased risk among people with low levels of education, and this association was stronger in women.

Sieurin J, Andel R, Tillander A, et al. Occupational stress and risk for Parkinson’s disease: a nationwide cohort study. Mov Disord. 2018 Aug 25 [Epub ahead of print].

FDA Approves Tiglutik for ALS

The FDA has approved Tiglutik (riluzole) oral suspension for the treatment of amyotrophic lateral sclerosis (ALS). Tiglutik is a thickened liquid taken twice daily by oral syringe. The approval of Tiglutik is based on bioavailability studies comparing oral riluzole tablets to Tiglutik oral suspension. The most common side effects of Tiglutik are consistent with the established clinical profile of riluzole and include oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, and abdominal pain. The recommended dosage is 50 mg/10 mL. The drug should be taken at least one hour before or two hours after a meal. In clinical studies, riluzole modulated glutamate neurotransmission by inhibiting glutamate release and postsynaptic glutamate receptor signaling. ITF Pharma, which markets the drug, is headquartered in Berwyn, Pennsylvania.

—Kimberly Williams

Future epigenetic drugs could activate human endogenous retroviruses (HERVs) in cancer cells to enable immunotherapy, investigators suggest.

Activated HERVs may sensitize cancer cells or serve as novel tumor-associated antigenic targets, reported Anders Steenholdt Attermann, PhD, of the department of micro- and nanotechnology at the Technical University of Denmark in Kongens Lyngby, and colleagues.

A remarkable 8% of the human genome is composed of HERVs.

“They are remnants of retroviral germline infections that resulted in chromosomal integration into all the cells of the progeny, but their viral replication is defective in the present-day human genome,” the authors wrote in Annals of Oncology.

The therapeutic potential for these remnants is complex, as is their relationship with the immune system and neoplasia. Studies dating back to 2002 have found unique associations between HERVs and various types of cancer, including renal cell carcinoma, melanoma, gastrointestinal cancer, colorectal cancer, and breast cancer.

“Early data point towards distinct features for the expression profiles of different HERVs,” the authors wrote, “but these characteristics remain to be fully elucidated. There may be substantial differences in their biological effects, potential roles in immune sensitization, and ability to form an antigen reservoir.”

HERVs may be activated by cancer or epigenetic drugs. While certain cancers may activate particular HERVs into targetable antigens, other cancer-activated HERVs actually shield tumors from the immune system. Still other HERVs require epigenetic drugs for activation, such as DNA methyltransferase inhibitors. These drugs could transform HERVs into “intrinsic adjuvants” or novel antigens; either of which may improve the efficacy of existing immunotherapies like checkpoint inhibitors.

To leverage HERVs for immunotherapy, a better understanding of immune tolerance is needed. Some research suggests that since HERVs share similarities with exogenous viruses, tolerance to HERVs must be incomplete to allow for immune responses to exogenous viruses. In contrast, incomplete tolerance would conceivably lead to autoimmune disease.

“Hence, peripheral tolerance and ignorance mechanisms may play prominent roles in the control of HERV-specific T-cell recognition in healthy individuals,” the authors wrote. “Understanding the differences in HERV expression in the thymus and peripheral tissues would be of great importance for the use of HERVs as immunotherapeutic targets.”

When more clearly understood, HERVs may feature in emerging combination therapies.

“The combination of epigenetic drugs and immunotherapy is exciting for future cancer therapy,” the authors wrote, “especially for cancer types with low mutational burden that respond poorly to immunotherapy or cancer types with poor responses to immune checkpoint inhibitor treatment.”

It appears that the authors’ excitement is shared – almost 50 clinical trials are currently studying epigenetic drug/immunotherapy combinations.

Study funding was provided by the Lundbeck Foundation Fellowship, the European Research Council, the stand-up-to-cancer (SU2C) epigenetic dream team, and StG 677268 NextDART.
 

SOURCE: Attermann et al. Ann Oncol. 2018 Sep 18. doi: 10.1093/annonc/mdy413.

Future epigenetic drugs could activate human endogenous retroviruses (HERVs) in cancer cells to enable immunotherapy, investigators suggest.

Activated HERVs may sensitize cancer cells or serve as novel tumor-associated antigenic targets, reported Anders Steenholdt Attermann, PhD, of the department of micro- and nanotechnology at the Technical University of Denmark in Kongens Lyngby, and colleagues.

A remarkable 8% of the human genome is composed of HERVs.

“They are remnants of retroviral germline infections that resulted in chromosomal integration into all the cells of the progeny, but their viral replication is defective in the present-day human genome,” the authors wrote in Annals of Oncology.

The therapeutic potential for these remnants is complex, as is their relationship with the immune system and neoplasia. Studies dating back to 2002 have found unique associations between HERVs and various types of cancer, including renal cell carcinoma, melanoma, gastrointestinal cancer, colorectal cancer, and breast cancer.

“Early data point towards distinct features for the expression profiles of different HERVs,” the authors wrote, “but these characteristics remain to be fully elucidated. There may be substantial differences in their biological effects, potential roles in immune sensitization, and ability to form an antigen reservoir.”

HERVs may be activated by cancer or epigenetic drugs. While certain cancers may activate particular HERVs into targetable antigens, other cancer-activated HERVs actually shield tumors from the immune system. Still other HERVs require epigenetic drugs for activation, such as DNA methyltransferase inhibitors. These drugs could transform HERVs into “intrinsic adjuvants” or novel antigens; either of which may improve the efficacy of existing immunotherapies like checkpoint inhibitors.

To leverage HERVs for immunotherapy, a better understanding of immune tolerance is needed. Some research suggests that since HERVs share similarities with exogenous viruses, tolerance to HERVs must be incomplete to allow for immune responses to exogenous viruses. In contrast, incomplete tolerance would conceivably lead to autoimmune disease.

“Hence, peripheral tolerance and ignorance mechanisms may play prominent roles in the control of HERV-specific T-cell recognition in healthy individuals,” the authors wrote. “Understanding the differences in HERV expression in the thymus and peripheral tissues would be of great importance for the use of HERVs as immunotherapeutic targets.”

When more clearly understood, HERVs may feature in emerging combination therapies.

“The combination of epigenetic drugs and immunotherapy is exciting for future cancer therapy,” the authors wrote, “especially for cancer types with low mutational burden that respond poorly to immunotherapy or cancer types with poor responses to immune checkpoint inhibitor treatment.”

It appears that the authors’ excitement is shared – almost 50 clinical trials are currently studying epigenetic drug/immunotherapy combinations.

Study funding was provided by the Lundbeck Foundation Fellowship, the European Research Council, the stand-up-to-cancer (SU2C) epigenetic dream team, and StG 677268 NextDART.
 

SOURCE: Attermann et al. Ann Oncol. 2018 Sep 18. doi: 10.1093/annonc/mdy413.

Future epigenetic drugs could activate human endogenous retroviruses (HERVs) in cancer cells to enable immunotherapy, investigators suggest.

Activated HERVs may sensitize cancer cells or serve as novel tumor-associated antigenic targets, reported Anders Steenholdt Attermann, PhD, of the department of micro- and nanotechnology at the Technical University of Denmark in Kongens Lyngby, and colleagues.

A remarkable 8% of the human genome is composed of HERVs.

“They are remnants of retroviral germline infections that resulted in chromosomal integration into all the cells of the progeny, but their viral replication is defective in the present-day human genome,” the authors wrote in Annals of Oncology.

The therapeutic potential for these remnants is complex, as is their relationship with the immune system and neoplasia. Studies dating back to 2002 have found unique associations between HERVs and various types of cancer, including renal cell carcinoma, melanoma, gastrointestinal cancer, colorectal cancer, and breast cancer.

“Early data point towards distinct features for the expression profiles of different HERVs,” the authors wrote, “but these characteristics remain to be fully elucidated. There may be substantial differences in their biological effects, potential roles in immune sensitization, and ability to form an antigen reservoir.”

HERVs may be activated by cancer or epigenetic drugs. While certain cancers may activate particular HERVs into targetable antigens, other cancer-activated HERVs actually shield tumors from the immune system. Still other HERVs require epigenetic drugs for activation, such as DNA methyltransferase inhibitors. These drugs could transform HERVs into “intrinsic adjuvants” or novel antigens; either of which may improve the efficacy of existing immunotherapies like checkpoint inhibitors.

To leverage HERVs for immunotherapy, a better understanding of immune tolerance is needed. Some research suggests that since HERVs share similarities with exogenous viruses, tolerance to HERVs must be incomplete to allow for immune responses to exogenous viruses. In contrast, incomplete tolerance would conceivably lead to autoimmune disease.

“Hence, peripheral tolerance and ignorance mechanisms may play prominent roles in the control of HERV-specific T-cell recognition in healthy individuals,” the authors wrote. “Understanding the differences in HERV expression in the thymus and peripheral tissues would be of great importance for the use of HERVs as immunotherapeutic targets.”

When more clearly understood, HERVs may feature in emerging combination therapies.

“The combination of epigenetic drugs and immunotherapy is exciting for future cancer therapy,” the authors wrote, “especially for cancer types with low mutational burden that respond poorly to immunotherapy or cancer types with poor responses to immune checkpoint inhibitor treatment.”

It appears that the authors’ excitement is shared – almost 50 clinical trials are currently studying epigenetic drug/immunotherapy combinations.

Study funding was provided by the Lundbeck Foundation Fellowship, the European Research Council, the stand-up-to-cancer (SU2C) epigenetic dream team, and StG 677268 NextDART.
 

SOURCE: Attermann et al. Ann Oncol. 2018 Sep 18. doi: 10.1093/annonc/mdy413.

The answer is none.

The question (for $1,000, Alex) is how many of the dozens of proposals to create physician-focused alternative payment models (APMs) have been approved under the new federal Quality Payment Program?

However, ACEP’s submission, entitled the Acute Unscheduled Care Model (AUCM): Enhancing Appropriate Admissions, seems to have gotten close to a nod when federal health care leaders showed up at a recent meeting on the model.

Reviewers from the Physician-Focused Payment Model Technical Advisory Committee “thought that we met all 10 criteria for models that the secretary put forth for evaluating physician-focused payment models,” Jeffrey Davis, ACEP director of regulatory affairs, said in an interview, adding that the attendance at the meeting of Alex Azar, secretary of Health & Human Serviecs, and Seema Verma, administrator of the Centers for Medicare & Medicaid Services, was a positive development.

To read our full story, check out the link below.

Key sessions at ACEP18 on QPP, MACRA, APMs, and MIPS include:

MO-058 Goodbye SGR! Hello MACRA and MIPS
Monday, Oct. 1 | 1:30 PM

TU-131 FAST FACTS: Reimbursement Topics for the Practicing Emergency Physician
Tuesday, Oct. 2 | 10:00 AM

TU-187 Alternative Payment Models: The New Reimbursement Frontier
Tuesday, Oct. 2 | 4:00 PM

The answer is none.

The question (for $1,000, Alex) is how many of the dozens of proposals to create physician-focused alternative payment models (APMs) have been approved under the new federal Quality Payment Program?

However, ACEP’s submission, entitled the Acute Unscheduled Care Model (AUCM): Enhancing Appropriate Admissions, seems to have gotten close to a nod when federal health care leaders showed up at a recent meeting on the model.

Reviewers from the Physician-Focused Payment Model Technical Advisory Committee “thought that we met all 10 criteria for models that the secretary put forth for evaluating physician-focused payment models,” Jeffrey Davis, ACEP director of regulatory affairs, said in an interview, adding that the attendance at the meeting of Alex Azar, secretary of Health & Human Serviecs, and Seema Verma, administrator of the Centers for Medicare & Medicaid Services, was a positive development.

To read our full story, check out the link below.

Key sessions at ACEP18 on QPP, MACRA, APMs, and MIPS include:

MO-058 Goodbye SGR! Hello MACRA and MIPS
Monday, Oct. 1 | 1:30 PM

TU-131 FAST FACTS: Reimbursement Topics for the Practicing Emergency Physician
Tuesday, Oct. 2 | 10:00 AM

TU-187 Alternative Payment Models: The New Reimbursement Frontier
Tuesday, Oct. 2 | 4:00 PM

The answer is none.

The question (for $1,000, Alex) is how many of the dozens of proposals to create physician-focused alternative payment models (APMs) have been approved under the new federal Quality Payment Program?

However, ACEP’s submission, entitled the Acute Unscheduled Care Model (AUCM): Enhancing Appropriate Admissions, seems to have gotten close to a nod when federal health care leaders showed up at a recent meeting on the model.

Reviewers from the Physician-Focused Payment Model Technical Advisory Committee “thought that we met all 10 criteria for models that the secretary put forth for evaluating physician-focused payment models,” Jeffrey Davis, ACEP director of regulatory affairs, said in an interview, adding that the attendance at the meeting of Alex Azar, secretary of Health & Human Serviecs, and Seema Verma, administrator of the Centers for Medicare & Medicaid Services, was a positive development.

To read our full story, check out the link below.

Key sessions at ACEP18 on QPP, MACRA, APMs, and MIPS include:

MO-058 Goodbye SGR! Hello MACRA and MIPS
Monday, Oct. 1 | 1:30 PM

TU-131 FAST FACTS: Reimbursement Topics for the Practicing Emergency Physician
Tuesday, Oct. 2 | 10:00 AM

TU-187 Alternative Payment Models: The New Reimbursement Frontier
Tuesday, Oct. 2 | 4:00 PM

Despite concerns that resident involvement in operations might pose a risk to the patient, the inclusion of general surgery residents in high-risk surgery cases does not negatively impact outcomes, according to a database study of more than 25,000 patients.

Adrienne N. Cobb, MD, of Loyola University Medical Center, Maywood, Ill., and her colleagues used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2012) to identify all patients undergoing any of six high-risk procedures on an elective basis.

Dr. Cobb and her colleagues compared outcomes for 25,363 patients who had procedures with and without resident participation: 4,018 and 21,345 patients, respectively. They also evaluated selected outcomes by postgraduate year (PGY). Junior residents were considered as PGY 1-2, senior residents were considered PGY 3, 4, and 5, and participants were considered fellows if they were PGY 6 or higher, according to their report published in the Journal of Surgical Research.

The six procedures assessed were esophagectomy (1,233 patients), open abdominal aortic aneurysm repair (162), laparoscopic paraesophageal resection with Nissen fundoplication (2,316), pancreaticoduodenectomy (Whipple, 10,309), abdominoperineal resection (2,003), and hepatectomy (9,329).

The primary outcome of the study was 30-day mortality with the exposure being resident involvement. Secondary outcomes that had complications included superficial and deep surgical site infection, wound disruption, bleeding requiring transfusion, return to the operating room, pneumonia, unplanned reintubation, pulmonary embolism, acute renal failure, stroke, MI, sepsis, urinary tract infection (UTI), and deep vein thrombosis, operative time, and length of stay.

In both univariate and multivariate analysis, there were no significant differences in mortality between patients who did or did not have procedures in which resident participation at any level of training was involved.

Overall, resident participation did increase the odds of a prolonged operative time (odds ratio, 1.5; 95% confidence interval, 1.1-2.1). Only abdominal perineal resection showed an increased odds risk of having a prolonged operation when residents were involved (OR, 4.3; 95% CI, 1.1-4.8). With regard to these results, the authors commented: “We assert that the additional time spent with trainees in the OR is integral to the production of confident and competent surgeons and does not lead to poorer outcomes for patients. It may, however, lead to increasing costs for the hospital and the patient.”

When risk-adjusted odds were calculated for all the other secondary outcomes and postoperative outcomes tested, UTI was the only one to show a negative impact when residents were involved (OR, 2.3; 95% CI, 1.1-4.8).

The study limitations include the age of the data and the limited number of procedures evaluated, and thus might not be generalizable to a more modern era and other procedures, according to the authors.

“Apart from UTI rates, resident participation did not significantly increase patient morbidity or mortality. Residents should continue to be given active and engaging roles in the OR, even in the most challenging cases,” Dr. Cobb and her colleagues concluded.

The study was funded by the National Institutes of Health. The authors reported that they had no disclosures.

[email protected]

SOURCE: Cobb AN et al. J Surg Res. 2018 Dec; 232:308-17.

Despite concerns that resident involvement in operations might pose a risk to the patient, the inclusion of general surgery residents in high-risk surgery cases does not negatively impact outcomes, according to a database study of more than 25,000 patients.

Adrienne N. Cobb, MD, of Loyola University Medical Center, Maywood, Ill., and her colleagues used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2012) to identify all patients undergoing any of six high-risk procedures on an elective basis.

Dr. Cobb and her colleagues compared outcomes for 25,363 patients who had procedures with and without resident participation: 4,018 and 21,345 patients, respectively. They also evaluated selected outcomes by postgraduate year (PGY). Junior residents were considered as PGY 1-2, senior residents were considered PGY 3, 4, and 5, and participants were considered fellows if they were PGY 6 or higher, according to their report published in the Journal of Surgical Research.

The six procedures assessed were esophagectomy (1,233 patients), open abdominal aortic aneurysm repair (162), laparoscopic paraesophageal resection with Nissen fundoplication (2,316), pancreaticoduodenectomy (Whipple, 10,309), abdominoperineal resection (2,003), and hepatectomy (9,329).

The primary outcome of the study was 30-day mortality with the exposure being resident involvement. Secondary outcomes that had complications included superficial and deep surgical site infection, wound disruption, bleeding requiring transfusion, return to the operating room, pneumonia, unplanned reintubation, pulmonary embolism, acute renal failure, stroke, MI, sepsis, urinary tract infection (UTI), and deep vein thrombosis, operative time, and length of stay.

In both univariate and multivariate analysis, there were no significant differences in mortality between patients who did or did not have procedures in which resident participation at any level of training was involved.

Overall, resident participation did increase the odds of a prolonged operative time (odds ratio, 1.5; 95% confidence interval, 1.1-2.1). Only abdominal perineal resection showed an increased odds risk of having a prolonged operation when residents were involved (OR, 4.3; 95% CI, 1.1-4.8). With regard to these results, the authors commented: “We assert that the additional time spent with trainees in the OR is integral to the production of confident and competent surgeons and does not lead to poorer outcomes for patients. It may, however, lead to increasing costs for the hospital and the patient.”

When risk-adjusted odds were calculated for all the other secondary outcomes and postoperative outcomes tested, UTI was the only one to show a negative impact when residents were involved (OR, 2.3; 95% CI, 1.1-4.8).

The study limitations include the age of the data and the limited number of procedures evaluated, and thus might not be generalizable to a more modern era and other procedures, according to the authors.

“Apart from UTI rates, resident participation did not significantly increase patient morbidity or mortality. Residents should continue to be given active and engaging roles in the OR, even in the most challenging cases,” Dr. Cobb and her colleagues concluded.

The study was funded by the National Institutes of Health. The authors reported that they had no disclosures.

[email protected]

SOURCE: Cobb AN et al. J Surg Res. 2018 Dec; 232:308-17.

Despite concerns that resident involvement in operations might pose a risk to the patient, the inclusion of general surgery residents in high-risk surgery cases does not negatively impact outcomes, according to a database study of more than 25,000 patients.

Adrienne N. Cobb, MD, of Loyola University Medical Center, Maywood, Ill., and her colleagues used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2012) to identify all patients undergoing any of six high-risk procedures on an elective basis.

Dr. Cobb and her colleagues compared outcomes for 25,363 patients who had procedures with and without resident participation: 4,018 and 21,345 patients, respectively. They also evaluated selected outcomes by postgraduate year (PGY). Junior residents were considered as PGY 1-2, senior residents were considered PGY 3, 4, and 5, and participants were considered fellows if they were PGY 6 or higher, according to their report published in the Journal of Surgical Research.

The six procedures assessed were esophagectomy (1,233 patients), open abdominal aortic aneurysm repair (162), laparoscopic paraesophageal resection with Nissen fundoplication (2,316), pancreaticoduodenectomy (Whipple, 10,309), abdominoperineal resection (2,003), and hepatectomy (9,329).

The primary outcome of the study was 30-day mortality with the exposure being resident involvement. Secondary outcomes that had complications included superficial and deep surgical site infection, wound disruption, bleeding requiring transfusion, return to the operating room, pneumonia, unplanned reintubation, pulmonary embolism, acute renal failure, stroke, MI, sepsis, urinary tract infection (UTI), and deep vein thrombosis, operative time, and length of stay.

In both univariate and multivariate analysis, there were no significant differences in mortality between patients who did or did not have procedures in which resident participation at any level of training was involved.

Overall, resident participation did increase the odds of a prolonged operative time (odds ratio, 1.5; 95% confidence interval, 1.1-2.1). Only abdominal perineal resection showed an increased odds risk of having a prolonged operation when residents were involved (OR, 4.3; 95% CI, 1.1-4.8). With regard to these results, the authors commented: “We assert that the additional time spent with trainees in the OR is integral to the production of confident and competent surgeons and does not lead to poorer outcomes for patients. It may, however, lead to increasing costs for the hospital and the patient.”

When risk-adjusted odds were calculated for all the other secondary outcomes and postoperative outcomes tested, UTI was the only one to show a negative impact when residents were involved (OR, 2.3; 95% CI, 1.1-4.8).

The study limitations include the age of the data and the limited number of procedures evaluated, and thus might not be generalizable to a more modern era and other procedures, according to the authors.

“Apart from UTI rates, resident participation did not significantly increase patient morbidity or mortality. Residents should continue to be given active and engaging roles in the OR, even in the most challenging cases,” Dr. Cobb and her colleagues concluded.

The study was funded by the National Institutes of Health. The authors reported that they had no disclosures.

[email protected]

SOURCE: Cobb AN et al. J Surg Res. 2018 Dec; 232:308-17.

Between 2009 and 2015, the number of emergency department visits related to mental health increased 56% among pediatric patients and 41% among adults, according to data that will be presented at the annual meeting of the American College of Emergency Physicians.

“The current mental health system is in crisis and the impact on emergency departments continues to increase,” lead researcher Genevieve Santillanes, MD, said in an interview in advance of the meeting. “We are seeing more patients with mental health disorders and when patients with mental health disorders require inpatient care, they board in the ED for long periods of time.”

Look to our onsite meeting coverage October 1-4 for additional details on this study and more news from ACEP18!
 

Between 2009 and 2015, the number of emergency department visits related to mental health increased 56% among pediatric patients and 41% among adults, according to data that will be presented at the annual meeting of the American College of Emergency Physicians.

“The current mental health system is in crisis and the impact on emergency departments continues to increase,” lead researcher Genevieve Santillanes, MD, said in an interview in advance of the meeting. “We are seeing more patients with mental health disorders and when patients with mental health disorders require inpatient care, they board in the ED for long periods of time.”

Look to our onsite meeting coverage October 1-4 for additional details on this study and more news from ACEP18!
 

Between 2009 and 2015, the number of emergency department visits related to mental health increased 56% among pediatric patients and 41% among adults, according to data that will be presented at the annual meeting of the American College of Emergency Physicians.

“The current mental health system is in crisis and the impact on emergency departments continues to increase,” lead researcher Genevieve Santillanes, MD, said in an interview in advance of the meeting. “We are seeing more patients with mental health disorders and when patients with mental health disorders require inpatient care, they board in the ED for long periods of time.”

Look to our onsite meeting coverage October 1-4 for additional details on this study and more news from ACEP18!
 

The dangers of synthetic drugs and heroin, and the opioid epidemic, are hitting emergency departments hard. A lack of guidelines and poor presentation to follow-up care make treatment decisions difficult. Pockets of outbreaks emerge when dangerous toxins are added to already dangerous drugs. One such regional outbreak occurred in March 2018 when synthetic cannabinoids laced with superwarfarin were led to 150 patients presenting to hospitals with severe coagulopathy in Illinois.

ACEP18 will feature a plethora of toxicology presentations and workshops, such as “Emergency Toxicology: Emerging Trends – Cases in Poisoning Management” on Tuesday, Oct. 2 at 8 am, led my Patrick M. Lank, MD, FACEP. Dr. Lark, an emergency medicine specialist in Chicago, will also be leading  “Critical Update in Toxicology 2018" on Monday, Oct. 1, at 12:30 pm and “FAST FACTS: High-Yield Toxicology,” on Monday, at 4:30 pm.

The dangers of synthetic drugs and heroin, and the opioid epidemic, are hitting emergency departments hard. A lack of guidelines and poor presentation to follow-up care make treatment decisions difficult. Pockets of outbreaks emerge when dangerous toxins are added to already dangerous drugs. One such regional outbreak occurred in March 2018 when synthetic cannabinoids laced with superwarfarin were led to 150 patients presenting to hospitals with severe coagulopathy in Illinois.

ACEP18 will feature a plethora of toxicology presentations and workshops, such as “Emergency Toxicology: Emerging Trends – Cases in Poisoning Management” on Tuesday, Oct. 2 at 8 am, led my Patrick M. Lank, MD, FACEP. Dr. Lark, an emergency medicine specialist in Chicago, will also be leading  “Critical Update in Toxicology 2018" on Monday, Oct. 1, at 12:30 pm and “FAST FACTS: High-Yield Toxicology,” on Monday, at 4:30 pm.

The dangers of synthetic drugs and heroin, and the opioid epidemic, are hitting emergency departments hard. A lack of guidelines and poor presentation to follow-up care make treatment decisions difficult. Pockets of outbreaks emerge when dangerous toxins are added to already dangerous drugs. One such regional outbreak occurred in March 2018 when synthetic cannabinoids laced with superwarfarin were led to 150 patients presenting to hospitals with severe coagulopathy in Illinois.

ACEP18 will feature a plethora of toxicology presentations and workshops, such as “Emergency Toxicology: Emerging Trends – Cases in Poisoning Management” on Tuesday, Oct. 2 at 8 am, led my Patrick M. Lank, MD, FACEP. Dr. Lark, an emergency medicine specialist in Chicago, will also be leading  “Critical Update in Toxicology 2018" on Monday, Oct. 1, at 12:30 pm and “FAST FACTS: High-Yield Toxicology,” on Monday, at 4:30 pm.

SAN DIEGO – In patients with atrial fibrillation and stable coronary artery disease, a randomized trial of oral anticoagulation alone versus an anticoagulant plus a single antiplatelet agent failed to establish noninferiority of the single-agent approach. The trial could not demonstrate its primary endpoint of all-cause death, myocardial infarction, stroke, or systemic embolism.

But a secondary endpoint that included major bleeding did demonstrate equivalence, leading the researchers to suggest that oral anticoagulation (OAC) alone may be sufficient in most patients.

“Combined OAC and single antiplatelet therapy is unlikely to provide net clinical benefit over OAC alone. Thus, OAC alone might be reasonable for AF [atrial fibrillation] patients beyond 1 year after coronary stenting,” Yukiko Nakano, MD, of Kyoto (Japan) University Graduate School of Medicine, said during a press conference at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation. The report was simultaneously published Sept. 24 in Circulation (doi: 10.1161/CIRCULATIONAHA.118.036768).

Jim Kling/MDedge News

The study was stopped prematurely because of insufficient recruitment, which may have contributed to the failed primary endpoint. It’s a shortcoming that befalls many such studies, perhaps because cardiologists tend to be set in their ways when it comes to treatment of patients after a stent implant. “Cardiologists just think they know the answer, and they don’t want to expose their patients (to a clinical trial). They say, ‘I have my patients on whatever regimen. It seems to be working, and they’re not bleeding, so I don’t want to change it.’ This study suggests that we probably can stop one of the two (antiplatelet drugs) and get by with a single agent, and in this case they got by with no agent (in the monotherapy arm),” said C. Michael Gibson, MD, chief of clinical research in the division of cardiology at Beth Israel Deaconess Medical Center, Boston, who was a discussant at the press conference.

The study recruited 696 patients who were receiving OAC plus single antiplatelet therapy (SAPT) 1 year after receiving a stent. They were randomized 1:1 to continue combined therapy or to stop SAPT and then followed for a median of 2.5 years. A total of 74% of patients who received OAC alone were taking warfarin, while 26% were taking a direct oral anticoagulant. The SAPT group took aspirin or clopidogrel.

Overall, 15.7% of OAC patients experienced the primary endpoint, compared with 13.6% of the combined group (noninferiority P = .20). None of the individual components of the primary endpoint were statistically significantly different between the groups. International Society on Thrombosis and Haemostasis major bleeding and Thrombolysis in Myocardial Infarction major bleeding trended in favor of OAC alone. The secondary endpoint (primary endpoint plus major bleeding) achieved noninferiority, occurring in 19.5% of the OAC group and 19.4% of the combined therapy group (noninferiority P = .016; superiority P = .96).

Daiichi-Sankyo funded the trial. Dr. Nakano had no conflicts of interest. Dr. Gibson reported numerous financial ties to pharmaceutical companies, including Daiichi-Sankyo.

SAN DIEGO – In patients with atrial fibrillation and stable coronary artery disease, a randomized trial of oral anticoagulation alone versus an anticoagulant plus a single antiplatelet agent failed to establish noninferiority of the single-agent approach. The trial could not demonstrate its primary endpoint of all-cause death, myocardial infarction, stroke, or systemic embolism.

But a secondary endpoint that included major bleeding did demonstrate equivalence, leading the researchers to suggest that oral anticoagulation (OAC) alone may be sufficient in most patients.

“Combined OAC and single antiplatelet therapy is unlikely to provide net clinical benefit over OAC alone. Thus, OAC alone might be reasonable for AF [atrial fibrillation] patients beyond 1 year after coronary stenting,” Yukiko Nakano, MD, of Kyoto (Japan) University Graduate School of Medicine, said during a press conference at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation. The report was simultaneously published Sept. 24 in Circulation (doi: 10.1161/CIRCULATIONAHA.118.036768).

Jim Kling/MDedge News

The study was stopped prematurely because of insufficient recruitment, which may have contributed to the failed primary endpoint. It’s a shortcoming that befalls many such studies, perhaps because cardiologists tend to be set in their ways when it comes to treatment of patients after a stent implant. “Cardiologists just think they know the answer, and they don’t want to expose their patients (to a clinical trial). They say, ‘I have my patients on whatever regimen. It seems to be working, and they’re not bleeding, so I don’t want to change it.’ This study suggests that we probably can stop one of the two (antiplatelet drugs) and get by with a single agent, and in this case they got by with no agent (in the monotherapy arm),” said C. Michael Gibson, MD, chief of clinical research in the division of cardiology at Beth Israel Deaconess Medical Center, Boston, who was a discussant at the press conference.

The study recruited 696 patients who were receiving OAC plus single antiplatelet therapy (SAPT) 1 year after receiving a stent. They were randomized 1:1 to continue combined therapy or to stop SAPT and then followed for a median of 2.5 years. A total of 74% of patients who received OAC alone were taking warfarin, while 26% were taking a direct oral anticoagulant. The SAPT group took aspirin or clopidogrel.

Overall, 15.7% of OAC patients experienced the primary endpoint, compared with 13.6% of the combined group (noninferiority P = .20). None of the individual components of the primary endpoint were statistically significantly different between the groups. International Society on Thrombosis and Haemostasis major bleeding and Thrombolysis in Myocardial Infarction major bleeding trended in favor of OAC alone. The secondary endpoint (primary endpoint plus major bleeding) achieved noninferiority, occurring in 19.5% of the OAC group and 19.4% of the combined therapy group (noninferiority P = .016; superiority P = .96).

Daiichi-Sankyo funded the trial. Dr. Nakano had no conflicts of interest. Dr. Gibson reported numerous financial ties to pharmaceutical companies, including Daiichi-Sankyo.

SAN DIEGO – In patients with atrial fibrillation and stable coronary artery disease, a randomized trial of oral anticoagulation alone versus an anticoagulant plus a single antiplatelet agent failed to establish noninferiority of the single-agent approach. The trial could not demonstrate its primary endpoint of all-cause death, myocardial infarction, stroke, or systemic embolism.

But a secondary endpoint that included major bleeding did demonstrate equivalence, leading the researchers to suggest that oral anticoagulation (OAC) alone may be sufficient in most patients.

“Combined OAC and single antiplatelet therapy is unlikely to provide net clinical benefit over OAC alone. Thus, OAC alone might be reasonable for AF [atrial fibrillation] patients beyond 1 year after coronary stenting,” Yukiko Nakano, MD, of Kyoto (Japan) University Graduate School of Medicine, said during a press conference at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation. The report was simultaneously published Sept. 24 in Circulation (doi: 10.1161/CIRCULATIONAHA.118.036768).

Jim Kling/MDedge News

The study was stopped prematurely because of insufficient recruitment, which may have contributed to the failed primary endpoint. It’s a shortcoming that befalls many such studies, perhaps because cardiologists tend to be set in their ways when it comes to treatment of patients after a stent implant. “Cardiologists just think they know the answer, and they don’t want to expose their patients (to a clinical trial). They say, ‘I have my patients on whatever regimen. It seems to be working, and they’re not bleeding, so I don’t want to change it.’ This study suggests that we probably can stop one of the two (antiplatelet drugs) and get by with a single agent, and in this case they got by with no agent (in the monotherapy arm),” said C. Michael Gibson, MD, chief of clinical research in the division of cardiology at Beth Israel Deaconess Medical Center, Boston, who was a discussant at the press conference.

The study recruited 696 patients who were receiving OAC plus single antiplatelet therapy (SAPT) 1 year after receiving a stent. They were randomized 1:1 to continue combined therapy or to stop SAPT and then followed for a median of 2.5 years. A total of 74% of patients who received OAC alone were taking warfarin, while 26% were taking a direct oral anticoagulant. The SAPT group took aspirin or clopidogrel.

Overall, 15.7% of OAC patients experienced the primary endpoint, compared with 13.6% of the combined group (noninferiority P = .20). None of the individual components of the primary endpoint were statistically significantly different between the groups. International Society on Thrombosis and Haemostasis major bleeding and Thrombolysis in Myocardial Infarction major bleeding trended in favor of OAC alone. The secondary endpoint (primary endpoint plus major bleeding) achieved noninferiority, occurring in 19.5% of the OAC group and 19.4% of the combined therapy group (noninferiority P = .016; superiority P = .96).

Daiichi-Sankyo funded the trial. Dr. Nakano had no conflicts of interest. Dr. Gibson reported numerous financial ties to pharmaceutical companies, including Daiichi-Sankyo.

PARIS – Patients with stable angina and a fractional flow reserve (FFR) value in the grey zone of 0.75-0.81 experienced a significant reduction in myocardial ischemia and substantially greater quality of life improvement if they were randomized to percutaneous coronary intervention (PCI) plus optimal medical therapy than to optimal medical therapy alone in the Scottish Grey-zone FFR Study.

Bruce Jancin/MDedge News

The Grey-zone FFR Study was a single-center, prospective, unblinded, randomized trial that included 100 patients with stable angina, single-vessel disease, and a fractional flow reserve in the grey zone of 0.75-0.81. While broad consensus exists that an FFR below 0.75 constitutes evidence of a hemodynamically significant coronary lesion warranting revascularization and an FFR greater than 0.80 indicates a lesion isn’t functionally significant and therefore PCI can safely be deferred, there has been uncertainty on what to do about lesions in the grey zone, which are frequently encountered in the cardiac catheterization laboratory.

“In my clinical practice, I tend to go ahead with PCI for patients in the grey zone if I felt it was clinically feasible and safe to do so, particularly if I was worried about their lesion morphology,” Barry Hennigan, MD, said in response to questions after presenting the results at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions. “If it’s a proximal LAD [left anterior descending artery] lesion and it’s a grey zone patient, particularly if it’s a lesion morphology that you’re not comfortable with, I think you need to be very careful before you defer a case.”

The twin purposes of the Scottish study were to define the prevalence of major ischemia by stress MRI and invasive flow assessment via a pressure wire in grey zone patients – something which hadn’t been done before – and to determine if PCI deferral in such patients is appropriate in terms of symptom control. The primary outcome was change in angina severity at 3 months follow-up using the Seattle Angina Questionnaire (SAQ).

Scores on two of the five domains of the SAQ – anginal frequency and quality of life – were significantly improved in the PCI group. Anginal frequency scores improved by a mean of 20.58 points in the PCI plus optimal medical therapy (OMT) group, compared with a 9.39-point improvement with OMT alone. Quality of life scores improved by 24.04 points in the PCI group versus 9.39 points in controls, said Dr. Hennigan, an interventional cardiologist at the University of Glasgow and Golden Jubilee National Hospital. Scores in the other three SAQ domains – physical limitations, anginal stability, and treatment satisfaction – didn’t differ significantly between the two study arms, although consistently greater improvements were seen in the PCI group.

Baseline stress perfusion MRI as assessed by two blinded observers demonstrated that 17.4% of patients with stable angina and a grey zone FFR had major ischemia, while any ischemia – major or minor – was present in 24.4%. Follow-up scans at 3 months showed a roughly 50% reduction in the prevalence of ischemia in the PCI group, with 7.3% of treated patients still having major ischemia and 12.2% having any ischemia.

Also, 28% of participants had evidence of ischemia at baseline based upon their coronary flow reserve measurements and 8% had a hyperemic stenosis resistance measurement indicative of ischemia. So the FFR grey zone encompasses a range of cardiovascular risks.

In the PCI plus OMT group, 89% of patients (eight of nine) with baseline ischemia on stress MRI had a greater than 10-point improvement in quality of life scores on the SAQ at follow-up in contrast to 53% of patients without ischemia, which made for a statistically significant difference. An improvement of that magnitude is generally considered clinically meaningful. In contrast, in the OMT-only group, 9 of 14 patients with baseline ischemia (64.2%) had a greater than 10-point quality of life improvement, which wasn’t significantly different from the 45.5% improvement rate in patients with no ischemia.

The lessons? Grey zone patients who benefit most from prompt revascularization are those with demonstrable ischemia. In addition, roughly half of grey zone patients with stable angina will improve their quality of life scores by more than 10 points with OMT alone regardless of the presence of myocardial ischemia or not.

Dr. Hennigan was repeatedly asked how he reconciles the results of the grey zone study with those of the much-discussed ORBITA trial, the first and only randomized trial of real versus sham PCI in patients with stable angina. ORBITA didn’t find a significant quality of life advantage for real PCI over sham PCI.

“It is quite possible that a lot of the effect that we saw in our PCI group was placebo related,” he conceded. “However, we do have objective evidence that we reduced ischemia on MRI. Also, 29% of ORBITA patients had an FFR above 0.8, whereas nearly all our patients were below that threshold. So we perhaps had more prevalent ischemia than the ORBITA cohort.”

Also informative is a comparison of SAQ scores at follow-up in the sham PCI ORBITA control group versus the grey zone Scottish PCI group, Dr. Hennigan continued. The Scottish PCI group had a mean 20.6-point improvement in anginal frequency scores while on an average of 1.3 antianginal medications, compared with a 9.6-point improvement in ORBITA patients on 2.9 drugs. The grey zone group who got PCI plus OMT also had a mean 16.1-point improvement in the SAQ physical limitations domain, versus a 5.0-point improvement in the ORBITA controls.

The Grey-zone FFR Study was supported by the British Heart Foundation. Dr. Hennigan reported having no financial conflicts of interest.

[email protected]

PARIS – Patients with stable angina and a fractional flow reserve (FFR) value in the grey zone of 0.75-0.81 experienced a significant reduction in myocardial ischemia and substantially greater quality of life improvement if they were randomized to percutaneous coronary intervention (PCI) plus optimal medical therapy than to optimal medical therapy alone in the Scottish Grey-zone FFR Study.

Bruce Jancin/MDedge News

The Grey-zone FFR Study was a single-center, prospective, unblinded, randomized trial that included 100 patients with stable angina, single-vessel disease, and a fractional flow reserve in the grey zone of 0.75-0.81. While broad consensus exists that an FFR below 0.75 constitutes evidence of a hemodynamically significant coronary lesion warranting revascularization and an FFR greater than 0.80 indicates a lesion isn’t functionally significant and therefore PCI can safely be deferred, there has been uncertainty on what to do about lesions in the grey zone, which are frequently encountered in the cardiac catheterization laboratory.

“In my clinical practice, I tend to go ahead with PCI for patients in the grey zone if I felt it was clinically feasible and safe to do so, particularly if I was worried about their lesion morphology,” Barry Hennigan, MD, said in response to questions after presenting the results at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions. “If it’s a proximal LAD [left anterior descending artery] lesion and it’s a grey zone patient, particularly if it’s a lesion morphology that you’re not comfortable with, I think you need to be very careful before you defer a case.”

The twin purposes of the Scottish study were to define the prevalence of major ischemia by stress MRI and invasive flow assessment via a pressure wire in grey zone patients – something which hadn’t been done before – and to determine if PCI deferral in such patients is appropriate in terms of symptom control. The primary outcome was change in angina severity at 3 months follow-up using the Seattle Angina Questionnaire (SAQ).

Scores on two of the five domains of the SAQ – anginal frequency and quality of life – were significantly improved in the PCI group. Anginal frequency scores improved by a mean of 20.58 points in the PCI plus optimal medical therapy (OMT) group, compared with a 9.39-point improvement with OMT alone. Quality of life scores improved by 24.04 points in the PCI group versus 9.39 points in controls, said Dr. Hennigan, an interventional cardiologist at the University of Glasgow and Golden Jubilee National Hospital. Scores in the other three SAQ domains – physical limitations, anginal stability, and treatment satisfaction – didn’t differ significantly between the two study arms, although consistently greater improvements were seen in the PCI group.

Baseline stress perfusion MRI as assessed by two blinded observers demonstrated that 17.4% of patients with stable angina and a grey zone FFR had major ischemia, while any ischemia – major or minor – was present in 24.4%. Follow-up scans at 3 months showed a roughly 50% reduction in the prevalence of ischemia in the PCI group, with 7.3% of treated patients still having major ischemia and 12.2% having any ischemia.

Also, 28% of participants had evidence of ischemia at baseline based upon their coronary flow reserve measurements and 8% had a hyperemic stenosis resistance measurement indicative of ischemia. So the FFR grey zone encompasses a range of cardiovascular risks.

In the PCI plus OMT group, 89% of patients (eight of nine) with baseline ischemia on stress MRI had a greater than 10-point improvement in quality of life scores on the SAQ at follow-up in contrast to 53% of patients without ischemia, which made for a statistically significant difference. An improvement of that magnitude is generally considered clinically meaningful. In contrast, in the OMT-only group, 9 of 14 patients with baseline ischemia (64.2%) had a greater than 10-point quality of life improvement, which wasn’t significantly different from the 45.5% improvement rate in patients with no ischemia.

The lessons? Grey zone patients who benefit most from prompt revascularization are those with demonstrable ischemia. In addition, roughly half of grey zone patients with stable angina will improve their quality of life scores by more than 10 points with OMT alone regardless of the presence of myocardial ischemia or not.

Dr. Hennigan was repeatedly asked how he reconciles the results of the grey zone study with those of the much-discussed ORBITA trial, the first and only randomized trial of real versus sham PCI in patients with stable angina. ORBITA didn’t find a significant quality of life advantage for real PCI over sham PCI.

“It is quite possible that a lot of the effect that we saw in our PCI group was placebo related,” he conceded. “However, we do have objective evidence that we reduced ischemia on MRI. Also, 29% of ORBITA patients had an FFR above 0.8, whereas nearly all our patients were below that threshold. So we perhaps had more prevalent ischemia than the ORBITA cohort.”

Also informative is a comparison of SAQ scores at follow-up in the sham PCI ORBITA control group versus the grey zone Scottish PCI group, Dr. Hennigan continued. The Scottish PCI group had a mean 20.6-point improvement in anginal frequency scores while on an average of 1.3 antianginal medications, compared with a 9.6-point improvement in ORBITA patients on 2.9 drugs. The grey zone group who got PCI plus OMT also had a mean 16.1-point improvement in the SAQ physical limitations domain, versus a 5.0-point improvement in the ORBITA controls.

The Grey-zone FFR Study was supported by the British Heart Foundation. Dr. Hennigan reported having no financial conflicts of interest.

[email protected]

PARIS – Patients with stable angina and a fractional flow reserve (FFR) value in the grey zone of 0.75-0.81 experienced a significant reduction in myocardial ischemia and substantially greater quality of life improvement if they were randomized to percutaneous coronary intervention (PCI) plus optimal medical therapy than to optimal medical therapy alone in the Scottish Grey-zone FFR Study.

Bruce Jancin/MDedge News

The Grey-zone FFR Study was a single-center, prospective, unblinded, randomized trial that included 100 patients with stable angina, single-vessel disease, and a fractional flow reserve in the grey zone of 0.75-0.81. While broad consensus exists that an FFR below 0.75 constitutes evidence of a hemodynamically significant coronary lesion warranting revascularization and an FFR greater than 0.80 indicates a lesion isn’t functionally significant and therefore PCI can safely be deferred, there has been uncertainty on what to do about lesions in the grey zone, which are frequently encountered in the cardiac catheterization laboratory.

“In my clinical practice, I tend to go ahead with PCI for patients in the grey zone if I felt it was clinically feasible and safe to do so, particularly if I was worried about their lesion morphology,” Barry Hennigan, MD, said in response to questions after presenting the results at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions. “If it’s a proximal LAD [left anterior descending artery] lesion and it’s a grey zone patient, particularly if it’s a lesion morphology that you’re not comfortable with, I think you need to be very careful before you defer a case.”

The twin purposes of the Scottish study were to define the prevalence of major ischemia by stress MRI and invasive flow assessment via a pressure wire in grey zone patients – something which hadn’t been done before – and to determine if PCI deferral in such patients is appropriate in terms of symptom control. The primary outcome was change in angina severity at 3 months follow-up using the Seattle Angina Questionnaire (SAQ).

Scores on two of the five domains of the SAQ – anginal frequency and quality of life – were significantly improved in the PCI group. Anginal frequency scores improved by a mean of 20.58 points in the PCI plus optimal medical therapy (OMT) group, compared with a 9.39-point improvement with OMT alone. Quality of life scores improved by 24.04 points in the PCI group versus 9.39 points in controls, said Dr. Hennigan, an interventional cardiologist at the University of Glasgow and Golden Jubilee National Hospital. Scores in the other three SAQ domains – physical limitations, anginal stability, and treatment satisfaction – didn’t differ significantly between the two study arms, although consistently greater improvements were seen in the PCI group.

Baseline stress perfusion MRI as assessed by two blinded observers demonstrated that 17.4% of patients with stable angina and a grey zone FFR had major ischemia, while any ischemia – major or minor – was present in 24.4%. Follow-up scans at 3 months showed a roughly 50% reduction in the prevalence of ischemia in the PCI group, with 7.3% of treated patients still having major ischemia and 12.2% having any ischemia.

Also, 28% of participants had evidence of ischemia at baseline based upon their coronary flow reserve measurements and 8% had a hyperemic stenosis resistance measurement indicative of ischemia. So the FFR grey zone encompasses a range of cardiovascular risks.

In the PCI plus OMT group, 89% of patients (eight of nine) with baseline ischemia on stress MRI had a greater than 10-point improvement in quality of life scores on the SAQ at follow-up in contrast to 53% of patients without ischemia, which made for a statistically significant difference. An improvement of that magnitude is generally considered clinically meaningful. In contrast, in the OMT-only group, 9 of 14 patients with baseline ischemia (64.2%) had a greater than 10-point quality of life improvement, which wasn’t significantly different from the 45.5% improvement rate in patients with no ischemia.

The lessons? Grey zone patients who benefit most from prompt revascularization are those with demonstrable ischemia. In addition, roughly half of grey zone patients with stable angina will improve their quality of life scores by more than 10 points with OMT alone regardless of the presence of myocardial ischemia or not.

Dr. Hennigan was repeatedly asked how he reconciles the results of the grey zone study with those of the much-discussed ORBITA trial, the first and only randomized trial of real versus sham PCI in patients with stable angina. ORBITA didn’t find a significant quality of life advantage for real PCI over sham PCI.

“It is quite possible that a lot of the effect that we saw in our PCI group was placebo related,” he conceded. “However, we do have objective evidence that we reduced ischemia on MRI. Also, 29% of ORBITA patients had an FFR above 0.8, whereas nearly all our patients were below that threshold. So we perhaps had more prevalent ischemia than the ORBITA cohort.”

Also informative is a comparison of SAQ scores at follow-up in the sham PCI ORBITA control group versus the grey zone Scottish PCI group, Dr. Hennigan continued. The Scottish PCI group had a mean 20.6-point improvement in anginal frequency scores while on an average of 1.3 antianginal medications, compared with a 9.6-point improvement in ORBITA patients on 2.9 drugs. The grey zone group who got PCI plus OMT also had a mean 16.1-point improvement in the SAQ physical limitations domain, versus a 5.0-point improvement in the ORBITA controls.

The Grey-zone FFR Study was supported by the British Heart Foundation. Dr. Hennigan reported having no financial conflicts of interest.

[email protected]

SAN FRANCISCO—A brief course of mindfulness training for patients with chronic migraine after their withdrawal from overuse of acute migraine medications proved as effective as prophylactic medication over the course of 12 months of follow-up, said Frank Andrasik, PhD, and colleagues at the 60th Annual Scientific Meeting of the American Headache Society.

“The effects of mindfulness by and large rivaled those of medication alone. Although [it was]not specifically assessed, patients commented that mindfulness did not have side effects and promoted greater involvement and adherence,” said Dr. Andrasik, Professor and Chair of the Department of Psychology and Director of the Center for Behavioral Medicine at the University of Memphis.

He noted that his study, which was published in the Journal of Headache Pain, is best considered exploratory because of its small size and nonrandomized design.

After five days of structured acute medication withdrawal in an outpatient day hospital setting, study participants were treated with either pharmacologic prophylaxis for migraine—most often using botulinum toxin—or a brief course in mindfulness training entailing six once-weekly 45-minute sessions plus home practice for seven to 10 minutes per day. “While this study design does not rise to level one randomized trial evidence, it does reflect real-world clinical practice, where patients often have a big say in choosing their treatment plan,” Dr. Andrasik observed.

At baseline, all 44 patients met diagnostic criteria for chronic migraine with associated acute medication overuse. They averaged 20.5 headache days per month, with 18.4 days of acute migraine medication use. At three, six, and 12 months of follow-up, the 22 patients in the mindfulness group averaged 8.3, 10.4, and 12.4 headache days per month, while the 22 on pharmacologic prophylaxis averaged 8.8, 11, and 8.6 headache days per month. Both groups averaged similar seven- to 10-day reductions in days of acute migraine medication use per month.

Using the widely accepted end point of at least a 50% reduction in headache days per month, 50% of the mindfulness-only group and 52.6% of the prophylactic medication-only group met that standard at 12 months of follow-up. Moreover, at 12 months, 65% of the mindfulness therapy group and 73.7% of the preventive medication group no longer met diagnostic criteria for chronic migraine.

The mindfulness protocol used in the study was based upon the popular mindfulness-based stress reduction program developed by Jon Kabat-Zinn, PhD, and colleagues in the mid 1980s.

Scores on the Migraine Disability Assessment (MIDAS) measure and the Beck Depression Inventory improved significantly and to a similar extent from baseline in both groups. In contrast, scores on the State-Trait Anxiety Inventory did not change significantly in either study arm.

Mindfulness for Migraine Is Still Emerging

Dr. Andrasik and session chair Elizabeth K. Seng, PhD, cautioned that despite solid evidence of efficacy for mindfulness training in the treatment of depression and several chronic pain disorders, mindfulness for treatment of migraine is still in its infancy. Large randomized, controlled clinical trials are ongoing or in the planning stages, and no results are available.

Dr. Seng, a Research Assistant Professor at Albert Einstein College of Medicine in New York, described mindfulness and acceptance as “third-wave” behavioral treatments for migraine. The first-wave therapies focused on fostering behavioral changes to reduce perceived stress to avoid triggering migraine attacks. Second-wave therapies involved interactions aimed at helping patients reframe maladaptive automatic thoughts to reduce stress stemming from the daily hassles of life.

“The focus in the first- and second-wave therapies is, ‘Change something and your life will be better. Change your behaviors, clean up your act, change your thoughts because your thoughts are not helping you, and thereby reduce stress and reduce migraine.’ These mindfulness therapies are incredibly different from that,” she explained.

Third-wave therapies are not directed toward changing daily stress or automatic thoughts; instead, they seek to change the patient’s relationship to them such that they no longer create barriers to engaging in life activities that the patient finds nourishing and meaningful. It is a matter of creating a willingness to experience pain to achieve worthwhile objectives, Dr. Seng explained.

Measuring Success

It is unclear that a reduction in migraine days—the traditional yardstick for therapeutic efficacy in migraine research—is the right primary outcome measure for third-wave therapies, according to the psychologist. “So far, our evidence would suggest that mindfulness-based therapies do not reduce migraine days as much as other behavioral treatments, but what they are doing is increasing migraine-related quality of life and reducing migraine-related disability to the same or possibly larger extent than our other behavioral treatments,” Dr. Seng said. “Maybe what these third-wave therapies are actually doing is impacting our cognitive and emotional functioning, and even if patients still experience similar levels of headache frequency, their reaction to those headache days no longer leads to suffering. That could be a clinically relevant outcome.”

Dr. Seng plans to formally study mindfulness therapies in a subgroup of migraine patients with high levels of depression. They might respond especially well, she hypothesized, since mindfulness was originally developed as a treatment for severe depression. “Patients who are depressed have a hard time overcoming barriers to engaging in nourishing life activities, and when they have a headache day, it is even worse. That is one of the things that is leading them to have migraine-related disability,” she said.

Dr. Andrasik, whose study was supported by the European Commission and an Italian research foundation, reported having no financial conflicts of interest regarding his presentation. Dr. Seng reported serving as a consultant to GlaxoSmithKline.

—Bruce Jancin

Suggested Reading

Grazzi L, Sansone E, Raggi A, et al. Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with chronic migraine: an effectiveness trial with a one-year follow-up. J Headache Pain. 2017;18(1):15.

Kabat-Zinn J, Lipworth L, Burney R. The clinical use of mindfulness meditation for the self-regulation of chronic pain. J Behav Med. 1985;8(2):163-190.

SAN FRANCISCO—A brief course of mindfulness training for patients with chronic migraine after their withdrawal from overuse of acute migraine medications proved as effective as prophylactic medication over the course of 12 months of follow-up, said Frank Andrasik, PhD, and colleagues at the 60th Annual Scientific Meeting of the American Headache Society.

“The effects of mindfulness by and large rivaled those of medication alone. Although [it was]not specifically assessed, patients commented that mindfulness did not have side effects and promoted greater involvement and adherence,” said Dr. Andrasik, Professor and Chair of the Department of Psychology and Director of the Center for Behavioral Medicine at the University of Memphis.

He noted that his study, which was published in the Journal of Headache Pain, is best considered exploratory because of its small size and nonrandomized design.

After five days of structured acute medication withdrawal in an outpatient day hospital setting, study participants were treated with either pharmacologic prophylaxis for migraine—most often using botulinum toxin—or a brief course in mindfulness training entailing six once-weekly 45-minute sessions plus home practice for seven to 10 minutes per day. “While this study design does not rise to level one randomized trial evidence, it does reflect real-world clinical practice, where patients often have a big say in choosing their treatment plan,” Dr. Andrasik observed.

At baseline, all 44 patients met diagnostic criteria for chronic migraine with associated acute medication overuse. They averaged 20.5 headache days per month, with 18.4 days of acute migraine medication use. At three, six, and 12 months of follow-up, the 22 patients in the mindfulness group averaged 8.3, 10.4, and 12.4 headache days per month, while the 22 on pharmacologic prophylaxis averaged 8.8, 11, and 8.6 headache days per month. Both groups averaged similar seven- to 10-day reductions in days of acute migraine medication use per month.

Using the widely accepted end point of at least a 50% reduction in headache days per month, 50% of the mindfulness-only group and 52.6% of the prophylactic medication-only group met that standard at 12 months of follow-up. Moreover, at 12 months, 65% of the mindfulness therapy group and 73.7% of the preventive medication group no longer met diagnostic criteria for chronic migraine.

The mindfulness protocol used in the study was based upon the popular mindfulness-based stress reduction program developed by Jon Kabat-Zinn, PhD, and colleagues in the mid 1980s.

Scores on the Migraine Disability Assessment (MIDAS) measure and the Beck Depression Inventory improved significantly and to a similar extent from baseline in both groups. In contrast, scores on the State-Trait Anxiety Inventory did not change significantly in either study arm.

Mindfulness for Migraine Is Still Emerging

Dr. Andrasik and session chair Elizabeth K. Seng, PhD, cautioned that despite solid evidence of efficacy for mindfulness training in the treatment of depression and several chronic pain disorders, mindfulness for treatment of migraine is still in its infancy. Large randomized, controlled clinical trials are ongoing or in the planning stages, and no results are available.

Dr. Seng, a Research Assistant Professor at Albert Einstein College of Medicine in New York, described mindfulness and acceptance as “third-wave” behavioral treatments for migraine. The first-wave therapies focused on fostering behavioral changes to reduce perceived stress to avoid triggering migraine attacks. Second-wave therapies involved interactions aimed at helping patients reframe maladaptive automatic thoughts to reduce stress stemming from the daily hassles of life.

“The focus in the first- and second-wave therapies is, ‘Change something and your life will be better. Change your behaviors, clean up your act, change your thoughts because your thoughts are not helping you, and thereby reduce stress and reduce migraine.’ These mindfulness therapies are incredibly different from that,” she explained.

Third-wave therapies are not directed toward changing daily stress or automatic thoughts; instead, they seek to change the patient’s relationship to them such that they no longer create barriers to engaging in life activities that the patient finds nourishing and meaningful. It is a matter of creating a willingness to experience pain to achieve worthwhile objectives, Dr. Seng explained.

Measuring Success

It is unclear that a reduction in migraine days—the traditional yardstick for therapeutic efficacy in migraine research—is the right primary outcome measure for third-wave therapies, according to the psychologist. “So far, our evidence would suggest that mindfulness-based therapies do not reduce migraine days as much as other behavioral treatments, but what they are doing is increasing migraine-related quality of life and reducing migraine-related disability to the same or possibly larger extent than our other behavioral treatments,” Dr. Seng said. “Maybe what these third-wave therapies are actually doing is impacting our cognitive and emotional functioning, and even if patients still experience similar levels of headache frequency, their reaction to those headache days no longer leads to suffering. That could be a clinically relevant outcome.”

Dr. Seng plans to formally study mindfulness therapies in a subgroup of migraine patients with high levels of depression. They might respond especially well, she hypothesized, since mindfulness was originally developed as a treatment for severe depression. “Patients who are depressed have a hard time overcoming barriers to engaging in nourishing life activities, and when they have a headache day, it is even worse. That is one of the things that is leading them to have migraine-related disability,” she said.

Dr. Andrasik, whose study was supported by the European Commission and an Italian research foundation, reported having no financial conflicts of interest regarding his presentation. Dr. Seng reported serving as a consultant to GlaxoSmithKline.

—Bruce Jancin

Suggested Reading

Grazzi L, Sansone E, Raggi A, et al. Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with chronic migraine: an effectiveness trial with a one-year follow-up. J Headache Pain. 2017;18(1):15.

Kabat-Zinn J, Lipworth L, Burney R. The clinical use of mindfulness meditation for the self-regulation of chronic pain. J Behav Med. 1985;8(2):163-190.

SAN FRANCISCO—A brief course of mindfulness training for patients with chronic migraine after their withdrawal from overuse of acute migraine medications proved as effective as prophylactic medication over the course of 12 months of follow-up, said Frank Andrasik, PhD, and colleagues at the 60th Annual Scientific Meeting of the American Headache Society.

“The effects of mindfulness by and large rivaled those of medication alone. Although [it was]not specifically assessed, patients commented that mindfulness did not have side effects and promoted greater involvement and adherence,” said Dr. Andrasik, Professor and Chair of the Department of Psychology and Director of the Center for Behavioral Medicine at the University of Memphis.

He noted that his study, which was published in the Journal of Headache Pain, is best considered exploratory because of its small size and nonrandomized design.

After five days of structured acute medication withdrawal in an outpatient day hospital setting, study participants were treated with either pharmacologic prophylaxis for migraine—most often using botulinum toxin—or a brief course in mindfulness training entailing six once-weekly 45-minute sessions plus home practice for seven to 10 minutes per day. “While this study design does not rise to level one randomized trial evidence, it does reflect real-world clinical practice, where patients often have a big say in choosing their treatment plan,” Dr. Andrasik observed.

At baseline, all 44 patients met diagnostic criteria for chronic migraine with associated acute medication overuse. They averaged 20.5 headache days per month, with 18.4 days of acute migraine medication use. At three, six, and 12 months of follow-up, the 22 patients in the mindfulness group averaged 8.3, 10.4, and 12.4 headache days per month, while the 22 on pharmacologic prophylaxis averaged 8.8, 11, and 8.6 headache days per month. Both groups averaged similar seven- to 10-day reductions in days of acute migraine medication use per month.

Using the widely accepted end point of at least a 50% reduction in headache days per month, 50% of the mindfulness-only group and 52.6% of the prophylactic medication-only group met that standard at 12 months of follow-up. Moreover, at 12 months, 65% of the mindfulness therapy group and 73.7% of the preventive medication group no longer met diagnostic criteria for chronic migraine.

The mindfulness protocol used in the study was based upon the popular mindfulness-based stress reduction program developed by Jon Kabat-Zinn, PhD, and colleagues in the mid 1980s.

Scores on the Migraine Disability Assessment (MIDAS) measure and the Beck Depression Inventory improved significantly and to a similar extent from baseline in both groups. In contrast, scores on the State-Trait Anxiety Inventory did not change significantly in either study arm.

Mindfulness for Migraine Is Still Emerging

Dr. Andrasik and session chair Elizabeth K. Seng, PhD, cautioned that despite solid evidence of efficacy for mindfulness training in the treatment of depression and several chronic pain disorders, mindfulness for treatment of migraine is still in its infancy. Large randomized, controlled clinical trials are ongoing or in the planning stages, and no results are available.

Dr. Seng, a Research Assistant Professor at Albert Einstein College of Medicine in New York, described mindfulness and acceptance as “third-wave” behavioral treatments for migraine. The first-wave therapies focused on fostering behavioral changes to reduce perceived stress to avoid triggering migraine attacks. Second-wave therapies involved interactions aimed at helping patients reframe maladaptive automatic thoughts to reduce stress stemming from the daily hassles of life.

“The focus in the first- and second-wave therapies is, ‘Change something and your life will be better. Change your behaviors, clean up your act, change your thoughts because your thoughts are not helping you, and thereby reduce stress and reduce migraine.’ These mindfulness therapies are incredibly different from that,” she explained.

Third-wave therapies are not directed toward changing daily stress or automatic thoughts; instead, they seek to change the patient’s relationship to them such that they no longer create barriers to engaging in life activities that the patient finds nourishing and meaningful. It is a matter of creating a willingness to experience pain to achieve worthwhile objectives, Dr. Seng explained.

Measuring Success

It is unclear that a reduction in migraine days—the traditional yardstick for therapeutic efficacy in migraine research—is the right primary outcome measure for third-wave therapies, according to the psychologist. “So far, our evidence would suggest that mindfulness-based therapies do not reduce migraine days as much as other behavioral treatments, but what they are doing is increasing migraine-related quality of life and reducing migraine-related disability to the same or possibly larger extent than our other behavioral treatments,” Dr. Seng said. “Maybe what these third-wave therapies are actually doing is impacting our cognitive and emotional functioning, and even if patients still experience similar levels of headache frequency, their reaction to those headache days no longer leads to suffering. That could be a clinically relevant outcome.”

Dr. Seng plans to formally study mindfulness therapies in a subgroup of migraine patients with high levels of depression. They might respond especially well, she hypothesized, since mindfulness was originally developed as a treatment for severe depression. “Patients who are depressed have a hard time overcoming barriers to engaging in nourishing life activities, and when they have a headache day, it is even worse. That is one of the things that is leading them to have migraine-related disability,” she said.

Dr. Andrasik, whose study was supported by the European Commission and an Italian research foundation, reported having no financial conflicts of interest regarding his presentation. Dr. Seng reported serving as a consultant to GlaxoSmithKline.

—Bruce Jancin

Suggested Reading

Grazzi L, Sansone E, Raggi A, et al. Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with chronic migraine: an effectiveness trial with a one-year follow-up. J Headache Pain. 2017;18(1):15.

Kabat-Zinn J, Lipworth L, Burney R. The clinical use of mindfulness meditation for the self-regulation of chronic pain. J Behav Med. 1985;8(2):163-190.

Optimal measures of cardiovascular health are associated with brain health in adults, according to two studies published in the August 21 issue of JAMA.

In a French population-based cohort study, adults ages 65 and older with more cardiovascular health measures at ideal levels had a lower risk of dementia and lower rates of cognitive decline than did those with fewer optimal cardiovascular measures, such as blood pressure and physical activity.

In addition, a preliminary, cross-sectional study of younger adults found that the number of modifiable cardiovascular risk factors at recommended levels was associated with brain vessel structure and function and the number of white matter hyperintensities.

Cardiovascular Health in Older Age

Vascular dementia is the second most common neuropathologic basis of dementia, after Alzheimer’s disease, and “most cases of dementia arise from a combination of [Alzheimer’s disease] and cerebrovascular pathology,” the editorialists noted. Studies have suggested a connection between cardiovascular health and dementia, but the evidence is limited.

Cécilia Samieri, PhD, a Senior Researcher at the Bordeaux Population Health Research Center at the Université de Bordeaux in France, and colleagues studied people age 65 and older from Bordeaux, Dijon, and Montpellier, France, to examine the association between cardiovascular health level and risk of dementia and cognitive decline in older adults.

Cerebrovascular Structure and Function in Young Adults

Wilby Williamson, BMBS, Sports and Exercise Medicine Physician and Clinical Research Fellow in Cardiovascular Medicine at the University of Oxford, United Kingdom, and colleagues conducted a cross-sectional, observational study to examine relationships between modifiable cardiovascular risk factors and cerebrovascular structure, function, and white matter integrity in young adults. The study included 125 adults ages 18 to 40 without clinical evidence of cerebrovascular disease. Participants had a mean age of 25, and 49% were women.

The researchers assessed patients’ cerebral vessel density, caliber, and tortuosity and brain white matter hyperintensity lesion count. In a subgroup of 52 participants, they assessed cerebral blood flow.

The researchers determined for each participant how many of eight modifiable risk factors were at recommended levels (ie, BMI < 25, highest tertile of cardiovascular fitness or physical activity, alcohol consumption < eight drinks per week, nonsmoker for more than six months, blood pressure on awake ambulatory monitoring < 130/80 mm Hg, a nonhypertensive diastolic response to exercise [ie, peak diastolic blood pressure < 90 mm Hg], total cholesterol < 200 mg/dL, and fasting glucose < 100 mg/dL).

On average, participants had six of the eight modifiable cardiovascular risk factors at recommended levels.

In multivariable models, cardiovascular risk factors were associated with cerebrovascular structure and the number of white matter hyperintensities. “For each additional modifiable risk factor categorized as healthy, vessel density was greater by 0.3 vessels/cm³, vessel caliber was greater by 8 μm, and white matter hyperintensity lesions were fewer by 1.6 lesions. Among the 52 participants with available data, cerebral blood flow varied with vessel density and was 2.5 mL/100 g/min higher for each healthier category of a modifiable risk factor,” Dr. Williamson and colleagues said.

The findings suggest that “some individuals may be starting to diverge to different risk trajectories for brain vascular health in early adulthood,” the researchers said. The study was exploratory, however, and follow-up studies are needed to determine the clinical significance of these findings, they said.

“The magnitude of changes was generally much less than would be expected to produce clinical symptoms such as cognitive impairment or gait difficulty,” said Drs. Saver and Cushman. The changes, however, “may portend more substantial abnormalities later in life,” they said. “Even during the late-life period, when septuagenarians become octogenarians, cardiovascular health is associated with substantial differences in cognitive trajectory and dementia onset.”

—Jake Remaly

Suggested Reading

Samieri C, Perier MC, Gaye B, et al. Association of cardiovascular health level in older age with cognitive decline and incident dementia. JAMA. 2018;320(7):657-664.

Saver JL, Cushman M. Striving for ideal cardiovascular and brain health: It is never too early or too late. JAMA. 2018; 320(7):645-647.

Williamson W, Lewandowski AJ, Forkert ND, et al. Association of cardiovascular risk factors with MRI indices of cerebrovascular structure and function and white matter hyperintensities in young adults. JAMA. 2018;320(7):665-673.

Optimal measures of cardiovascular health are associated with brain health in adults, according to two studies published in the August 21 issue of JAMA.

In a French population-based cohort study, adults ages 65 and older with more cardiovascular health measures at ideal levels had a lower risk of dementia and lower rates of cognitive decline than did those with fewer optimal cardiovascular measures, such as blood pressure and physical activity.

In addition, a preliminary, cross-sectional study of younger adults found that the number of modifiable cardiovascular risk factors at recommended levels was associated with brain vessel structure and function and the number of white matter hyperintensities.

Cardiovascular Health in Older Age

Vascular dementia is the second most common neuropathologic basis of dementia, after Alzheimer’s disease, and “most cases of dementia arise from a combination of [Alzheimer’s disease] and cerebrovascular pathology,” the editorialists noted. Studies have suggested a connection between cardiovascular health and dementia, but the evidence is limited.

Cécilia Samieri, PhD, a Senior Researcher at the Bordeaux Population Health Research Center at the Université de Bordeaux in France, and colleagues studied people age 65 and older from Bordeaux, Dijon, and Montpellier, France, to examine the association between cardiovascular health level and risk of dementia and cognitive decline in older adults.

Cerebrovascular Structure and Function in Young Adults

Wilby Williamson, BMBS, Sports and Exercise Medicine Physician and Clinical Research Fellow in Cardiovascular Medicine at the University of Oxford, United Kingdom, and colleagues conducted a cross-sectional, observational study to examine relationships between modifiable cardiovascular risk factors and cerebrovascular structure, function, and white matter integrity in young adults. The study included 125 adults ages 18 to 40 without clinical evidence of cerebrovascular disease. Participants had a mean age of 25, and 49% were women.

The researchers assessed patients’ cerebral vessel density, caliber, and tortuosity and brain white matter hyperintensity lesion count. In a subgroup of 52 participants, they assessed cerebral blood flow.

The researchers determined for each participant how many of eight modifiable risk factors were at recommended levels (ie, BMI < 25, highest tertile of cardiovascular fitness or physical activity, alcohol consumption < eight drinks per week, nonsmoker for more than six months, blood pressure on awake ambulatory monitoring < 130/80 mm Hg, a nonhypertensive diastolic response to exercise [ie, peak diastolic blood pressure < 90 mm Hg], total cholesterol < 200 mg/dL, and fasting glucose < 100 mg/dL).

On average, participants had six of the eight modifiable cardiovascular risk factors at recommended levels.

In multivariable models, cardiovascular risk factors were associated with cerebrovascular structure and the number of white matter hyperintensities. “For each additional modifiable risk factor categorized as healthy, vessel density was greater by 0.3 vessels/cm³, vessel caliber was greater by 8 μm, and white matter hyperintensity lesions were fewer by 1.6 lesions. Among the 52 participants with available data, cerebral blood flow varied with vessel density and was 2.5 mL/100 g/min higher for each healthier category of a modifiable risk factor,” Dr. Williamson and colleagues said.

The findings suggest that “some individuals may be starting to diverge to different risk trajectories for brain vascular health in early adulthood,” the researchers said. The study was exploratory, however, and follow-up studies are needed to determine the clinical significance of these findings, they said.

“The magnitude of changes was generally much less than would be expected to produce clinical symptoms such as cognitive impairment or gait difficulty,” said Drs. Saver and Cushman. The changes, however, “may portend more substantial abnormalities later in life,” they said. “Even during the late-life period, when septuagenarians become octogenarians, cardiovascular health is associated with substantial differences in cognitive trajectory and dementia onset.”

—Jake Remaly

Suggested Reading

Samieri C, Perier MC, Gaye B, et al. Association of cardiovascular health level in older age with cognitive decline and incident dementia. JAMA. 2018;320(7):657-664.

Saver JL, Cushman M. Striving for ideal cardiovascular and brain health: It is never too early or too late. JAMA. 2018; 320(7):645-647.

Williamson W, Lewandowski AJ, Forkert ND, et al. Association of cardiovascular risk factors with MRI indices of cerebrovascular structure and function and white matter hyperintensities in young adults. JAMA. 2018;320(7):665-673.

Optimal measures of cardiovascular health are associated with brain health in adults, according to two studies published in the August 21 issue of JAMA.

In a French population-based cohort study, adults ages 65 and older with more cardiovascular health measures at ideal levels had a lower risk of dementia and lower rates of cognitive decline than did those with fewer optimal cardiovascular measures, such as blood pressure and physical activity.

In addition, a preliminary, cross-sectional study of younger adults found that the number of modifiable cardiovascular risk factors at recommended levels was associated with brain vessel structure and function and the number of white matter hyperintensities.

Cardiovascular Health in Older Age

Vascular dementia is the second most common neuropathologic basis of dementia, after Alzheimer’s disease, and “most cases of dementia arise from a combination of [Alzheimer’s disease] and cerebrovascular pathology,” the editorialists noted. Studies have suggested a connection between cardiovascular health and dementia, but the evidence is limited.

Cécilia Samieri, PhD, a Senior Researcher at the Bordeaux Population Health Research Center at the Université de Bordeaux in France, and colleagues studied people age 65 and older from Bordeaux, Dijon, and Montpellier, France, to examine the association between cardiovascular health level and risk of dementia and cognitive decline in older adults.

Cerebrovascular Structure and Function in Young Adults

Wilby Williamson, BMBS, Sports and Exercise Medicine Physician and Clinical Research Fellow in Cardiovascular Medicine at the University of Oxford, United Kingdom, and colleagues conducted a cross-sectional, observational study to examine relationships between modifiable cardiovascular risk factors and cerebrovascular structure, function, and white matter integrity in young adults. The study included 125 adults ages 18 to 40 without clinical evidence of cerebrovascular disease. Participants had a mean age of 25, and 49% were women.

The researchers assessed patients’ cerebral vessel density, caliber, and tortuosity and brain white matter hyperintensity lesion count. In a subgroup of 52 participants, they assessed cerebral blood flow.

The researchers determined for each participant how many of eight modifiable risk factors were at recommended levels (ie, BMI < 25, highest tertile of cardiovascular fitness or physical activity, alcohol consumption < eight drinks per week, nonsmoker for more than six months, blood pressure on awake ambulatory monitoring < 130/80 mm Hg, a nonhypertensive diastolic response to exercise [ie, peak diastolic blood pressure < 90 mm Hg], total cholesterol < 200 mg/dL, and fasting glucose < 100 mg/dL).

On average, participants had six of the eight modifiable cardiovascular risk factors at recommended levels.

In multivariable models, cardiovascular risk factors were associated with cerebrovascular structure and the number of white matter hyperintensities. “For each additional modifiable risk factor categorized as healthy, vessel density was greater by 0.3 vessels/cm³, vessel caliber was greater by 8 μm, and white matter hyperintensity lesions were fewer by 1.6 lesions. Among the 52 participants with available data, cerebral blood flow varied with vessel density and was 2.5 mL/100 g/min higher for each healthier category of a modifiable risk factor,” Dr. Williamson and colleagues said.

The findings suggest that “some individuals may be starting to diverge to different risk trajectories for brain vascular health in early adulthood,” the researchers said. The study was exploratory, however, and follow-up studies are needed to determine the clinical significance of these findings, they said.

“The magnitude of changes was generally much less than would be expected to produce clinical symptoms such as cognitive impairment or gait difficulty,” said Drs. Saver and Cushman. The changes, however, “may portend more substantial abnormalities later in life,” they said. “Even during the late-life period, when septuagenarians become octogenarians, cardiovascular health is associated with substantial differences in cognitive trajectory and dementia onset.”

—Jake Remaly

Suggested Reading

Samieri C, Perier MC, Gaye B, et al. Association of cardiovascular health level in older age with cognitive decline and incident dementia. JAMA. 2018;320(7):657-664.

Saver JL, Cushman M. Striving for ideal cardiovascular and brain health: It is never too early or too late. JAMA. 2018; 320(7):645-647.

Williamson W, Lewandowski AJ, Forkert ND, et al. Association of cardiovascular risk factors with MRI indices of cerebrovascular structure and function and white matter hyperintensities in young adults. JAMA. 2018;320(7):665-673.