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Hypotension ‘dose’ drives mortality in traumatic brain injury

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– The severity and duration of hypotension in traumatic brain injury patients during EMS transport to an emergency department has a tight and essentially linear relationship to their mortality rate during subsequent weeks of recovery, according to an analysis of more than 7,500 brain-injured patients.

For each doubling of the combined severity and duration of hypotension during the prehospital period, when systolic blood pressure was less than 90 mm Hg, patient mortality rose by 19%, Daniel W. Spaite, MD, reported at the American Heart Association scientific sessions.

However, the results do not address whether aggressive treatment of hypotension by EMS technicians in a patient with traumatic brain injury (TBI) leads to reduced mortality. That question is being assessed as part of the primary endpoint of the Excellence in Prehospital Injury Care-Traumatic Brain Injury (EPIC-TBI) study, which should have an answer by the end of 2017, said Dr. Spaite, professor of emergency medicine at the University of Arizona in Tuscon.

Mitchel L. Zoler/Frontline Medical News
Dr. Daniel W. Spaite
Results from prior studies have clearly linked prehospital hypotension with worse survival in TBI patients. But until now, no appreciation existed that not all hypotensive episodes are equal, and that both the severity of hypotension and its duration incrementally contribute to mortality as the “dose” of hypotension a patient experiences increases. In large part, that’s because until now prehospital hypotension has been recorded simply as a dichotomous, yes/no condition.

The innovation introduced by Dr. Spaite and his associates in their analysis of the EPIC-TBI data was to drill down into each patient’s hypotensive event, made possible by the 16,711 patients enrolled in EPIC-TBI.

The calculation they performed was limited to patients with EMS records of at least two blood pressure measurements during prehospital transport. These data allowed them to use both the extent to which systolic blood pressure dropped below 90 mm Hg and the amount of time pressure was below this threshold to better define the total hypotension exposure each patient received.

This meant that a TBI patient with a systolic pressure of 80 mm Hg for 10 minutes had twice the hypotension exposure of both a patient with a pressure of 85 mm Hg for 10 minutes, and a patient with a pressure of 80 mm Hg for 5 minutes.

Their analysis also adjusted the relationship of this total hypotensive dose and subsequent mortality based on several baseline demographic and clinical variables, including age, sex, injury severity, trauma type, and head-region severity score. After adjustment, the researchers found a “strikingly linear relationship” between hypotension dose and mortality, Dr. Spaite said, although a clear dose-response relationship was also evident in the unadjusted data.

EPIC-TBI enrolled TBI patients age 10 years or older during 2007-2014 through participation by dozens of EMS providers throughout Arizona. For the current analysis, the researchers identified 7,521 patients from the total group who had at least two blood pressure measurements taken during their prehospital EMS care and also met other inclusion criteria.

The best way to manage hypotension in TBI patients during the prehospital period remains unclear. Simply raising blood pressure with fluid infusion may not necessarily help, because it could exacerbate a patient’s bleeding, Dr. Spaite noted during an interview.

The primary goal of EPIC-TBI is to assess the impact of the third edition of the traumatic brain injury guidelines released in 2007 by the Brain Trauma Foundation. (The fourth edition of these guidelines came out in August 2016.) The new finding by Dr. Spaite and his associates will allow the full EPIC-TBI analysis to correlate patient outcomes with the impact that acute, prehospital treatment had on the hypotension dose received by each patient, he noted.

“What’s remarkable is that the single, prehospital parameter of hypotension for just a few minutes during transport can have such a strong impact on survival, given all the other factors that can influence outcomes” in TBI patients once they reach a hospital and during the period they remain hospitalized, Dr. Spaite said.
 

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– The severity and duration of hypotension in traumatic brain injury patients during EMS transport to an emergency department has a tight and essentially linear relationship to their mortality rate during subsequent weeks of recovery, according to an analysis of more than 7,500 brain-injured patients.

For each doubling of the combined severity and duration of hypotension during the prehospital period, when systolic blood pressure was less than 90 mm Hg, patient mortality rose by 19%, Daniel W. Spaite, MD, reported at the American Heart Association scientific sessions.

However, the results do not address whether aggressive treatment of hypotension by EMS technicians in a patient with traumatic brain injury (TBI) leads to reduced mortality. That question is being assessed as part of the primary endpoint of the Excellence in Prehospital Injury Care-Traumatic Brain Injury (EPIC-TBI) study, which should have an answer by the end of 2017, said Dr. Spaite, professor of emergency medicine at the University of Arizona in Tuscon.

Mitchel L. Zoler/Frontline Medical News
Dr. Daniel W. Spaite
Results from prior studies have clearly linked prehospital hypotension with worse survival in TBI patients. But until now, no appreciation existed that not all hypotensive episodes are equal, and that both the severity of hypotension and its duration incrementally contribute to mortality as the “dose” of hypotension a patient experiences increases. In large part, that’s because until now prehospital hypotension has been recorded simply as a dichotomous, yes/no condition.

The innovation introduced by Dr. Spaite and his associates in their analysis of the EPIC-TBI data was to drill down into each patient’s hypotensive event, made possible by the 16,711 patients enrolled in EPIC-TBI.

The calculation they performed was limited to patients with EMS records of at least two blood pressure measurements during prehospital transport. These data allowed them to use both the extent to which systolic blood pressure dropped below 90 mm Hg and the amount of time pressure was below this threshold to better define the total hypotension exposure each patient received.

This meant that a TBI patient with a systolic pressure of 80 mm Hg for 10 minutes had twice the hypotension exposure of both a patient with a pressure of 85 mm Hg for 10 minutes, and a patient with a pressure of 80 mm Hg for 5 minutes.

Their analysis also adjusted the relationship of this total hypotensive dose and subsequent mortality based on several baseline demographic and clinical variables, including age, sex, injury severity, trauma type, and head-region severity score. After adjustment, the researchers found a “strikingly linear relationship” between hypotension dose and mortality, Dr. Spaite said, although a clear dose-response relationship was also evident in the unadjusted data.

EPIC-TBI enrolled TBI patients age 10 years or older during 2007-2014 through participation by dozens of EMS providers throughout Arizona. For the current analysis, the researchers identified 7,521 patients from the total group who had at least two blood pressure measurements taken during their prehospital EMS care and also met other inclusion criteria.

The best way to manage hypotension in TBI patients during the prehospital period remains unclear. Simply raising blood pressure with fluid infusion may not necessarily help, because it could exacerbate a patient’s bleeding, Dr. Spaite noted during an interview.

The primary goal of EPIC-TBI is to assess the impact of the third edition of the traumatic brain injury guidelines released in 2007 by the Brain Trauma Foundation. (The fourth edition of these guidelines came out in August 2016.) The new finding by Dr. Spaite and his associates will allow the full EPIC-TBI analysis to correlate patient outcomes with the impact that acute, prehospital treatment had on the hypotension dose received by each patient, he noted.

“What’s remarkable is that the single, prehospital parameter of hypotension for just a few minutes during transport can have such a strong impact on survival, given all the other factors that can influence outcomes” in TBI patients once they reach a hospital and during the period they remain hospitalized, Dr. Spaite said.
 

 

– The severity and duration of hypotension in traumatic brain injury patients during EMS transport to an emergency department has a tight and essentially linear relationship to their mortality rate during subsequent weeks of recovery, according to an analysis of more than 7,500 brain-injured patients.

For each doubling of the combined severity and duration of hypotension during the prehospital period, when systolic blood pressure was less than 90 mm Hg, patient mortality rose by 19%, Daniel W. Spaite, MD, reported at the American Heart Association scientific sessions.

However, the results do not address whether aggressive treatment of hypotension by EMS technicians in a patient with traumatic brain injury (TBI) leads to reduced mortality. That question is being assessed as part of the primary endpoint of the Excellence in Prehospital Injury Care-Traumatic Brain Injury (EPIC-TBI) study, which should have an answer by the end of 2017, said Dr. Spaite, professor of emergency medicine at the University of Arizona in Tuscon.

Mitchel L. Zoler/Frontline Medical News
Dr. Daniel W. Spaite
Results from prior studies have clearly linked prehospital hypotension with worse survival in TBI patients. But until now, no appreciation existed that not all hypotensive episodes are equal, and that both the severity of hypotension and its duration incrementally contribute to mortality as the “dose” of hypotension a patient experiences increases. In large part, that’s because until now prehospital hypotension has been recorded simply as a dichotomous, yes/no condition.

The innovation introduced by Dr. Spaite and his associates in their analysis of the EPIC-TBI data was to drill down into each patient’s hypotensive event, made possible by the 16,711 patients enrolled in EPIC-TBI.

The calculation they performed was limited to patients with EMS records of at least two blood pressure measurements during prehospital transport. These data allowed them to use both the extent to which systolic blood pressure dropped below 90 mm Hg and the amount of time pressure was below this threshold to better define the total hypotension exposure each patient received.

This meant that a TBI patient with a systolic pressure of 80 mm Hg for 10 minutes had twice the hypotension exposure of both a patient with a pressure of 85 mm Hg for 10 minutes, and a patient with a pressure of 80 mm Hg for 5 minutes.

Their analysis also adjusted the relationship of this total hypotensive dose and subsequent mortality based on several baseline demographic and clinical variables, including age, sex, injury severity, trauma type, and head-region severity score. After adjustment, the researchers found a “strikingly linear relationship” between hypotension dose and mortality, Dr. Spaite said, although a clear dose-response relationship was also evident in the unadjusted data.

EPIC-TBI enrolled TBI patients age 10 years or older during 2007-2014 through participation by dozens of EMS providers throughout Arizona. For the current analysis, the researchers identified 7,521 patients from the total group who had at least two blood pressure measurements taken during their prehospital EMS care and also met other inclusion criteria.

The best way to manage hypotension in TBI patients during the prehospital period remains unclear. Simply raising blood pressure with fluid infusion may not necessarily help, because it could exacerbate a patient’s bleeding, Dr. Spaite noted during an interview.

The primary goal of EPIC-TBI is to assess the impact of the third edition of the traumatic brain injury guidelines released in 2007 by the Brain Trauma Foundation. (The fourth edition of these guidelines came out in August 2016.) The new finding by Dr. Spaite and his associates will allow the full EPIC-TBI analysis to correlate patient outcomes with the impact that acute, prehospital treatment had on the hypotension dose received by each patient, he noted.

“What’s remarkable is that the single, prehospital parameter of hypotension for just a few minutes during transport can have such a strong impact on survival, given all the other factors that can influence outcomes” in TBI patients once they reach a hospital and during the period they remain hospitalized, Dr. Spaite said.
 

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Key clinical point: Both the duration and severity of hypotension a traumatic brain injury patient has during transport to an emergency department has a significant, linear impact on subsequent mortality.

Major finding: For each doubling of the dose of prehospital hypotension (a function of severity and duration), mortality rose by 19%.

Data source: EPIC-TBI, a multicenter study with 16,711 patients, including 7,521 who met inclusion criteria for the current analysis.

Disclosures: Dr. Spaite had no disclosures.

New and Noteworthy Information—November 2016

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Exercise may be associated with a small benefit for elderly people who have memory and thinking problems, according to a study published online ahead of print October 19 in Neurology. Researchers studied 70 adults randomized to six months of aerobic exercise training or usual care plus education on cognitive and everyday function. The aerobic exercise training group had significantly improved Alzheimer's Disease Assessment Scale-Cognitive subscale performance, compared with controls. This difference was not significant at six-month follow-up, however. There were no significant between-group differences at intervention completion and at the six-month follow-up in Executive Interview or Alzheimer's Disease Cooperative Study-Activities of Daily Living performance. Examination of secondary measures showed between-group differences at intervention completion favoring the exercise training program group in six-minute walk distance and in diastolic blood pressure.  
 
The FDA has approved Carnexiv (carbamazepine) injection as a short-term replacement therapy for oral carbamazepine formulations in adults with certain seizure types when oral administration is temporarily not feasible. Carnexiv has received orphan drug designation for this indication and will be the first available IV formulation of carbamazepine. The drug is intended for people with partial seizures with complex symptomatology, generalized tonic-clonic seizures, mixed seizure patterns, or other partial or generalized seizures. Carnexiv is not indicated for the treatment of absence seizures. People taking Carnexiv should not discontinue the drug abruptly because of the risk of seizures, status epilepticus, and other withdrawal signs and symptoms. In addition, Carnexiv should not be used in patients with moderate or severe renal impairment. The drug is marketed by Lundbeck, which is headquartered in Deerfield, Illinois.  
 
Chiropractic spinal manipulative therapy (CSMT) is no more effective than placebo for migraine, according to a study published online ahead of print October 2 in the European Journal of Neurology. Investigators randomized 104 migraineurs with at least one migraine attack per month to CSMT, sham chiropractic, or usual pharmacologic management for 17 months. Migraine days were significantly reduced within all three groups from baseline to post treatment. The effect continued in the CSMT and placebo groups at all follow-up time points, but the control group returned to baseline. The reduction in migraine days was not significantly different between the groups. Migraine duration and headache index were reduced significantly more in the CSMT group than in the control group toward the end of follow-up.   
 
Video monitoring facilitates nocturnal surveillance of patients with epilepsy, but the costs are high, according to a study published online ahead of print September 30 in Epilepsia. For six months, researchers asked caregivers at an epilepsy unit to specify whether an acoustic detection system, bed motion sensor, or video monitoring alerted them to seizures and whether the alerts led to interventions. They identified 1,208 seizures in 37 people. Four people had no nocturnal seizures, and 33% of seizures were seen only on video. In 14% of seizures, including 10% of seizures seen only on video, an intervention was made. The extra costs of monitoring were 7,035 euro per seizure seen only on video and leading to an intervention. The results underscore the need for reliable seizure-detection devices, said the authors.  
 
A higher level of physical activity may not reduce a woman's risk of multiple sclerosis (MS), according to a study published online ahead of print September 28 in Neurology. Researchers calculated total metabolic equivalent hours of physical activity per week for women participating in the Nurses' Health Study (NHS) and NHS II. There were 341 confirmed MS cases with first symptoms after baseline. Participants also reported early-life activity. The investigators analyzed the data with Cox proportional hazards models. Compared with women in the lowest baseline physical activity quartile, women in the highest quartile had a 27% reduced rate of MS. This trend was not present in six-year lagged analyses, however. In NHS II, total early life activity at ages 12 to 22 was not associated with MS.  
 
Youth with primary hypertension have significantly worse performance on neurocognitive testing, compared with normotensive controls, according to a study published online ahead of print September 27 in the Journal of Pediatrics.Seventy-five children with newly diagnosed, untreated hypertension and 75 frequency-matched normotensive controls had baseline neurocognitive testing as part of a prospective multicenter study of cognition in primary hypertension. The participants completed general intelligence, attention, memory, executive function, and processing speed tests. Parents rated participants' executive function and sleep disordered breathing. The study groups were well matched. Hypertension was independently associated with worse memory, attention, and executive function, compared with normotension. Results indicated a significant interaction between disordered sleep and hypertension on ratings of executive function. Hypertension heightened the association between increased disordered sleep and worse executive function.
 
Headache disorders may be associated with an increased risk for the development of new-onset hypothyroidism, according to a study published online ahead of print September 27 in Headache. This longitudinal retrospective cohort study used data from 8,412 participants enrolled in the Fernald Medical Monitoring Program. Participants underwent physical examinations and thyroid function testing every three years during the 20-year program. The primary outcome measure was new-onset hypothyroidism, defined as the initiation of thyroid replacement therapy or thyroid-stimulating hormone test value greater than or equal to 10 without thyroid medication. Headache disorders were present in about 26% of the participants, and new-onset hypothyroidism developed in approximately 7% of participants. The hazard ratio for the development of new-onset hypothyroidism was 1.21 for people with headache disorders.
 
People with epilepsy can face various psychosocial adversities and extensively report feeling discriminated against, compared with the general population, according to a study published online ahead of print September 16 in Epilepsia. The Adult Psychiatric Morbidity Survey 2007 included comprehensive interviews with 7,403 people. Overall, people with epilepsy were sevenfold more likely to have reported experiencing discrimination due to health problems than the general population without epilepsy. People with epilepsy also had greater odds of experiencing domestic violence and sexual abuse than the general population, although these associations were also found in people with other chronic conditions. There was less evidence of an association between epilepsy and a history of physical abuse or having a greater burden of other stressful life events.  
 
Short episodes of atrial tachycardia or fibrillation are not associated with increased risk of clinical events, compared with absence of these episodes, according to a study published October 18 in Circulation. The Registry of Atrial Tachycardia and Atrial Fibrillation Episodes enrolled 5,379 patients with pacemakers or implantable cardioverter defibrillators. There were 478 hospitalizations among 342 patients for clinical events. Study authors adjudicated 37,531 electrograms. Patients with clinical events were more likely than those without them to have long atrial tachycardia or fibrillation. Only short episodes of atrial tachycardia or fibrillation were documented in 9% of patients with pacemakers and in 16% of patients with implantable cardioverter defibrillators. Patients with clinical events were no more likely than those without them to have short atrial tachycardia or fibrillation.
 
A brain signature identifies patients with fibromyalgia with 93% accuracy, according to a study published online ahead of print August 31 in Pain. Researchers examined 37 patients with fibromyalgia and 35 matched healthy controls. They analyzed participants' functional MRI responses to painful pressure and nonpainful multisensory stimulation. Investigators used machine-learning techniques to identify a brain-based fibromyalgia signature. When exposed to the same painful stimuli, patients with fibromyalgia had greater Neurologic Pain Signature responses. Furthermore, a new pain-related classifier revealed augmented responses in sensory integration and self-referential regions in fibromyalgia, and reduced responses in the lateral frontal cortex. Combined activity in the Neurologic Pain Signature, fibromyalgia pain, and multisensory patterns classified patients vs. controls with 92% sensitivity and 94% specificity in individuals who were not part of the study sample.  
 
Children have measurable brain changes after a single season of youth football, even when they do not sustain a concussion, according to a study published online ahead of print October 24 in Radiology. Head impact data were recorded using the Head Impact Telemetry system and quantified as the combined-probability risk-weighted cumulative exposure. Twenty-five male participants were evaluated for seasonal fractional anisotropy changes in the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus. There were statistically significant linear relationships between risk-weighted cumulative exposure and decreased fractional anisotropy in the whole, core, and terminals of the left inferior fronto-occipital fasciculus. A trend toward statistical significance in the right superior longitudinal fasciculus was observed. Decrease in fractional anisotropy of the right superior longitudinal fasciculus terminal was significantly correlated with risk-weighted cumulative exposure.
 
Zika virus contributes to the development of Guillain-Barré syndrome, according to a study published online ahead of print October 5 in the New England Journal of Medicine. From November 2015 through March 2016, clusters of cases of Guillain-Barré syndrome were observed during an outbreak of Zika virus in Colombia. Researchers characterized the clinical features of 68 patients with Guillain-Barré syndrome during the outbreak and investigated their relationship with Zika virus infection. In all, 97% of patients had symptoms compatible with Zika virus infection before the onset of Guillain-Barré syndrome. Among the 42 patients who had samples tested for Zika virus infection, the results were positive in 40%. Most of the positive results were in urine samples, although three samples of CSF were also positive.  
 
Among patients with amnestic mild cognitive impairment (aMCI), women have better verbal memory than men despite similar levels of brain hypometabolism, according to a study published online ahead of print October 5 in Neurology. In the Alzheimer's Disease Neuroimaging Initiative, 390 controls, 672 participants with aMCI, and 254 people with Alzheimer's disease dementia completed the Rey Auditory Verbal Learning Test and [18F]-fluorodeoxyglucose-PET. Female sex, higher temporal lobe glucose metabolic rates (TLGluMR), and the interaction of the two factors were associated with better verbal memory. The female advantage in verbal memory was greatest in people with moderate to high TLGluMR and minimal or absent among individuals with lower TLGluMR. Diagnosis-stratified analyses revealed that this interaction was driven by the aMCI group.

Kimberly Williams

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Exercise may be associated with a small benefit for elderly people who have memory and thinking problems, according to a study published online ahead of print October 19 in Neurology. Researchers studied 70 adults randomized to six months of aerobic exercise training or usual care plus education on cognitive and everyday function. The aerobic exercise training group had significantly improved Alzheimer's Disease Assessment Scale-Cognitive subscale performance, compared with controls. This difference was not significant at six-month follow-up, however. There were no significant between-group differences at intervention completion and at the six-month follow-up in Executive Interview or Alzheimer's Disease Cooperative Study-Activities of Daily Living performance. Examination of secondary measures showed between-group differences at intervention completion favoring the exercise training program group in six-minute walk distance and in diastolic blood pressure.  
 
The FDA has approved Carnexiv (carbamazepine) injection as a short-term replacement therapy for oral carbamazepine formulations in adults with certain seizure types when oral administration is temporarily not feasible. Carnexiv has received orphan drug designation for this indication and will be the first available IV formulation of carbamazepine. The drug is intended for people with partial seizures with complex symptomatology, generalized tonic-clonic seizures, mixed seizure patterns, or other partial or generalized seizures. Carnexiv is not indicated for the treatment of absence seizures. People taking Carnexiv should not discontinue the drug abruptly because of the risk of seizures, status epilepticus, and other withdrawal signs and symptoms. In addition, Carnexiv should not be used in patients with moderate or severe renal impairment. The drug is marketed by Lundbeck, which is headquartered in Deerfield, Illinois.  
 
Chiropractic spinal manipulative therapy (CSMT) is no more effective than placebo for migraine, according to a study published online ahead of print October 2 in the European Journal of Neurology. Investigators randomized 104 migraineurs with at least one migraine attack per month to CSMT, sham chiropractic, or usual pharmacologic management for 17 months. Migraine days were significantly reduced within all three groups from baseline to post treatment. The effect continued in the CSMT and placebo groups at all follow-up time points, but the control group returned to baseline. The reduction in migraine days was not significantly different between the groups. Migraine duration and headache index were reduced significantly more in the CSMT group than in the control group toward the end of follow-up.   
 
Video monitoring facilitates nocturnal surveillance of patients with epilepsy, but the costs are high, according to a study published online ahead of print September 30 in Epilepsia. For six months, researchers asked caregivers at an epilepsy unit to specify whether an acoustic detection system, bed motion sensor, or video monitoring alerted them to seizures and whether the alerts led to interventions. They identified 1,208 seizures in 37 people. Four people had no nocturnal seizures, and 33% of seizures were seen only on video. In 14% of seizures, including 10% of seizures seen only on video, an intervention was made. The extra costs of monitoring were 7,035 euro per seizure seen only on video and leading to an intervention. The results underscore the need for reliable seizure-detection devices, said the authors.  
 
A higher level of physical activity may not reduce a woman's risk of multiple sclerosis (MS), according to a study published online ahead of print September 28 in Neurology. Researchers calculated total metabolic equivalent hours of physical activity per week for women participating in the Nurses' Health Study (NHS) and NHS II. There were 341 confirmed MS cases with first symptoms after baseline. Participants also reported early-life activity. The investigators analyzed the data with Cox proportional hazards models. Compared with women in the lowest baseline physical activity quartile, women in the highest quartile had a 27% reduced rate of MS. This trend was not present in six-year lagged analyses, however. In NHS II, total early life activity at ages 12 to 22 was not associated with MS.  
 
Youth with primary hypertension have significantly worse performance on neurocognitive testing, compared with normotensive controls, according to a study published online ahead of print September 27 in the Journal of Pediatrics.Seventy-five children with newly diagnosed, untreated hypertension and 75 frequency-matched normotensive controls had baseline neurocognitive testing as part of a prospective multicenter study of cognition in primary hypertension. The participants completed general intelligence, attention, memory, executive function, and processing speed tests. Parents rated participants' executive function and sleep disordered breathing. The study groups were well matched. Hypertension was independently associated with worse memory, attention, and executive function, compared with normotension. Results indicated a significant interaction between disordered sleep and hypertension on ratings of executive function. Hypertension heightened the association between increased disordered sleep and worse executive function.
 
Headache disorders may be associated with an increased risk for the development of new-onset hypothyroidism, according to a study published online ahead of print September 27 in Headache. This longitudinal retrospective cohort study used data from 8,412 participants enrolled in the Fernald Medical Monitoring Program. Participants underwent physical examinations and thyroid function testing every three years during the 20-year program. The primary outcome measure was new-onset hypothyroidism, defined as the initiation of thyroid replacement therapy or thyroid-stimulating hormone test value greater than or equal to 10 without thyroid medication. Headache disorders were present in about 26% of the participants, and new-onset hypothyroidism developed in approximately 7% of participants. The hazard ratio for the development of new-onset hypothyroidism was 1.21 for people with headache disorders.
 
People with epilepsy can face various psychosocial adversities and extensively report feeling discriminated against, compared with the general population, according to a study published online ahead of print September 16 in Epilepsia. The Adult Psychiatric Morbidity Survey 2007 included comprehensive interviews with 7,403 people. Overall, people with epilepsy were sevenfold more likely to have reported experiencing discrimination due to health problems than the general population without epilepsy. People with epilepsy also had greater odds of experiencing domestic violence and sexual abuse than the general population, although these associations were also found in people with other chronic conditions. There was less evidence of an association between epilepsy and a history of physical abuse or having a greater burden of other stressful life events.  
 
Short episodes of atrial tachycardia or fibrillation are not associated with increased risk of clinical events, compared with absence of these episodes, according to a study published October 18 in Circulation. The Registry of Atrial Tachycardia and Atrial Fibrillation Episodes enrolled 5,379 patients with pacemakers or implantable cardioverter defibrillators. There were 478 hospitalizations among 342 patients for clinical events. Study authors adjudicated 37,531 electrograms. Patients with clinical events were more likely than those without them to have long atrial tachycardia or fibrillation. Only short episodes of atrial tachycardia or fibrillation were documented in 9% of patients with pacemakers and in 16% of patients with implantable cardioverter defibrillators. Patients with clinical events were no more likely than those without them to have short atrial tachycardia or fibrillation.
 
A brain signature identifies patients with fibromyalgia with 93% accuracy, according to a study published online ahead of print August 31 in Pain. Researchers examined 37 patients with fibromyalgia and 35 matched healthy controls. They analyzed participants' functional MRI responses to painful pressure and nonpainful multisensory stimulation. Investigators used machine-learning techniques to identify a brain-based fibromyalgia signature. When exposed to the same painful stimuli, patients with fibromyalgia had greater Neurologic Pain Signature responses. Furthermore, a new pain-related classifier revealed augmented responses in sensory integration and self-referential regions in fibromyalgia, and reduced responses in the lateral frontal cortex. Combined activity in the Neurologic Pain Signature, fibromyalgia pain, and multisensory patterns classified patients vs. controls with 92% sensitivity and 94% specificity in individuals who were not part of the study sample.  
 
Children have measurable brain changes after a single season of youth football, even when they do not sustain a concussion, according to a study published online ahead of print October 24 in Radiology. Head impact data were recorded using the Head Impact Telemetry system and quantified as the combined-probability risk-weighted cumulative exposure. Twenty-five male participants were evaluated for seasonal fractional anisotropy changes in the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus. There were statistically significant linear relationships between risk-weighted cumulative exposure and decreased fractional anisotropy in the whole, core, and terminals of the left inferior fronto-occipital fasciculus. A trend toward statistical significance in the right superior longitudinal fasciculus was observed. Decrease in fractional anisotropy of the right superior longitudinal fasciculus terminal was significantly correlated with risk-weighted cumulative exposure.
 
Zika virus contributes to the development of Guillain-Barré syndrome, according to a study published online ahead of print October 5 in the New England Journal of Medicine. From November 2015 through March 2016, clusters of cases of Guillain-Barré syndrome were observed during an outbreak of Zika virus in Colombia. Researchers characterized the clinical features of 68 patients with Guillain-Barré syndrome during the outbreak and investigated their relationship with Zika virus infection. In all, 97% of patients had symptoms compatible with Zika virus infection before the onset of Guillain-Barré syndrome. Among the 42 patients who had samples tested for Zika virus infection, the results were positive in 40%. Most of the positive results were in urine samples, although three samples of CSF were also positive.  
 
Among patients with amnestic mild cognitive impairment (aMCI), women have better verbal memory than men despite similar levels of brain hypometabolism, according to a study published online ahead of print October 5 in Neurology. In the Alzheimer's Disease Neuroimaging Initiative, 390 controls, 672 participants with aMCI, and 254 people with Alzheimer's disease dementia completed the Rey Auditory Verbal Learning Test and [18F]-fluorodeoxyglucose-PET. Female sex, higher temporal lobe glucose metabolic rates (TLGluMR), and the interaction of the two factors were associated with better verbal memory. The female advantage in verbal memory was greatest in people with moderate to high TLGluMR and minimal or absent among individuals with lower TLGluMR. Diagnosis-stratified analyses revealed that this interaction was driven by the aMCI group.

Kimberly Williams

Exercise may be associated with a small benefit for elderly people who have memory and thinking problems, according to a study published online ahead of print October 19 in Neurology. Researchers studied 70 adults randomized to six months of aerobic exercise training or usual care plus education on cognitive and everyday function. The aerobic exercise training group had significantly improved Alzheimer's Disease Assessment Scale-Cognitive subscale performance, compared with controls. This difference was not significant at six-month follow-up, however. There were no significant between-group differences at intervention completion and at the six-month follow-up in Executive Interview or Alzheimer's Disease Cooperative Study-Activities of Daily Living performance. Examination of secondary measures showed between-group differences at intervention completion favoring the exercise training program group in six-minute walk distance and in diastolic blood pressure.  
 
The FDA has approved Carnexiv (carbamazepine) injection as a short-term replacement therapy for oral carbamazepine formulations in adults with certain seizure types when oral administration is temporarily not feasible. Carnexiv has received orphan drug designation for this indication and will be the first available IV formulation of carbamazepine. The drug is intended for people with partial seizures with complex symptomatology, generalized tonic-clonic seizures, mixed seizure patterns, or other partial or generalized seizures. Carnexiv is not indicated for the treatment of absence seizures. People taking Carnexiv should not discontinue the drug abruptly because of the risk of seizures, status epilepticus, and other withdrawal signs and symptoms. In addition, Carnexiv should not be used in patients with moderate or severe renal impairment. The drug is marketed by Lundbeck, which is headquartered in Deerfield, Illinois.  
 
Chiropractic spinal manipulative therapy (CSMT) is no more effective than placebo for migraine, according to a study published online ahead of print October 2 in the European Journal of Neurology. Investigators randomized 104 migraineurs with at least one migraine attack per month to CSMT, sham chiropractic, or usual pharmacologic management for 17 months. Migraine days were significantly reduced within all three groups from baseline to post treatment. The effect continued in the CSMT and placebo groups at all follow-up time points, but the control group returned to baseline. The reduction in migraine days was not significantly different between the groups. Migraine duration and headache index were reduced significantly more in the CSMT group than in the control group toward the end of follow-up.   
 
Video monitoring facilitates nocturnal surveillance of patients with epilepsy, but the costs are high, according to a study published online ahead of print September 30 in Epilepsia. For six months, researchers asked caregivers at an epilepsy unit to specify whether an acoustic detection system, bed motion sensor, or video monitoring alerted them to seizures and whether the alerts led to interventions. They identified 1,208 seizures in 37 people. Four people had no nocturnal seizures, and 33% of seizures were seen only on video. In 14% of seizures, including 10% of seizures seen only on video, an intervention was made. The extra costs of monitoring were 7,035 euro per seizure seen only on video and leading to an intervention. The results underscore the need for reliable seizure-detection devices, said the authors.  
 
A higher level of physical activity may not reduce a woman's risk of multiple sclerosis (MS), according to a study published online ahead of print September 28 in Neurology. Researchers calculated total metabolic equivalent hours of physical activity per week for women participating in the Nurses' Health Study (NHS) and NHS II. There were 341 confirmed MS cases with first symptoms after baseline. Participants also reported early-life activity. The investigators analyzed the data with Cox proportional hazards models. Compared with women in the lowest baseline physical activity quartile, women in the highest quartile had a 27% reduced rate of MS. This trend was not present in six-year lagged analyses, however. In NHS II, total early life activity at ages 12 to 22 was not associated with MS.  
 
Youth with primary hypertension have significantly worse performance on neurocognitive testing, compared with normotensive controls, according to a study published online ahead of print September 27 in the Journal of Pediatrics.Seventy-five children with newly diagnosed, untreated hypertension and 75 frequency-matched normotensive controls had baseline neurocognitive testing as part of a prospective multicenter study of cognition in primary hypertension. The participants completed general intelligence, attention, memory, executive function, and processing speed tests. Parents rated participants' executive function and sleep disordered breathing. The study groups were well matched. Hypertension was independently associated with worse memory, attention, and executive function, compared with normotension. Results indicated a significant interaction between disordered sleep and hypertension on ratings of executive function. Hypertension heightened the association between increased disordered sleep and worse executive function.
 
Headache disorders may be associated with an increased risk for the development of new-onset hypothyroidism, according to a study published online ahead of print September 27 in Headache. This longitudinal retrospective cohort study used data from 8,412 participants enrolled in the Fernald Medical Monitoring Program. Participants underwent physical examinations and thyroid function testing every three years during the 20-year program. The primary outcome measure was new-onset hypothyroidism, defined as the initiation of thyroid replacement therapy or thyroid-stimulating hormone test value greater than or equal to 10 without thyroid medication. Headache disorders were present in about 26% of the participants, and new-onset hypothyroidism developed in approximately 7% of participants. The hazard ratio for the development of new-onset hypothyroidism was 1.21 for people with headache disorders.
 
People with epilepsy can face various psychosocial adversities and extensively report feeling discriminated against, compared with the general population, according to a study published online ahead of print September 16 in Epilepsia. The Adult Psychiatric Morbidity Survey 2007 included comprehensive interviews with 7,403 people. Overall, people with epilepsy were sevenfold more likely to have reported experiencing discrimination due to health problems than the general population without epilepsy. People with epilepsy also had greater odds of experiencing domestic violence and sexual abuse than the general population, although these associations were also found in people with other chronic conditions. There was less evidence of an association between epilepsy and a history of physical abuse or having a greater burden of other stressful life events.  
 
Short episodes of atrial tachycardia or fibrillation are not associated with increased risk of clinical events, compared with absence of these episodes, according to a study published October 18 in Circulation. The Registry of Atrial Tachycardia and Atrial Fibrillation Episodes enrolled 5,379 patients with pacemakers or implantable cardioverter defibrillators. There were 478 hospitalizations among 342 patients for clinical events. Study authors adjudicated 37,531 electrograms. Patients with clinical events were more likely than those without them to have long atrial tachycardia or fibrillation. Only short episodes of atrial tachycardia or fibrillation were documented in 9% of patients with pacemakers and in 16% of patients with implantable cardioverter defibrillators. Patients with clinical events were no more likely than those without them to have short atrial tachycardia or fibrillation.
 
A brain signature identifies patients with fibromyalgia with 93% accuracy, according to a study published online ahead of print August 31 in Pain. Researchers examined 37 patients with fibromyalgia and 35 matched healthy controls. They analyzed participants' functional MRI responses to painful pressure and nonpainful multisensory stimulation. Investigators used machine-learning techniques to identify a brain-based fibromyalgia signature. When exposed to the same painful stimuli, patients with fibromyalgia had greater Neurologic Pain Signature responses. Furthermore, a new pain-related classifier revealed augmented responses in sensory integration and self-referential regions in fibromyalgia, and reduced responses in the lateral frontal cortex. Combined activity in the Neurologic Pain Signature, fibromyalgia pain, and multisensory patterns classified patients vs. controls with 92% sensitivity and 94% specificity in individuals who were not part of the study sample.  
 
Children have measurable brain changes after a single season of youth football, even when they do not sustain a concussion, according to a study published online ahead of print October 24 in Radiology. Head impact data were recorded using the Head Impact Telemetry system and quantified as the combined-probability risk-weighted cumulative exposure. Twenty-five male participants were evaluated for seasonal fractional anisotropy changes in the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus. There were statistically significant linear relationships between risk-weighted cumulative exposure and decreased fractional anisotropy in the whole, core, and terminals of the left inferior fronto-occipital fasciculus. A trend toward statistical significance in the right superior longitudinal fasciculus was observed. Decrease in fractional anisotropy of the right superior longitudinal fasciculus terminal was significantly correlated with risk-weighted cumulative exposure.
 
Zika virus contributes to the development of Guillain-Barré syndrome, according to a study published online ahead of print October 5 in the New England Journal of Medicine. From November 2015 through March 2016, clusters of cases of Guillain-Barré syndrome were observed during an outbreak of Zika virus in Colombia. Researchers characterized the clinical features of 68 patients with Guillain-Barré syndrome during the outbreak and investigated their relationship with Zika virus infection. In all, 97% of patients had symptoms compatible with Zika virus infection before the onset of Guillain-Barré syndrome. Among the 42 patients who had samples tested for Zika virus infection, the results were positive in 40%. Most of the positive results were in urine samples, although three samples of CSF were also positive.  
 
Among patients with amnestic mild cognitive impairment (aMCI), women have better verbal memory than men despite similar levels of brain hypometabolism, according to a study published online ahead of print October 5 in Neurology. In the Alzheimer's Disease Neuroimaging Initiative, 390 controls, 672 participants with aMCI, and 254 people with Alzheimer's disease dementia completed the Rey Auditory Verbal Learning Test and [18F]-fluorodeoxyglucose-PET. Female sex, higher temporal lobe glucose metabolic rates (TLGluMR), and the interaction of the two factors were associated with better verbal memory. The female advantage in verbal memory was greatest in people with moderate to high TLGluMR and minimal or absent among individuals with lower TLGluMR. Diagnosis-stratified analyses revealed that this interaction was driven by the aMCI group.

Kimberly Williams

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Deep brain stimulation for early Parkinson’s disease has long-term benefit

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– The use of subthalamic nucleus deep brain stimulation (DBS) along with optimal drug therapy in patients with early stage Parkinson’s disease produced clinically meaningful improvements in clinician-assessed motor control that lasted at least 5 years in a prospective pilot study.

If the findings bear out a phase III trial that has been approved, DBS may become a valuable method to achieve long-term improvement in motor skills in patients with Parkinson’s disease.

Dr. Mallory Hacker
Mallory Hacker, PhD, of Vanderbilt University, Nashville, Tenn., presented the latest results of a subanalysis of a pilot, prospective, randomized, controlled, single-blind clinical trial as a poster and a brief oral presentation at the annual meeting of the American Neurological Association.

The pilot trial involved 30 patients with Parkinson’s disease, aged 50-75 years, and demonstrated the safety and benefit of DBS in conjunction with optimal drug therapy (ODT) – involving drugs such as carbidopa/levodopa, pramipexole, ropinirole, and selegiline – compared with ODT alone in improving motor scores of the patients through 2 years (Parkinsonism Relat Disord. 2014. 20[7]:731-7). The latest subanalysis of the trial data took a longer look, examining the effect of DBS through 5 years.

The subanalysis involved 28 patients; 14 in the DBS plus ODT group and 14 in the ODT-only group. Both groups were predominantly male and were similar in age at baseline (about 61 years). Motor control was assessed during the periods when DBS was applied and not applied by using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III (clinician assessed) and the Hoehn and Yahr scale.

Over the 5-year period, mean UPDRS motor scores progressively worsened for the ODT group but improved for patients receiving DBS. Patients who received DBS plus ODT had improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.

“These results demonstrate that subthalamic nucleus deep brain stimulation applied in early-stage Parkinson’s disease may provide long-term, clinically meaningful improvement in motor function over standard clinical therapy,” Dr. Hacker said.

The exact mechanism of DBS is still unknown. But, there is evidence that synaptic plasticity is involved. Dr. Hacker speculated that in early Parkinson’s, the DBS intervention comes at a time of relative neuronal stability, which is then maintained.

The results of the pilot trial led to Food and Drug Administration approval of a large-scale, multicenter clinical trial. All participants will be implanted with a DBS device and will receive ODT. Some of the subjects will be randomized to receive DBS during the first 2 years, along with ODT, with the remainder receiving ODT only. In the next 2 years, all subjects will receive DBS and ODT.

Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research. Dr. Hacker had no disclosures.

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– The use of subthalamic nucleus deep brain stimulation (DBS) along with optimal drug therapy in patients with early stage Parkinson’s disease produced clinically meaningful improvements in clinician-assessed motor control that lasted at least 5 years in a prospective pilot study.

If the findings bear out a phase III trial that has been approved, DBS may become a valuable method to achieve long-term improvement in motor skills in patients with Parkinson’s disease.

Dr. Mallory Hacker
Mallory Hacker, PhD, of Vanderbilt University, Nashville, Tenn., presented the latest results of a subanalysis of a pilot, prospective, randomized, controlled, single-blind clinical trial as a poster and a brief oral presentation at the annual meeting of the American Neurological Association.

The pilot trial involved 30 patients with Parkinson’s disease, aged 50-75 years, and demonstrated the safety and benefit of DBS in conjunction with optimal drug therapy (ODT) – involving drugs such as carbidopa/levodopa, pramipexole, ropinirole, and selegiline – compared with ODT alone in improving motor scores of the patients through 2 years (Parkinsonism Relat Disord. 2014. 20[7]:731-7). The latest subanalysis of the trial data took a longer look, examining the effect of DBS through 5 years.

The subanalysis involved 28 patients; 14 in the DBS plus ODT group and 14 in the ODT-only group. Both groups were predominantly male and were similar in age at baseline (about 61 years). Motor control was assessed during the periods when DBS was applied and not applied by using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III (clinician assessed) and the Hoehn and Yahr scale.

Over the 5-year period, mean UPDRS motor scores progressively worsened for the ODT group but improved for patients receiving DBS. Patients who received DBS plus ODT had improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.

“These results demonstrate that subthalamic nucleus deep brain stimulation applied in early-stage Parkinson’s disease may provide long-term, clinically meaningful improvement in motor function over standard clinical therapy,” Dr. Hacker said.

The exact mechanism of DBS is still unknown. But, there is evidence that synaptic plasticity is involved. Dr. Hacker speculated that in early Parkinson’s, the DBS intervention comes at a time of relative neuronal stability, which is then maintained.

The results of the pilot trial led to Food and Drug Administration approval of a large-scale, multicenter clinical trial. All participants will be implanted with a DBS device and will receive ODT. Some of the subjects will be randomized to receive DBS during the first 2 years, along with ODT, with the remainder receiving ODT only. In the next 2 years, all subjects will receive DBS and ODT.

Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research. Dr. Hacker had no disclosures.

 

– The use of subthalamic nucleus deep brain stimulation (DBS) along with optimal drug therapy in patients with early stage Parkinson’s disease produced clinically meaningful improvements in clinician-assessed motor control that lasted at least 5 years in a prospective pilot study.

If the findings bear out a phase III trial that has been approved, DBS may become a valuable method to achieve long-term improvement in motor skills in patients with Parkinson’s disease.

Dr. Mallory Hacker
Mallory Hacker, PhD, of Vanderbilt University, Nashville, Tenn., presented the latest results of a subanalysis of a pilot, prospective, randomized, controlled, single-blind clinical trial as a poster and a brief oral presentation at the annual meeting of the American Neurological Association.

The pilot trial involved 30 patients with Parkinson’s disease, aged 50-75 years, and demonstrated the safety and benefit of DBS in conjunction with optimal drug therapy (ODT) – involving drugs such as carbidopa/levodopa, pramipexole, ropinirole, and selegiline – compared with ODT alone in improving motor scores of the patients through 2 years (Parkinsonism Relat Disord. 2014. 20[7]:731-7). The latest subanalysis of the trial data took a longer look, examining the effect of DBS through 5 years.

The subanalysis involved 28 patients; 14 in the DBS plus ODT group and 14 in the ODT-only group. Both groups were predominantly male and were similar in age at baseline (about 61 years). Motor control was assessed during the periods when DBS was applied and not applied by using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III (clinician assessed) and the Hoehn and Yahr scale.

Over the 5-year period, mean UPDRS motor scores progressively worsened for the ODT group but improved for patients receiving DBS. Patients who received DBS plus ODT had improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.

“These results demonstrate that subthalamic nucleus deep brain stimulation applied in early-stage Parkinson’s disease may provide long-term, clinically meaningful improvement in motor function over standard clinical therapy,” Dr. Hacker said.

The exact mechanism of DBS is still unknown. But, there is evidence that synaptic plasticity is involved. Dr. Hacker speculated that in early Parkinson’s, the DBS intervention comes at a time of relative neuronal stability, which is then maintained.

The results of the pilot trial led to Food and Drug Administration approval of a large-scale, multicenter clinical trial. All participants will be implanted with a DBS device and will receive ODT. Some of the subjects will be randomized to receive DBS during the first 2 years, along with ODT, with the remainder receiving ODT only. In the next 2 years, all subjects will receive DBS and ODT.

Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research. Dr. Hacker had no disclosures.

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Key clinical point: Deep brain stimulation applied in early-stage Parkinson’s disease can provide clinically meaningful, long-term improvement in motor function.

Major finding: Patients who received DBS plus ODT had UPDRS motor score improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.

Data source: Secondary analysis of a pilot, prospective, randomized, controlled, single-blind clinical trial involving 30 patients with early Parkinson’s disease.

Disclosures: Dr. Hacker had no disclosures. Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research.

Computed tomography angiography after NCCT delays thrombectomy

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– Performing computed tomography angiography (CTA) following noncontrast computed tomography (NCCT) to obtain a high-resolution image of the large-vessel occlusion significantly delays the time to thrombectomy.

Dr. Kunakorn Atchaneeyasakul
The surgical removal of thrombi can be a more effective way of dealing with proximal anterior circulation–related ischemic strokes than injection of tissue plasminogen activator (tPA). Very accurate imaging of thrombi can be achieved by using CTA right after NCCT. But the accuracy comes at the cost of increased imaging time, which could be important in the thrombectomy outcome.

This study retrospectively compared the time from imaging to groin puncture, which is the first step in thrombectomy, in patients who received NCCT followed by CTA with those who received just NCCT for anterior circulation occlusion at the tertiary care University of Miami medical center. Of the 289 patients who received thrombectomy, 255 were excluded because of transfer from another hospital, occurrence of stroke while hospitalized, or use of other imaging prior to thrombectomy.

The remaining 34 patients were all evaluated with thin (0.625-mm) NCCT with automated image reconstruction. Fourteen received NCCT only, and 20 received CTA in addition to NCCT. The two groups were similar in mean age (64-71 years), gender (50% were female in each group), prevalence of hypertension (64% and 70% in the NCCT and NCCT + CTA group, respectively), and prevalence of diabetes, hyperlipidemia, atrial fibrillation, smoking, occlusion site, modified Rankin Scale score at discharge, and National Institutes of Health Stroke Scale scores at presentation and discharge. All 14 NCCT patients received intravenous tPA in contrast to 11 of the 20 (55%) NCCT + CTA patients (P = .003).

The middle cerebral artery was visualized on NCCT in about 85% of patients in each treatment group. Reperfusion was successful in 64% and 80% of patients receiving NCCT and NCCT + CTA, respectively (P = .31).

The total duration of imaging was 2 minutes (range, 1-6) in the NCCT group. The duration was significantly longer in the NCCT + CTA group (28 minutes; range, 23-65; P less than .001). The time from imaging to groin puncture was 68 minutes (range, 32-99) in the NCCT group. This was more than 30 minutes shorter than the NCCT + CTA group (104 minutes; range, 79-128; P = .030).

The times from emergency department admission to NCCT and from admission to groin puncture were similar in both groups.

“Avoiding advanced imaging in patients with anterior circulation large-vessel occlusion in whom thin-section NCCT with maximum-intensity projections reveals a hyperdense sign significantly shortens the imaging to groin puncture time,” concluded Dr. Atchaneeyasakul.

In the scenario, the detection of hyperdense middle cerebral artery would fast track the patient to the angiography suite, forgoing CTA. The result, according to Dr. Atchaneeyasakul, could alleviate a delay in thrombectomy, which could better preserve brain function.

Funding information was not provided.

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– Performing computed tomography angiography (CTA) following noncontrast computed tomography (NCCT) to obtain a high-resolution image of the large-vessel occlusion significantly delays the time to thrombectomy.

Dr. Kunakorn Atchaneeyasakul
The surgical removal of thrombi can be a more effective way of dealing with proximal anterior circulation–related ischemic strokes than injection of tissue plasminogen activator (tPA). Very accurate imaging of thrombi can be achieved by using CTA right after NCCT. But the accuracy comes at the cost of increased imaging time, which could be important in the thrombectomy outcome.

This study retrospectively compared the time from imaging to groin puncture, which is the first step in thrombectomy, in patients who received NCCT followed by CTA with those who received just NCCT for anterior circulation occlusion at the tertiary care University of Miami medical center. Of the 289 patients who received thrombectomy, 255 were excluded because of transfer from another hospital, occurrence of stroke while hospitalized, or use of other imaging prior to thrombectomy.

The remaining 34 patients were all evaluated with thin (0.625-mm) NCCT with automated image reconstruction. Fourteen received NCCT only, and 20 received CTA in addition to NCCT. The two groups were similar in mean age (64-71 years), gender (50% were female in each group), prevalence of hypertension (64% and 70% in the NCCT and NCCT + CTA group, respectively), and prevalence of diabetes, hyperlipidemia, atrial fibrillation, smoking, occlusion site, modified Rankin Scale score at discharge, and National Institutes of Health Stroke Scale scores at presentation and discharge. All 14 NCCT patients received intravenous tPA in contrast to 11 of the 20 (55%) NCCT + CTA patients (P = .003).

The middle cerebral artery was visualized on NCCT in about 85% of patients in each treatment group. Reperfusion was successful in 64% and 80% of patients receiving NCCT and NCCT + CTA, respectively (P = .31).

The total duration of imaging was 2 minutes (range, 1-6) in the NCCT group. The duration was significantly longer in the NCCT + CTA group (28 minutes; range, 23-65; P less than .001). The time from imaging to groin puncture was 68 minutes (range, 32-99) in the NCCT group. This was more than 30 minutes shorter than the NCCT + CTA group (104 minutes; range, 79-128; P = .030).

The times from emergency department admission to NCCT and from admission to groin puncture were similar in both groups.

“Avoiding advanced imaging in patients with anterior circulation large-vessel occlusion in whom thin-section NCCT with maximum-intensity projections reveals a hyperdense sign significantly shortens the imaging to groin puncture time,” concluded Dr. Atchaneeyasakul.

In the scenario, the detection of hyperdense middle cerebral artery would fast track the patient to the angiography suite, forgoing CTA. The result, according to Dr. Atchaneeyasakul, could alleviate a delay in thrombectomy, which could better preserve brain function.

Funding information was not provided.

 

– Performing computed tomography angiography (CTA) following noncontrast computed tomography (NCCT) to obtain a high-resolution image of the large-vessel occlusion significantly delays the time to thrombectomy.

Dr. Kunakorn Atchaneeyasakul
The surgical removal of thrombi can be a more effective way of dealing with proximal anterior circulation–related ischemic strokes than injection of tissue plasminogen activator (tPA). Very accurate imaging of thrombi can be achieved by using CTA right after NCCT. But the accuracy comes at the cost of increased imaging time, which could be important in the thrombectomy outcome.

This study retrospectively compared the time from imaging to groin puncture, which is the first step in thrombectomy, in patients who received NCCT followed by CTA with those who received just NCCT for anterior circulation occlusion at the tertiary care University of Miami medical center. Of the 289 patients who received thrombectomy, 255 were excluded because of transfer from another hospital, occurrence of stroke while hospitalized, or use of other imaging prior to thrombectomy.

The remaining 34 patients were all evaluated with thin (0.625-mm) NCCT with automated image reconstruction. Fourteen received NCCT only, and 20 received CTA in addition to NCCT. The two groups were similar in mean age (64-71 years), gender (50% were female in each group), prevalence of hypertension (64% and 70% in the NCCT and NCCT + CTA group, respectively), and prevalence of diabetes, hyperlipidemia, atrial fibrillation, smoking, occlusion site, modified Rankin Scale score at discharge, and National Institutes of Health Stroke Scale scores at presentation and discharge. All 14 NCCT patients received intravenous tPA in contrast to 11 of the 20 (55%) NCCT + CTA patients (P = .003).

The middle cerebral artery was visualized on NCCT in about 85% of patients in each treatment group. Reperfusion was successful in 64% and 80% of patients receiving NCCT and NCCT + CTA, respectively (P = .31).

The total duration of imaging was 2 minutes (range, 1-6) in the NCCT group. The duration was significantly longer in the NCCT + CTA group (28 minutes; range, 23-65; P less than .001). The time from imaging to groin puncture was 68 minutes (range, 32-99) in the NCCT group. This was more than 30 minutes shorter than the NCCT + CTA group (104 minutes; range, 79-128; P = .030).

The times from emergency department admission to NCCT and from admission to groin puncture were similar in both groups.

“Avoiding advanced imaging in patients with anterior circulation large-vessel occlusion in whom thin-section NCCT with maximum-intensity projections reveals a hyperdense sign significantly shortens the imaging to groin puncture time,” concluded Dr. Atchaneeyasakul.

In the scenario, the detection of hyperdense middle cerebral artery would fast track the patient to the angiography suite, forgoing CTA. The result, according to Dr. Atchaneeyasakul, could alleviate a delay in thrombectomy, which could better preserve brain function.

Funding information was not provided.

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Key clinical point: Avoiding advanced imaging in patients with large-vessel occlusion with hyperdense sign significantly shortens the imaging to groin puncture time.

Major finding: Time from imaging to groin puncture was 68 minutes for NCCT vs. 104 minutes for NCCT + CTA.

Data source: Retrospective cohort study of prospectively collected data.

Disclosures: Dr. Atchaneeyasakul had no disclosures.

Asleep deep brain stimulation placement offers advantages in Parkinson’s

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– Performing deep brain stimulation surgery for Parkinson’s disease using intraoperative CT imaging while the patient is under general anesthesia had clinical advantages and no disadvantages over surgery using microelectrode recording for lead placement with the patient awake, in a prospective, open-label study of 64 patients.

Regarding motor outcomes after asleep surgery, “We found that it was noninferior, so in other words, the change in scores following surgery were the same for asleep and awake patients,” physician assistant and study coauthor Shannon Anderson said during a poster session at the World Parkinson Congress. “What was surprising to us was that verbal fluency ... the ability to come up with the right word, actually improved in our asleep DBS [deep brain stimulation] group, which is a huge complication for patients [and] has a really negative impact on their life.”

Shannon Anderson
Shannon Anderson
Awake surgery with microelectrode recording (MER) for lead targeting has been the preferred method. Surgery under general anesthesia with intraoperative CT (ICT) has been known to have lower morbidity and better cost effectiveness, but comparative clinical outcomes were previously not known.

Patients with Parkinson’s disease and motor complications (n = 64) were enrolled prospectively at the Oregon Health & Science University in Portland. Thirty received asleep procedures under general anesthesia with ICT guidance for lead targeting to the globus pallidus pars interna (GPi; n = 21) or to the subthalamic nucleus (STN; n = 9). Thirty-four patients received DBS devices with MER guidance (15 STN; 19 GPi). At baseline, the two groups were similar in age (mean 61.1-62.7 years) and off-medication motor subscale scores of the Unified Parkinson’s Disease Rating Scale (mUPDRS; mean 43.0-43.5). The university investigators optimized the DBS parameters at 1, 2, 3, and 6 months after implantation. The same surgeon performed all the procedures at the same medical center.

Motor improvements were similar between the asleep and awake cohorts. At 6 months, the ICT (asleep) group experienced a mean improvement in motor abilities of 14.3 (plus or minus 10.88) on the mUPDRS off-medication and on DBS, compared with an improvement of 17.6 (plus or minus 12.26) for the MER (awake) group (P = .25).

Better language measures with asleep DBS

Asleep DBS with ICT resulted in improvements in aspects of language, whereas awake patients lost language abilities. The asleep group showed a 0.8-point increase in phonemic fluency and a 1.0-point increase in semantic fluency at 6 months versus a worsening on both language measures (–3.5 points and –4.7 points, respectively; both P less than .001) if DBS was performed via MER on awake patients.

Although both cohorts showed significant improvements on the 39-item Parkinson’s Disease Questionnaire at 6 months, the cohorts did not differ in their degrees of improvement. Similarly, both had improvements on scores of activities of daily living, and both cohorts had a 4-4.5 hours/day increase in “on” time without dyskinesia and a 2.6-3.5 hours/day decrease in “on” time with dyskinesia.

Patients tolerated asleep DBS well, and there were no serious complications.

The sleep surgery is much shorter, “so it’s about 2 hours long as opposed to 4, 5, sometimes 8, 10 hours with the awake. There [are fewer] complications, so less risk of hemorrhage or seizures or things like that,” Ms. Anderson said. “In a separate study, we found that it’s a much more accurate placement of the electrodes so the target is much more accurate. So, all of those things considered, we feel the asleep version is definitely the superior choice between the two.”

Being asleep is much more comfortable for the patient, added study leader Matthew Brodsky, MD. “But the biggest advantage is that it’s a single pass into the brain as opposed to multiple passes.” The average number of passes using MER is two to three per side of the brain, and in some centers, four or more. “Problems such as speech prosody are related to pokes in the brain, if you will, rather than stimulation,” he said.

Ms. Anderson said MER “is a fantastic research tool, and it gives us a lot of information on the electrophysiology, but really, there’s no need for it in the clinical application of DBS.”

Based on the asleep procedure’s accuracy, lower rate of complications, shorter operating room time, and noninferiority in terms of motor outcomes, she said, “Our recommendation is that more centers, more neurosurgeons be trained in this technique ... We’d like to see the clinical field move toward that area and really reserve microelectrode recording for the research side of things.”

“If you talk to folks who are considering brain surgery for their Parkinson’s, for some of them, the idea of being awake in the operating room and undergoing this is a barrier that they can’t quite overcome,” Dr. Brodsky said. “So, having this as an option makes it easier for them to sign up for the process.”

Richard Smeyne, PhD, director of the Jefferson Comprehensive Parkinson’s Center at Thomas Jefferson University in Philadelphia, said that the asleep procedure is the newer one and can target either the GPi or the STN. “The asleep DBS seems to have a little bit better improvement on speech afterwards than the awake DBS, and there could be several causes of this,” he said. “Some might be operative in that you can make smaller holes, you can get really nice guidance, you don’t have to sort of move around as in the awake DBS.”

In addition, CT scanning with the patients asleep in the operating room allows more time in the scanner and greater precision in anatomical placement of the DBS leads.

“If I had to choose, looking at this particular study, it would suggest that the asleep DBS is actually a better overall way to go,” Dr. Smeyne said. However, he had no objection to awake procedures “if the neurosurgeon has a record of good results with it ... But if you have the option ... that becomes an individual choice that you should discuss with the neurosurgeon.”

Some of the work presented in the study was supported by a research grant from Medtronic. Ms. Anderson and Dr. Brodsky reported having no other financial disclosures. Dr. Smeyne reported having no financial disclosures.

 

 

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– Performing deep brain stimulation surgery for Parkinson’s disease using intraoperative CT imaging while the patient is under general anesthesia had clinical advantages and no disadvantages over surgery using microelectrode recording for lead placement with the patient awake, in a prospective, open-label study of 64 patients.

Regarding motor outcomes after asleep surgery, “We found that it was noninferior, so in other words, the change in scores following surgery were the same for asleep and awake patients,” physician assistant and study coauthor Shannon Anderson said during a poster session at the World Parkinson Congress. “What was surprising to us was that verbal fluency ... the ability to come up with the right word, actually improved in our asleep DBS [deep brain stimulation] group, which is a huge complication for patients [and] has a really negative impact on their life.”

Shannon Anderson
Shannon Anderson
Awake surgery with microelectrode recording (MER) for lead targeting has been the preferred method. Surgery under general anesthesia with intraoperative CT (ICT) has been known to have lower morbidity and better cost effectiveness, but comparative clinical outcomes were previously not known.

Patients with Parkinson’s disease and motor complications (n = 64) were enrolled prospectively at the Oregon Health & Science University in Portland. Thirty received asleep procedures under general anesthesia with ICT guidance for lead targeting to the globus pallidus pars interna (GPi; n = 21) or to the subthalamic nucleus (STN; n = 9). Thirty-four patients received DBS devices with MER guidance (15 STN; 19 GPi). At baseline, the two groups were similar in age (mean 61.1-62.7 years) and off-medication motor subscale scores of the Unified Parkinson’s Disease Rating Scale (mUPDRS; mean 43.0-43.5). The university investigators optimized the DBS parameters at 1, 2, 3, and 6 months after implantation. The same surgeon performed all the procedures at the same medical center.

Motor improvements were similar between the asleep and awake cohorts. At 6 months, the ICT (asleep) group experienced a mean improvement in motor abilities of 14.3 (plus or minus 10.88) on the mUPDRS off-medication and on DBS, compared with an improvement of 17.6 (plus or minus 12.26) for the MER (awake) group (P = .25).

Better language measures with asleep DBS

Asleep DBS with ICT resulted in improvements in aspects of language, whereas awake patients lost language abilities. The asleep group showed a 0.8-point increase in phonemic fluency and a 1.0-point increase in semantic fluency at 6 months versus a worsening on both language measures (–3.5 points and –4.7 points, respectively; both P less than .001) if DBS was performed via MER on awake patients.

Although both cohorts showed significant improvements on the 39-item Parkinson’s Disease Questionnaire at 6 months, the cohorts did not differ in their degrees of improvement. Similarly, both had improvements on scores of activities of daily living, and both cohorts had a 4-4.5 hours/day increase in “on” time without dyskinesia and a 2.6-3.5 hours/day decrease in “on” time with dyskinesia.

Patients tolerated asleep DBS well, and there were no serious complications.

The sleep surgery is much shorter, “so it’s about 2 hours long as opposed to 4, 5, sometimes 8, 10 hours with the awake. There [are fewer] complications, so less risk of hemorrhage or seizures or things like that,” Ms. Anderson said. “In a separate study, we found that it’s a much more accurate placement of the electrodes so the target is much more accurate. So, all of those things considered, we feel the asleep version is definitely the superior choice between the two.”

Being asleep is much more comfortable for the patient, added study leader Matthew Brodsky, MD. “But the biggest advantage is that it’s a single pass into the brain as opposed to multiple passes.” The average number of passes using MER is two to three per side of the brain, and in some centers, four or more. “Problems such as speech prosody are related to pokes in the brain, if you will, rather than stimulation,” he said.

Ms. Anderson said MER “is a fantastic research tool, and it gives us a lot of information on the electrophysiology, but really, there’s no need for it in the clinical application of DBS.”

Based on the asleep procedure’s accuracy, lower rate of complications, shorter operating room time, and noninferiority in terms of motor outcomes, she said, “Our recommendation is that more centers, more neurosurgeons be trained in this technique ... We’d like to see the clinical field move toward that area and really reserve microelectrode recording for the research side of things.”

“If you talk to folks who are considering brain surgery for their Parkinson’s, for some of them, the idea of being awake in the operating room and undergoing this is a barrier that they can’t quite overcome,” Dr. Brodsky said. “So, having this as an option makes it easier for them to sign up for the process.”

Richard Smeyne, PhD, director of the Jefferson Comprehensive Parkinson’s Center at Thomas Jefferson University in Philadelphia, said that the asleep procedure is the newer one and can target either the GPi or the STN. “The asleep DBS seems to have a little bit better improvement on speech afterwards than the awake DBS, and there could be several causes of this,” he said. “Some might be operative in that you can make smaller holes, you can get really nice guidance, you don’t have to sort of move around as in the awake DBS.”

In addition, CT scanning with the patients asleep in the operating room allows more time in the scanner and greater precision in anatomical placement of the DBS leads.

“If I had to choose, looking at this particular study, it would suggest that the asleep DBS is actually a better overall way to go,” Dr. Smeyne said. However, he had no objection to awake procedures “if the neurosurgeon has a record of good results with it ... But if you have the option ... that becomes an individual choice that you should discuss with the neurosurgeon.”

Some of the work presented in the study was supported by a research grant from Medtronic. Ms. Anderson and Dr. Brodsky reported having no other financial disclosures. Dr. Smeyne reported having no financial disclosures.

 

 

 

– Performing deep brain stimulation surgery for Parkinson’s disease using intraoperative CT imaging while the patient is under general anesthesia had clinical advantages and no disadvantages over surgery using microelectrode recording for lead placement with the patient awake, in a prospective, open-label study of 64 patients.

Regarding motor outcomes after asleep surgery, “We found that it was noninferior, so in other words, the change in scores following surgery were the same for asleep and awake patients,” physician assistant and study coauthor Shannon Anderson said during a poster session at the World Parkinson Congress. “What was surprising to us was that verbal fluency ... the ability to come up with the right word, actually improved in our asleep DBS [deep brain stimulation] group, which is a huge complication for patients [and] has a really negative impact on their life.”

Shannon Anderson
Shannon Anderson
Awake surgery with microelectrode recording (MER) for lead targeting has been the preferred method. Surgery under general anesthesia with intraoperative CT (ICT) has been known to have lower morbidity and better cost effectiveness, but comparative clinical outcomes were previously not known.

Patients with Parkinson’s disease and motor complications (n = 64) were enrolled prospectively at the Oregon Health & Science University in Portland. Thirty received asleep procedures under general anesthesia with ICT guidance for lead targeting to the globus pallidus pars interna (GPi; n = 21) or to the subthalamic nucleus (STN; n = 9). Thirty-four patients received DBS devices with MER guidance (15 STN; 19 GPi). At baseline, the two groups were similar in age (mean 61.1-62.7 years) and off-medication motor subscale scores of the Unified Parkinson’s Disease Rating Scale (mUPDRS; mean 43.0-43.5). The university investigators optimized the DBS parameters at 1, 2, 3, and 6 months after implantation. The same surgeon performed all the procedures at the same medical center.

Motor improvements were similar between the asleep and awake cohorts. At 6 months, the ICT (asleep) group experienced a mean improvement in motor abilities of 14.3 (plus or minus 10.88) on the mUPDRS off-medication and on DBS, compared with an improvement of 17.6 (plus or minus 12.26) for the MER (awake) group (P = .25).

Better language measures with asleep DBS

Asleep DBS with ICT resulted in improvements in aspects of language, whereas awake patients lost language abilities. The asleep group showed a 0.8-point increase in phonemic fluency and a 1.0-point increase in semantic fluency at 6 months versus a worsening on both language measures (–3.5 points and –4.7 points, respectively; both P less than .001) if DBS was performed via MER on awake patients.

Although both cohorts showed significant improvements on the 39-item Parkinson’s Disease Questionnaire at 6 months, the cohorts did not differ in their degrees of improvement. Similarly, both had improvements on scores of activities of daily living, and both cohorts had a 4-4.5 hours/day increase in “on” time without dyskinesia and a 2.6-3.5 hours/day decrease in “on” time with dyskinesia.

Patients tolerated asleep DBS well, and there were no serious complications.

The sleep surgery is much shorter, “so it’s about 2 hours long as opposed to 4, 5, sometimes 8, 10 hours with the awake. There [are fewer] complications, so less risk of hemorrhage or seizures or things like that,” Ms. Anderson said. “In a separate study, we found that it’s a much more accurate placement of the electrodes so the target is much more accurate. So, all of those things considered, we feel the asleep version is definitely the superior choice between the two.”

Being asleep is much more comfortable for the patient, added study leader Matthew Brodsky, MD. “But the biggest advantage is that it’s a single pass into the brain as opposed to multiple passes.” The average number of passes using MER is two to three per side of the brain, and in some centers, four or more. “Problems such as speech prosody are related to pokes in the brain, if you will, rather than stimulation,” he said.

Ms. Anderson said MER “is a fantastic research tool, and it gives us a lot of information on the electrophysiology, but really, there’s no need for it in the clinical application of DBS.”

Based on the asleep procedure’s accuracy, lower rate of complications, shorter operating room time, and noninferiority in terms of motor outcomes, she said, “Our recommendation is that more centers, more neurosurgeons be trained in this technique ... We’d like to see the clinical field move toward that area and really reserve microelectrode recording for the research side of things.”

“If you talk to folks who are considering brain surgery for their Parkinson’s, for some of them, the idea of being awake in the operating room and undergoing this is a barrier that they can’t quite overcome,” Dr. Brodsky said. “So, having this as an option makes it easier for them to sign up for the process.”

Richard Smeyne, PhD, director of the Jefferson Comprehensive Parkinson’s Center at Thomas Jefferson University in Philadelphia, said that the asleep procedure is the newer one and can target either the GPi or the STN. “The asleep DBS seems to have a little bit better improvement on speech afterwards than the awake DBS, and there could be several causes of this,” he said. “Some might be operative in that you can make smaller holes, you can get really nice guidance, you don’t have to sort of move around as in the awake DBS.”

In addition, CT scanning with the patients asleep in the operating room allows more time in the scanner and greater precision in anatomical placement of the DBS leads.

“If I had to choose, looking at this particular study, it would suggest that the asleep DBS is actually a better overall way to go,” Dr. Smeyne said. However, he had no objection to awake procedures “if the neurosurgeon has a record of good results with it ... But if you have the option ... that becomes an individual choice that you should discuss with the neurosurgeon.”

Some of the work presented in the study was supported by a research grant from Medtronic. Ms. Anderson and Dr. Brodsky reported having no other financial disclosures. Dr. Smeyne reported having no financial disclosures.

 

 

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Key clinical point: Asleep DBS placement offers additional advantages over awake placement in patients with Parkinson’s disease.

Major finding: The asleep group showed a 0.8-point increase in phonemic fluency and a 1.0-point increase in semantic fluency at 6 months versus a worsening on both language measures (–3.5 points and –4.7 points, respectively; both P less than .001) if DBS was performed via MER on awake patients.

Data source: Prospective, open-label study of 64 patients receiving either awake or asleep deep brain stimulation placement.

Disclosures: Some of the work presented in the study was supported by a research grant from Medtronic. Ms. Anderson and Dr. Brodsky reported having no other financial disclosures. Dr. Smeyne reported having no financial disclosures.

New and Noteworthy Information—October 2016

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Resective surgery for epilepsy is cost-effective in the medium term, according to a study published online ahead of print September 5 in Epilepsia. A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed for more than five years in 15 French centers. During the second year of follow-up, the proportion of patients who had been completely seizure-free for the previous 12 months was 69.0% among participants who underwent surgery and 12.3% in the medical group. The respective rates of seizure freedom were 76.8% and 21% during the fifth year. Direct costs became significantly lower in the surgical group during the third year after surgery as a result of decreased antiepileptic drug use. Surgery became cost-effective between nine and 10 years after surgery.  
 
The NIH Toolbox Cognitive Battery can assess important dimensions of cognition in persons with intellectual disabilities, and several tests may be useful for tracking response to interventions, according to a study published September 6 in the Journal of Neurodevelopmental Disorders. In separate pilot studies of patients with fragile X syndrome, Down syndrome, and idiopathic intellectual disabilities, researchers used the web-based NIH Toolbox Cognitive Battery to measure processing speed, executive function, episodic memory, word and letter reading, receptive vocabulary, and working memory. The test's feasibility was good to excellent for people above mental age 4 for all tests except list sorting. Test-retest stability was good to excellent. More extensive psychometric studies are needed to determine the battery's true utility as a set of outcome measures, said the researchers.  
 
Graded aerobic treadmill testing is a safe, tolerable, and clinically valuable tool that can assist in the evaluation and management of pediatric sports-related concussion, according to a study published online ahead of print September 13 in the Journal of Neurosurgery: Pediatrics. Researchers conducted a retrospective chart review of 106 pediatric patients with sports-related concussion who were referred to a multidisciplinary pediatric concussion program and underwent graded aerobic treadmill testing between October 9, 2014, and February 11, 2016. Treadmill testing confirmed physiologic recovery in 96.9% of 65 patients tested, allowing successful return to play in 93.8% of patients. Of the 41 patients with physiologic post-concussion disorder who had complete follow-up and were treated with tailored submaximal exercise, 90.2% were classified as clinically improved and 80.5% successfully returned to sporting activities.  
 
Exposure to MRI during the first trimester of pregnancy, compared with nonexposure, is not associated with increased risk of harm to the fetus or in early childhood, according to a study published September 6 in JAMA. Gadolinium MRI, however, was associated with an increased risk of rheumatologic, inflammatory, or infiltrative skin conditions, and stillbirth or neonatal death. The study included 1,424,105 deliveries. Researchers compared first-trimester MRI exposure to no MRI exposure. The adjusted relative risk of stillbirth, congenital anomalies, neoplasm, or vision or hearing loss for first-trimester MRI was not significantly higher, compared with no MRI exposure. Comparing gadolinium MRI with no MRI, the adjusted hazard ratio of any rheumatologic, inflammatory, or infiltrative skin condition for first-trimester MRI was 1.36, for an adjusted risk difference of 45.3 per 1,000 person-years.  
 
In women in the United Kingdom, higher BMI is associated with increased risk of ischemic stroke, but decreased risk of hemorrhagic stroke, according to a study published online ahead of print September 7 in Neurology. Researchers recruited 1.3 million previously stroke-free women from the UK between 1996 and 2001 and followed them by record linkage for hospital admissions and deaths. Increased BMI was associated with an increased risk of ischemic stroke, but a decreased risk of hemorrhagic stroke. The BMI-associated trends for ischemic and hemorrhagic stroke were significantly different, but were not significantly different for intracerebral hemorrhage and subarachnoid hemorrhage. Published data from prospective studies showed consistently greater BMI-associated relative risks for ischemic stroke than hemorrhagic stroke, with most evidence before this study coming from Asian populations.
 
Data confirm the relevance of complement biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease, according to a study published September 6 in the Journal of Alzheimer's Disease. Results also indicate the value of multiparameter models for disease prediction and stratification. Researchers studied 292 people to measure five complement proteins and four activation products in plasma from donors with MCI, those with Alzheimer's disease, and healthy controls. Only clusterin differed significantly between control and Alzheimer's disease plasma. Overall, a model combining clusterin with relevant covariables was highly predictive of disease. Clusterin, factor I, and terminal complement complex were significantly different between individuals with MCI who had converted to dementia one year later compared with nonconverters. A model combining these three analytes with informative covariables was highly predictive of conversion.
 
Prenatal exposure to levetiracetam or topiramate may not impair a child's thinking skills, according to a study published online ahead of print August 31 in Neurology. For this cross-sectional observational study, researchers followed women enrolled in the UK Epilepsy and Pregnancy Register. The women received monotherapy levetiracetam, topiramate, or valproate, or took no therapy. Physicians conducted assessor-blinded neuropsychologic assessments of the women's children between ages 5 and 9. In the adjusted analyses, prenatal exposure to levetiracetam and topiramate were not found to be associated with reductions in children's cognitive abilities, and adverse outcomes were not associated with increasing dose. Increasing the dose of valproate was associated with poorer full-scale IQ, verbal abilities, nonverbal abilities, and expressive language ability. The evidence base for newer antiepileptic drugs is limited, said the authors.  
 
At six months, decompressive craniectomy in patients with traumatic brain injury (TBI) and refractory intracranial hypertension results in lower mortality and higher rates of vegetative state and severe disability, compared with medical care, according to a study published online ahead of print September 7 in the New England Journal of Medicine. Researchers randomly assigned 408 patients, ages 10 to 65, with TBI and refractory elevated intracranial pressure to undergo decompressive craniectomy or receive ongoing medical care. At six months, approximately 27% of patients who received a craniectomy had died, compared with 49% of patients who received medical management. Patients who survived after a craniectomy were more likely to be dependent on others for care. At 12 months, mortality was 30% among surgical patients and 52% among medical patients.
 
Contralaterally controlled functional electrical stimulation (CCFES) improves hand dexterity after stroke more than cyclic neuromuscular electrical stimulation (cNMES) does, according to a study published online ahead of print September 8 in Stroke. Researchers enrolled 80 patients with stroke and chronic moderate to severe upper extremity hemiparesis in the study. Participants were randomized to receive 10 sessions per week of CCFES- or cNMES-assisted hand-opening exercise at home, along with 20 sessions of functional task practice in the laboratory for 12 weeks. At six months post treatment, the CCFES group had an improvement of 4.6 on the Box and Block Test, compared with an improvement of 1.8 for the cNMES group. Fugl-Meyer performance and Arm Motor Abilities Test performance did not differ between groups, however.  
 
Antipsychotic use is associated with higher risk of pneumonia, regardless of the choice of drug, according to a study published online ahead of print June 11 in Chest. Researchers investigated whether incident antipsychotic use or specific antipsychotics are related to higher risk of hospitalization or death due to pneumonia in the MEDALZ cohort. The cohort includes all persons who received a clinically verified diagnosis of Alzheimer's disease in Finland from 2005 to 2011. A matched comparison cohort without Alzheimer's disease was used to compare the magnitude of risk. Antipsychotic use was associated with higher risk of pneumonia in the Alzheimer's disease cohort and with somewhat higher risk in the comparison cohort. No major differences were observed between the most commonly used antipsychotics.
 
The FDA has allowed the marketing of two Trevo clot-retrieval devices as an initial therapy to reduce paralysis, speech difficulties, and other disabilities following ischemic stroke. The agency evaluated data from a clinical trial comparing 96 randomly selected patients treated with the Trevo device and t-PA and medical management  with 249 patients who received only t-PA and medical management. Twenty-nine percent of patients treated with the Trevo device were functionally independent at three months after stroke, compared with 19% of patients who were not treated with the Trevo device. These devices should be used within six hours of symptom onset and only following treatment with a clot-dissolving drug, which needs to be given within three hours of symptom onset, said the FDA. Concentric Medical, headquartered in Mountain View, California, markets Trevo.  
 
Class I evidence suggests that for boys with Duchenne muscular dystrophy, daily use of deflazacort or prednisone is effective in preserving muscle strength over a 12-week period, according to a study published online ahead of print August 26 in Neurology. This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated the muscle strength of 196 boys ages 5 to 15 with Duchenne muscular dystrophy during a 52-week period. Participants received deflazacort, prednisone, or placebo for 12 weeks. At week 13, patients continued active treatment or switched from placebo to active treatment. All treatment groups demonstrated significant improvement in muscle strength, compared with placebo, at 12 weeks. Participants taking prednisone had significantly more weight gain than other participants at 12 weeks and at 52 weeks.  
 
The FDA has granted tentative approval to Supernus Pharmaceuticals's Supplemental New Drug Application (sNDA) requesting a label expansion for Trokendi XR (topiramate) to include prophylaxis of migraine headache in adults. The approval of the sNDA is tentative because the FDA has determined that the drug meets all of the required quality, safety, and efficacy standards for approval, but is subject to the pediatric exclusivity, which expires on March 28, 2017. Final approval may not be made effective until this exclusivity period has expired. The FDA also has granted final approval to expand the label for Trokendi XR for monotherapy treatment of partial onset seizures to include adults and pediatric patients age six and older, rather than age 10 and older. Supernus Pharmaceuticals is headquartered in Rockville, Maryland.

Kimberly Williams

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Resective surgery for epilepsy is cost-effective in the medium term, according to a study published online ahead of print September 5 in Epilepsia. A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed for more than five years in 15 French centers. During the second year of follow-up, the proportion of patients who had been completely seizure-free for the previous 12 months was 69.0% among participants who underwent surgery and 12.3% in the medical group. The respective rates of seizure freedom were 76.8% and 21% during the fifth year. Direct costs became significantly lower in the surgical group during the third year after surgery as a result of decreased antiepileptic drug use. Surgery became cost-effective between nine and 10 years after surgery.  
 
The NIH Toolbox Cognitive Battery can assess important dimensions of cognition in persons with intellectual disabilities, and several tests may be useful for tracking response to interventions, according to a study published September 6 in the Journal of Neurodevelopmental Disorders. In separate pilot studies of patients with fragile X syndrome, Down syndrome, and idiopathic intellectual disabilities, researchers used the web-based NIH Toolbox Cognitive Battery to measure processing speed, executive function, episodic memory, word and letter reading, receptive vocabulary, and working memory. The test's feasibility was good to excellent for people above mental age 4 for all tests except list sorting. Test-retest stability was good to excellent. More extensive psychometric studies are needed to determine the battery's true utility as a set of outcome measures, said the researchers.  
 
Graded aerobic treadmill testing is a safe, tolerable, and clinically valuable tool that can assist in the evaluation and management of pediatric sports-related concussion, according to a study published online ahead of print September 13 in the Journal of Neurosurgery: Pediatrics. Researchers conducted a retrospective chart review of 106 pediatric patients with sports-related concussion who were referred to a multidisciplinary pediatric concussion program and underwent graded aerobic treadmill testing between October 9, 2014, and February 11, 2016. Treadmill testing confirmed physiologic recovery in 96.9% of 65 patients tested, allowing successful return to play in 93.8% of patients. Of the 41 patients with physiologic post-concussion disorder who had complete follow-up and were treated with tailored submaximal exercise, 90.2% were classified as clinically improved and 80.5% successfully returned to sporting activities.  
 
Exposure to MRI during the first trimester of pregnancy, compared with nonexposure, is not associated with increased risk of harm to the fetus or in early childhood, according to a study published September 6 in JAMA. Gadolinium MRI, however, was associated with an increased risk of rheumatologic, inflammatory, or infiltrative skin conditions, and stillbirth or neonatal death. The study included 1,424,105 deliveries. Researchers compared first-trimester MRI exposure to no MRI exposure. The adjusted relative risk of stillbirth, congenital anomalies, neoplasm, or vision or hearing loss for first-trimester MRI was not significantly higher, compared with no MRI exposure. Comparing gadolinium MRI with no MRI, the adjusted hazard ratio of any rheumatologic, inflammatory, or infiltrative skin condition for first-trimester MRI was 1.36, for an adjusted risk difference of 45.3 per 1,000 person-years.  
 
In women in the United Kingdom, higher BMI is associated with increased risk of ischemic stroke, but decreased risk of hemorrhagic stroke, according to a study published online ahead of print September 7 in Neurology. Researchers recruited 1.3 million previously stroke-free women from the UK between 1996 and 2001 and followed them by record linkage for hospital admissions and deaths. Increased BMI was associated with an increased risk of ischemic stroke, but a decreased risk of hemorrhagic stroke. The BMI-associated trends for ischemic and hemorrhagic stroke were significantly different, but were not significantly different for intracerebral hemorrhage and subarachnoid hemorrhage. Published data from prospective studies showed consistently greater BMI-associated relative risks for ischemic stroke than hemorrhagic stroke, with most evidence before this study coming from Asian populations.
 
Data confirm the relevance of complement biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease, according to a study published September 6 in the Journal of Alzheimer's Disease. Results also indicate the value of multiparameter models for disease prediction and stratification. Researchers studied 292 people to measure five complement proteins and four activation products in plasma from donors with MCI, those with Alzheimer's disease, and healthy controls. Only clusterin differed significantly between control and Alzheimer's disease plasma. Overall, a model combining clusterin with relevant covariables was highly predictive of disease. Clusterin, factor I, and terminal complement complex were significantly different between individuals with MCI who had converted to dementia one year later compared with nonconverters. A model combining these three analytes with informative covariables was highly predictive of conversion.
 
Prenatal exposure to levetiracetam or topiramate may not impair a child's thinking skills, according to a study published online ahead of print August 31 in Neurology. For this cross-sectional observational study, researchers followed women enrolled in the UK Epilepsy and Pregnancy Register. The women received monotherapy levetiracetam, topiramate, or valproate, or took no therapy. Physicians conducted assessor-blinded neuropsychologic assessments of the women's children between ages 5 and 9. In the adjusted analyses, prenatal exposure to levetiracetam and topiramate were not found to be associated with reductions in children's cognitive abilities, and adverse outcomes were not associated with increasing dose. Increasing the dose of valproate was associated with poorer full-scale IQ, verbal abilities, nonverbal abilities, and expressive language ability. The evidence base for newer antiepileptic drugs is limited, said the authors.  
 
At six months, decompressive craniectomy in patients with traumatic brain injury (TBI) and refractory intracranial hypertension results in lower mortality and higher rates of vegetative state and severe disability, compared with medical care, according to a study published online ahead of print September 7 in the New England Journal of Medicine. Researchers randomly assigned 408 patients, ages 10 to 65, with TBI and refractory elevated intracranial pressure to undergo decompressive craniectomy or receive ongoing medical care. At six months, approximately 27% of patients who received a craniectomy had died, compared with 49% of patients who received medical management. Patients who survived after a craniectomy were more likely to be dependent on others for care. At 12 months, mortality was 30% among surgical patients and 52% among medical patients.
 
Contralaterally controlled functional electrical stimulation (CCFES) improves hand dexterity after stroke more than cyclic neuromuscular electrical stimulation (cNMES) does, according to a study published online ahead of print September 8 in Stroke. Researchers enrolled 80 patients with stroke and chronic moderate to severe upper extremity hemiparesis in the study. Participants were randomized to receive 10 sessions per week of CCFES- or cNMES-assisted hand-opening exercise at home, along with 20 sessions of functional task practice in the laboratory for 12 weeks. At six months post treatment, the CCFES group had an improvement of 4.6 on the Box and Block Test, compared with an improvement of 1.8 for the cNMES group. Fugl-Meyer performance and Arm Motor Abilities Test performance did not differ between groups, however.  
 
Antipsychotic use is associated with higher risk of pneumonia, regardless of the choice of drug, according to a study published online ahead of print June 11 in Chest. Researchers investigated whether incident antipsychotic use or specific antipsychotics are related to higher risk of hospitalization or death due to pneumonia in the MEDALZ cohort. The cohort includes all persons who received a clinically verified diagnosis of Alzheimer's disease in Finland from 2005 to 2011. A matched comparison cohort without Alzheimer's disease was used to compare the magnitude of risk. Antipsychotic use was associated with higher risk of pneumonia in the Alzheimer's disease cohort and with somewhat higher risk in the comparison cohort. No major differences were observed between the most commonly used antipsychotics.
 
The FDA has allowed the marketing of two Trevo clot-retrieval devices as an initial therapy to reduce paralysis, speech difficulties, and other disabilities following ischemic stroke. The agency evaluated data from a clinical trial comparing 96 randomly selected patients treated with the Trevo device and t-PA and medical management  with 249 patients who received only t-PA and medical management. Twenty-nine percent of patients treated with the Trevo device were functionally independent at three months after stroke, compared with 19% of patients who were not treated with the Trevo device. These devices should be used within six hours of symptom onset and only following treatment with a clot-dissolving drug, which needs to be given within three hours of symptom onset, said the FDA. Concentric Medical, headquartered in Mountain View, California, markets Trevo.  
 
Class I evidence suggests that for boys with Duchenne muscular dystrophy, daily use of deflazacort or prednisone is effective in preserving muscle strength over a 12-week period, according to a study published online ahead of print August 26 in Neurology. This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated the muscle strength of 196 boys ages 5 to 15 with Duchenne muscular dystrophy during a 52-week period. Participants received deflazacort, prednisone, or placebo for 12 weeks. At week 13, patients continued active treatment or switched from placebo to active treatment. All treatment groups demonstrated significant improvement in muscle strength, compared with placebo, at 12 weeks. Participants taking prednisone had significantly more weight gain than other participants at 12 weeks and at 52 weeks.  
 
The FDA has granted tentative approval to Supernus Pharmaceuticals's Supplemental New Drug Application (sNDA) requesting a label expansion for Trokendi XR (topiramate) to include prophylaxis of migraine headache in adults. The approval of the sNDA is tentative because the FDA has determined that the drug meets all of the required quality, safety, and efficacy standards for approval, but is subject to the pediatric exclusivity, which expires on March 28, 2017. Final approval may not be made effective until this exclusivity period has expired. The FDA also has granted final approval to expand the label for Trokendi XR for monotherapy treatment of partial onset seizures to include adults and pediatric patients age six and older, rather than age 10 and older. Supernus Pharmaceuticals is headquartered in Rockville, Maryland.

Kimberly Williams

Resective surgery for epilepsy is cost-effective in the medium term, according to a study published online ahead of print September 5 in Epilepsia. A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed for more than five years in 15 French centers. During the second year of follow-up, the proportion of patients who had been completely seizure-free for the previous 12 months was 69.0% among participants who underwent surgery and 12.3% in the medical group. The respective rates of seizure freedom were 76.8% and 21% during the fifth year. Direct costs became significantly lower in the surgical group during the third year after surgery as a result of decreased antiepileptic drug use. Surgery became cost-effective between nine and 10 years after surgery.  
 
The NIH Toolbox Cognitive Battery can assess important dimensions of cognition in persons with intellectual disabilities, and several tests may be useful for tracking response to interventions, according to a study published September 6 in the Journal of Neurodevelopmental Disorders. In separate pilot studies of patients with fragile X syndrome, Down syndrome, and idiopathic intellectual disabilities, researchers used the web-based NIH Toolbox Cognitive Battery to measure processing speed, executive function, episodic memory, word and letter reading, receptive vocabulary, and working memory. The test's feasibility was good to excellent for people above mental age 4 for all tests except list sorting. Test-retest stability was good to excellent. More extensive psychometric studies are needed to determine the battery's true utility as a set of outcome measures, said the researchers.  
 
Graded aerobic treadmill testing is a safe, tolerable, and clinically valuable tool that can assist in the evaluation and management of pediatric sports-related concussion, according to a study published online ahead of print September 13 in the Journal of Neurosurgery: Pediatrics. Researchers conducted a retrospective chart review of 106 pediatric patients with sports-related concussion who were referred to a multidisciplinary pediatric concussion program and underwent graded aerobic treadmill testing between October 9, 2014, and February 11, 2016. Treadmill testing confirmed physiologic recovery in 96.9% of 65 patients tested, allowing successful return to play in 93.8% of patients. Of the 41 patients with physiologic post-concussion disorder who had complete follow-up and were treated with tailored submaximal exercise, 90.2% were classified as clinically improved and 80.5% successfully returned to sporting activities.  
 
Exposure to MRI during the first trimester of pregnancy, compared with nonexposure, is not associated with increased risk of harm to the fetus or in early childhood, according to a study published September 6 in JAMA. Gadolinium MRI, however, was associated with an increased risk of rheumatologic, inflammatory, or infiltrative skin conditions, and stillbirth or neonatal death. The study included 1,424,105 deliveries. Researchers compared first-trimester MRI exposure to no MRI exposure. The adjusted relative risk of stillbirth, congenital anomalies, neoplasm, or vision or hearing loss for first-trimester MRI was not significantly higher, compared with no MRI exposure. Comparing gadolinium MRI with no MRI, the adjusted hazard ratio of any rheumatologic, inflammatory, or infiltrative skin condition for first-trimester MRI was 1.36, for an adjusted risk difference of 45.3 per 1,000 person-years.  
 
In women in the United Kingdom, higher BMI is associated with increased risk of ischemic stroke, but decreased risk of hemorrhagic stroke, according to a study published online ahead of print September 7 in Neurology. Researchers recruited 1.3 million previously stroke-free women from the UK between 1996 and 2001 and followed them by record linkage for hospital admissions and deaths. Increased BMI was associated with an increased risk of ischemic stroke, but a decreased risk of hemorrhagic stroke. The BMI-associated trends for ischemic and hemorrhagic stroke were significantly different, but were not significantly different for intracerebral hemorrhage and subarachnoid hemorrhage. Published data from prospective studies showed consistently greater BMI-associated relative risks for ischemic stroke than hemorrhagic stroke, with most evidence before this study coming from Asian populations.
 
Data confirm the relevance of complement biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease, according to a study published September 6 in the Journal of Alzheimer's Disease. Results also indicate the value of multiparameter models for disease prediction and stratification. Researchers studied 292 people to measure five complement proteins and four activation products in plasma from donors with MCI, those with Alzheimer's disease, and healthy controls. Only clusterin differed significantly between control and Alzheimer's disease plasma. Overall, a model combining clusterin with relevant covariables was highly predictive of disease. Clusterin, factor I, and terminal complement complex were significantly different between individuals with MCI who had converted to dementia one year later compared with nonconverters. A model combining these three analytes with informative covariables was highly predictive of conversion.
 
Prenatal exposure to levetiracetam or topiramate may not impair a child's thinking skills, according to a study published online ahead of print August 31 in Neurology. For this cross-sectional observational study, researchers followed women enrolled in the UK Epilepsy and Pregnancy Register. The women received monotherapy levetiracetam, topiramate, or valproate, or took no therapy. Physicians conducted assessor-blinded neuropsychologic assessments of the women's children between ages 5 and 9. In the adjusted analyses, prenatal exposure to levetiracetam and topiramate were not found to be associated with reductions in children's cognitive abilities, and adverse outcomes were not associated with increasing dose. Increasing the dose of valproate was associated with poorer full-scale IQ, verbal abilities, nonverbal abilities, and expressive language ability. The evidence base for newer antiepileptic drugs is limited, said the authors.  
 
At six months, decompressive craniectomy in patients with traumatic brain injury (TBI) and refractory intracranial hypertension results in lower mortality and higher rates of vegetative state and severe disability, compared with medical care, according to a study published online ahead of print September 7 in the New England Journal of Medicine. Researchers randomly assigned 408 patients, ages 10 to 65, with TBI and refractory elevated intracranial pressure to undergo decompressive craniectomy or receive ongoing medical care. At six months, approximately 27% of patients who received a craniectomy had died, compared with 49% of patients who received medical management. Patients who survived after a craniectomy were more likely to be dependent on others for care. At 12 months, mortality was 30% among surgical patients and 52% among medical patients.
 
Contralaterally controlled functional electrical stimulation (CCFES) improves hand dexterity after stroke more than cyclic neuromuscular electrical stimulation (cNMES) does, according to a study published online ahead of print September 8 in Stroke. Researchers enrolled 80 patients with stroke and chronic moderate to severe upper extremity hemiparesis in the study. Participants were randomized to receive 10 sessions per week of CCFES- or cNMES-assisted hand-opening exercise at home, along with 20 sessions of functional task practice in the laboratory for 12 weeks. At six months post treatment, the CCFES group had an improvement of 4.6 on the Box and Block Test, compared with an improvement of 1.8 for the cNMES group. Fugl-Meyer performance and Arm Motor Abilities Test performance did not differ between groups, however.  
 
Antipsychotic use is associated with higher risk of pneumonia, regardless of the choice of drug, according to a study published online ahead of print June 11 in Chest. Researchers investigated whether incident antipsychotic use or specific antipsychotics are related to higher risk of hospitalization or death due to pneumonia in the MEDALZ cohort. The cohort includes all persons who received a clinically verified diagnosis of Alzheimer's disease in Finland from 2005 to 2011. A matched comparison cohort without Alzheimer's disease was used to compare the magnitude of risk. Antipsychotic use was associated with higher risk of pneumonia in the Alzheimer's disease cohort and with somewhat higher risk in the comparison cohort. No major differences were observed between the most commonly used antipsychotics.
 
The FDA has allowed the marketing of two Trevo clot-retrieval devices as an initial therapy to reduce paralysis, speech difficulties, and other disabilities following ischemic stroke. The agency evaluated data from a clinical trial comparing 96 randomly selected patients treated with the Trevo device and t-PA and medical management  with 249 patients who received only t-PA and medical management. Twenty-nine percent of patients treated with the Trevo device were functionally independent at three months after stroke, compared with 19% of patients who were not treated with the Trevo device. These devices should be used within six hours of symptom onset and only following treatment with a clot-dissolving drug, which needs to be given within three hours of symptom onset, said the FDA. Concentric Medical, headquartered in Mountain View, California, markets Trevo.  
 
Class I evidence suggests that for boys with Duchenne muscular dystrophy, daily use of deflazacort or prednisone is effective in preserving muscle strength over a 12-week period, according to a study published online ahead of print August 26 in Neurology. This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated the muscle strength of 196 boys ages 5 to 15 with Duchenne muscular dystrophy during a 52-week period. Participants received deflazacort, prednisone, or placebo for 12 weeks. At week 13, patients continued active treatment or switched from placebo to active treatment. All treatment groups demonstrated significant improvement in muscle strength, compared with placebo, at 12 weeks. Participants taking prednisone had significantly more weight gain than other participants at 12 weeks and at 52 weeks.  
 
The FDA has granted tentative approval to Supernus Pharmaceuticals's Supplemental New Drug Application (sNDA) requesting a label expansion for Trokendi XR (topiramate) to include prophylaxis of migraine headache in adults. The approval of the sNDA is tentative because the FDA has determined that the drug meets all of the required quality, safety, and efficacy standards for approval, but is subject to the pediatric exclusivity, which expires on March 28, 2017. Final approval may not be made effective until this exclusivity period has expired. The FDA also has granted final approval to expand the label for Trokendi XR for monotherapy treatment of partial onset seizures to include adults and pediatric patients age six and older, rather than age 10 and older. Supernus Pharmaceuticals is headquartered in Rockville, Maryland.

Kimberly Williams

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CSF lactate concentration identifies postneurosurgical bacterial meningitis

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CSF lactate concentration identifies postneurosurgical bacterial meningitis

The concentration of lactate in the cerebrospinal fluid accurately identifies bacterial meningitis that develops after neurosurgery, distinguishing it from other conditions, according to a report published in BMC Infectious Diseases.

In patients who have undergone neurosurgery, failure to promptly identify and treat bacterial meningitis is associated with patient mortality as high as 50%, reported Xiong Xiao of the department of neurosurgery and the China National Clinical Research Center for Neurological Diseases at Beijing Tiantan Hospital and Capital Medical University, Beijing, and associates.

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Neisseria meningitidis colonies are shown on a blood agar plate.

A recent small study suggested that cerebrospinal fluid (CSF) lactate was accurate at differentiating postoperative bacterial meningitis from aseptic meningitis. To examine this possibility in a larger patient population, Dr. Xiao and associates reviewed 1,672 articles in the medical literature. They found few high-quality studies of this topic, but were able to perform a meta-analysis and pool the data from five studies involving 404 postneurosurgical patients treated during a 15-year period.

CSF lactate concentration identified bacterial meningitis with a pooled sensitivity of 92% and a pooled specificity of 88%. “Moreover, this test is fast, simple, objective, and affordable, and can be widely applied in hospitals,” the investigators wrote (BMC Infect Dis. 2016;16:483. doi: 10.1186/s12879-016-1818-2).Larger prospective studies are needed to confirm this finding and to provide a more thorough understanding of the indicators of postneurosurgical meningitis, Dr. Xiao and associates added.

This study was supported by Beijing Tiantan Hospital Funds for Young Scholars, the Ministry of Science and Technology of China, and the Beijing Talents Fund. Dr. Xiao and associates reported having no relevant financial disclosures.

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The concentration of lactate in the cerebrospinal fluid accurately identifies bacterial meningitis that develops after neurosurgery, distinguishing it from other conditions, according to a report published in BMC Infectious Diseases.

In patients who have undergone neurosurgery, failure to promptly identify and treat bacterial meningitis is associated with patient mortality as high as 50%, reported Xiong Xiao of the department of neurosurgery and the China National Clinical Research Center for Neurological Diseases at Beijing Tiantan Hospital and Capital Medical University, Beijing, and associates.

Courtesy CDC
Neisseria meningitidis colonies are shown on a blood agar plate.

A recent small study suggested that cerebrospinal fluid (CSF) lactate was accurate at differentiating postoperative bacterial meningitis from aseptic meningitis. To examine this possibility in a larger patient population, Dr. Xiao and associates reviewed 1,672 articles in the medical literature. They found few high-quality studies of this topic, but were able to perform a meta-analysis and pool the data from five studies involving 404 postneurosurgical patients treated during a 15-year period.

CSF lactate concentration identified bacterial meningitis with a pooled sensitivity of 92% and a pooled specificity of 88%. “Moreover, this test is fast, simple, objective, and affordable, and can be widely applied in hospitals,” the investigators wrote (BMC Infect Dis. 2016;16:483. doi: 10.1186/s12879-016-1818-2).Larger prospective studies are needed to confirm this finding and to provide a more thorough understanding of the indicators of postneurosurgical meningitis, Dr. Xiao and associates added.

This study was supported by Beijing Tiantan Hospital Funds for Young Scholars, the Ministry of Science and Technology of China, and the Beijing Talents Fund. Dr. Xiao and associates reported having no relevant financial disclosures.

The concentration of lactate in the cerebrospinal fluid accurately identifies bacterial meningitis that develops after neurosurgery, distinguishing it from other conditions, according to a report published in BMC Infectious Diseases.

In patients who have undergone neurosurgery, failure to promptly identify and treat bacterial meningitis is associated with patient mortality as high as 50%, reported Xiong Xiao of the department of neurosurgery and the China National Clinical Research Center for Neurological Diseases at Beijing Tiantan Hospital and Capital Medical University, Beijing, and associates.

Courtesy CDC
Neisseria meningitidis colonies are shown on a blood agar plate.

A recent small study suggested that cerebrospinal fluid (CSF) lactate was accurate at differentiating postoperative bacterial meningitis from aseptic meningitis. To examine this possibility in a larger patient population, Dr. Xiao and associates reviewed 1,672 articles in the medical literature. They found few high-quality studies of this topic, but were able to perform a meta-analysis and pool the data from five studies involving 404 postneurosurgical patients treated during a 15-year period.

CSF lactate concentration identified bacterial meningitis with a pooled sensitivity of 92% and a pooled specificity of 88%. “Moreover, this test is fast, simple, objective, and affordable, and can be widely applied in hospitals,” the investigators wrote (BMC Infect Dis. 2016;16:483. doi: 10.1186/s12879-016-1818-2).Larger prospective studies are needed to confirm this finding and to provide a more thorough understanding of the indicators of postneurosurgical meningitis, Dr. Xiao and associates added.

This study was supported by Beijing Tiantan Hospital Funds for Young Scholars, the Ministry of Science and Technology of China, and the Beijing Talents Fund. Dr. Xiao and associates reported having no relevant financial disclosures.

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Key clinical point: CSF lactate concentration accurately identifies bacterial meningitis that develops after neurosurgery.

Major finding: CSF lactate concentration identified bacterial meningitis with a pooled sensitivity of 92% and a pooled specificity of 88%.

Data source: A meta-analysis of five published studies involving 404 patients during a 15-year period.

Disclosures: This study was supported by Beijing Tiantan Hospital Funds for Young Scholars, the Ministry of Science and Technology of China, and the Beijing Talents Fund. Dr. Xiao and associates reported having no relevant financial disclosures.

Cognitive-behavioral therapy eases postconcussive symptoms in teens

Adding CBT adds value if patients are receptive
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Cognitive-behavioral therapy eases postconcussive symptoms in teens

Adolescents who underwent cognitive-behavioral therapy (CBT) as part of postconcussion care reported significantly lower levels of postconcussive symptoms and depressive symptoms in a randomized trial of 49 patients aged 11-17 years. The report was published online Sept. 12 in Pediatrics.

“Affective symptoms, including depression and anxiety, commonly co-occur with cognitive and somatic symptoms and may prolong recovery from postconcussive symptoms, wrote Carolyn A. McCarty, PhD, of Seattle Children’s Hospital, Washington, and her colleagues. “The complexities of managing persistent postconcussive symptoms in conjunction with comorbid psychological symptoms create a significant burden for injured children and adolescents, their families, and schools” (Pediatrics. 2016. doi: 10.1542/peds.2016-0459).

©s-c-s/Thinkstock

To determine the impact of CBT on persistent symptoms in adolescents with concussions, the researchers randomized 49 patients to usual care or a collaborative care plan that included usual care plus CBT.

After 6 months, approximately 13% of the teens in the CBT group reported high levels of postconcussive symptoms, compared with 42% of controls. In addition, 78% of CBT patients reported a depressive symptom reduction of more than 50%, compared with 46% of controls.

Concussions were diagnosed by sports medicine or rehabilitative medicine specialists. The patients assigned to CBT received usual care management, CBT, and possible psychopharmacological consultation. Control patients received usual concussion care, generally defined as an initial visit with a sports medicine physician and assessments at 1, 3, and 6 months. Usual care also could include MRI, sleep medication, and subthreshold exercise, depending on the patient. No serious adverse events were reported. The average age of the patients was 15 years, approximately 65% were girls, and 76% were white.

Overall, 83% of the CBT patients and 87% of their parents were “very satisfied” with their care, compared with 46% of patients and 29% of parents in the control group.

“Although patients in both groups showed symptom reduction in the first 3 months, only those who received collaborative care demonstrated sustained improvements through 6 months of follow-up,” Dr. McCarty and her colleagues wrote.

The results were limited by several factors including the small size of the study, the researchers said. However, the findings “prompt more investigation into the role of affective symptoms in perpetuating physical symptoms secondary to prolonged recovery from sports-related concussion,” and also suggest that collaborative care can help improve persistent postconcussive symptoms in teens.

Dr. McCarty and her colleagues had no relevant financial conflicts to disclose. The Seattle Sports Concussion Research Collaborative supported the study.

 

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Increasing numbers of adolescents are presenting to physicians for management of concussions. This is mainly because of much greater awareness of the signs, symptoms, and potential adverse effects. While the majority of concussed teens recover in less than 2 weeks, 10%-15% will have prolonged symptoms (greater than 1 month), which has significant negative impact on their health, mood, social functioning, and academic performance. This is the first study to provide evidence-based guidance for treating these slow-to-recover teens.

I definitely believe there is value in adding CBT to postconcussive therapy for teens. I have seen CBT help a large number of my own patients who are suffering from prolonged postconcussion symptoms, so it is good to see the results of this well-done study support this approach. One caveat with CBT is that its success hinges on the patient’s being receptive to the idea of CBT and consistent with applying it in daily life, so it may not work for teens who are not motivated to learn and apply its techniques.

I am not surprised by these results of the study. A large proportion of the adolescents I treat for concussions are those referred from their pediatricians because they are suffering from prolonged symptoms. We have anecdotally noted that when a collaborative care model is applied, similar to what was provided for the intervention group in this study, including CBT, patients experience more rapid decrease in symptoms, improved mood, and smoother transition back to baseline functioning, especially in school. I suspect this is because CBT teaches them effective coping skills, and the bonus is that these skills are incredibly useful across one’s lifetime, not just for concussion recovery.

Adolescents who are slow to recover from a concussion commonly experience depressive symptoms. This study suggests CBT is a promising treatment for improving mood and facilitating recovery for these teens. However, a larger study is needed with more diverse subject population. This study included only 49 subjects, and the majority of them were white females. A larger study is needed to determine whether CBT is as feasible and effective for other populations of teens with prolonged concussion symptoms. Also, longer-term longitudinal studies are needed to better understand the etiology of persistent postconcussive symptoms and long-term effects 10-20 years down the road.

Cynthia LaBella, MD, is director of the concussion program at Ann & Robert H. Lurie Children’s Hospital of Chicago. Dr. LaBella said she had no relevant financial disclosures.

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Increasing numbers of adolescents are presenting to physicians for management of concussions. This is mainly because of much greater awareness of the signs, symptoms, and potential adverse effects. While the majority of concussed teens recover in less than 2 weeks, 10%-15% will have prolonged symptoms (greater than 1 month), which has significant negative impact on their health, mood, social functioning, and academic performance. This is the first study to provide evidence-based guidance for treating these slow-to-recover teens.

I definitely believe there is value in adding CBT to postconcussive therapy for teens. I have seen CBT help a large number of my own patients who are suffering from prolonged postconcussion symptoms, so it is good to see the results of this well-done study support this approach. One caveat with CBT is that its success hinges on the patient’s being receptive to the idea of CBT and consistent with applying it in daily life, so it may not work for teens who are not motivated to learn and apply its techniques.

I am not surprised by these results of the study. A large proportion of the adolescents I treat for concussions are those referred from their pediatricians because they are suffering from prolonged symptoms. We have anecdotally noted that when a collaborative care model is applied, similar to what was provided for the intervention group in this study, including CBT, patients experience more rapid decrease in symptoms, improved mood, and smoother transition back to baseline functioning, especially in school. I suspect this is because CBT teaches them effective coping skills, and the bonus is that these skills are incredibly useful across one’s lifetime, not just for concussion recovery.

Adolescents who are slow to recover from a concussion commonly experience depressive symptoms. This study suggests CBT is a promising treatment for improving mood and facilitating recovery for these teens. However, a larger study is needed with more diverse subject population. This study included only 49 subjects, and the majority of them were white females. A larger study is needed to determine whether CBT is as feasible and effective for other populations of teens with prolonged concussion symptoms. Also, longer-term longitudinal studies are needed to better understand the etiology of persistent postconcussive symptoms and long-term effects 10-20 years down the road.

Cynthia LaBella, MD, is director of the concussion program at Ann & Robert H. Lurie Children’s Hospital of Chicago. Dr. LaBella said she had no relevant financial disclosures.

Body

Increasing numbers of adolescents are presenting to physicians for management of concussions. This is mainly because of much greater awareness of the signs, symptoms, and potential adverse effects. While the majority of concussed teens recover in less than 2 weeks, 10%-15% will have prolonged symptoms (greater than 1 month), which has significant negative impact on their health, mood, social functioning, and academic performance. This is the first study to provide evidence-based guidance for treating these slow-to-recover teens.

I definitely believe there is value in adding CBT to postconcussive therapy for teens. I have seen CBT help a large number of my own patients who are suffering from prolonged postconcussion symptoms, so it is good to see the results of this well-done study support this approach. One caveat with CBT is that its success hinges on the patient’s being receptive to the idea of CBT and consistent with applying it in daily life, so it may not work for teens who are not motivated to learn and apply its techniques.

I am not surprised by these results of the study. A large proportion of the adolescents I treat for concussions are those referred from their pediatricians because they are suffering from prolonged symptoms. We have anecdotally noted that when a collaborative care model is applied, similar to what was provided for the intervention group in this study, including CBT, patients experience more rapid decrease in symptoms, improved mood, and smoother transition back to baseline functioning, especially in school. I suspect this is because CBT teaches them effective coping skills, and the bonus is that these skills are incredibly useful across one’s lifetime, not just for concussion recovery.

Adolescents who are slow to recover from a concussion commonly experience depressive symptoms. This study suggests CBT is a promising treatment for improving mood and facilitating recovery for these teens. However, a larger study is needed with more diverse subject population. This study included only 49 subjects, and the majority of them were white females. A larger study is needed to determine whether CBT is as feasible and effective for other populations of teens with prolonged concussion symptoms. Also, longer-term longitudinal studies are needed to better understand the etiology of persistent postconcussive symptoms and long-term effects 10-20 years down the road.

Cynthia LaBella, MD, is director of the concussion program at Ann & Robert H. Lurie Children’s Hospital of Chicago. Dr. LaBella said she had no relevant financial disclosures.

Title
Adding CBT adds value if patients are receptive
Adding CBT adds value if patients are receptive

Adolescents who underwent cognitive-behavioral therapy (CBT) as part of postconcussion care reported significantly lower levels of postconcussive symptoms and depressive symptoms in a randomized trial of 49 patients aged 11-17 years. The report was published online Sept. 12 in Pediatrics.

“Affective symptoms, including depression and anxiety, commonly co-occur with cognitive and somatic symptoms and may prolong recovery from postconcussive symptoms, wrote Carolyn A. McCarty, PhD, of Seattle Children’s Hospital, Washington, and her colleagues. “The complexities of managing persistent postconcussive symptoms in conjunction with comorbid psychological symptoms create a significant burden for injured children and adolescents, their families, and schools” (Pediatrics. 2016. doi: 10.1542/peds.2016-0459).

©s-c-s/Thinkstock

To determine the impact of CBT on persistent symptoms in adolescents with concussions, the researchers randomized 49 patients to usual care or a collaborative care plan that included usual care plus CBT.

After 6 months, approximately 13% of the teens in the CBT group reported high levels of postconcussive symptoms, compared with 42% of controls. In addition, 78% of CBT patients reported a depressive symptom reduction of more than 50%, compared with 46% of controls.

Concussions were diagnosed by sports medicine or rehabilitative medicine specialists. The patients assigned to CBT received usual care management, CBT, and possible psychopharmacological consultation. Control patients received usual concussion care, generally defined as an initial visit with a sports medicine physician and assessments at 1, 3, and 6 months. Usual care also could include MRI, sleep medication, and subthreshold exercise, depending on the patient. No serious adverse events were reported. The average age of the patients was 15 years, approximately 65% were girls, and 76% were white.

Overall, 83% of the CBT patients and 87% of their parents were “very satisfied” with their care, compared with 46% of patients and 29% of parents in the control group.

“Although patients in both groups showed symptom reduction in the first 3 months, only those who received collaborative care demonstrated sustained improvements through 6 months of follow-up,” Dr. McCarty and her colleagues wrote.

The results were limited by several factors including the small size of the study, the researchers said. However, the findings “prompt more investigation into the role of affective symptoms in perpetuating physical symptoms secondary to prolonged recovery from sports-related concussion,” and also suggest that collaborative care can help improve persistent postconcussive symptoms in teens.

Dr. McCarty and her colleagues had no relevant financial conflicts to disclose. The Seattle Sports Concussion Research Collaborative supported the study.

 

Adolescents who underwent cognitive-behavioral therapy (CBT) as part of postconcussion care reported significantly lower levels of postconcussive symptoms and depressive symptoms in a randomized trial of 49 patients aged 11-17 years. The report was published online Sept. 12 in Pediatrics.

“Affective symptoms, including depression and anxiety, commonly co-occur with cognitive and somatic symptoms and may prolong recovery from postconcussive symptoms, wrote Carolyn A. McCarty, PhD, of Seattle Children’s Hospital, Washington, and her colleagues. “The complexities of managing persistent postconcussive symptoms in conjunction with comorbid psychological symptoms create a significant burden for injured children and adolescents, their families, and schools” (Pediatrics. 2016. doi: 10.1542/peds.2016-0459).

©s-c-s/Thinkstock

To determine the impact of CBT on persistent symptoms in adolescents with concussions, the researchers randomized 49 patients to usual care or a collaborative care plan that included usual care plus CBT.

After 6 months, approximately 13% of the teens in the CBT group reported high levels of postconcussive symptoms, compared with 42% of controls. In addition, 78% of CBT patients reported a depressive symptom reduction of more than 50%, compared with 46% of controls.

Concussions were diagnosed by sports medicine or rehabilitative medicine specialists. The patients assigned to CBT received usual care management, CBT, and possible psychopharmacological consultation. Control patients received usual concussion care, generally defined as an initial visit with a sports medicine physician and assessments at 1, 3, and 6 months. Usual care also could include MRI, sleep medication, and subthreshold exercise, depending on the patient. No serious adverse events were reported. The average age of the patients was 15 years, approximately 65% were girls, and 76% were white.

Overall, 83% of the CBT patients and 87% of their parents were “very satisfied” with their care, compared with 46% of patients and 29% of parents in the control group.

“Although patients in both groups showed symptom reduction in the first 3 months, only those who received collaborative care demonstrated sustained improvements through 6 months of follow-up,” Dr. McCarty and her colleagues wrote.

The results were limited by several factors including the small size of the study, the researchers said. However, the findings “prompt more investigation into the role of affective symptoms in perpetuating physical symptoms secondary to prolonged recovery from sports-related concussion,” and also suggest that collaborative care can help improve persistent postconcussive symptoms in teens.

Dr. McCarty and her colleagues had no relevant financial conflicts to disclose. The Seattle Sports Concussion Research Collaborative supported the study.

 

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Key clinical point: Adolescents with persistent postconcussive symptoms and depressive symptoms improved significantly after the addition of CBT to usual care.

Major finding: After 6 months, 13% of teens who underwent CBT plus usual care reported high levels of postconcussive symptoms, compared with 42% of controls.

Data source: A randomized trial of 49 adolescents aged 11-17 years with persistent postconcussive symptoms at least 1 month after a sports-related concussion,

Disclosures: The researchers had no financial conflicts to disclose. The Seattle Sports Concussion Research Collaborative supported the study.

FDA: New labeling warns against combining opioids, benzodiazepines

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Labeling for prescription opioid pain or cough medicines and benzodiazepines will now carry the strongest available warning regarding serious side effects and death associated with their combined use, according to the Food and Drug Administration.

The new boxed warnings urge health care professionals to limit prescribing opioid pain medicines with benzodiazepines or other central nervous system depressants only to patients for whom alternative treatment options are inadequate, and to limit dosages and treatment duration to the minimum possible while achieving the desired clinical effect.

 

“First, the FDA is requiring companies to update their product labeling for ... benzodiazepines and opioids to include possible harms when they are used together. Second, we are requiring new or updated medication guides for these drugs reflecting those same warnings,” said Doug Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research, during a telebriefing.

Opioids will include a warning regarding prescribing with benzodiazepines and other central nervous system depressants, including alcohol. Benzodiazepines will include a warning regarding prescribing with opioids.

In addition, the FDA has issued a safety communication to “warn the public about the serious risk of taking these products together to help make doctors more cautious and patients better informed,” Dr. Throckmorton said.

The action comes amid ongoing efforts to address an epidemic of opioid addiction across the United States, and in response to a first-of-its-kind “citizen petition” calling for the boxed warnings.

A coalition of health officials from multiple cities, states, and U.S. territories initiated that petition in February, and thousands of concerned community members started an additional online petition. Those petitions were in response to both the increasing combined use of opioids and benzodiazepines and a concomitant increase in the risk of serious side effects and deaths associated with their combined use, according to Baltimore City Health Commissioner Leana Wen, MD.

As an emergency physician, Dr. Wen said that she has seen firsthand the alarming trends; one in three unintentional overdose deaths from prescribed opioids also involve benzodiazepines, she noted.

“In my state of Maryland in 2014, benzodiazepines were associated with 19% of prescription opioid deaths, and 59% of benzodiazepine-associated deaths involved prescription opioids. We also noted the growing biological evidence that combining these medications caused sleepiness and slowed breathing, increasing the likelihood of a fatal overdose,” she said.

Dr. Throckmorton further noted that emergency department visits and deaths involving patients prescribed both opioids and benzodiazepines have increased significantly over time. From 2004 to 2011, the rate of nonmedical use–related emergency department visits increased significantly each year, and overdose deaths involving both drug classes during that period nearly tripled on an annual basis.

 

Dr. Robert Califf

“Communities have been seeing this trend for some time, but ultimately we needed data in order to act today,” FDA Commissioner Robert Califf, MD, said during the telebriefing.

The current action is just “one part of a larger effort to address this epidemic.

“We remain focused and deeply committed to contributing to the comprehensive effort to address the opioid epidemic,” Dr. Califf said. The FDA “will continue to monitor these products carefully and take additional actions as needed, and will share updates with the public as necessary as we work to address this public health crisis.”

Dr. Califf noted that the current action is part of the FDA’s Opioids Action Plan, which is “importantly not meant just to cover illicit or abusive use of opioids.”

“So, you’ll be hearing a lot more from us, because this is a national crisis that is not going away. We’re making progress on the prescribing, and we’re seeing a reduction in the use of opioids now,” he noted. “But we’re still seeing many overdoses.

“This is a continuum, and we’ll continue to try to do everything we can to address the epidemic,” Dr. Califf concluded.

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Labeling for prescription opioid pain or cough medicines and benzodiazepines will now carry the strongest available warning regarding serious side effects and death associated with their combined use, according to the Food and Drug Administration.

The new boxed warnings urge health care professionals to limit prescribing opioid pain medicines with benzodiazepines or other central nervous system depressants only to patients for whom alternative treatment options are inadequate, and to limit dosages and treatment duration to the minimum possible while achieving the desired clinical effect.

 

“First, the FDA is requiring companies to update their product labeling for ... benzodiazepines and opioids to include possible harms when they are used together. Second, we are requiring new or updated medication guides for these drugs reflecting those same warnings,” said Doug Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research, during a telebriefing.

Opioids will include a warning regarding prescribing with benzodiazepines and other central nervous system depressants, including alcohol. Benzodiazepines will include a warning regarding prescribing with opioids.

In addition, the FDA has issued a safety communication to “warn the public about the serious risk of taking these products together to help make doctors more cautious and patients better informed,” Dr. Throckmorton said.

The action comes amid ongoing efforts to address an epidemic of opioid addiction across the United States, and in response to a first-of-its-kind “citizen petition” calling for the boxed warnings.

A coalition of health officials from multiple cities, states, and U.S. territories initiated that petition in February, and thousands of concerned community members started an additional online petition. Those petitions were in response to both the increasing combined use of opioids and benzodiazepines and a concomitant increase in the risk of serious side effects and deaths associated with their combined use, according to Baltimore City Health Commissioner Leana Wen, MD.

As an emergency physician, Dr. Wen said that she has seen firsthand the alarming trends; one in three unintentional overdose deaths from prescribed opioids also involve benzodiazepines, she noted.

“In my state of Maryland in 2014, benzodiazepines were associated with 19% of prescription opioid deaths, and 59% of benzodiazepine-associated deaths involved prescription opioids. We also noted the growing biological evidence that combining these medications caused sleepiness and slowed breathing, increasing the likelihood of a fatal overdose,” she said.

Dr. Throckmorton further noted that emergency department visits and deaths involving patients prescribed both opioids and benzodiazepines have increased significantly over time. From 2004 to 2011, the rate of nonmedical use–related emergency department visits increased significantly each year, and overdose deaths involving both drug classes during that period nearly tripled on an annual basis.

 

Dr. Robert Califf

“Communities have been seeing this trend for some time, but ultimately we needed data in order to act today,” FDA Commissioner Robert Califf, MD, said during the telebriefing.

The current action is just “one part of a larger effort to address this epidemic.

“We remain focused and deeply committed to contributing to the comprehensive effort to address the opioid epidemic,” Dr. Califf said. The FDA “will continue to monitor these products carefully and take additional actions as needed, and will share updates with the public as necessary as we work to address this public health crisis.”

Dr. Califf noted that the current action is part of the FDA’s Opioids Action Plan, which is “importantly not meant just to cover illicit or abusive use of opioids.”

“So, you’ll be hearing a lot more from us, because this is a national crisis that is not going away. We’re making progress on the prescribing, and we’re seeing a reduction in the use of opioids now,” he noted. “But we’re still seeing many overdoses.

“This is a continuum, and we’ll continue to try to do everything we can to address the epidemic,” Dr. Califf concluded.

[email protected]

Labeling for prescription opioid pain or cough medicines and benzodiazepines will now carry the strongest available warning regarding serious side effects and death associated with their combined use, according to the Food and Drug Administration.

The new boxed warnings urge health care professionals to limit prescribing opioid pain medicines with benzodiazepines or other central nervous system depressants only to patients for whom alternative treatment options are inadequate, and to limit dosages and treatment duration to the minimum possible while achieving the desired clinical effect.

 

“First, the FDA is requiring companies to update their product labeling for ... benzodiazepines and opioids to include possible harms when they are used together. Second, we are requiring new or updated medication guides for these drugs reflecting those same warnings,” said Doug Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research, during a telebriefing.

Opioids will include a warning regarding prescribing with benzodiazepines and other central nervous system depressants, including alcohol. Benzodiazepines will include a warning regarding prescribing with opioids.

In addition, the FDA has issued a safety communication to “warn the public about the serious risk of taking these products together to help make doctors more cautious and patients better informed,” Dr. Throckmorton said.

The action comes amid ongoing efforts to address an epidemic of opioid addiction across the United States, and in response to a first-of-its-kind “citizen petition” calling for the boxed warnings.

A coalition of health officials from multiple cities, states, and U.S. territories initiated that petition in February, and thousands of concerned community members started an additional online petition. Those petitions were in response to both the increasing combined use of opioids and benzodiazepines and a concomitant increase in the risk of serious side effects and deaths associated with their combined use, according to Baltimore City Health Commissioner Leana Wen, MD.

As an emergency physician, Dr. Wen said that she has seen firsthand the alarming trends; one in three unintentional overdose deaths from prescribed opioids also involve benzodiazepines, she noted.

“In my state of Maryland in 2014, benzodiazepines were associated with 19% of prescription opioid deaths, and 59% of benzodiazepine-associated deaths involved prescription opioids. We also noted the growing biological evidence that combining these medications caused sleepiness and slowed breathing, increasing the likelihood of a fatal overdose,” she said.

Dr. Throckmorton further noted that emergency department visits and deaths involving patients prescribed both opioids and benzodiazepines have increased significantly over time. From 2004 to 2011, the rate of nonmedical use–related emergency department visits increased significantly each year, and overdose deaths involving both drug classes during that period nearly tripled on an annual basis.

 

Dr. Robert Califf

“Communities have been seeing this trend for some time, but ultimately we needed data in order to act today,” FDA Commissioner Robert Califf, MD, said during the telebriefing.

The current action is just “one part of a larger effort to address this epidemic.

“We remain focused and deeply committed to contributing to the comprehensive effort to address the opioid epidemic,” Dr. Califf said. The FDA “will continue to monitor these products carefully and take additional actions as needed, and will share updates with the public as necessary as we work to address this public health crisis.”

Dr. Califf noted that the current action is part of the FDA’s Opioids Action Plan, which is “importantly not meant just to cover illicit or abusive use of opioids.”

“So, you’ll be hearing a lot more from us, because this is a national crisis that is not going away. We’re making progress on the prescribing, and we’re seeing a reduction in the use of opioids now,” he noted. “But we’re still seeing many overdoses.

“This is a continuum, and we’ll continue to try to do everything we can to address the epidemic,” Dr. Califf concluded.

[email protected]

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Removal from play reduces concussion recovery time in athletes

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Sport-related concussion (SRC) recovery time can be reduced if athletes are removed from game participation, according to R.J. Elbin, PhD, of the University of Arkansas, Fayetteville, and his associates.

In the prospective study, 95 athletes sought care for an SRC at a concussion specialty clinic between Sept. 1 and Dec. 1, 2014. The athletes were divided into two groups: those who continued to play after experiencing signs and symptoms of an SRC and those who were immediately removed from play. The played group took longer to recover (44 days) than did the removed group (22 days) (P = .003).

 

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Post hoc analyses revealed that the played group demonstrated significantly worse verbal and visual memory, processing speed, and reaction time, and higher symptoms (all P less than or equal to .001), compared with the removed group at 1-7 days. From 8 to 30 days post injury, the played group demonstrated worse verbal memory (P = .009), visual memory (P less than or equal to .001), processing speed (P = .001), and greater symptoms (P = .001), compared with the removed group.

The study also showed that athletes in the played group were 8.80 times more likely to experience a protracted recovery, compared with athletes in the removed group (21 days or longer) (P less than .001). Athletes participated in a variety of sports including football, soccer, ice hockey, volleyball, field hockey, rugby, basketball, and wrestling.

“This study is the first to show that athletes who continue to play with an SRC experience a longer recovery and more time away from the sport,” researchers concluded. “These findings should be incorporated into SRC education and awareness programs for athletes, coaches, parents, and medical professionals.”

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0910).

[email protected]

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Sport-related concussion (SRC) recovery time can be reduced if athletes are removed from game participation, according to R.J. Elbin, PhD, of the University of Arkansas, Fayetteville, and his associates.

In the prospective study, 95 athletes sought care for an SRC at a concussion specialty clinic between Sept. 1 and Dec. 1, 2014. The athletes were divided into two groups: those who continued to play after experiencing signs and symptoms of an SRC and those who were immediately removed from play. The played group took longer to recover (44 days) than did the removed group (22 days) (P = .003).

 

©s-c-s/Thinkstock

Post hoc analyses revealed that the played group demonstrated significantly worse verbal and visual memory, processing speed, and reaction time, and higher symptoms (all P less than or equal to .001), compared with the removed group at 1-7 days. From 8 to 30 days post injury, the played group demonstrated worse verbal memory (P = .009), visual memory (P less than or equal to .001), processing speed (P = .001), and greater symptoms (P = .001), compared with the removed group.

The study also showed that athletes in the played group were 8.80 times more likely to experience a protracted recovery, compared with athletes in the removed group (21 days or longer) (P less than .001). Athletes participated in a variety of sports including football, soccer, ice hockey, volleyball, field hockey, rugby, basketball, and wrestling.

“This study is the first to show that athletes who continue to play with an SRC experience a longer recovery and more time away from the sport,” researchers concluded. “These findings should be incorporated into SRC education and awareness programs for athletes, coaches, parents, and medical professionals.”

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0910).

[email protected]

Sport-related concussion (SRC) recovery time can be reduced if athletes are removed from game participation, according to R.J. Elbin, PhD, of the University of Arkansas, Fayetteville, and his associates.

In the prospective study, 95 athletes sought care for an SRC at a concussion specialty clinic between Sept. 1 and Dec. 1, 2014. The athletes were divided into two groups: those who continued to play after experiencing signs and symptoms of an SRC and those who were immediately removed from play. The played group took longer to recover (44 days) than did the removed group (22 days) (P = .003).

 

©s-c-s/Thinkstock

Post hoc analyses revealed that the played group demonstrated significantly worse verbal and visual memory, processing speed, and reaction time, and higher symptoms (all P less than or equal to .001), compared with the removed group at 1-7 days. From 8 to 30 days post injury, the played group demonstrated worse verbal memory (P = .009), visual memory (P less than or equal to .001), processing speed (P = .001), and greater symptoms (P = .001), compared with the removed group.

The study also showed that athletes in the played group were 8.80 times more likely to experience a protracted recovery, compared with athletes in the removed group (21 days or longer) (P less than .001). Athletes participated in a variety of sports including football, soccer, ice hockey, volleyball, field hockey, rugby, basketball, and wrestling.

“This study is the first to show that athletes who continue to play with an SRC experience a longer recovery and more time away from the sport,” researchers concluded. “These findings should be incorporated into SRC education and awareness programs for athletes, coaches, parents, and medical professionals.”

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0910).

[email protected]

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