Literature Review

In order to determine if there is an association between ictal fear and other auras and with patients’ gender and age, investigators analyzed 536 participants in the Epilepsy Phenome/Genome Project.  Among 36 patients with confirmed ictal fear, the phenomenon was associated with temporal lobe auras, including cephalic, olfactory, and visceral symptoms, as well as déjà vu and derealization. Aphasias were also correlated with ictal fear but researchers found no link between such fear and age or gender.

Chong DJ, Dugan P; The EPGP Investigators. Ictal fear: associations with age, gender, and other experiential phenomena. Epilepsy Behav. 2016;62:153-158. 

In order to determine if there is an association between ictal fear and other auras and with patients’ gender and age, investigators analyzed 536 participants in the Epilepsy Phenome/Genome Project.  Among 36 patients with confirmed ictal fear, the phenomenon was associated with temporal lobe auras, including cephalic, olfactory, and visceral symptoms, as well as déjà vu and derealization. Aphasias were also correlated with ictal fear but researchers found no link between such fear and age or gender.

Chong DJ, Dugan P; The EPGP Investigators. Ictal fear: associations with age, gender, and other experiential phenomena. Epilepsy Behav. 2016;62:153-158. 

In order to determine if there is an association between ictal fear and other auras and with patients’ gender and age, investigators analyzed 536 participants in the Epilepsy Phenome/Genome Project.  Among 36 patients with confirmed ictal fear, the phenomenon was associated with temporal lobe auras, including cephalic, olfactory, and visceral symptoms, as well as déjà vu and derealization. Aphasias were also correlated with ictal fear but researchers found no link between such fear and age or gender.

Chong DJ, Dugan P; The EPGP Investigators. Ictal fear: associations with age, gender, and other experiential phenomena. Epilepsy Behav. 2016;62:153-158. 

Background: Older hospitalized patients experience decreased mobility while in the hospital and suffer from impaired function and mobility after they are discharged. The efficacy and safety of inpatient mobility programs are unknown.

Study design: Randomized, single-blinded controlled trial.

Setting: Birmingham Veterans Affairs Medical Center, Alabama.

Synopsis: The study included 100 patients age 65 years and older admitted to general medical wards. Researchers excluded cognitively impaired patients and patients with limited life expectancy. Intervention patients received a standardized hospital mobility protocol, with up to twice daily 15- to 20-minute visits by research personnel. Visits sought to progressively increase mobility from assisted sitting to ambulation. Physical activity was coupled with a behavioral intervention focused on goal setting and mobility barrier resolution. The comparison group received usual care. Outcomes included changes in activities of daily living (ADLs) and community mobility one month after hospital discharge.

One month after hospitalization, there were no differences in ADLs between intervention and control patients. Patients in the mobility protocol arm, however, maintained their prehospital community mobility, whereas usual-care patients had a statistically significant decrease in mobility as measured by the Life-Space Assessment. There was no difference in falls between groups.

Bottom line: A hospital mobility intervention was a safe and effective means of preserving community mobility. Future effectiveness studies are needed to demonstrate feasibility and outcomes in real-world settings.

Citation: Brown CJ, Foley KT, Lowman JD Jr, et al. Comparison of posthospitalization function and community mobility in hospital mobility program and usual care patients: a randomized clinical trial. JAMA Intern Med. 2016;176(7):921-927.

Short Take

Topical NSAIDs Effective for Back Pain

Using ketoprofen gel in addition to intravenous dexketoprofen improves pain relief in patients presenting to the emergency department with low back pain.

Citation: Serinken M, Eken C, Tunay K, Golcuk Y. Ketoprofen gel improves low back pain in addition to IV dexkeoprofen: a randomized placebo-controlled trial. Am J Emerg Med. 2016;34(8):1458-1461.

Background: Older hospitalized patients experience decreased mobility while in the hospital and suffer from impaired function and mobility after they are discharged. The efficacy and safety of inpatient mobility programs are unknown.

Study design: Randomized, single-blinded controlled trial.

Setting: Birmingham Veterans Affairs Medical Center, Alabama.

Synopsis: The study included 100 patients age 65 years and older admitted to general medical wards. Researchers excluded cognitively impaired patients and patients with limited life expectancy. Intervention patients received a standardized hospital mobility protocol, with up to twice daily 15- to 20-minute visits by research personnel. Visits sought to progressively increase mobility from assisted sitting to ambulation. Physical activity was coupled with a behavioral intervention focused on goal setting and mobility barrier resolution. The comparison group received usual care. Outcomes included changes in activities of daily living (ADLs) and community mobility one month after hospital discharge.

One month after hospitalization, there were no differences in ADLs between intervention and control patients. Patients in the mobility protocol arm, however, maintained their prehospital community mobility, whereas usual-care patients had a statistically significant decrease in mobility as measured by the Life-Space Assessment. There was no difference in falls between groups.

Bottom line: A hospital mobility intervention was a safe and effective means of preserving community mobility. Future effectiveness studies are needed to demonstrate feasibility and outcomes in real-world settings.

Citation: Brown CJ, Foley KT, Lowman JD Jr, et al. Comparison of posthospitalization function and community mobility in hospital mobility program and usual care patients: a randomized clinical trial. JAMA Intern Med. 2016;176(7):921-927.

Short Take

Topical NSAIDs Effective for Back Pain

Using ketoprofen gel in addition to intravenous dexketoprofen improves pain relief in patients presenting to the emergency department with low back pain.

Citation: Serinken M, Eken C, Tunay K, Golcuk Y. Ketoprofen gel improves low back pain in addition to IV dexkeoprofen: a randomized placebo-controlled trial. Am J Emerg Med. 2016;34(8):1458-1461.

Background: Older hospitalized patients experience decreased mobility while in the hospital and suffer from impaired function and mobility after they are discharged. The efficacy and safety of inpatient mobility programs are unknown.

Study design: Randomized, single-blinded controlled trial.

Setting: Birmingham Veterans Affairs Medical Center, Alabama.

Synopsis: The study included 100 patients age 65 years and older admitted to general medical wards. Researchers excluded cognitively impaired patients and patients with limited life expectancy. Intervention patients received a standardized hospital mobility protocol, with up to twice daily 15- to 20-minute visits by research personnel. Visits sought to progressively increase mobility from assisted sitting to ambulation. Physical activity was coupled with a behavioral intervention focused on goal setting and mobility barrier resolution. The comparison group received usual care. Outcomes included changes in activities of daily living (ADLs) and community mobility one month after hospital discharge.

One month after hospitalization, there were no differences in ADLs between intervention and control patients. Patients in the mobility protocol arm, however, maintained their prehospital community mobility, whereas usual-care patients had a statistically significant decrease in mobility as measured by the Life-Space Assessment. There was no difference in falls between groups.

Bottom line: A hospital mobility intervention was a safe and effective means of preserving community mobility. Future effectiveness studies are needed to demonstrate feasibility and outcomes in real-world settings.

Citation: Brown CJ, Foley KT, Lowman JD Jr, et al. Comparison of posthospitalization function and community mobility in hospital mobility program and usual care patients: a randomized clinical trial. JAMA Intern Med. 2016;176(7):921-927.

Short Take

Topical NSAIDs Effective for Back Pain

Using ketoprofen gel in addition to intravenous dexketoprofen improves pain relief in patients presenting to the emergency department with low back pain.

Citation: Serinken M, Eken C, Tunay K, Golcuk Y. Ketoprofen gel improves low back pain in addition to IV dexkeoprofen: a randomized placebo-controlled trial. Am J Emerg Med. 2016;34(8):1458-1461.

Background: Checklists, goal assessment, and clinician prompting have shown promise in improving communication, care-process adherence, and clinical outcomes in ICUs and acute-care settings, but existing studies are limited by nonrandomized design and high-income settings.

Study design: Cluster randomized trial.

Setting: 118 academic and nonacademic ICUs in Brazil.

Synopsis: Researchers randomized 6,761 patients to a quality improvement (QI) intervention with daily round checklists, goal setting, and clinician prompting. Analyses were adjusted for patient’s severity of illness and the ICU’s adjusted mortality ratio. There was no significant difference in in-hospital mortality (odds ratio, 1.02; 95% CI, 0.82–1.26). The QI intervention had no effect on 10 secondary clinical outcomes (e.g., ventilator-associated pneumonia). The intervention improved adherence with four of seven care processes (e.g., use of low tidal volumes) and two of six factors of the safety climate. After adjusting for multiple comparisons, only urinary catheter use remained statistically significant.

Strengths of this study are the large number of ICUs involved and a high rate of QI adherence. Limitations include the setting in a resource-constrained nation, limited success with adopting changes in care processes, and relatively short intervention period of six months.

Bottom line: In a large Brazilian randomized control trial, implementation of daily round checklists, along with goal setting and clinician prompting, did not change in-hospital mortality. It is possible that a longer intervention period would have found improved outcomes.

Citation: Writing Group for the CHECKLIST-ICU Investigators and the Brazilian Research in Intensive Care Network (BRICNet), Cavalcanti AB, Bozza FA, et al. Effect of a quality improvement intervention with daily round checklists, goal setting, and clinician prompting on mortality of critically ill patients: a randomized clinical trial. JAMA. 2016;315(14):1480-1490.

Short Take

More Restrictions on Fluoroquinolones

The U.S. Food and Drug Administration has recommended avoidance of fluoroquinolone drugs, which are often used for patients with acute bronchitis, acute sinusitis, and uncomplicated UTI, due to the potential of serious side effects. Exceptions should be made for cases with no other treatment options.

Citation: Fluoroquinolone antibacterial drugs: drug safety communication - FDA advises restricting use for certain uncomplicated infections. U.S. Food and Drug Administration website.

Background: Checklists, goal assessment, and clinician prompting have shown promise in improving communication, care-process adherence, and clinical outcomes in ICUs and acute-care settings, but existing studies are limited by nonrandomized design and high-income settings.

Study design: Cluster randomized trial.

Setting: 118 academic and nonacademic ICUs in Brazil.

Synopsis: Researchers randomized 6,761 patients to a quality improvement (QI) intervention with daily round checklists, goal setting, and clinician prompting. Analyses were adjusted for patient’s severity of illness and the ICU’s adjusted mortality ratio. There was no significant difference in in-hospital mortality (odds ratio, 1.02; 95% CI, 0.82–1.26). The QI intervention had no effect on 10 secondary clinical outcomes (e.g., ventilator-associated pneumonia). The intervention improved adherence with four of seven care processes (e.g., use of low tidal volumes) and two of six factors of the safety climate. After adjusting for multiple comparisons, only urinary catheter use remained statistically significant.

Strengths of this study are the large number of ICUs involved and a high rate of QI adherence. Limitations include the setting in a resource-constrained nation, limited success with adopting changes in care processes, and relatively short intervention period of six months.

Bottom line: In a large Brazilian randomized control trial, implementation of daily round checklists, along with goal setting and clinician prompting, did not change in-hospital mortality. It is possible that a longer intervention period would have found improved outcomes.

Citation: Writing Group for the CHECKLIST-ICU Investigators and the Brazilian Research in Intensive Care Network (BRICNet), Cavalcanti AB, Bozza FA, et al. Effect of a quality improvement intervention with daily round checklists, goal setting, and clinician prompting on mortality of critically ill patients: a randomized clinical trial. JAMA. 2016;315(14):1480-1490.

Short Take

More Restrictions on Fluoroquinolones

The U.S. Food and Drug Administration has recommended avoidance of fluoroquinolone drugs, which are often used for patients with acute bronchitis, acute sinusitis, and uncomplicated UTI, due to the potential of serious side effects. Exceptions should be made for cases with no other treatment options.

Citation: Fluoroquinolone antibacterial drugs: drug safety communication - FDA advises restricting use for certain uncomplicated infections. U.S. Food and Drug Administration website.

Background: Checklists, goal assessment, and clinician prompting have shown promise in improving communication, care-process adherence, and clinical outcomes in ICUs and acute-care settings, but existing studies are limited by nonrandomized design and high-income settings.

Study design: Cluster randomized trial.

Setting: 118 academic and nonacademic ICUs in Brazil.

Synopsis: Researchers randomized 6,761 patients to a quality improvement (QI) intervention with daily round checklists, goal setting, and clinician prompting. Analyses were adjusted for patient’s severity of illness and the ICU’s adjusted mortality ratio. There was no significant difference in in-hospital mortality (odds ratio, 1.02; 95% CI, 0.82–1.26). The QI intervention had no effect on 10 secondary clinical outcomes (e.g., ventilator-associated pneumonia). The intervention improved adherence with four of seven care processes (e.g., use of low tidal volumes) and two of six factors of the safety climate. After adjusting for multiple comparisons, only urinary catheter use remained statistically significant.

Strengths of this study are the large number of ICUs involved and a high rate of QI adherence. Limitations include the setting in a resource-constrained nation, limited success with adopting changes in care processes, and relatively short intervention period of six months.

Bottom line: In a large Brazilian randomized control trial, implementation of daily round checklists, along with goal setting and clinician prompting, did not change in-hospital mortality. It is possible that a longer intervention period would have found improved outcomes.

Citation: Writing Group for the CHECKLIST-ICU Investigators and the Brazilian Research in Intensive Care Network (BRICNet), Cavalcanti AB, Bozza FA, et al. Effect of a quality improvement intervention with daily round checklists, goal setting, and clinician prompting on mortality of critically ill patients: a randomized clinical trial. JAMA. 2016;315(14):1480-1490.

Short Take

More Restrictions on Fluoroquinolones

The U.S. Food and Drug Administration has recommended avoidance of fluoroquinolone drugs, which are often used for patients with acute bronchitis, acute sinusitis, and uncomplicated UTI, due to the potential of serious side effects. Exceptions should be made for cases with no other treatment options.

Citation: Fluoroquinolone antibacterial drugs: drug safety communication - FDA advises restricting use for certain uncomplicated infections. U.S. Food and Drug Administration website.

Neuroscientists cautioned patients about the dangers of self-administered transcranial direct current stimulation (tDCS) in an open letter published July 7 in Annals of Neurology. “We perceive an ethical obligation to draw the attention of both professionals and ‘do it yourself’ (DIY) users to some of these issues,” said Michael D. Fox, MD, PhD, Assistant Professor of Neurology at Harvard Medical School in Boston. The open letter, written by four neuroscientists and signed by 39 colleagues, addresses several less commonly recognized complications of self-administered brain stimulation.

Noninvasive electrical brain stimulation may help ameliorate symptoms of anxiety and depression; however, neuroscientists say that much about this technique remains unknown and could present potential risks for DIY users. “We have never formally studied tDCS at the frequencies many DIY users experiment with—for example, stimulating daily for months or longer. Because we know that stimulation from just a few sessions can be quite lasting, we infer that changes induced by these protocols may be even more so,” said Dr. Fox.

A further consideration is that tDCS affects more of the brain than people may think. Although electrodes are normally placed in specific scalp locations to target specific parts of the brain, stimulation extends beyond the regions beneath the electrodes and can result in unintended altering of brain functions.

Self-administered brain stimulation may have a different impact on neurons that are active during stimulation versus neurons that are inactive during stimulation, according to the neurologists. “Because of this feature, the cognitive or behavioral activity occurring while tDCS is applied will modify the effects,” said Dr. Fox. Stimulation may affect the brain differently depending on whether it is applied while the subject is watching TV, sleeping, or performing other daily tasks, he added.

In addition, while some cognitive abilities may be enhanced with tDCS, other abilities may be impacted negatively. “Such cognitive tradeoffs could develop over time and only become recognizable long after the stimulation,” said Dr. Fox. Also, small changes in tDCS settings such as current amplitude and electrode activity could result in negative effects on brain function, said the neurologists.

The authors emphasized that the response to tDCS is unpredictable; subjects respond differently to changes in cortical excitability. For example, age, gender, hormones, cognitive ability, and head anatomy can modify the effects of tDCS in the brain. “Up to 30% of experimental subjects respond with changes in cortical excitability in the opposite direction from other subjects using identical tDCS settings,” said Dr. Fox.

“We encourage consideration of these issues and involvement of health care providers in making decisions regarding DIY brain stimulation,” said Dr. Fox. He and his coauthors recommended that parents weigh the risks before using this device for children, especially since minors are not able to fully assess the potential dangers of tDCS.

—Erica Robinson

Neuroscientists cautioned patients about the dangers of self-administered transcranial direct current stimulation (tDCS) in an open letter published July 7 in Annals of Neurology. “We perceive an ethical obligation to draw the attention of both professionals and ‘do it yourself’ (DIY) users to some of these issues,” said Michael D. Fox, MD, PhD, Assistant Professor of Neurology at Harvard Medical School in Boston. The open letter, written by four neuroscientists and signed by 39 colleagues, addresses several less commonly recognized complications of self-administered brain stimulation.

Noninvasive electrical brain stimulation may help ameliorate symptoms of anxiety and depression; however, neuroscientists say that much about this technique remains unknown and could present potential risks for DIY users. “We have never formally studied tDCS at the frequencies many DIY users experiment with—for example, stimulating daily for months or longer. Because we know that stimulation from just a few sessions can be quite lasting, we infer that changes induced by these protocols may be even more so,” said Dr. Fox.

A further consideration is that tDCS affects more of the brain than people may think. Although electrodes are normally placed in specific scalp locations to target specific parts of the brain, stimulation extends beyond the regions beneath the electrodes and can result in unintended altering of brain functions.

Self-administered brain stimulation may have a different impact on neurons that are active during stimulation versus neurons that are inactive during stimulation, according to the neurologists. “Because of this feature, the cognitive or behavioral activity occurring while tDCS is applied will modify the effects,” said Dr. Fox. Stimulation may affect the brain differently depending on whether it is applied while the subject is watching TV, sleeping, or performing other daily tasks, he added.

In addition, while some cognitive abilities may be enhanced with tDCS, other abilities may be impacted negatively. “Such cognitive tradeoffs could develop over time and only become recognizable long after the stimulation,” said Dr. Fox. Also, small changes in tDCS settings such as current amplitude and electrode activity could result in negative effects on brain function, said the neurologists.

The authors emphasized that the response to tDCS is unpredictable; subjects respond differently to changes in cortical excitability. For example, age, gender, hormones, cognitive ability, and head anatomy can modify the effects of tDCS in the brain. “Up to 30% of experimental subjects respond with changes in cortical excitability in the opposite direction from other subjects using identical tDCS settings,” said Dr. Fox.

“We encourage consideration of these issues and involvement of health care providers in making decisions regarding DIY brain stimulation,” said Dr. Fox. He and his coauthors recommended that parents weigh the risks before using this device for children, especially since minors are not able to fully assess the potential dangers of tDCS.

—Erica Robinson

Neuroscientists cautioned patients about the dangers of self-administered transcranial direct current stimulation (tDCS) in an open letter published July 7 in Annals of Neurology. “We perceive an ethical obligation to draw the attention of both professionals and ‘do it yourself’ (DIY) users to some of these issues,” said Michael D. Fox, MD, PhD, Assistant Professor of Neurology at Harvard Medical School in Boston. The open letter, written by four neuroscientists and signed by 39 colleagues, addresses several less commonly recognized complications of self-administered brain stimulation.

Noninvasive electrical brain stimulation may help ameliorate symptoms of anxiety and depression; however, neuroscientists say that much about this technique remains unknown and could present potential risks for DIY users. “We have never formally studied tDCS at the frequencies many DIY users experiment with—for example, stimulating daily for months or longer. Because we know that stimulation from just a few sessions can be quite lasting, we infer that changes induced by these protocols may be even more so,” said Dr. Fox.

A further consideration is that tDCS affects more of the brain than people may think. Although electrodes are normally placed in specific scalp locations to target specific parts of the brain, stimulation extends beyond the regions beneath the electrodes and can result in unintended altering of brain functions.

Self-administered brain stimulation may have a different impact on neurons that are active during stimulation versus neurons that are inactive during stimulation, according to the neurologists. “Because of this feature, the cognitive or behavioral activity occurring while tDCS is applied will modify the effects,” said Dr. Fox. Stimulation may affect the brain differently depending on whether it is applied while the subject is watching TV, sleeping, or performing other daily tasks, he added.

In addition, while some cognitive abilities may be enhanced with tDCS, other abilities may be impacted negatively. “Such cognitive tradeoffs could develop over time and only become recognizable long after the stimulation,” said Dr. Fox. Also, small changes in tDCS settings such as current amplitude and electrode activity could result in negative effects on brain function, said the neurologists.

The authors emphasized that the response to tDCS is unpredictable; subjects respond differently to changes in cortical excitability. For example, age, gender, hormones, cognitive ability, and head anatomy can modify the effects of tDCS in the brain. “Up to 30% of experimental subjects respond with changes in cortical excitability in the opposite direction from other subjects using identical tDCS settings,” said Dr. Fox.

“We encourage consideration of these issues and involvement of health care providers in making decisions regarding DIY brain stimulation,” said Dr. Fox. He and his coauthors recommended that parents weigh the risks before using this device for children, especially since minors are not able to fully assess the potential dangers of tDCS.

—Erica Robinson

Patients with multiple system atrophy (MSA) have decreased levels of plasma coenzyme Q10 (CoQ10), regardless of their COQ2 genotype, according to a study published in the August issue of JAMA Neurology. This finding, researchers said, supports the hypothesis that supplementation with CoQ10 is beneficial for patients with MSA.

It has been reported that functionally impaired variants of COQ2, which encodes an essential enzyme in the biosynthetic pathway of CoQ10, are associated with MSA. However, little is known about blood levels of CoQ10 in patients with or without COQ2 mutations or about the role of CoQ10 in the pathogenesis of MSA.

To explore whether there are associations between levels of CoQ10 in the blood and MSA, Jun Mitsui, MD, PhD, a neurogeneticist at the University of Tokyo, and colleagues compared the levels of plasma CoQ10 in patients with MSA with those in age-, sex-, and COQ2 genotype-matched controls.

The study included 44 Japanese patients with MSA (mean age, 63.7) and, for comparison, 39 Japanese control patients (mean age, 60.3).

The authors reported that the mean plasma level of CoQ10 in patients with MSA was lower than that in controls (0.51 μg/mL vs 0.72 μg/mL). The mean plasma levels of CoQ10 in patients with the cerebellar variant of MSA and those with the parkinsonian variant of MSA were 0.58 μg/mL and 0.49 μg/mL, respectively. After adjusting for age, sex, and COQ2 genotype, the plasma levels of CoQ10 were significantly associated with MSA.

“Prospective cohort studies are warranted to determine the longitudinal effects of plasma levels of CoQ10 on the development of MSA. Furthermore, future clinical trials of supplementation with CoQ10 in patients with MSA are required to confirm our hypothesis,” Dr. Mitsui and colleagues said.

In an accompanying editorial, Sheng-Han Kuo, MD, and Catarina M. Quinzii, MD, both of Columbia University in New York, said, “The recent discoveries of COQ2 mutations in rare patients with MSA and of CoQ10 deficiency in the brain and blood of patients with MSA may lead to mechanism-based and rational therapies for MSA, a rapidly progressive disorder in need of a disease-modifying therapy.”

—Glenn S. Williams

Patients with multiple system atrophy (MSA) have decreased levels of plasma coenzyme Q10 (CoQ10), regardless of their COQ2 genotype, according to a study published in the August issue of JAMA Neurology. This finding, researchers said, supports the hypothesis that supplementation with CoQ10 is beneficial for patients with MSA.

It has been reported that functionally impaired variants of COQ2, which encodes an essential enzyme in the biosynthetic pathway of CoQ10, are associated with MSA. However, little is known about blood levels of CoQ10 in patients with or without COQ2 mutations or about the role of CoQ10 in the pathogenesis of MSA.

To explore whether there are associations between levels of CoQ10 in the blood and MSA, Jun Mitsui, MD, PhD, a neurogeneticist at the University of Tokyo, and colleagues compared the levels of plasma CoQ10 in patients with MSA with those in age-, sex-, and COQ2 genotype-matched controls.

The study included 44 Japanese patients with MSA (mean age, 63.7) and, for comparison, 39 Japanese control patients (mean age, 60.3).

The authors reported that the mean plasma level of CoQ10 in patients with MSA was lower than that in controls (0.51 μg/mL vs 0.72 μg/mL). The mean plasma levels of CoQ10 in patients with the cerebellar variant of MSA and those with the parkinsonian variant of MSA were 0.58 μg/mL and 0.49 μg/mL, respectively. After adjusting for age, sex, and COQ2 genotype, the plasma levels of CoQ10 were significantly associated with MSA.

“Prospective cohort studies are warranted to determine the longitudinal effects of plasma levels of CoQ10 on the development of MSA. Furthermore, future clinical trials of supplementation with CoQ10 in patients with MSA are required to confirm our hypothesis,” Dr. Mitsui and colleagues said.

In an accompanying editorial, Sheng-Han Kuo, MD, and Catarina M. Quinzii, MD, both of Columbia University in New York, said, “The recent discoveries of COQ2 mutations in rare patients with MSA and of CoQ10 deficiency in the brain and blood of patients with MSA may lead to mechanism-based and rational therapies for MSA, a rapidly progressive disorder in need of a disease-modifying therapy.”

—Glenn S. Williams

Patients with multiple system atrophy (MSA) have decreased levels of plasma coenzyme Q10 (CoQ10), regardless of their COQ2 genotype, according to a study published in the August issue of JAMA Neurology. This finding, researchers said, supports the hypothesis that supplementation with CoQ10 is beneficial for patients with MSA.

It has been reported that functionally impaired variants of COQ2, which encodes an essential enzyme in the biosynthetic pathway of CoQ10, are associated with MSA. However, little is known about blood levels of CoQ10 in patients with or without COQ2 mutations or about the role of CoQ10 in the pathogenesis of MSA.

To explore whether there are associations between levels of CoQ10 in the blood and MSA, Jun Mitsui, MD, PhD, a neurogeneticist at the University of Tokyo, and colleagues compared the levels of plasma CoQ10 in patients with MSA with those in age-, sex-, and COQ2 genotype-matched controls.

The study included 44 Japanese patients with MSA (mean age, 63.7) and, for comparison, 39 Japanese control patients (mean age, 60.3).

The authors reported that the mean plasma level of CoQ10 in patients with MSA was lower than that in controls (0.51 μg/mL vs 0.72 μg/mL). The mean plasma levels of CoQ10 in patients with the cerebellar variant of MSA and those with the parkinsonian variant of MSA were 0.58 μg/mL and 0.49 μg/mL, respectively. After adjusting for age, sex, and COQ2 genotype, the plasma levels of CoQ10 were significantly associated with MSA.

“Prospective cohort studies are warranted to determine the longitudinal effects of plasma levels of CoQ10 on the development of MSA. Furthermore, future clinical trials of supplementation with CoQ10 in patients with MSA are required to confirm our hypothesis,” Dr. Mitsui and colleagues said.

In an accompanying editorial, Sheng-Han Kuo, MD, and Catarina M. Quinzii, MD, both of Columbia University in New York, said, “The recent discoveries of COQ2 mutations in rare patients with MSA and of CoQ10 deficiency in the brain and blood of patients with MSA may lead to mechanism-based and rational therapies for MSA, a rapidly progressive disorder in need of a disease-modifying therapy.”

—Glenn S. Williams

When treating an acute hypertensive response in patients with intracerebral hemorrhage, intensive blood pressure treatment does not result in a lower rate of death or disability than standard blood pressure treatment, according to a study published online ahead of print June 22 in the New England Journal of Medicine.

Chronic hypertension is the greatest risk factor for intracerebral hemorrhage, and an acute hypertensive response is common among patients with intracerebral hemorrhage. Studies have suggested that controlling blood pressure early and aggressively in patients with acute intracerebral hemorrhage may reduce hematoma expansion and rates of subsequent death or disability, but optimal blood pressure targets and treatment windows have not been established.

To test whether intensive reduction of blood pressure (ie, targeting a systolic blood pressure of 110 mm Hg to 139 mm Hg) is superior to standard blood pressure reduction (ie, a target of 140 mm Hg to 179 mm Hg), Adnan I. Qureshi, MD, Professor of Neurology, Neurosurgery, and Radiology at the Zeenat Qureshi Stroke Research Center at the University of Minnesota in Minneapolis, and colleagues conducted the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial. The trial was conducted at 110 sites in the United States, Japan, China, Taiwan, South Korea, and Germany.

The investigators enrolled 1,000 patients with spontaneous supratentorial intracerebral hemorrhage who had a Glasgow Coma Scale score of five or more and at least one systolic blood pressure reading of 180 mm Hg or more between symptom onset and initiation of IV antihypertensive treatment.

Five hundred patients were assigned to intensive treatment, and 500 patients were assigned to standard treatment. Patients had a mean age of 61.9, 38% were women, and 56.2% were Asian. Patients had an average systolic blood pressure of 200.6 mm Hg at baseline.

Investigators administered IV nicardipine to lower blood pressure within four and a half hours following symptom onset, and researchers continued this treatment for the next 24 hours.

Investigators followed up with patients by telephone after a month and in person after three months. Death or disability (ie, modified Rankin scale score of 4 to 6) was the primary outcome.

The trial was designed to enroll 1,280 participants, but researchers stopped the trial early for futility after a prespecified interim analysis found that patients who received intensive treatment did not have a lower rate of death or disability than those who received standard treatment. The rate of death or disability was 38.7% in the intensive treatment group and 37.7% in the standard treatment group. "Our results do not support the notion that acute reduction to a target systolic blood pressure of 110 to 139 mm Hg in patients with intracerebral hemorrhage is more effective in improving functional outcome than a reduction to a target systolic blood pressure of 140 to 179 mm Hg," the researchers said.

Serious adverse events within 72 hours of randomization that were considered to be related to treatment were reported in 1.6% of patients in the intensive treatment group, compared with 1.2% of patients in the standard treatment group. The rate of renal adverse events within seven days was significantly higher in the intensive treatment group than in the standard treatment group (9% vs 4%).

The overall death and severe disability rate in this study was lower than that in previous stroke studies (38% vs 60%). This difference may be due to the inclusion of patients with relatively minor strokes in the current study. In addition, "we may have seen a global benefit of careful monitoring and standardized care for patients with acute cerebral hemorrhage," said Dr. Qureshi.

—Erica Robinson

When treating an acute hypertensive response in patients with intracerebral hemorrhage, intensive blood pressure treatment does not result in a lower rate of death or disability than standard blood pressure treatment, according to a study published online ahead of print June 22 in the New England Journal of Medicine.

Chronic hypertension is the greatest risk factor for intracerebral hemorrhage, and an acute hypertensive response is common among patients with intracerebral hemorrhage. Studies have suggested that controlling blood pressure early and aggressively in patients with acute intracerebral hemorrhage may reduce hematoma expansion and rates of subsequent death or disability, but optimal blood pressure targets and treatment windows have not been established.

To test whether intensive reduction of blood pressure (ie, targeting a systolic blood pressure of 110 mm Hg to 139 mm Hg) is superior to standard blood pressure reduction (ie, a target of 140 mm Hg to 179 mm Hg), Adnan I. Qureshi, MD, Professor of Neurology, Neurosurgery, and Radiology at the Zeenat Qureshi Stroke Research Center at the University of Minnesota in Minneapolis, and colleagues conducted the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial. The trial was conducted at 110 sites in the United States, Japan, China, Taiwan, South Korea, and Germany.

The investigators enrolled 1,000 patients with spontaneous supratentorial intracerebral hemorrhage who had a Glasgow Coma Scale score of five or more and at least one systolic blood pressure reading of 180 mm Hg or more between symptom onset and initiation of IV antihypertensive treatment.

Five hundred patients were assigned to intensive treatment, and 500 patients were assigned to standard treatment. Patients had a mean age of 61.9, 38% were women, and 56.2% were Asian. Patients had an average systolic blood pressure of 200.6 mm Hg at baseline.

Investigators administered IV nicardipine to lower blood pressure within four and a half hours following symptom onset, and researchers continued this treatment for the next 24 hours.

Investigators followed up with patients by telephone after a month and in person after three months. Death or disability (ie, modified Rankin scale score of 4 to 6) was the primary outcome.

The trial was designed to enroll 1,280 participants, but researchers stopped the trial early for futility after a prespecified interim analysis found that patients who received intensive treatment did not have a lower rate of death or disability than those who received standard treatment. The rate of death or disability was 38.7% in the intensive treatment group and 37.7% in the standard treatment group. "Our results do not support the notion that acute reduction to a target systolic blood pressure of 110 to 139 mm Hg in patients with intracerebral hemorrhage is more effective in improving functional outcome than a reduction to a target systolic blood pressure of 140 to 179 mm Hg," the researchers said.

Serious adverse events within 72 hours of randomization that were considered to be related to treatment were reported in 1.6% of patients in the intensive treatment group, compared with 1.2% of patients in the standard treatment group. The rate of renal adverse events within seven days was significantly higher in the intensive treatment group than in the standard treatment group (9% vs 4%).

The overall death and severe disability rate in this study was lower than that in previous stroke studies (38% vs 60%). This difference may be due to the inclusion of patients with relatively minor strokes in the current study. In addition, "we may have seen a global benefit of careful monitoring and standardized care for patients with acute cerebral hemorrhage," said Dr. Qureshi.

—Erica Robinson

When treating an acute hypertensive response in patients with intracerebral hemorrhage, intensive blood pressure treatment does not result in a lower rate of death or disability than standard blood pressure treatment, according to a study published online ahead of print June 22 in the New England Journal of Medicine.

Chronic hypertension is the greatest risk factor for intracerebral hemorrhage, and an acute hypertensive response is common among patients with intracerebral hemorrhage. Studies have suggested that controlling blood pressure early and aggressively in patients with acute intracerebral hemorrhage may reduce hematoma expansion and rates of subsequent death or disability, but optimal blood pressure targets and treatment windows have not been established.

To test whether intensive reduction of blood pressure (ie, targeting a systolic blood pressure of 110 mm Hg to 139 mm Hg) is superior to standard blood pressure reduction (ie, a target of 140 mm Hg to 179 mm Hg), Adnan I. Qureshi, MD, Professor of Neurology, Neurosurgery, and Radiology at the Zeenat Qureshi Stroke Research Center at the University of Minnesota in Minneapolis, and colleagues conducted the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial. The trial was conducted at 110 sites in the United States, Japan, China, Taiwan, South Korea, and Germany.

The investigators enrolled 1,000 patients with spontaneous supratentorial intracerebral hemorrhage who had a Glasgow Coma Scale score of five or more and at least one systolic blood pressure reading of 180 mm Hg or more between symptom onset and initiation of IV antihypertensive treatment.

Five hundred patients were assigned to intensive treatment, and 500 patients were assigned to standard treatment. Patients had a mean age of 61.9, 38% were women, and 56.2% were Asian. Patients had an average systolic blood pressure of 200.6 mm Hg at baseline.

Investigators administered IV nicardipine to lower blood pressure within four and a half hours following symptom onset, and researchers continued this treatment for the next 24 hours.

Investigators followed up with patients by telephone after a month and in person after three months. Death or disability (ie, modified Rankin scale score of 4 to 6) was the primary outcome.

The trial was designed to enroll 1,280 participants, but researchers stopped the trial early for futility after a prespecified interim analysis found that patients who received intensive treatment did not have a lower rate of death or disability than those who received standard treatment. The rate of death or disability was 38.7% in the intensive treatment group and 37.7% in the standard treatment group. "Our results do not support the notion that acute reduction to a target systolic blood pressure of 110 to 139 mm Hg in patients with intracerebral hemorrhage is more effective in improving functional outcome than a reduction to a target systolic blood pressure of 140 to 179 mm Hg," the researchers said.

Serious adverse events within 72 hours of randomization that were considered to be related to treatment were reported in 1.6% of patients in the intensive treatment group, compared with 1.2% of patients in the standard treatment group. The rate of renal adverse events within seven days was significantly higher in the intensive treatment group than in the standard treatment group (9% vs 4%).

The overall death and severe disability rate in this study was lower than that in previous stroke studies (38% vs 60%). This difference may be due to the inclusion of patients with relatively minor strokes in the current study. In addition, "we may have seen a global benefit of careful monitoring and standardized care for patients with acute cerebral hemorrhage," said Dr. Qureshi.

—Erica Robinson

Researchers have found a correlation between multiple sclerosis (MS) and changes in the human gut microbiome, according to data published June 28 in Nature Communications. "There are a number of ways that the microbiome could play a role in MS, and this opens up a whole new world of looking at the disease in a way that it's never been looked at before," said Howard L. Weiner, MD, Director of the Partners MS Center and Codirector of the Ann Romney Center for Neurologic Disease at Brigham and Women's Hospital in Boston.

Previous studies have suggested a connection between bacteria in the gut and MS, as well as inflammatory bowel disease, type 1 diabetes, and rheumatoid arthritis. In one study of 20 patients with MS and 40 healthy controls, researchers found decreased numbers of Faecalibacterium, Prevotella, and Anaerostipes in patients with MS. The connection between microbiota, treatment, and changes in immunity, however, was not investigated. Because the gut microbiome plays a vital role in immune function and autoimmune disease, Dr. Weiner and his colleagues conducted research to detect changes in the intestinal microbiota in patients with MS, compared with controls. "If further studies demonstrate that these candidate microorganisms play an active role in either contributing to or ameliorating MS, then there is potential to develop new diagnostics and therapies to combat the disease," said Dr. Weiner.

The investigators examined data and collected stool samples from 60 untreated and treated patients with relapsing-remitting MS and 43 healthy control subjects. Subjects were part of the Comprehensive Longitudinal Investigation of Multiple Sclerosis study. None of the patients had an active relapse at the time of study enrollment. For the study, microbial DNA was removed from fecal samples, and gene sequencing was performed with two platforms using primers targeting the V3-5 or the V4 variable regions. Investigators also collected breath samples from a second cohort of 41 patients with MS and 32 controls after they participated in an overnight fast.

Patients with MS had microbial changes in the gut that were associated with the activity of genes that play a role in the immune system. Specifically, researchers found that the gut microbiome in patients with MS contained higher levels of Methanobrevibacter and Akkermansia, and lower levels of Butyricimonas, compared with healthy controls. Increased levels of Methanobrevibacter in patients with MS resulted in higher levels of methane in their breath samples, said the researchers. In addition, patients with MS on disease-modifying treatment had increased abundances of Prevotella and Sutterella, and decreased levels of Sarcina, compared with untreated patients with MS.

"This work provides a window into how the gut can affect the immune system, which can then affect the brain. Characterizing the gut microbiome in those with MS may provide new opportunities to diagnose MS and point us toward new interventions to help prevent disease development in those who are risk," said Dr. Weiner.

The researchers plan to continue studying the connection between gut bacteria and the immune system in hopes of developing improved treatment strategies. "In addition, characterization of the gut microbiome in MS may provide biomarkers for assessing disease activity and could theoretically be an avenue to prevent MS in young at-risk populations," said Dr. Weiner.

—Erica Robinson

Researchers have found a correlation between multiple sclerosis (MS) and changes in the human gut microbiome, according to data published June 28 in Nature Communications. "There are a number of ways that the microbiome could play a role in MS, and this opens up a whole new world of looking at the disease in a way that it's never been looked at before," said Howard L. Weiner, MD, Director of the Partners MS Center and Codirector of the Ann Romney Center for Neurologic Disease at Brigham and Women's Hospital in Boston.

Previous studies have suggested a connection between bacteria in the gut and MS, as well as inflammatory bowel disease, type 1 diabetes, and rheumatoid arthritis. In one study of 20 patients with MS and 40 healthy controls, researchers found decreased numbers of Faecalibacterium, Prevotella, and Anaerostipes in patients with MS. The connection between microbiota, treatment, and changes in immunity, however, was not investigated. Because the gut microbiome plays a vital role in immune function and autoimmune disease, Dr. Weiner and his colleagues conducted research to detect changes in the intestinal microbiota in patients with MS, compared with controls. "If further studies demonstrate that these candidate microorganisms play an active role in either contributing to or ameliorating MS, then there is potential to develop new diagnostics and therapies to combat the disease," said Dr. Weiner.

The investigators examined data and collected stool samples from 60 untreated and treated patients with relapsing-remitting MS and 43 healthy control subjects. Subjects were part of the Comprehensive Longitudinal Investigation of Multiple Sclerosis study. None of the patients had an active relapse at the time of study enrollment. For the study, microbial DNA was removed from fecal samples, and gene sequencing was performed with two platforms using primers targeting the V3-5 or the V4 variable regions. Investigators also collected breath samples from a second cohort of 41 patients with MS and 32 controls after they participated in an overnight fast.

Patients with MS had microbial changes in the gut that were associated with the activity of genes that play a role in the immune system. Specifically, researchers found that the gut microbiome in patients with MS contained higher levels of Methanobrevibacter and Akkermansia, and lower levels of Butyricimonas, compared with healthy controls. Increased levels of Methanobrevibacter in patients with MS resulted in higher levels of methane in their breath samples, said the researchers. In addition, patients with MS on disease-modifying treatment had increased abundances of Prevotella and Sutterella, and decreased levels of Sarcina, compared with untreated patients with MS.

"This work provides a window into how the gut can affect the immune system, which can then affect the brain. Characterizing the gut microbiome in those with MS may provide new opportunities to diagnose MS and point us toward new interventions to help prevent disease development in those who are risk," said Dr. Weiner.

The researchers plan to continue studying the connection between gut bacteria and the immune system in hopes of developing improved treatment strategies. "In addition, characterization of the gut microbiome in MS may provide biomarkers for assessing disease activity and could theoretically be an avenue to prevent MS in young at-risk populations," said Dr. Weiner.

—Erica Robinson

Researchers have found a correlation between multiple sclerosis (MS) and changes in the human gut microbiome, according to data published June 28 in Nature Communications. "There are a number of ways that the microbiome could play a role in MS, and this opens up a whole new world of looking at the disease in a way that it's never been looked at before," said Howard L. Weiner, MD, Director of the Partners MS Center and Codirector of the Ann Romney Center for Neurologic Disease at Brigham and Women's Hospital in Boston.

Previous studies have suggested a connection between bacteria in the gut and MS, as well as inflammatory bowel disease, type 1 diabetes, and rheumatoid arthritis. In one study of 20 patients with MS and 40 healthy controls, researchers found decreased numbers of Faecalibacterium, Prevotella, and Anaerostipes in patients with MS. The connection between microbiota, treatment, and changes in immunity, however, was not investigated. Because the gut microbiome plays a vital role in immune function and autoimmune disease, Dr. Weiner and his colleagues conducted research to detect changes in the intestinal microbiota in patients with MS, compared with controls. "If further studies demonstrate that these candidate microorganisms play an active role in either contributing to or ameliorating MS, then there is potential to develop new diagnostics and therapies to combat the disease," said Dr. Weiner.

The investigators examined data and collected stool samples from 60 untreated and treated patients with relapsing-remitting MS and 43 healthy control subjects. Subjects were part of the Comprehensive Longitudinal Investigation of Multiple Sclerosis study. None of the patients had an active relapse at the time of study enrollment. For the study, microbial DNA was removed from fecal samples, and gene sequencing was performed with two platforms using primers targeting the V3-5 or the V4 variable regions. Investigators also collected breath samples from a second cohort of 41 patients with MS and 32 controls after they participated in an overnight fast.

Patients with MS had microbial changes in the gut that were associated with the activity of genes that play a role in the immune system. Specifically, researchers found that the gut microbiome in patients with MS contained higher levels of Methanobrevibacter and Akkermansia, and lower levels of Butyricimonas, compared with healthy controls. Increased levels of Methanobrevibacter in patients with MS resulted in higher levels of methane in their breath samples, said the researchers. In addition, patients with MS on disease-modifying treatment had increased abundances of Prevotella and Sutterella, and decreased levels of Sarcina, compared with untreated patients with MS.

"This work provides a window into how the gut can affect the immune system, which can then affect the brain. Characterizing the gut microbiome in those with MS may provide new opportunities to diagnose MS and point us toward new interventions to help prevent disease development in those who are risk," said Dr. Weiner.

The researchers plan to continue studying the connection between gut bacteria and the immune system in hopes of developing improved treatment strategies. "In addition, characterization of the gut microbiome in MS may provide biomarkers for assessing disease activity and could theoretically be an avenue to prevent MS in young at-risk populations," said Dr. Weiner.

—Erica Robinson

Abatacept does not reduce the number of new gadolinium-enhancing lesions on MRI in patients with relapsing-remitting multiple sclerosis (MS), according to results from the double-blind, randomized, placebo-controlled phase II ACCLAIM study published online ahead of print August 1 in Multiple Sclerosis.

In the ACCLAIM (A Cooperative Clinical Study of Abatacept in MS) study, 42 patients who received abatacept (Orencia) developed a mean of 0.43 new gadolinium-enhancing lesions by week 24, compared with 1.66 lesions for 20 placebo-treated patients. None of the secondary MRI end points (ie, lesion volume change and percent brain volume change) and clinical end points (ie, changes in MS Functional Composite score, Expanded Disability Status Scale [EDSS], and annualized relapse rate) at 24 weeks differed significantly between the groups. The rate of patients who met criteria for no evidence of disease activity or its components (ie, no EDSS progression, no clinical exacerbations, and no new gadolinium-enhancing MRI lesion) from week 8 and before week 28 did not differ between the groups.

During a 28-week extension phase in which the groups switched treatments, patients who switched from abatacept to placebo had a greater number of gadolinium-enhancing lesions than did those who switched from placebo to abatacept (1.25 vs 0.60, respectively), but the difference was not statistically significant.

Abatacept, which is approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis, is a CTLA4 immunoglobulin fusion protein that inhibits the activation of T lymphocytes by blocking the CD28-B7 costimulatory pathway. It was thought to have potential to reduce immune-mediated disease activity in relapsing-remitting MS because T lymphocytes have been implicated in its pathogenesis.

The investigators closed enrollment for the trial early because of slow accrual. The 65 patients who were enrolled in the trial were about half of the population considered to be required (ie, 123) to demonstrate a treatment effect of 50% reduction of new gadolinium-enhancing MRI lesions.

—Jeff Evans

Abatacept does not reduce the number of new gadolinium-enhancing lesions on MRI in patients with relapsing-remitting multiple sclerosis (MS), according to results from the double-blind, randomized, placebo-controlled phase II ACCLAIM study published online ahead of print August 1 in Multiple Sclerosis.

In the ACCLAIM (A Cooperative Clinical Study of Abatacept in MS) study, 42 patients who received abatacept (Orencia) developed a mean of 0.43 new gadolinium-enhancing lesions by week 24, compared with 1.66 lesions for 20 placebo-treated patients. None of the secondary MRI end points (ie, lesion volume change and percent brain volume change) and clinical end points (ie, changes in MS Functional Composite score, Expanded Disability Status Scale [EDSS], and annualized relapse rate) at 24 weeks differed significantly between the groups. The rate of patients who met criteria for no evidence of disease activity or its components (ie, no EDSS progression, no clinical exacerbations, and no new gadolinium-enhancing MRI lesion) from week 8 and before week 28 did not differ between the groups.

During a 28-week extension phase in which the groups switched treatments, patients who switched from abatacept to placebo had a greater number of gadolinium-enhancing lesions than did those who switched from placebo to abatacept (1.25 vs 0.60, respectively), but the difference was not statistically significant.

Abatacept, which is approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis, is a CTLA4 immunoglobulin fusion protein that inhibits the activation of T lymphocytes by blocking the CD28-B7 costimulatory pathway. It was thought to have potential to reduce immune-mediated disease activity in relapsing-remitting MS because T lymphocytes have been implicated in its pathogenesis.

The investigators closed enrollment for the trial early because of slow accrual. The 65 patients who were enrolled in the trial were about half of the population considered to be required (ie, 123) to demonstrate a treatment effect of 50% reduction of new gadolinium-enhancing MRI lesions.

—Jeff Evans

Abatacept does not reduce the number of new gadolinium-enhancing lesions on MRI in patients with relapsing-remitting multiple sclerosis (MS), according to results from the double-blind, randomized, placebo-controlled phase II ACCLAIM study published online ahead of print August 1 in Multiple Sclerosis.

In the ACCLAIM (A Cooperative Clinical Study of Abatacept in MS) study, 42 patients who received abatacept (Orencia) developed a mean of 0.43 new gadolinium-enhancing lesions by week 24, compared with 1.66 lesions for 20 placebo-treated patients. None of the secondary MRI end points (ie, lesion volume change and percent brain volume change) and clinical end points (ie, changes in MS Functional Composite score, Expanded Disability Status Scale [EDSS], and annualized relapse rate) at 24 weeks differed significantly between the groups. The rate of patients who met criteria for no evidence of disease activity or its components (ie, no EDSS progression, no clinical exacerbations, and no new gadolinium-enhancing MRI lesion) from week 8 and before week 28 did not differ between the groups.

During a 28-week extension phase in which the groups switched treatments, patients who switched from abatacept to placebo had a greater number of gadolinium-enhancing lesions than did those who switched from placebo to abatacept (1.25 vs 0.60, respectively), but the difference was not statistically significant.

Abatacept, which is approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis, is a CTLA4 immunoglobulin fusion protein that inhibits the activation of T lymphocytes by blocking the CD28-B7 costimulatory pathway. It was thought to have potential to reduce immune-mediated disease activity in relapsing-remitting MS because T lymphocytes have been implicated in its pathogenesis.

The investigators closed enrollment for the trial early because of slow accrual. The 65 patients who were enrolled in the trial were about half of the population considered to be required (ie, 123) to demonstrate a treatment effect of 50% reduction of new gadolinium-enhancing MRI lesions.

—Jeff Evans

The American Headache Society (AHS) has released a new guideline for the treatment of cluster headache. According to the authors, the AHS guideline can be used for understanding which therapies are superior to placebo or sham treatment in the management of cluster headache. “In clinical practice, these recommendations should be considered in concert with other variables, including safety, side effects, patient preferences, clinician experience, cost, and the invasiveness of the intervention,” said lead author Matthew S. Robbins, MD, an Associate Professor of Clinical Neurology at Montefiore Headache Center at Albert Einstein College of Medicine in the Bronx, New York, and his coauthors. The guideline was published in the July/August issue of Headache.

The guideline is based on a systematic review of the literature regarding abortive and preventive treatment of cluster headache, and represents an update of the American Academy of Neurology’s 2010 recommendations. “The interval of time that has elapsed since completion of the 2010 literature review necessitates these updated recommendations,” the authors said.

For the current literature review, the authors searched the Medline, PubMed, and EMBASE databases for double-blind, randomized, controlled trials that investigated treatment of cluster headache in adults.

For acute treatment, sumatriptan subcutaneous, zolmitriptan nasal spray, and high-flow oxygen remain the treatments with a Level A recommendation. A study of sphenopalatine ganglion stimulation conducted after the 2010 review was added to the current guideline with a Level B recommendation.

The previous guideline included no Level A recommendation for prophylactic therapy. For the current guideline, suboccipital steroid injections have emerged as the only treatment to receive a Level A recommendation, due to the publication of a second Class I study in the literature. Other newly evaluated treatments since the 2010 guideline include a negative study of deep brain stimulation (Level B), a positive study of warfarin (Level C), and negative studies of cimetidine/chlorpheniramine (Level C), and a negative study of candesartan (Level C). Frovatriptan received a Level U recommendation.

The authors concluded that “given the lack of Class I evidence and Level A recommendations, particularly for a number of commonly used preventive therapies, further studies are warranted to demonstrate safety and efficacy for established and emerging therapies.”

—Glenn S. Williams

The American Headache Society (AHS) has released a new guideline for the treatment of cluster headache. According to the authors, the AHS guideline can be used for understanding which therapies are superior to placebo or sham treatment in the management of cluster headache. “In clinical practice, these recommendations should be considered in concert with other variables, including safety, side effects, patient preferences, clinician experience, cost, and the invasiveness of the intervention,” said lead author Matthew S. Robbins, MD, an Associate Professor of Clinical Neurology at Montefiore Headache Center at Albert Einstein College of Medicine in the Bronx, New York, and his coauthors. The guideline was published in the July/August issue of Headache.

The guideline is based on a systematic review of the literature regarding abortive and preventive treatment of cluster headache, and represents an update of the American Academy of Neurology’s 2010 recommendations. “The interval of time that has elapsed since completion of the 2010 literature review necessitates these updated recommendations,” the authors said.

For the current literature review, the authors searched the Medline, PubMed, and EMBASE databases for double-blind, randomized, controlled trials that investigated treatment of cluster headache in adults.

For acute treatment, sumatriptan subcutaneous, zolmitriptan nasal spray, and high-flow oxygen remain the treatments with a Level A recommendation. A study of sphenopalatine ganglion stimulation conducted after the 2010 review was added to the current guideline with a Level B recommendation.

The previous guideline included no Level A recommendation for prophylactic therapy. For the current guideline, suboccipital steroid injections have emerged as the only treatment to receive a Level A recommendation, due to the publication of a second Class I study in the literature. Other newly evaluated treatments since the 2010 guideline include a negative study of deep brain stimulation (Level B), a positive study of warfarin (Level C), and negative studies of cimetidine/chlorpheniramine (Level C), and a negative study of candesartan (Level C). Frovatriptan received a Level U recommendation.

The authors concluded that “given the lack of Class I evidence and Level A recommendations, particularly for a number of commonly used preventive therapies, further studies are warranted to demonstrate safety and efficacy for established and emerging therapies.”

—Glenn S. Williams

The American Headache Society (AHS) has released a new guideline for the treatment of cluster headache. According to the authors, the AHS guideline can be used for understanding which therapies are superior to placebo or sham treatment in the management of cluster headache. “In clinical practice, these recommendations should be considered in concert with other variables, including safety, side effects, patient preferences, clinician experience, cost, and the invasiveness of the intervention,” said lead author Matthew S. Robbins, MD, an Associate Professor of Clinical Neurology at Montefiore Headache Center at Albert Einstein College of Medicine in the Bronx, New York, and his coauthors. The guideline was published in the July/August issue of Headache.

The guideline is based on a systematic review of the literature regarding abortive and preventive treatment of cluster headache, and represents an update of the American Academy of Neurology’s 2010 recommendations. “The interval of time that has elapsed since completion of the 2010 literature review necessitates these updated recommendations,” the authors said.

For the current literature review, the authors searched the Medline, PubMed, and EMBASE databases for double-blind, randomized, controlled trials that investigated treatment of cluster headache in adults.

For acute treatment, sumatriptan subcutaneous, zolmitriptan nasal spray, and high-flow oxygen remain the treatments with a Level A recommendation. A study of sphenopalatine ganglion stimulation conducted after the 2010 review was added to the current guideline with a Level B recommendation.

The previous guideline included no Level A recommendation for prophylactic therapy. For the current guideline, suboccipital steroid injections have emerged as the only treatment to receive a Level A recommendation, due to the publication of a second Class I study in the literature. Other newly evaluated treatments since the 2010 guideline include a negative study of deep brain stimulation (Level B), a positive study of warfarin (Level C), and negative studies of cimetidine/chlorpheniramine (Level C), and a negative study of candesartan (Level C). Frovatriptan received a Level U recommendation.

The authors concluded that “given the lack of Class I evidence and Level A recommendations, particularly for a number of commonly used preventive therapies, further studies are warranted to demonstrate safety and efficacy for established and emerging therapies.”

—Glenn S. Williams

Background: Patients with dementia often exhibit behavioral problems, such as agitation and psychosis. The American Psychiatric Association (APA) produced a consensus report on the use of antipsychotics in patients with dementia who also exhibit agitation/psychosis.

Study design: Expert panel review of multiple studies and consensus opinions of experienced clinicians.

Synopsis: While the use of antipsychotics to treat behavioral symptoms in patients with dementia is common, it is important to use these medications judiciously, especially in nonemergency cases. The APA recommends antipsychotics for treatment of agitation in these patients only when symptoms are severe or dangerous or cause significant distress to the patient.

When providers determine that benefits exceed risks, antipsychotic treatment should be initiated at a low dose and carefully titrated up to the minimum effective dose. If there is no significant response after a four-week trial of an adequate dose, tapering and withdrawing antipsychotic medication is recommended. Haloperidol should not be used as a first-line agent. The APA guidelines are not intended to apply to treatment in an urgent context, such as acute delirium.

Bottom line: The APA has provided practical guidelines to direct care of dementia patients. These guidelines are not intended to apply to individuals who are receiving antipsychotics in an urgent context or who receive antipsychotics for other disorders (e.g., chronic psychotic illness).

Citation: Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association practice guidelines on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;173(5):543-546.

Short Take

Colistin-Resistant E. coli in the U.S.

The presence of mcr-1, a plasmid-borne colistin resistance gene indicating the presence of a truly pan-drug-resistant bacteria, has been identified for the first time in the United States.

Citation: McGann P, Snesrud E, Maybank R, et al. Escherichia coli harboring mcr-1 and blaCTX-M on a novel IncF plasmid: first report of mcr-1 in the United States. Antimicrob Agents Chemother. 2016;60(7):4420-4421.

Background: Patients with dementia often exhibit behavioral problems, such as agitation and psychosis. The American Psychiatric Association (APA) produced a consensus report on the use of antipsychotics in patients with dementia who also exhibit agitation/psychosis.

Study design: Expert panel review of multiple studies and consensus opinions of experienced clinicians.

Synopsis: While the use of antipsychotics to treat behavioral symptoms in patients with dementia is common, it is important to use these medications judiciously, especially in nonemergency cases. The APA recommends antipsychotics for treatment of agitation in these patients only when symptoms are severe or dangerous or cause significant distress to the patient.

When providers determine that benefits exceed risks, antipsychotic treatment should be initiated at a low dose and carefully titrated up to the minimum effective dose. If there is no significant response after a four-week trial of an adequate dose, tapering and withdrawing antipsychotic medication is recommended. Haloperidol should not be used as a first-line agent. The APA guidelines are not intended to apply to treatment in an urgent context, such as acute delirium.

Bottom line: The APA has provided practical guidelines to direct care of dementia patients. These guidelines are not intended to apply to individuals who are receiving antipsychotics in an urgent context or who receive antipsychotics for other disorders (e.g., chronic psychotic illness).

Citation: Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association practice guidelines on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;173(5):543-546.

Short Take

Colistin-Resistant E. coli in the U.S.

The presence of mcr-1, a plasmid-borne colistin resistance gene indicating the presence of a truly pan-drug-resistant bacteria, has been identified for the first time in the United States.

Citation: McGann P, Snesrud E, Maybank R, et al. Escherichia coli harboring mcr-1 and blaCTX-M on a novel IncF plasmid: first report of mcr-1 in the United States. Antimicrob Agents Chemother. 2016;60(7):4420-4421.

Background: Patients with dementia often exhibit behavioral problems, such as agitation and psychosis. The American Psychiatric Association (APA) produced a consensus report on the use of antipsychotics in patients with dementia who also exhibit agitation/psychosis.

Study design: Expert panel review of multiple studies and consensus opinions of experienced clinicians.

Synopsis: While the use of antipsychotics to treat behavioral symptoms in patients with dementia is common, it is important to use these medications judiciously, especially in nonemergency cases. The APA recommends antipsychotics for treatment of agitation in these patients only when symptoms are severe or dangerous or cause significant distress to the patient.

When providers determine that benefits exceed risks, antipsychotic treatment should be initiated at a low dose and carefully titrated up to the minimum effective dose. If there is no significant response after a four-week trial of an adequate dose, tapering and withdrawing antipsychotic medication is recommended. Haloperidol should not be used as a first-line agent. The APA guidelines are not intended to apply to treatment in an urgent context, such as acute delirium.

Bottom line: The APA has provided practical guidelines to direct care of dementia patients. These guidelines are not intended to apply to individuals who are receiving antipsychotics in an urgent context or who receive antipsychotics for other disorders (e.g., chronic psychotic illness).

Citation: Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association practice guidelines on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;173(5):543-546.

Short Take

Colistin-Resistant E. coli in the U.S.

The presence of mcr-1, a plasmid-borne colistin resistance gene indicating the presence of a truly pan-drug-resistant bacteria, has been identified for the first time in the United States.

Citation: McGann P, Snesrud E, Maybank R, et al. Escherichia coli harboring mcr-1 and blaCTX-M on a novel IncF plasmid: first report of mcr-1 in the United States. Antimicrob Agents Chemother. 2016;60(7):4420-4421.