A new subtype of multiple sclerosis (MS) called myelocortical MS is characterized by demyelination only in the spinal cord and cerebral cortex and not in the cerebral white matter, according to a study published online ahead of print August 21 in Lancet Neurology. The findings are based on an examination of the brains and spinal cords of 100 patients who died of MS.

Bruce D. Trapp, PhD, the Morris R. and Ruth V. Graham Endowed Chair in Biomedical Research at the Lerner Research Institute at the Cleveland Clinic in Ohio, and his coauthors said that while the demyelination of cerebral white matter is a pathologic hallmark of MS, previous research has found that only around half of cerebral T2-weighted hyperintense white matter lesions are demyelinated, and these lesions account for less than a third of variance in the rate of brain atrophy.

“In the absence of specific MRI metrics for demyelination, the relationship between cerebral white-matter demyelination and neurodegeneration remains speculative,” they said.

Not Typical MS

They found that while individuals with myelocortical MS did not have demyelinated lesions in the cerebral white matter, they had areas of demyelinated lesions in the cerebral cortex similar to those of individuals with typical MS (median 4.45% vs 9.74%, respectively). However, the individuals with myelocortical MS had a significantly smaller area of spinal cord demyelination (median 3.81% vs 13.81%).

Individuals with myelocortical MS also had significantly lower mean cortical neuronal densities, compared with healthy control brains, in layer III, layer V, and layer VI. But individuals with typical MS only had a lower cortical neuronal density in layer V when compared with controls.

Dr. Trapp and colleagues also saw that in typical MS, neuronal density decreased as the area of brain white-matter demyelination increased. However, this negative linear correlation was not seen in myelocortical MS.

On MRI, researchers were still able to see abnormalities in the cerebral white matter in individuals with myelocortical MS, in T2-weighted, T1-weighted, and magnetization transfer ratios (MTR) images. They also found similar total T2-weighted and T1-weighted lesion volumes in individuals with myelocortical MS and those with typical MS, although individuals with typical MS had significantly greater MTR lesion volumes.

The Hallmarks of Myelocortical MS

“We propose that myelocortical MS is characterized by spinal cord demyelination, subpial cortical demyelination, and an absence of cerebral white-matter demyelination,” Dr. Trapp and colleagues wrote. “Our findings indicate that abnormal cerebral white-matter T2-T1-MTR regions of interest are not always demyelinated, and this pathologic evidence suggests that cerebral white-matter demyelination and cortical neuronal degeneration can be independent events in myelocortical MS.”

The authors acknowledged that one limitation of their study may have been selection bias, as all the patients in the study died from complications of advanced MS. They suggested that it was therefore not appropriate to conclude that the prevalence of myelocortical MS seen in their sample would be similar across the entire MS population, nor were the findings likely to apply to pateints with earlier stage disease.

The study received funding from the NIH and the National MS Society. One author is an employee of Renovo Neural, and three authors are employees of Biogen. One author declared a pending patent related to automated lesion segmentation from MRI images, and four authors declared funding, fees, and nonfinancial support from pharmaceutical companies.

—Bianca Nogrady

Suggested Reading

Trapp BD, Vignos M, Dudman J, et al. Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study. Lancet Neurol. 2018 Aug 21 [Epub ahead of print].

A new subtype of multiple sclerosis (MS) called myelocortical MS is characterized by demyelination only in the spinal cord and cerebral cortex and not in the cerebral white matter, according to a study published online ahead of print August 21 in Lancet Neurology. The findings are based on an examination of the brains and spinal cords of 100 patients who died of MS.

Bruce D. Trapp, PhD, the Morris R. and Ruth V. Graham Endowed Chair in Biomedical Research at the Lerner Research Institute at the Cleveland Clinic in Ohio, and his coauthors said that while the demyelination of cerebral white matter is a pathologic hallmark of MS, previous research has found that only around half of cerebral T2-weighted hyperintense white matter lesions are demyelinated, and these lesions account for less than a third of variance in the rate of brain atrophy.

“In the absence of specific MRI metrics for demyelination, the relationship between cerebral white-matter demyelination and neurodegeneration remains speculative,” they said.

Not Typical MS

They found that while individuals with myelocortical MS did not have demyelinated lesions in the cerebral white matter, they had areas of demyelinated lesions in the cerebral cortex similar to those of individuals with typical MS (median 4.45% vs 9.74%, respectively). However, the individuals with myelocortical MS had a significantly smaller area of spinal cord demyelination (median 3.81% vs 13.81%).

Individuals with myelocortical MS also had significantly lower mean cortical neuronal densities, compared with healthy control brains, in layer III, layer V, and layer VI. But individuals with typical MS only had a lower cortical neuronal density in layer V when compared with controls.

Dr. Trapp and colleagues also saw that in typical MS, neuronal density decreased as the area of brain white-matter demyelination increased. However, this negative linear correlation was not seen in myelocortical MS.

On MRI, researchers were still able to see abnormalities in the cerebral white matter in individuals with myelocortical MS, in T2-weighted, T1-weighted, and magnetization transfer ratios (MTR) images. They also found similar total T2-weighted and T1-weighted lesion volumes in individuals with myelocortical MS and those with typical MS, although individuals with typical MS had significantly greater MTR lesion volumes.

The Hallmarks of Myelocortical MS

“We propose that myelocortical MS is characterized by spinal cord demyelination, subpial cortical demyelination, and an absence of cerebral white-matter demyelination,” Dr. Trapp and colleagues wrote. “Our findings indicate that abnormal cerebral white-matter T2-T1-MTR regions of interest are not always demyelinated, and this pathologic evidence suggests that cerebral white-matter demyelination and cortical neuronal degeneration can be independent events in myelocortical MS.”

The authors acknowledged that one limitation of their study may have been selection bias, as all the patients in the study died from complications of advanced MS. They suggested that it was therefore not appropriate to conclude that the prevalence of myelocortical MS seen in their sample would be similar across the entire MS population, nor were the findings likely to apply to pateints with earlier stage disease.

The study received funding from the NIH and the National MS Society. One author is an employee of Renovo Neural, and three authors are employees of Biogen. One author declared a pending patent related to automated lesion segmentation from MRI images, and four authors declared funding, fees, and nonfinancial support from pharmaceutical companies.

—Bianca Nogrady

Suggested Reading

Trapp BD, Vignos M, Dudman J, et al. Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study. Lancet Neurol. 2018 Aug 21 [Epub ahead of print].

A new subtype of multiple sclerosis (MS) called myelocortical MS is characterized by demyelination only in the spinal cord and cerebral cortex and not in the cerebral white matter, according to a study published online ahead of print August 21 in Lancet Neurology. The findings are based on an examination of the brains and spinal cords of 100 patients who died of MS.

Bruce D. Trapp, PhD, the Morris R. and Ruth V. Graham Endowed Chair in Biomedical Research at the Lerner Research Institute at the Cleveland Clinic in Ohio, and his coauthors said that while the demyelination of cerebral white matter is a pathologic hallmark of MS, previous research has found that only around half of cerebral T2-weighted hyperintense white matter lesions are demyelinated, and these lesions account for less than a third of variance in the rate of brain atrophy.

“In the absence of specific MRI metrics for demyelination, the relationship between cerebral white-matter demyelination and neurodegeneration remains speculative,” they said.

Not Typical MS

They found that while individuals with myelocortical MS did not have demyelinated lesions in the cerebral white matter, they had areas of demyelinated lesions in the cerebral cortex similar to those of individuals with typical MS (median 4.45% vs 9.74%, respectively). However, the individuals with myelocortical MS had a significantly smaller area of spinal cord demyelination (median 3.81% vs 13.81%).

Individuals with myelocortical MS also had significantly lower mean cortical neuronal densities, compared with healthy control brains, in layer III, layer V, and layer VI. But individuals with typical MS only had a lower cortical neuronal density in layer V when compared with controls.

Dr. Trapp and colleagues also saw that in typical MS, neuronal density decreased as the area of brain white-matter demyelination increased. However, this negative linear correlation was not seen in myelocortical MS.

On MRI, researchers were still able to see abnormalities in the cerebral white matter in individuals with myelocortical MS, in T2-weighted, T1-weighted, and magnetization transfer ratios (MTR) images. They also found similar total T2-weighted and T1-weighted lesion volumes in individuals with myelocortical MS and those with typical MS, although individuals with typical MS had significantly greater MTR lesion volumes.

The Hallmarks of Myelocortical MS

“We propose that myelocortical MS is characterized by spinal cord demyelination, subpial cortical demyelination, and an absence of cerebral white-matter demyelination,” Dr. Trapp and colleagues wrote. “Our findings indicate that abnormal cerebral white-matter T2-T1-MTR regions of interest are not always demyelinated, and this pathologic evidence suggests that cerebral white-matter demyelination and cortical neuronal degeneration can be independent events in myelocortical MS.”

The authors acknowledged that one limitation of their study may have been selection bias, as all the patients in the study died from complications of advanced MS. They suggested that it was therefore not appropriate to conclude that the prevalence of myelocortical MS seen in their sample would be similar across the entire MS population, nor were the findings likely to apply to pateints with earlier stage disease.

The study received funding from the NIH and the National MS Society. One author is an employee of Renovo Neural, and three authors are employees of Biogen. One author declared a pending patent related to automated lesion segmentation from MRI images, and four authors declared funding, fees, and nonfinancial support from pharmaceutical companies.

—Bianca Nogrady

Suggested Reading

Trapp BD, Vignos M, Dudman J, et al. Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study. Lancet Neurol. 2018 Aug 21 [Epub ahead of print].

The prevalence of adult obesity was at or above 35% for seven states in 2017, which is up from five states in 2016 and no states in 2012, according to the Centers for Disease Control and Prevention.

Iowa and Oklahoma, the two newest states with prevalences at or exceeding 35%, joined Alabama, Arkansas, Louisiana, Mississippi, and West Virginia, which has the country’s highest rate of adult obesity at 38.1%. Colorado’s 22.6% rate is the lowest prevalence among all states. The District of Columbia and Hawaii also have prevalences under 25%; previously, Massachusetts also was in this group, but its prevalence went up to 25.9% last year, the CDC reported.

Regional disparities in self-reported adult obesity put the South (32.4%) and the Midwest (32.3%) well ahead of the Northeast (27.7%) and the West (26.1%) in 2017. Racial and ethnic disparities also were seen, with large gaps between blacks, who had a prevalence of 39%, and Hispanics (32.4%) and whites (29.3%). Obesity prevalence was 35% or higher among black adults in 31 states and D.C., while this was true among Hispanics in eight states and among whites in one (West Virginia), although the prevalence was at or above 35% for multiple racial groups in some of these states, the CDC reported based on data from the Behavioral Risk Factor Surveillance System.

“Obesity costs the United States health care system over $147 billion a year [and] research has shown that obesity affects work productivity and military readiness,” the CDC said in a written statement. “To protect the health of the next generation, support for healthy behaviors such as healthy eating, better sleep, stress management, and physical activity should start early and expand to reach Americans across the lifespan in the communities where they live, learn, work, and play.”

The AGA Obesity Practice Guide provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at http://ow.ly/p1Fh30lOXYD

[email protected]

The prevalence of adult obesity was at or above 35% for seven states in 2017, which is up from five states in 2016 and no states in 2012, according to the Centers for Disease Control and Prevention.

Iowa and Oklahoma, the two newest states with prevalences at or exceeding 35%, joined Alabama, Arkansas, Louisiana, Mississippi, and West Virginia, which has the country’s highest rate of adult obesity at 38.1%. Colorado’s 22.6% rate is the lowest prevalence among all states. The District of Columbia and Hawaii also have prevalences under 25%; previously, Massachusetts also was in this group, but its prevalence went up to 25.9% last year, the CDC reported.

Regional disparities in self-reported adult obesity put the South (32.4%) and the Midwest (32.3%) well ahead of the Northeast (27.7%) and the West (26.1%) in 2017. Racial and ethnic disparities also were seen, with large gaps between blacks, who had a prevalence of 39%, and Hispanics (32.4%) and whites (29.3%). Obesity prevalence was 35% or higher among black adults in 31 states and D.C., while this was true among Hispanics in eight states and among whites in one (West Virginia), although the prevalence was at or above 35% for multiple racial groups in some of these states, the CDC reported based on data from the Behavioral Risk Factor Surveillance System.

“Obesity costs the United States health care system over $147 billion a year [and] research has shown that obesity affects work productivity and military readiness,” the CDC said in a written statement. “To protect the health of the next generation, support for healthy behaviors such as healthy eating, better sleep, stress management, and physical activity should start early and expand to reach Americans across the lifespan in the communities where they live, learn, work, and play.”

The AGA Obesity Practice Guide provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at http://ow.ly/p1Fh30lOXYD

[email protected]

The prevalence of adult obesity was at or above 35% for seven states in 2017, which is up from five states in 2016 and no states in 2012, according to the Centers for Disease Control and Prevention.

Iowa and Oklahoma, the two newest states with prevalences at or exceeding 35%, joined Alabama, Arkansas, Louisiana, Mississippi, and West Virginia, which has the country’s highest rate of adult obesity at 38.1%. Colorado’s 22.6% rate is the lowest prevalence among all states. The District of Columbia and Hawaii also have prevalences under 25%; previously, Massachusetts also was in this group, but its prevalence went up to 25.9% last year, the CDC reported.

Regional disparities in self-reported adult obesity put the South (32.4%) and the Midwest (32.3%) well ahead of the Northeast (27.7%) and the West (26.1%) in 2017. Racial and ethnic disparities also were seen, with large gaps between blacks, who had a prevalence of 39%, and Hispanics (32.4%) and whites (29.3%). Obesity prevalence was 35% or higher among black adults in 31 states and D.C., while this was true among Hispanics in eight states and among whites in one (West Virginia), although the prevalence was at or above 35% for multiple racial groups in some of these states, the CDC reported based on data from the Behavioral Risk Factor Surveillance System.

“Obesity costs the United States health care system over $147 billion a year [and] research has shown that obesity affects work productivity and military readiness,” the CDC said in a written statement. “To protect the health of the next generation, support for healthy behaviors such as healthy eating, better sleep, stress management, and physical activity should start early and expand to reach Americans across the lifespan in the communities where they live, learn, work, and play.”

The AGA Obesity Practice Guide provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at http://ow.ly/p1Fh30lOXYD

[email protected]

For patients who undergo allogeneic hematopoietic stem cell transplant (allo-HSCT) with intensive antibiotics, a subsequent autologous fecal transplant (auto-FMT) can restore intestinal microbiota, a recent study found.

Courtesy Memorial Sloan Kettering Cancer Center

Loss of normal gut bacteria after allo-HSCT and antibiotics is a common occurrence and known risk factor for graft-versus-host disease (GVHD) and intestinal infection.

“Overall, patients who lose gut microbiota diversity at the time of hematopoietic stem cell engraftment have higher rates of transplant-related death,” reported Ying Taur, MD, of the Memorial Sloan Kettering Cancer Center in New York, and his colleagues. “We explored whether the microbiota could be restored in allo-HSCT patients through the use of auto-FMT.”

Allo-HSCT patients are immune suppressed for months after engraftment, so safety concerns led the investigators to use auto-FMT rather than a fecal transplant from another individual. The complex population of viruses, fungi, archaea, bacteria, and protozoa that inhabit the human gut remains poorly understood, as does the infectious potential of a heterologous fecal donor.

“Despite remarkable advances in recent years, current technologies are incapable of comprehensively determining fecal composition,” the authors wrote in Science Translational Medicine.

The study involved 25 patients undergoing allo-HSCT with intensive antibiotic therapy. Prior to engraftment, fecal samples were collected from all patients and analyzed for composition and diversity, measured by inverse Simpson index.

Samples were then frozen and stored. Fecal analysis also was performed after engraftment, and again after the auto-FMT time point. Auto-FMT was performed in 14 patients; 11 patients served as controls and did not receive treatment. Patients were followed for 1 year.

The investigators found that all of the patients who underwent auto-FMT recovered their pre–allo-HSCT microbiota composition and diversity, compared with none of the controls (P less than .0001). Further analysis showed that auto-FMT increased diversity (inverse Simpson index) by 64%, compared with 38% in controls.

“We have demonstrated the potential of auto-FMT as a clinical intervention to restore intestinal microbiota diversity to levels deemed safe in patients, thereby reversing the disruptive effects of broad-spectrum antibiotic treatment for patients undergoing allo-HSCT transplant,” the investigators concluded.

Study funding was provided by the Leonard Tow Foundation and the Memorial Sloan Kettering’s Center for Microbes, Inflammation, and Cancer. The authors reported financial relationships with Merck, AbbVie, Nektar Therapeutics, Novartis, and others.

SOURCE: Taur Y et al. Sci Transl Med. 2018 Sep 26. doi: 10.1126/scitranslmed.aap9489.

For patients who undergo allogeneic hematopoietic stem cell transplant (allo-HSCT) with intensive antibiotics, a subsequent autologous fecal transplant (auto-FMT) can restore intestinal microbiota, a recent study found.

Courtesy Memorial Sloan Kettering Cancer Center

Loss of normal gut bacteria after allo-HSCT and antibiotics is a common occurrence and known risk factor for graft-versus-host disease (GVHD) and intestinal infection.

“Overall, patients who lose gut microbiota diversity at the time of hematopoietic stem cell engraftment have higher rates of transplant-related death,” reported Ying Taur, MD, of the Memorial Sloan Kettering Cancer Center in New York, and his colleagues. “We explored whether the microbiota could be restored in allo-HSCT patients through the use of auto-FMT.”

Allo-HSCT patients are immune suppressed for months after engraftment, so safety concerns led the investigators to use auto-FMT rather than a fecal transplant from another individual. The complex population of viruses, fungi, archaea, bacteria, and protozoa that inhabit the human gut remains poorly understood, as does the infectious potential of a heterologous fecal donor.

“Despite remarkable advances in recent years, current technologies are incapable of comprehensively determining fecal composition,” the authors wrote in Science Translational Medicine.

The study involved 25 patients undergoing allo-HSCT with intensive antibiotic therapy. Prior to engraftment, fecal samples were collected from all patients and analyzed for composition and diversity, measured by inverse Simpson index.

Samples were then frozen and stored. Fecal analysis also was performed after engraftment, and again after the auto-FMT time point. Auto-FMT was performed in 14 patients; 11 patients served as controls and did not receive treatment. Patients were followed for 1 year.

The investigators found that all of the patients who underwent auto-FMT recovered their pre–allo-HSCT microbiota composition and diversity, compared with none of the controls (P less than .0001). Further analysis showed that auto-FMT increased diversity (inverse Simpson index) by 64%, compared with 38% in controls.

“We have demonstrated the potential of auto-FMT as a clinical intervention to restore intestinal microbiota diversity to levels deemed safe in patients, thereby reversing the disruptive effects of broad-spectrum antibiotic treatment for patients undergoing allo-HSCT transplant,” the investigators concluded.

Study funding was provided by the Leonard Tow Foundation and the Memorial Sloan Kettering’s Center for Microbes, Inflammation, and Cancer. The authors reported financial relationships with Merck, AbbVie, Nektar Therapeutics, Novartis, and others.

SOURCE: Taur Y et al. Sci Transl Med. 2018 Sep 26. doi: 10.1126/scitranslmed.aap9489.

For patients who undergo allogeneic hematopoietic stem cell transplant (allo-HSCT) with intensive antibiotics, a subsequent autologous fecal transplant (auto-FMT) can restore intestinal microbiota, a recent study found.

Courtesy Memorial Sloan Kettering Cancer Center

Loss of normal gut bacteria after allo-HSCT and antibiotics is a common occurrence and known risk factor for graft-versus-host disease (GVHD) and intestinal infection.

“Overall, patients who lose gut microbiota diversity at the time of hematopoietic stem cell engraftment have higher rates of transplant-related death,” reported Ying Taur, MD, of the Memorial Sloan Kettering Cancer Center in New York, and his colleagues. “We explored whether the microbiota could be restored in allo-HSCT patients through the use of auto-FMT.”

Allo-HSCT patients are immune suppressed for months after engraftment, so safety concerns led the investigators to use auto-FMT rather than a fecal transplant from another individual. The complex population of viruses, fungi, archaea, bacteria, and protozoa that inhabit the human gut remains poorly understood, as does the infectious potential of a heterologous fecal donor.

“Despite remarkable advances in recent years, current technologies are incapable of comprehensively determining fecal composition,” the authors wrote in Science Translational Medicine.

The study involved 25 patients undergoing allo-HSCT with intensive antibiotic therapy. Prior to engraftment, fecal samples were collected from all patients and analyzed for composition and diversity, measured by inverse Simpson index.

Samples were then frozen and stored. Fecal analysis also was performed after engraftment, and again after the auto-FMT time point. Auto-FMT was performed in 14 patients; 11 patients served as controls and did not receive treatment. Patients were followed for 1 year.

The investigators found that all of the patients who underwent auto-FMT recovered their pre–allo-HSCT microbiota composition and diversity, compared with none of the controls (P less than .0001). Further analysis showed that auto-FMT increased diversity (inverse Simpson index) by 64%, compared with 38% in controls.

“We have demonstrated the potential of auto-FMT as a clinical intervention to restore intestinal microbiota diversity to levels deemed safe in patients, thereby reversing the disruptive effects of broad-spectrum antibiotic treatment for patients undergoing allo-HSCT transplant,” the investigators concluded.

Study funding was provided by the Leonard Tow Foundation and the Memorial Sloan Kettering’s Center for Microbes, Inflammation, and Cancer. The authors reported financial relationships with Merck, AbbVie, Nektar Therapeutics, Novartis, and others.

SOURCE: Taur Y et al. Sci Transl Med. 2018 Sep 26. doi: 10.1126/scitranslmed.aap9489.

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.