Neurosurgery & Trauma

Two new studies published by the New England Journal of Medicine show that progesterone has little-to-no clinical benefit when administered to patients after severe traumatic brain injury, contradicting the findings of several previous studies that were optimistic about the drug’s efficacy in treating this particular progressive disorder (doi:10.1056/NEJMoal1411090 and doi:10.1056/NEJMoa1404304).

“Progesterone has been shown to have broad neuroprotective properties in multiple animal species and in a variety of models of neurologic injury,” said Dr. Brett E. Skolnick of North Shore University Hospital, Manhasset, N.Y., who led the analysis of the Severe Traumatic Brain Injury (SYNAPSE) trial.

“A total of 20 research groups working with four species and 22 different models have found neuroprotective effects of progesterone in more than 180 experimental pharmacologic studies [and] two phase II randomized, controlled clinical trials with progesterone showed a clinical benefit,” he said.

For SYNAPSE – a multinational, placebo-controlled, prospective, randomized phase III clinical trial – investigators looked at 10,519 male and female patients, aged 16-70 years, admitted to level 1 or equivalent centers in 21 countries around the world. All individuals had nonpenetrating traumatic brain injury (TBI), Glasgow Coma Scale (GCS) scores of 8 or less, a Marshall classification score of II or higher, at least one reactive pupil, body weight of 99-298 pounds, and clinical indication for monitoring intracranial pressure. All subjects also underwent treatment within 8 hours of injury, and dosing continued for 120 hours.

Recruitment lasted from July 2010 to September 2013, with the final 6-month follow-up occurring in March 2014. Of the subjects who were randomized and went through full treatment and procedure, 591 received intravenous administration of progesterone, and 588 received a placebo. The primary outcome measure was GOS score at 6 months after initial injury, and secondary outcome measure was defined as GOS score at 3 months, mortality at 1 month and 6 months, and the GOS-E (Extended GOS) score.

Between the progesterone and placebo cohorts, there was no significant difference in the primary outcome: 189 subjects (32%) vs. 1,883 (31.1%) were in “good recovery,” 109 (18.4%) vs. 114 (19.4%) had “moderate disability,” 162 (27.4%) vs. 160 (27.2%) had “severe disability,” and 131 (22.2%) vs. 131 (22.3%) were in a “dead or vegetative state” 6 months after injury, respectively. Both adjusted and unadjusted data showed statistical insignificance (adjusted OR, 0.96).

Furthermore, mortality rates between both groups were similar, and the difference in proportion of subjects who received favorable GOS – with “good recovery” or “moderate disability,” as defined by the investigators – between the progesterone and placebo cohorts was negligible: 50.4% for progesterone vs. 50.5% for placebo.

“TBI is a complex, heterogeneous disorder, in which the primary injury initiates a variety of secondary injury cascades,” the authors noted. “These cascades involve various processes that may not be responsive to monotherapy [and] suggest that a successful therapeutic agent should influence rather than a single cascade. On the basis of the experimental data, progesterone would appear to be an appropriate candidate for this pluripotential role.”

The second study, “Progesterone for Traumatic Brain Injury: Experimental Clinical Treatment” (PROTECT III), was a double-blind, multicenter clinical trial with 882 patients randomized into cohorts receiving either progesterone or a placebo.

Subjects were randomized from April 2010 to October 2013, and were included on the basis of adults who had either severe, moderate to severe, or moderate TBI caused by a blunt mechanism, and a GOS of 4-12. Subjects were enrolled if they could begin treatment within 4 hours of initial injury. The median age of the patients was 35 years; 73.7% of subjects were men, 15.2% were black, and the mean Injury Severity Score was 24.4 on a scale of 0-75, with higher scores indicating greater severity of symptoms. The most common cause of TBI in subjects was motor vehicle accident.

Primary outcome measure was defined as the GOS-E score at 6 months after injury (1 = death, 2 = vegetative state, 3 or 4 = severe disability, 5 or 6 = moderate disability, and 7 or 8 = good recovery), while secondary outcomes measure “included mortality, the Disability Rating Scale score, the rates of nine prespecified adverse events that were considered to be potentially associated with treatment, and the rates of all reported adverse events and serious adverse events.” Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome at 6 months after injury.

The progesterone cohort comprised 442 subjects, while the remaining 440 received placebos. Investigators found that 213 (48.2%) of the progesterone subjects had favorable outcomes at 6 months after injury, and 232 (52.7%) were favorable in the placebo group; therefore, a total of 445 patients (50.5% of total population) had optimal response to treatment, and no significant difference between the two treatment options.

“Despite extensive preclinical data and two promising single-center trials, progesterone was not associated with any benefit over placebo, as measured by the GOS-E score at 6 months, in this large, multicenter clinical trial,” wrote lead author Dr. David W. Wright of Emory University, Atlanta, and his associates.

“The PROTECT III trial joins a growing list of negative or inconclusive trials in the arduous search for a treatment for TBI. To date, no treatment has succeeded at the confirmatory trial stage,” the researchers noted.

The SYNAPSE trial was funded by BHR Pharma, a division of Besins Healthcare. PROTECT III was funded by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke and the National Center for Advancing Translational Sciences; the Emory Emergency Neurosciences Laboratory at Emory University, Atlanta; and Grady Memorial Hospital, Atlanta. Several coauthors for each study had their own disclosures, as well.

[email protected]

Two new studies published by the New England Journal of Medicine show that progesterone has little-to-no clinical benefit when administered to patients after severe traumatic brain injury, contradicting the findings of several previous studies that were optimistic about the drug’s efficacy in treating this particular progressive disorder (doi:10.1056/NEJMoal1411090 and doi:10.1056/NEJMoa1404304).

“Progesterone has been shown to have broad neuroprotective properties in multiple animal species and in a variety of models of neurologic injury,” said Dr. Brett E. Skolnick of North Shore University Hospital, Manhasset, N.Y., who led the analysis of the Severe Traumatic Brain Injury (SYNAPSE) trial.

“A total of 20 research groups working with four species and 22 different models have found neuroprotective effects of progesterone in more than 180 experimental pharmacologic studies [and] two phase II randomized, controlled clinical trials with progesterone showed a clinical benefit,” he said.

For SYNAPSE – a multinational, placebo-controlled, prospective, randomized phase III clinical trial – investigators looked at 10,519 male and female patients, aged 16-70 years, admitted to level 1 or equivalent centers in 21 countries around the world. All individuals had nonpenetrating traumatic brain injury (TBI), Glasgow Coma Scale (GCS) scores of 8 or less, a Marshall classification score of II or higher, at least one reactive pupil, body weight of 99-298 pounds, and clinical indication for monitoring intracranial pressure. All subjects also underwent treatment within 8 hours of injury, and dosing continued for 120 hours.

Recruitment lasted from July 2010 to September 2013, with the final 6-month follow-up occurring in March 2014. Of the subjects who were randomized and went through full treatment and procedure, 591 received intravenous administration of progesterone, and 588 received a placebo. The primary outcome measure was GOS score at 6 months after initial injury, and secondary outcome measure was defined as GOS score at 3 months, mortality at 1 month and 6 months, and the GOS-E (Extended GOS) score.

Between the progesterone and placebo cohorts, there was no significant difference in the primary outcome: 189 subjects (32%) vs. 1,883 (31.1%) were in “good recovery,” 109 (18.4%) vs. 114 (19.4%) had “moderate disability,” 162 (27.4%) vs. 160 (27.2%) had “severe disability,” and 131 (22.2%) vs. 131 (22.3%) were in a “dead or vegetative state” 6 months after injury, respectively. Both adjusted and unadjusted data showed statistical insignificance (adjusted OR, 0.96).

Furthermore, mortality rates between both groups were similar, and the difference in proportion of subjects who received favorable GOS – with “good recovery” or “moderate disability,” as defined by the investigators – between the progesterone and placebo cohorts was negligible: 50.4% for progesterone vs. 50.5% for placebo.

“TBI is a complex, heterogeneous disorder, in which the primary injury initiates a variety of secondary injury cascades,” the authors noted. “These cascades involve various processes that may not be responsive to monotherapy [and] suggest that a successful therapeutic agent should influence rather than a single cascade. On the basis of the experimental data, progesterone would appear to be an appropriate candidate for this pluripotential role.”

The second study, “Progesterone for Traumatic Brain Injury: Experimental Clinical Treatment” (PROTECT III), was a double-blind, multicenter clinical trial with 882 patients randomized into cohorts receiving either progesterone or a placebo.

Subjects were randomized from April 2010 to October 2013, and were included on the basis of adults who had either severe, moderate to severe, or moderate TBI caused by a blunt mechanism, and a GOS of 4-12. Subjects were enrolled if they could begin treatment within 4 hours of initial injury. The median age of the patients was 35 years; 73.7% of subjects were men, 15.2% were black, and the mean Injury Severity Score was 24.4 on a scale of 0-75, with higher scores indicating greater severity of symptoms. The most common cause of TBI in subjects was motor vehicle accident.

Primary outcome measure was defined as the GOS-E score at 6 months after injury (1 = death, 2 = vegetative state, 3 or 4 = severe disability, 5 or 6 = moderate disability, and 7 or 8 = good recovery), while secondary outcomes measure “included mortality, the Disability Rating Scale score, the rates of nine prespecified adverse events that were considered to be potentially associated with treatment, and the rates of all reported adverse events and serious adverse events.” Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome at 6 months after injury.

The progesterone cohort comprised 442 subjects, while the remaining 440 received placebos. Investigators found that 213 (48.2%) of the progesterone subjects had favorable outcomes at 6 months after injury, and 232 (52.7%) were favorable in the placebo group; therefore, a total of 445 patients (50.5% of total population) had optimal response to treatment, and no significant difference between the two treatment options.

“Despite extensive preclinical data and two promising single-center trials, progesterone was not associated with any benefit over placebo, as measured by the GOS-E score at 6 months, in this large, multicenter clinical trial,” wrote lead author Dr. David W. Wright of Emory University, Atlanta, and his associates.

“The PROTECT III trial joins a growing list of negative or inconclusive trials in the arduous search for a treatment for TBI. To date, no treatment has succeeded at the confirmatory trial stage,” the researchers noted.

The SYNAPSE trial was funded by BHR Pharma, a division of Besins Healthcare. PROTECT III was funded by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke and the National Center for Advancing Translational Sciences; the Emory Emergency Neurosciences Laboratory at Emory University, Atlanta; and Grady Memorial Hospital, Atlanta. Several coauthors for each study had their own disclosures, as well.

[email protected]

Two new studies published by the New England Journal of Medicine show that progesterone has little-to-no clinical benefit when administered to patients after severe traumatic brain injury, contradicting the findings of several previous studies that were optimistic about the drug’s efficacy in treating this particular progressive disorder (doi:10.1056/NEJMoal1411090 and doi:10.1056/NEJMoa1404304).

“Progesterone has been shown to have broad neuroprotective properties in multiple animal species and in a variety of models of neurologic injury,” said Dr. Brett E. Skolnick of North Shore University Hospital, Manhasset, N.Y., who led the analysis of the Severe Traumatic Brain Injury (SYNAPSE) trial.

“A total of 20 research groups working with four species and 22 different models have found neuroprotective effects of progesterone in more than 180 experimental pharmacologic studies [and] two phase II randomized, controlled clinical trials with progesterone showed a clinical benefit,” he said.

For SYNAPSE – a multinational, placebo-controlled, prospective, randomized phase III clinical trial – investigators looked at 10,519 male and female patients, aged 16-70 years, admitted to level 1 or equivalent centers in 21 countries around the world. All individuals had nonpenetrating traumatic brain injury (TBI), Glasgow Coma Scale (GCS) scores of 8 or less, a Marshall classification score of II or higher, at least one reactive pupil, body weight of 99-298 pounds, and clinical indication for monitoring intracranial pressure. All subjects also underwent treatment within 8 hours of injury, and dosing continued for 120 hours.

Recruitment lasted from July 2010 to September 2013, with the final 6-month follow-up occurring in March 2014. Of the subjects who were randomized and went through full treatment and procedure, 591 received intravenous administration of progesterone, and 588 received a placebo. The primary outcome measure was GOS score at 6 months after initial injury, and secondary outcome measure was defined as GOS score at 3 months, mortality at 1 month and 6 months, and the GOS-E (Extended GOS) score.

Between the progesterone and placebo cohorts, there was no significant difference in the primary outcome: 189 subjects (32%) vs. 1,883 (31.1%) were in “good recovery,” 109 (18.4%) vs. 114 (19.4%) had “moderate disability,” 162 (27.4%) vs. 160 (27.2%) had “severe disability,” and 131 (22.2%) vs. 131 (22.3%) were in a “dead or vegetative state” 6 months after injury, respectively. Both adjusted and unadjusted data showed statistical insignificance (adjusted OR, 0.96).

Furthermore, mortality rates between both groups were similar, and the difference in proportion of subjects who received favorable GOS – with “good recovery” or “moderate disability,” as defined by the investigators – between the progesterone and placebo cohorts was negligible: 50.4% for progesterone vs. 50.5% for placebo.

“TBI is a complex, heterogeneous disorder, in which the primary injury initiates a variety of secondary injury cascades,” the authors noted. “These cascades involve various processes that may not be responsive to monotherapy [and] suggest that a successful therapeutic agent should influence rather than a single cascade. On the basis of the experimental data, progesterone would appear to be an appropriate candidate for this pluripotential role.”

The second study, “Progesterone for Traumatic Brain Injury: Experimental Clinical Treatment” (PROTECT III), was a double-blind, multicenter clinical trial with 882 patients randomized into cohorts receiving either progesterone or a placebo.

Subjects were randomized from April 2010 to October 2013, and were included on the basis of adults who had either severe, moderate to severe, or moderate TBI caused by a blunt mechanism, and a GOS of 4-12. Subjects were enrolled if they could begin treatment within 4 hours of initial injury. The median age of the patients was 35 years; 73.7% of subjects were men, 15.2% were black, and the mean Injury Severity Score was 24.4 on a scale of 0-75, with higher scores indicating greater severity of symptoms. The most common cause of TBI in subjects was motor vehicle accident.

Primary outcome measure was defined as the GOS-E score at 6 months after injury (1 = death, 2 = vegetative state, 3 or 4 = severe disability, 5 or 6 = moderate disability, and 7 or 8 = good recovery), while secondary outcomes measure “included mortality, the Disability Rating Scale score, the rates of nine prespecified adverse events that were considered to be potentially associated with treatment, and the rates of all reported adverse events and serious adverse events.” Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome at 6 months after injury.

The progesterone cohort comprised 442 subjects, while the remaining 440 received placebos. Investigators found that 213 (48.2%) of the progesterone subjects had favorable outcomes at 6 months after injury, and 232 (52.7%) were favorable in the placebo group; therefore, a total of 445 patients (50.5% of total population) had optimal response to treatment, and no significant difference between the two treatment options.

“Despite extensive preclinical data and two promising single-center trials, progesterone was not associated with any benefit over placebo, as measured by the GOS-E score at 6 months, in this large, multicenter clinical trial,” wrote lead author Dr. David W. Wright of Emory University, Atlanta, and his associates.

“The PROTECT III trial joins a growing list of negative or inconclusive trials in the arduous search for a treatment for TBI. To date, no treatment has succeeded at the confirmatory trial stage,” the researchers noted.

The SYNAPSE trial was funded by BHR Pharma, a division of Besins Healthcare. PROTECT III was funded by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke and the National Center for Advancing Translational Sciences; the Emory Emergency Neurosciences Laboratory at Emory University, Atlanta; and Grady Memorial Hospital, Atlanta. Several coauthors for each study had their own disclosures, as well.

[email protected]

SAN FRANCISCO – Obtaining palliative medicine consultations for geriatric trauma patients may help avoid futile interventions, suggests a retrospective cohort study reported at the annual clinical congress of the American College of Surgeons.

“The bulk of trauma in the United States has become geriatrics, and it’s falls from standing height,” noted lead investigator Dr. Christine C. Toevs, a trauma surgeon at Allegheny General Hospital in Pittsburgh; these older patients often have multiple comorbidities and are frail, and thus have a poor prognosis even with the best of care. “Clearly, this is a patient population that would benefit greatly from routine palliative medicine consultation,” she said.

Dr. Toevs and her colleagues performed a retrospective study of the charts of 5,261 trauma patients treated at their Level 1 trauma center during 2011-2013. One-third were geriatric, defined as aged 65 years or older.

Overall, 15% of geriatric patients and 2% of nongeriatric patients received a palliative medicine consult. The majority in both groups had a traumatic brain injury.

Within the geriatric age-group, about 90% of the patients who had a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 8% in this age-group overall, but 16% in the subset who received a consult.

“It seems that palliative medicine consult within the geriatric patient population does result in [fewer] procedures,” Dr. Toevs commented. “And studies have shown that when we talk to families and patients who participate in their care, they really do not want these procedures.”

Within the nongeriatric age–group, roughly 60% of patients with a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 3% in this age-group overall but 30% for those receiving the consult.

“Younger patients who receive palliative medicine consults seem to have the most severe injuries, not unexpectedly. These tend to be patients with the most severe traumatic brain injuries who still during their hospitalization are not demonstrating any signs of waking up. I think we all agree younger patients need a little more time than older patients, but some families don’t want to go down that route at all,” Dr. Toevs said. “So it’s reasonable before placing a trach in these patients with brain injuries, young or old, to have these discussions.”

Among all patients with a palliative medicine consult, geriatric patients were more likely to be discharged to a skilled nursing facility (32% vs. 15%), whereas nongeriatric patients were more likely to be discharged to a long-term acute care facility (13% vs. 5%) or rehabilitation facility (18% vs. 12%).

Whether avoiding long-term acute care facilities is a better outcome for geriatric patients “depends on how you look at it,” according to Dr. Toevs. “The bulk of the data suggest that 90% of all patients say that they really don’t want all that we do for them at the end of life, so most of us would consider this a better outcome.”

Three-fourths of all geriatric patients with a tracheostomy were discharged to a long-term acute care facility, although data suggest that few such patients survive to discharge. “So what we are doing is we are relocating the death rather than actually addressing the issues of what kind of life do they want,” she commented. “Do they really want the end of their lives to be in an ICU or a step-down ICU in a long-term acute care hospital? So if the patients ultimately get trached, the outcomes tend to be much worse as you can imagine and, in my mind, we have not done nearly as good a job as we should have initially; we should have in some way preempted this, and we didn’t explain to everyone well enough that this really was not considered a good outcome.”

The investigators plan further research in this area, according to Dr. Toevs, who disclosed that she had no relevant conflicts of interest. “We are looking at long-term survival data if we do send them to places after geriatric trauma – what really happens to them, what’s their survival at 6 months and a year – so that we can give [these] data to their families,” she elaborated. “We are also working with our rehab doctors to look at functional assessments and prognostication of these patients, and ultimately, really being able to quantify the benefits of palliative medicine and the goals of care discussions with these patients.”

Invited discussant Dr. Henri R. Ford, chief of surgery at the Children’s Hospital Los Angeles asked, “What were the specific criteria used, on average, to decide whether somebody should get a palliative medicine consultation? Have you tried to standardize that pretty much across the board for all of your trauma patients?”

Use of these consults at her hospital has increased since she began pushing for them, according to Dr. Toevs. “What I would like to do is to make it as routine as possible – every person on the trauma service gets a rehab consult; to some degree, every person on the trauma service should get a palliative medicine consult. It ought to be a checkbox. We are not quite there yet. But right now, I’m pushing for 80% and above, just to make it routine to begin the discussion: Do they have an advance directive? Do they have a power of attorney? Have they thought about these things long term?”

“Did you also compare the injury severity scores for the various patients, not only for the geriatric but also for those who received palliative medicine consultations versus those who did not?” Dr. Ford further asked. “That would be very, very interesting for us in terms of understanding selection bias.”

The investigators looked at these scores in another study, finding that they were lower for geriatric patients than for nongeriatric patients, as expected. “But because of their frailty, they do much poorer. And we are trying to correlate that long term when we are working with our rehab doctors and trying to look at the ability to prognosticate basically upon functional status prior to injury.”

Dr. Toevs disclosed that she had no relevant conflicts of interest.

SAN FRANCISCO – Obtaining palliative medicine consultations for geriatric trauma patients may help avoid futile interventions, suggests a retrospective cohort study reported at the annual clinical congress of the American College of Surgeons.

“The bulk of trauma in the United States has become geriatrics, and it’s falls from standing height,” noted lead investigator Dr. Christine C. Toevs, a trauma surgeon at Allegheny General Hospital in Pittsburgh; these older patients often have multiple comorbidities and are frail, and thus have a poor prognosis even with the best of care. “Clearly, this is a patient population that would benefit greatly from routine palliative medicine consultation,” she said.

Dr. Toevs and her colleagues performed a retrospective study of the charts of 5,261 trauma patients treated at their Level 1 trauma center during 2011-2013. One-third were geriatric, defined as aged 65 years or older.

Overall, 15% of geriatric patients and 2% of nongeriatric patients received a palliative medicine consult. The majority in both groups had a traumatic brain injury.

Within the geriatric age-group, about 90% of the patients who had a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 8% in this age-group overall, but 16% in the subset who received a consult.

“It seems that palliative medicine consult within the geriatric patient population does result in [fewer] procedures,” Dr. Toevs commented. “And studies have shown that when we talk to families and patients who participate in their care, they really do not want these procedures.”

Within the nongeriatric age–group, roughly 60% of patients with a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 3% in this age-group overall but 30% for those receiving the consult.

“Younger patients who receive palliative medicine consults seem to have the most severe injuries, not unexpectedly. These tend to be patients with the most severe traumatic brain injuries who still during their hospitalization are not demonstrating any signs of waking up. I think we all agree younger patients need a little more time than older patients, but some families don’t want to go down that route at all,” Dr. Toevs said. “So it’s reasonable before placing a trach in these patients with brain injuries, young or old, to have these discussions.”

Among all patients with a palliative medicine consult, geriatric patients were more likely to be discharged to a skilled nursing facility (32% vs. 15%), whereas nongeriatric patients were more likely to be discharged to a long-term acute care facility (13% vs. 5%) or rehabilitation facility (18% vs. 12%).

Whether avoiding long-term acute care facilities is a better outcome for geriatric patients “depends on how you look at it,” according to Dr. Toevs. “The bulk of the data suggest that 90% of all patients say that they really don’t want all that we do for them at the end of life, so most of us would consider this a better outcome.”

Three-fourths of all geriatric patients with a tracheostomy were discharged to a long-term acute care facility, although data suggest that few such patients survive to discharge. “So what we are doing is we are relocating the death rather than actually addressing the issues of what kind of life do they want,” she commented. “Do they really want the end of their lives to be in an ICU or a step-down ICU in a long-term acute care hospital? So if the patients ultimately get trached, the outcomes tend to be much worse as you can imagine and, in my mind, we have not done nearly as good a job as we should have initially; we should have in some way preempted this, and we didn’t explain to everyone well enough that this really was not considered a good outcome.”

The investigators plan further research in this area, according to Dr. Toevs, who disclosed that she had no relevant conflicts of interest. “We are looking at long-term survival data if we do send them to places after geriatric trauma – what really happens to them, what’s their survival at 6 months and a year – so that we can give [these] data to their families,” she elaborated. “We are also working with our rehab doctors to look at functional assessments and prognostication of these patients, and ultimately, really being able to quantify the benefits of palliative medicine and the goals of care discussions with these patients.”

Invited discussant Dr. Henri R. Ford, chief of surgery at the Children’s Hospital Los Angeles asked, “What were the specific criteria used, on average, to decide whether somebody should get a palliative medicine consultation? Have you tried to standardize that pretty much across the board for all of your trauma patients?”

Use of these consults at her hospital has increased since she began pushing for them, according to Dr. Toevs. “What I would like to do is to make it as routine as possible – every person on the trauma service gets a rehab consult; to some degree, every person on the trauma service should get a palliative medicine consult. It ought to be a checkbox. We are not quite there yet. But right now, I’m pushing for 80% and above, just to make it routine to begin the discussion: Do they have an advance directive? Do they have a power of attorney? Have they thought about these things long term?”

“Did you also compare the injury severity scores for the various patients, not only for the geriatric but also for those who received palliative medicine consultations versus those who did not?” Dr. Ford further asked. “That would be very, very interesting for us in terms of understanding selection bias.”

The investigators looked at these scores in another study, finding that they were lower for geriatric patients than for nongeriatric patients, as expected. “But because of their frailty, they do much poorer. And we are trying to correlate that long term when we are working with our rehab doctors and trying to look at the ability to prognosticate basically upon functional status prior to injury.”

Dr. Toevs disclosed that she had no relevant conflicts of interest.

SAN FRANCISCO – Obtaining palliative medicine consultations for geriatric trauma patients may help avoid futile interventions, suggests a retrospective cohort study reported at the annual clinical congress of the American College of Surgeons.

“The bulk of trauma in the United States has become geriatrics, and it’s falls from standing height,” noted lead investigator Dr. Christine C. Toevs, a trauma surgeon at Allegheny General Hospital in Pittsburgh; these older patients often have multiple comorbidities and are frail, and thus have a poor prognosis even with the best of care. “Clearly, this is a patient population that would benefit greatly from routine palliative medicine consultation,” she said.

Dr. Toevs and her colleagues performed a retrospective study of the charts of 5,261 trauma patients treated at their Level 1 trauma center during 2011-2013. One-third were geriatric, defined as aged 65 years or older.

Overall, 15% of geriatric patients and 2% of nongeriatric patients received a palliative medicine consult. The majority in both groups had a traumatic brain injury.

Within the geriatric age-group, about 90% of the patients who had a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 8% in this age-group overall, but 16% in the subset who received a consult.

“It seems that palliative medicine consult within the geriatric patient population does result in [fewer] procedures,” Dr. Toevs commented. “And studies have shown that when we talk to families and patients who participate in their care, they really do not want these procedures.”

Within the nongeriatric age–group, roughly 60% of patients with a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 3% in this age-group overall but 30% for those receiving the consult.

“Younger patients who receive palliative medicine consults seem to have the most severe injuries, not unexpectedly. These tend to be patients with the most severe traumatic brain injuries who still during their hospitalization are not demonstrating any signs of waking up. I think we all agree younger patients need a little more time than older patients, but some families don’t want to go down that route at all,” Dr. Toevs said. “So it’s reasonable before placing a trach in these patients with brain injuries, young or old, to have these discussions.”

Among all patients with a palliative medicine consult, geriatric patients were more likely to be discharged to a skilled nursing facility (32% vs. 15%), whereas nongeriatric patients were more likely to be discharged to a long-term acute care facility (13% vs. 5%) or rehabilitation facility (18% vs. 12%).

Whether avoiding long-term acute care facilities is a better outcome for geriatric patients “depends on how you look at it,” according to Dr. Toevs. “The bulk of the data suggest that 90% of all patients say that they really don’t want all that we do for them at the end of life, so most of us would consider this a better outcome.”

Three-fourths of all geriatric patients with a tracheostomy were discharged to a long-term acute care facility, although data suggest that few such patients survive to discharge. “So what we are doing is we are relocating the death rather than actually addressing the issues of what kind of life do they want,” she commented. “Do they really want the end of their lives to be in an ICU or a step-down ICU in a long-term acute care hospital? So if the patients ultimately get trached, the outcomes tend to be much worse as you can imagine and, in my mind, we have not done nearly as good a job as we should have initially; we should have in some way preempted this, and we didn’t explain to everyone well enough that this really was not considered a good outcome.”

The investigators plan further research in this area, according to Dr. Toevs, who disclosed that she had no relevant conflicts of interest. “We are looking at long-term survival data if we do send them to places after geriatric trauma – what really happens to them, what’s their survival at 6 months and a year – so that we can give [these] data to their families,” she elaborated. “We are also working with our rehab doctors to look at functional assessments and prognostication of these patients, and ultimately, really being able to quantify the benefits of palliative medicine and the goals of care discussions with these patients.”

Invited discussant Dr. Henri R. Ford, chief of surgery at the Children’s Hospital Los Angeles asked, “What were the specific criteria used, on average, to decide whether somebody should get a palliative medicine consultation? Have you tried to standardize that pretty much across the board for all of your trauma patients?”

Use of these consults at her hospital has increased since she began pushing for them, according to Dr. Toevs. “What I would like to do is to make it as routine as possible – every person on the trauma service gets a rehab consult; to some degree, every person on the trauma service should get a palliative medicine consult. It ought to be a checkbox. We are not quite there yet. But right now, I’m pushing for 80% and above, just to make it routine to begin the discussion: Do they have an advance directive? Do they have a power of attorney? Have they thought about these things long term?”

“Did you also compare the injury severity scores for the various patients, not only for the geriatric but also for those who received palliative medicine consultations versus those who did not?” Dr. Ford further asked. “That would be very, very interesting for us in terms of understanding selection bias.”

The investigators looked at these scores in another study, finding that they were lower for geriatric patients than for nongeriatric patients, as expected. “But because of their frailty, they do much poorer. And we are trying to correlate that long term when we are working with our rehab doctors and trying to look at the ability to prognosticate basically upon functional status prior to injury.”

Dr. Toevs disclosed that she had no relevant conflicts of interest.

Hyperbaric oxygen is no better than a sham procedure for treating persistent postconcussion symptoms in military personnel, according to results from the randomized HOPPS trial.

Both hyperbaric oxygen (HBO) and a sham treatment were associated with significant improvements in postconcussion symptoms and secondary outcomes, including posttraumatic stress disorder, depression, and sleep quality compared to routine post-concussion care, reported Dr. R. Scott Miller of the Uniformed Services University of the Health Sciences, Bethesda, Md., and his associates.

The results suggested that improvements in the chamber intervention groups were tied to placebo effects or the potential benefit of daily interactions with medical staff, the researchers said in the paper published Nov. 17 (JAMA Intern. Med. 2014; [doi:10.1001/jamainternmed.2014.5479]).

The Hyperbaric Oxygen Therapy for Persistent Postconcussive Symptoms After Mild Traumatic Brain Injury (HOPPS) double-blind study randomized 72 military service members who had persistent postconcussion symptoms for more than 4 months to 40 hyperbaric oxygen treatments, 40 sham treatments in an air-filled chamber, or routine postconcussion care.

No differences were seen between the groups for improvement of at least two points (defined as clinically significant) on the Rivermead Post Concussion Symptoms Questionnaire (RPQ) symptoms subscale (RPQ-3) (25% in the no intervention group, 52% in the HBO group, and 33% in the sham group; P = .24). Compared with the no intervention group (average change score, 0.5; P = .91), the HBO and sham groups showed improvement in symptoms on the RPQ total score (average change score, 5.4; P = .008 in the HBO group and 7.0; P = .02 in the sham group).

The results suggest that the improvements seen in the HBO and sham groups were not oxygen mediated but may reflect “nonspecific improvements related to placebo effects.

“Taken with results from other concurrent investigations our study does not support phase III trials of HBO for the treatment of PCS at this time,” the researchers concluded.

Hyperbaric oxygen 100% was administered at a dose of 1.5 atmospheres absolute for 60 minutes at a time. The sham treatment followed the same procedures but the chamber was pressurized to 1.2 atmospheres absolute.

The study sponsor is the U.S. Army Office of the Surgeon General who holds the investigational new drug application for hyperbaric oxygen to treat traumatic brain injury.

Hyperbaric oxygen is no better than a sham procedure for treating persistent postconcussion symptoms in military personnel, according to results from the randomized HOPPS trial.

Both hyperbaric oxygen (HBO) and a sham treatment were associated with significant improvements in postconcussion symptoms and secondary outcomes, including posttraumatic stress disorder, depression, and sleep quality compared to routine post-concussion care, reported Dr. R. Scott Miller of the Uniformed Services University of the Health Sciences, Bethesda, Md., and his associates.

The results suggested that improvements in the chamber intervention groups were tied to placebo effects or the potential benefit of daily interactions with medical staff, the researchers said in the paper published Nov. 17 (JAMA Intern. Med. 2014; [doi:10.1001/jamainternmed.2014.5479]).

The Hyperbaric Oxygen Therapy for Persistent Postconcussive Symptoms After Mild Traumatic Brain Injury (HOPPS) double-blind study randomized 72 military service members who had persistent postconcussion symptoms for more than 4 months to 40 hyperbaric oxygen treatments, 40 sham treatments in an air-filled chamber, or routine postconcussion care.

No differences were seen between the groups for improvement of at least two points (defined as clinically significant) on the Rivermead Post Concussion Symptoms Questionnaire (RPQ) symptoms subscale (RPQ-3) (25% in the no intervention group, 52% in the HBO group, and 33% in the sham group; P = .24). Compared with the no intervention group (average change score, 0.5; P = .91), the HBO and sham groups showed improvement in symptoms on the RPQ total score (average change score, 5.4; P = .008 in the HBO group and 7.0; P = .02 in the sham group).

The results suggest that the improvements seen in the HBO and sham groups were not oxygen mediated but may reflect “nonspecific improvements related to placebo effects.

“Taken with results from other concurrent investigations our study does not support phase III trials of HBO for the treatment of PCS at this time,” the researchers concluded.

Hyperbaric oxygen 100% was administered at a dose of 1.5 atmospheres absolute for 60 minutes at a time. The sham treatment followed the same procedures but the chamber was pressurized to 1.2 atmospheres absolute.

The study sponsor is the U.S. Army Office of the Surgeon General who holds the investigational new drug application for hyperbaric oxygen to treat traumatic brain injury.

Hyperbaric oxygen is no better than a sham procedure for treating persistent postconcussion symptoms in military personnel, according to results from the randomized HOPPS trial.

Both hyperbaric oxygen (HBO) and a sham treatment were associated with significant improvements in postconcussion symptoms and secondary outcomes, including posttraumatic stress disorder, depression, and sleep quality compared to routine post-concussion care, reported Dr. R. Scott Miller of the Uniformed Services University of the Health Sciences, Bethesda, Md., and his associates.

The results suggested that improvements in the chamber intervention groups were tied to placebo effects or the potential benefit of daily interactions with medical staff, the researchers said in the paper published Nov. 17 (JAMA Intern. Med. 2014; [doi:10.1001/jamainternmed.2014.5479]).

The Hyperbaric Oxygen Therapy for Persistent Postconcussive Symptoms After Mild Traumatic Brain Injury (HOPPS) double-blind study randomized 72 military service members who had persistent postconcussion symptoms for more than 4 months to 40 hyperbaric oxygen treatments, 40 sham treatments in an air-filled chamber, or routine postconcussion care.

No differences were seen between the groups for improvement of at least two points (defined as clinically significant) on the Rivermead Post Concussion Symptoms Questionnaire (RPQ) symptoms subscale (RPQ-3) (25% in the no intervention group, 52% in the HBO group, and 33% in the sham group; P = .24). Compared with the no intervention group (average change score, 0.5; P = .91), the HBO and sham groups showed improvement in symptoms on the RPQ total score (average change score, 5.4; P = .008 in the HBO group and 7.0; P = .02 in the sham group).

The results suggest that the improvements seen in the HBO and sham groups were not oxygen mediated but may reflect “nonspecific improvements related to placebo effects.

“Taken with results from other concurrent investigations our study does not support phase III trials of HBO for the treatment of PCS at this time,” the researchers concluded.

Hyperbaric oxygen 100% was administered at a dose of 1.5 atmospheres absolute for 60 minutes at a time. The sham treatment followed the same procedures but the chamber was pressurized to 1.2 atmospheres absolute.

The study sponsor is the U.S. Army Office of the Surgeon General who holds the investigational new drug application for hyperbaric oxygen to treat traumatic brain injury.

A new study found that adolescents who suffer traumatic brain injury are more likely to engage in harmful behavior and that the risk of engaging in such behavior is higher among girls than boys.

The data come from the 2011 Ontario Student Drug Use and Health Survey, which anonymously polled 9,288 Ontario boys and girls between grades 7 and 12 using self-administered questionnaires. Subjects were asked whether they had a history of traumatic brain injury (TBI) – defined by the study as “a hit or blow to the head that resulted in a 5-minute loss of consciousness or at least one overnight hospitalization due to symptoms associated with it.” The questionnaires also asked the subjects whether they had experienced any of 13 distinct harmful outcomes over the past year, such as binge drinking, smoking of tobacco and cannabis products, drug abuse, psychological distress, declining grades, physical and cyberbullying, and thoughts of suicide.

istockphoto.com

The findings revealed that of the 13 harmful outcomes, boys were at a higher risk of engaging in 9. Girls, however, were likely to engage in all 13, indicating that sex plays a major role in the long-term effects of TBI when such incidents occur at a young age (PLoS One 2014 Sept. 30).

“Both boys and girls were more likely to engage in a variety of harmful behaviours if they reported a history of TBI, but girls engaged in all 13 harmful behaviours we looked for, whereas boys were at higher risk of engaging in only nine,” Gabriela Ilie, Ph.D., lead author of the study and a postdoctoral fellow at Toronto’s St. Michael’s Hospital, said in a statement. “Sex matters when it comes to traumatic brain injuries.”

The study found that girls and boys with a history of TBI were all at an elevated risk for alcohol consumption, binge drinking, cannabis smoking, declining grades, bullying others at school, being bullied online, drug abuse, and being treated for physical injuries. But female adolescents in particular were found to be additionally susceptible to elevated psychological distress, past-year suicidal ideation, being bullied at school in the past year, and past-year cigarette smoking.

Dr. Ilie and her colleagues also found that the risk of engaging in alcohol consumption, daily cigarette smoking, and being treated for physical injuries changed depending on the age of the subjects. The average age at which subjects began smoking was 14, while the age at which subjects had their first alcoholic drink skewed similarly young. For physical injury treatment, the risk ran higher for girls aged 11-13 years, and for boys aged 17-20 years.

Across the board, children with TBI presented higher incidences of all harmful behaviors than those without a history of TBI. The study also found that the majority of TBI came from playing team sports – 63% for males and 46.9% for females. Falls were responsible for 5.1% of males and 24.7% of females with TBI histories, with bicycle accidents being responsible for 8.1% of males with TBI and 1.8% of females with TBI.

The researchers cited several limitations of the study. The most salient, they said, was that the data were based on self-reports. In addition, their sample did not include “adolescents who might be at high risk of TBI.”

Still, Dr. Ilie and her colleagues hope that the findings of this study will help shed light on the need for greater action in recognizing and treating adolescent TBI, warning that failure to properly care for these injuries at the right time will significantly increase the risk of detrimental long-term consequences down the road.

“The results point to important opportunities for prevention, such as early-stage medical interventions, as well as diagnosis and rehabilitation approaches that consider the relationship between TBI and its risk factors,” the investigators said. “We know both adolescent boys and girls with TBI are vulnerable to the co-occurrence of harmful psychological and behavioural conditions. Given that most brain injuries among adolescents occur during sports, a more ecological approach to injury prevention requiring involvement by government, schools, and parents may be needed.”

The research was funded by a Canadian Institute of Health Research Team Grant in Traumatic Brain Injury and Violence and by the Ontario Neurotrauma Foundation, with additional funding from the Ontario Ministry of Health and Long-Term Care, the Social Sciences and Humanities Research Council, Industry Canada, and AUTO21, a member of the Networks of Centres of Excellence program that is administered and funded by the Natural Sciences and Engineering Research Council.

[email protected]

A new study found that adolescents who suffer traumatic brain injury are more likely to engage in harmful behavior and that the risk of engaging in such behavior is higher among girls than boys.

The data come from the 2011 Ontario Student Drug Use and Health Survey, which anonymously polled 9,288 Ontario boys and girls between grades 7 and 12 using self-administered questionnaires. Subjects were asked whether they had a history of traumatic brain injury (TBI) – defined by the study as “a hit or blow to the head that resulted in a 5-minute loss of consciousness or at least one overnight hospitalization due to symptoms associated with it.” The questionnaires also asked the subjects whether they had experienced any of 13 distinct harmful outcomes over the past year, such as binge drinking, smoking of tobacco and cannabis products, drug abuse, psychological distress, declining grades, physical and cyberbullying, and thoughts of suicide.

istockphoto.com

The findings revealed that of the 13 harmful outcomes, boys were at a higher risk of engaging in 9. Girls, however, were likely to engage in all 13, indicating that sex plays a major role in the long-term effects of TBI when such incidents occur at a young age (PLoS One 2014 Sept. 30).

“Both boys and girls were more likely to engage in a variety of harmful behaviours if they reported a history of TBI, but girls engaged in all 13 harmful behaviours we looked for, whereas boys were at higher risk of engaging in only nine,” Gabriela Ilie, Ph.D., lead author of the study and a postdoctoral fellow at Toronto’s St. Michael’s Hospital, said in a statement. “Sex matters when it comes to traumatic brain injuries.”

The study found that girls and boys with a history of TBI were all at an elevated risk for alcohol consumption, binge drinking, cannabis smoking, declining grades, bullying others at school, being bullied online, drug abuse, and being treated for physical injuries. But female adolescents in particular were found to be additionally susceptible to elevated psychological distress, past-year suicidal ideation, being bullied at school in the past year, and past-year cigarette smoking.

Dr. Ilie and her colleagues also found that the risk of engaging in alcohol consumption, daily cigarette smoking, and being treated for physical injuries changed depending on the age of the subjects. The average age at which subjects began smoking was 14, while the age at which subjects had their first alcoholic drink skewed similarly young. For physical injury treatment, the risk ran higher for girls aged 11-13 years, and for boys aged 17-20 years.

Across the board, children with TBI presented higher incidences of all harmful behaviors than those without a history of TBI. The study also found that the majority of TBI came from playing team sports – 63% for males and 46.9% for females. Falls were responsible for 5.1% of males and 24.7% of females with TBI histories, with bicycle accidents being responsible for 8.1% of males with TBI and 1.8% of females with TBI.

The researchers cited several limitations of the study. The most salient, they said, was that the data were based on self-reports. In addition, their sample did not include “adolescents who might be at high risk of TBI.”

Still, Dr. Ilie and her colleagues hope that the findings of this study will help shed light on the need for greater action in recognizing and treating adolescent TBI, warning that failure to properly care for these injuries at the right time will significantly increase the risk of detrimental long-term consequences down the road.

“The results point to important opportunities for prevention, such as early-stage medical interventions, as well as diagnosis and rehabilitation approaches that consider the relationship between TBI and its risk factors,” the investigators said. “We know both adolescent boys and girls with TBI are vulnerable to the co-occurrence of harmful psychological and behavioural conditions. Given that most brain injuries among adolescents occur during sports, a more ecological approach to injury prevention requiring involvement by government, schools, and parents may be needed.”

The research was funded by a Canadian Institute of Health Research Team Grant in Traumatic Brain Injury and Violence and by the Ontario Neurotrauma Foundation, with additional funding from the Ontario Ministry of Health and Long-Term Care, the Social Sciences and Humanities Research Council, Industry Canada, and AUTO21, a member of the Networks of Centres of Excellence program that is administered and funded by the Natural Sciences and Engineering Research Council.

[email protected]

A new study found that adolescents who suffer traumatic brain injury are more likely to engage in harmful behavior and that the risk of engaging in such behavior is higher among girls than boys.

The data come from the 2011 Ontario Student Drug Use and Health Survey, which anonymously polled 9,288 Ontario boys and girls between grades 7 and 12 using self-administered questionnaires. Subjects were asked whether they had a history of traumatic brain injury (TBI) – defined by the study as “a hit or blow to the head that resulted in a 5-minute loss of consciousness or at least one overnight hospitalization due to symptoms associated with it.” The questionnaires also asked the subjects whether they had experienced any of 13 distinct harmful outcomes over the past year, such as binge drinking, smoking of tobacco and cannabis products, drug abuse, psychological distress, declining grades, physical and cyberbullying, and thoughts of suicide.

istockphoto.com

The findings revealed that of the 13 harmful outcomes, boys were at a higher risk of engaging in 9. Girls, however, were likely to engage in all 13, indicating that sex plays a major role in the long-term effects of TBI when such incidents occur at a young age (PLoS One 2014 Sept. 30).

“Both boys and girls were more likely to engage in a variety of harmful behaviours if they reported a history of TBI, but girls engaged in all 13 harmful behaviours we looked for, whereas boys were at higher risk of engaging in only nine,” Gabriela Ilie, Ph.D., lead author of the study and a postdoctoral fellow at Toronto’s St. Michael’s Hospital, said in a statement. “Sex matters when it comes to traumatic brain injuries.”

The study found that girls and boys with a history of TBI were all at an elevated risk for alcohol consumption, binge drinking, cannabis smoking, declining grades, bullying others at school, being bullied online, drug abuse, and being treated for physical injuries. But female adolescents in particular were found to be additionally susceptible to elevated psychological distress, past-year suicidal ideation, being bullied at school in the past year, and past-year cigarette smoking.

Dr. Ilie and her colleagues also found that the risk of engaging in alcohol consumption, daily cigarette smoking, and being treated for physical injuries changed depending on the age of the subjects. The average age at which subjects began smoking was 14, while the age at which subjects had their first alcoholic drink skewed similarly young. For physical injury treatment, the risk ran higher for girls aged 11-13 years, and for boys aged 17-20 years.

Across the board, children with TBI presented higher incidences of all harmful behaviors than those without a history of TBI. The study also found that the majority of TBI came from playing team sports – 63% for males and 46.9% for females. Falls were responsible for 5.1% of males and 24.7% of females with TBI histories, with bicycle accidents being responsible for 8.1% of males with TBI and 1.8% of females with TBI.

The researchers cited several limitations of the study. The most salient, they said, was that the data were based on self-reports. In addition, their sample did not include “adolescents who might be at high risk of TBI.”

Still, Dr. Ilie and her colleagues hope that the findings of this study will help shed light on the need for greater action in recognizing and treating adolescent TBI, warning that failure to properly care for these injuries at the right time will significantly increase the risk of detrimental long-term consequences down the road.

“The results point to important opportunities for prevention, such as early-stage medical interventions, as well as diagnosis and rehabilitation approaches that consider the relationship between TBI and its risk factors,” the investigators said. “We know both adolescent boys and girls with TBI are vulnerable to the co-occurrence of harmful psychological and behavioural conditions. Given that most brain injuries among adolescents occur during sports, a more ecological approach to injury prevention requiring involvement by government, schools, and parents may be needed.”

The research was funded by a Canadian Institute of Health Research Team Grant in Traumatic Brain Injury and Violence and by the Ontario Neurotrauma Foundation, with additional funding from the Ontario Ministry of Health and Long-Term Care, the Social Sciences and Humanities Research Council, Industry Canada, and AUTO21, a member of the Networks of Centres of Excellence program that is administered and funded by the Natural Sciences and Engineering Research Council.

[email protected]

Intra-abdominal vagal nerve blockade to treat morbid obesity didn’t meet prespecified efficacy objectives in the randomized, double-blind ReCharge study, but treated patients did experience significantly greater weight loss than did those who underwent a sham procedure.

Mean excess weight loss was 24.4% (9.2% of initial body weight loss) in 162 patients who had a body mass index of 40-45 kg/m² or 35-40 kg/m² plus one or more obesity-related conditions, who underwent vagal nerve block therapy, compared with 15.9% (6% of initial body weight loss) in 77 patients in the sham group, for a mean between-group difference of 8.5 percentage points.

The difference was statistically significant, but it was less than the prespecified 10-point superiority margin, Dr. Sayeed Ikramuddin of the University of Minnesota, Minneapolis, and colleagues reported online Sept. 2 in JAMA.

At 12 months, 20% or more excess weight loss was achieved by 52% of patients in the vagal nerve block group, compared with 32% of patients in the sham procedure group. A total of 25% or more excess weight loss was achieved by 38% and 23% of patients in the groups, respectively, the investigators said (JAMA 2014;312:915-22).

Patients in the treatment group experienced more heartburn and dyspepsia, abdominal and other nonspecific pain, dysphagia, nausea, and eructation or belching than those in the control group. But these side effects were generally mild or moderate in severity. Serious adverse events associated with vagal nerve blockade occurred in 3.7% of treatment group patients, which was well below the 15% upper threshold for safety in the trial.

Additional study is needed to compare vagal nerve block with other obesity treatments, and to assess long-term durability and safety of the procedure, the investigators concluded.

This study was supported by EnteroMedics, which makes the vagal nerve blockade device used in the study. Dr. Ikramudden reported serving on the advisory board for Novo Nordisk and Medica, serving as a consultant for Metamodix and on an expert panel for OptumHealth, and receiving grant support from USGI Medical, ReShape Medical, and Covidien.

Intra-abdominal vagal nerve blockade to treat morbid obesity didn’t meet prespecified efficacy objectives in the randomized, double-blind ReCharge study, but treated patients did experience significantly greater weight loss than did those who underwent a sham procedure.

Mean excess weight loss was 24.4% (9.2% of initial body weight loss) in 162 patients who had a body mass index of 40-45 kg/m² or 35-40 kg/m² plus one or more obesity-related conditions, who underwent vagal nerve block therapy, compared with 15.9% (6% of initial body weight loss) in 77 patients in the sham group, for a mean between-group difference of 8.5 percentage points.

The difference was statistically significant, but it was less than the prespecified 10-point superiority margin, Dr. Sayeed Ikramuddin of the University of Minnesota, Minneapolis, and colleagues reported online Sept. 2 in JAMA.

At 12 months, 20% or more excess weight loss was achieved by 52% of patients in the vagal nerve block group, compared with 32% of patients in the sham procedure group. A total of 25% or more excess weight loss was achieved by 38% and 23% of patients in the groups, respectively, the investigators said (JAMA 2014;312:915-22).

Patients in the treatment group experienced more heartburn and dyspepsia, abdominal and other nonspecific pain, dysphagia, nausea, and eructation or belching than those in the control group. But these side effects were generally mild or moderate in severity. Serious adverse events associated with vagal nerve blockade occurred in 3.7% of treatment group patients, which was well below the 15% upper threshold for safety in the trial.

Additional study is needed to compare vagal nerve block with other obesity treatments, and to assess long-term durability and safety of the procedure, the investigators concluded.

This study was supported by EnteroMedics, which makes the vagal nerve blockade device used in the study. Dr. Ikramudden reported serving on the advisory board for Novo Nordisk and Medica, serving as a consultant for Metamodix and on an expert panel for OptumHealth, and receiving grant support from USGI Medical, ReShape Medical, and Covidien.

Intra-abdominal vagal nerve blockade to treat morbid obesity didn’t meet prespecified efficacy objectives in the randomized, double-blind ReCharge study, but treated patients did experience significantly greater weight loss than did those who underwent a sham procedure.

Mean excess weight loss was 24.4% (9.2% of initial body weight loss) in 162 patients who had a body mass index of 40-45 kg/m² or 35-40 kg/m² plus one or more obesity-related conditions, who underwent vagal nerve block therapy, compared with 15.9% (6% of initial body weight loss) in 77 patients in the sham group, for a mean between-group difference of 8.5 percentage points.

The difference was statistically significant, but it was less than the prespecified 10-point superiority margin, Dr. Sayeed Ikramuddin of the University of Minnesota, Minneapolis, and colleagues reported online Sept. 2 in JAMA.

At 12 months, 20% or more excess weight loss was achieved by 52% of patients in the vagal nerve block group, compared with 32% of patients in the sham procedure group. A total of 25% or more excess weight loss was achieved by 38% and 23% of patients in the groups, respectively, the investigators said (JAMA 2014;312:915-22).

Patients in the treatment group experienced more heartburn and dyspepsia, abdominal and other nonspecific pain, dysphagia, nausea, and eructation or belching than those in the control group. But these side effects were generally mild or moderate in severity. Serious adverse events associated with vagal nerve blockade occurred in 3.7% of treatment group patients, which was well below the 15% upper threshold for safety in the trial.

Additional study is needed to compare vagal nerve block with other obesity treatments, and to assess long-term durability and safety of the procedure, the investigators concluded.

This study was supported by EnteroMedics, which makes the vagal nerve blockade device used in the study. Dr. Ikramudden reported serving on the advisory board for Novo Nordisk and Medica, serving as a consultant for Metamodix and on an expert panel for OptumHealth, and receiving grant support from USGI Medical, ReShape Medical, and Covidien.

A handheld device that uses a newly developed test can rapidly identify even mild concussion by measuring two key biomarkers of neuronal injury.

The new test for traumatic brain injury – the i-STAT concussion biomarker test – may be deployed within 2 years by the Department of Defense, according to Col. Dallas Hack, M.D., Brain Health Coordinator at the U.S. Army Medical Research and Materiel Command, Ft. Detrick, Md.

The test will be integrated into a device that the military already uses – the i-STAT System, manufactured by Abbott. The unit already performs a wide variety of tests, including measurements of glucose, blood gases, coagulation factors, and cardiac markers. Each test is loaded on a single-use cartridge. The new test for concussion biomarkers will be on a similar cartridge, eliminating the need to buy or train on a new device, Col. Hack said in an interview.

Whether used in a battle setting or on a military base, the rapid test will speed up diagnosis and treatment. "This test is going to provide definitive proof of a brain injury very quickly, and that will kick in our set of treatment algorithms, which are already in place," he said.

Although it’s being designed for use in a military setting, the i-STAT concussion biomarker test will eventually be available in the civilian world, where the need is just as great, Col. Hack added.

The search for biomarkers of brain injury has been a long one – and its birthday is ironic, he noted. "It was literally the morning of 9-11 (in 2001) at the Advanced Technology Applications for Combat Casualty Care Conference [a precursor to the Military Health Systems Research Symposium] when researchers from the military and the University of Florida decided to embark together on this project."

Thirteen years later, at the same conference where the concept was first proposed, researchers presented data on one of the candidate biomarkers – ubiquitin C-terminal hydrolase-L1 (UCH-L1) – which is released when neurons are damaged. "This is a very early marker, present as soon as 15 minutes after an injury," Col. Hack said.

Maj. Walter Carr, of the Walter Reed Army Institute of Research, Washington, presented the new data, drawn from an observational cohort study of 220 soldiers serving in Afghanistan. Of these, 70 had sustained a concussion and 74 had a nonconcussion injury; there were 76 uninjured control subjects. Each patient had two blood draws, one within 8 hours after injury and the second about 24 hours after the injury.

At both time points, UCH-L1 levels were significantly higher in the concussed patients than in either of the other groups.

The protein is one of two biomarkers that will be included in the new test, which is being developed in collaboration with Abbott. The other biomarker, glial fibrillary acidic protein (GFAP), indicates astrocyte activation after neuronal injury.

When the search for biomarkers of brain injury was proposed in 2001, some researchers considered the blood-brain barrier to be inviolate – an impenetrable block that would prevent any chemical signals of brain injury from escaping into the circulatory system.

But Army researchers partnered with a spin-out company from the University of Florida, and the search was on. "By 2010, we had phase I and II data showing that we could not only identify those with a severe brain injury but [also identify those with mild traumatic brain injury] in limited numbers of patients," Col. Hack said. The findings indicated even mild injuries can cause biochemical disruptions that release proteins into the blood. With continued improvements in the sensitivity also came recognition of proteins specific for a brain injury.

The approval process for the test in combination with the i-STAT device is underway, but the path probably won’t be completely straight, he added. Concussion biomarkers are a new concept with no place in any existing diagnostic guidelines – all of which rely exclusively on imaging findings.

"Because of the immature state of this field, the FDA [Food and Drug Administration] doesn’t recognize any comparison measure for brain injury except a CT scan showing a subdural hematoma. So when we did our pivotal trials, we were limited by this. A fundamental problem in brain injury research is this use of CT as the standard for validation," Col. Hack said.

"There have been several Institute of Medicine reports decrying the lack of research in this huge public health problem. In fact, there’s no national research program for trauma of any kind, except in the military. This is a huge problem because it’s our young people who are most at risk for these injuries," which often exert a lifelong effect, he added.

Of necessity, battlegrounds have always been a theater of frontline medical research. But those findings can eventually benefit patients in any setting, Col. Hack said. "Many changes we’ve made [in trauma treatment] over the past 10 years are now being implemented in emergency rooms. It’s gratifying to come back here and see that – it’s the reward of a lifetime."

[email protected]

On Twitter @alz_gal

A handheld device that uses a newly developed test can rapidly identify even mild concussion by measuring two key biomarkers of neuronal injury.

The new test for traumatic brain injury – the i-STAT concussion biomarker test – may be deployed within 2 years by the Department of Defense, according to Col. Dallas Hack, M.D., Brain Health Coordinator at the U.S. Army Medical Research and Materiel Command, Ft. Detrick, Md.

The test will be integrated into a device that the military already uses – the i-STAT System, manufactured by Abbott. The unit already performs a wide variety of tests, including measurements of glucose, blood gases, coagulation factors, and cardiac markers. Each test is loaded on a single-use cartridge. The new test for concussion biomarkers will be on a similar cartridge, eliminating the need to buy or train on a new device, Col. Hack said in an interview.

Whether used in a battle setting or on a military base, the rapid test will speed up diagnosis and treatment. "This test is going to provide definitive proof of a brain injury very quickly, and that will kick in our set of treatment algorithms, which are already in place," he said.

Although it’s being designed for use in a military setting, the i-STAT concussion biomarker test will eventually be available in the civilian world, where the need is just as great, Col. Hack added.

The search for biomarkers of brain injury has been a long one – and its birthday is ironic, he noted. "It was literally the morning of 9-11 (in 2001) at the Advanced Technology Applications for Combat Casualty Care Conference [a precursor to the Military Health Systems Research Symposium] when researchers from the military and the University of Florida decided to embark together on this project."

Thirteen years later, at the same conference where the concept was first proposed, researchers presented data on one of the candidate biomarkers – ubiquitin C-terminal hydrolase-L1 (UCH-L1) – which is released when neurons are damaged. "This is a very early marker, present as soon as 15 minutes after an injury," Col. Hack said.

Maj. Walter Carr, of the Walter Reed Army Institute of Research, Washington, presented the new data, drawn from an observational cohort study of 220 soldiers serving in Afghanistan. Of these, 70 had sustained a concussion and 74 had a nonconcussion injury; there were 76 uninjured control subjects. Each patient had two blood draws, one within 8 hours after injury and the second about 24 hours after the injury.

At both time points, UCH-L1 levels were significantly higher in the concussed patients than in either of the other groups.

The protein is one of two biomarkers that will be included in the new test, which is being developed in collaboration with Abbott. The other biomarker, glial fibrillary acidic protein (GFAP), indicates astrocyte activation after neuronal injury.

When the search for biomarkers of brain injury was proposed in 2001, some researchers considered the blood-brain barrier to be inviolate – an impenetrable block that would prevent any chemical signals of brain injury from escaping into the circulatory system.

But Army researchers partnered with a spin-out company from the University of Florida, and the search was on. "By 2010, we had phase I and II data showing that we could not only identify those with a severe brain injury but [also identify those with mild traumatic brain injury] in limited numbers of patients," Col. Hack said. The findings indicated even mild injuries can cause biochemical disruptions that release proteins into the blood. With continued improvements in the sensitivity also came recognition of proteins specific for a brain injury.

The approval process for the test in combination with the i-STAT device is underway, but the path probably won’t be completely straight, he added. Concussion biomarkers are a new concept with no place in any existing diagnostic guidelines – all of which rely exclusively on imaging findings.

"Because of the immature state of this field, the FDA [Food and Drug Administration] doesn’t recognize any comparison measure for brain injury except a CT scan showing a subdural hematoma. So when we did our pivotal trials, we were limited by this. A fundamental problem in brain injury research is this use of CT as the standard for validation," Col. Hack said.

"There have been several Institute of Medicine reports decrying the lack of research in this huge public health problem. In fact, there’s no national research program for trauma of any kind, except in the military. This is a huge problem because it’s our young people who are most at risk for these injuries," which often exert a lifelong effect, he added.

Of necessity, battlegrounds have always been a theater of frontline medical research. But those findings can eventually benefit patients in any setting, Col. Hack said. "Many changes we’ve made [in trauma treatment] over the past 10 years are now being implemented in emergency rooms. It’s gratifying to come back here and see that – it’s the reward of a lifetime."

[email protected]

On Twitter @alz_gal

A handheld device that uses a newly developed test can rapidly identify even mild concussion by measuring two key biomarkers of neuronal injury.

The new test for traumatic brain injury – the i-STAT concussion biomarker test – may be deployed within 2 years by the Department of Defense, according to Col. Dallas Hack, M.D., Brain Health Coordinator at the U.S. Army Medical Research and Materiel Command, Ft. Detrick, Md.

The test will be integrated into a device that the military already uses – the i-STAT System, manufactured by Abbott. The unit already performs a wide variety of tests, including measurements of glucose, blood gases, coagulation factors, and cardiac markers. Each test is loaded on a single-use cartridge. The new test for concussion biomarkers will be on a similar cartridge, eliminating the need to buy or train on a new device, Col. Hack said in an interview.

Whether used in a battle setting or on a military base, the rapid test will speed up diagnosis and treatment. "This test is going to provide definitive proof of a brain injury very quickly, and that will kick in our set of treatment algorithms, which are already in place," he said.

Although it’s being designed for use in a military setting, the i-STAT concussion biomarker test will eventually be available in the civilian world, where the need is just as great, Col. Hack added.

The search for biomarkers of brain injury has been a long one – and its birthday is ironic, he noted. "It was literally the morning of 9-11 (in 2001) at the Advanced Technology Applications for Combat Casualty Care Conference [a precursor to the Military Health Systems Research Symposium] when researchers from the military and the University of Florida decided to embark together on this project."

Thirteen years later, at the same conference where the concept was first proposed, researchers presented data on one of the candidate biomarkers – ubiquitin C-terminal hydrolase-L1 (UCH-L1) – which is released when neurons are damaged. "This is a very early marker, present as soon as 15 minutes after an injury," Col. Hack said.

Maj. Walter Carr, of the Walter Reed Army Institute of Research, Washington, presented the new data, drawn from an observational cohort study of 220 soldiers serving in Afghanistan. Of these, 70 had sustained a concussion and 74 had a nonconcussion injury; there were 76 uninjured control subjects. Each patient had two blood draws, one within 8 hours after injury and the second about 24 hours after the injury.

At both time points, UCH-L1 levels were significantly higher in the concussed patients than in either of the other groups.

The protein is one of two biomarkers that will be included in the new test, which is being developed in collaboration with Abbott. The other biomarker, glial fibrillary acidic protein (GFAP), indicates astrocyte activation after neuronal injury.

When the search for biomarkers of brain injury was proposed in 2001, some researchers considered the blood-brain barrier to be inviolate – an impenetrable block that would prevent any chemical signals of brain injury from escaping into the circulatory system.

But Army researchers partnered with a spin-out company from the University of Florida, and the search was on. "By 2010, we had phase I and II data showing that we could not only identify those with a severe brain injury but [also identify those with mild traumatic brain injury] in limited numbers of patients," Col. Hack said. The findings indicated even mild injuries can cause biochemical disruptions that release proteins into the blood. With continued improvements in the sensitivity also came recognition of proteins specific for a brain injury.

The approval process for the test in combination with the i-STAT device is underway, but the path probably won’t be completely straight, he added. Concussion biomarkers are a new concept with no place in any existing diagnostic guidelines – all of which rely exclusively on imaging findings.

"Because of the immature state of this field, the FDA [Food and Drug Administration] doesn’t recognize any comparison measure for brain injury except a CT scan showing a subdural hematoma. So when we did our pivotal trials, we were limited by this. A fundamental problem in brain injury research is this use of CT as the standard for validation," Col. Hack said.

"There have been several Institute of Medicine reports decrying the lack of research in this huge public health problem. In fact, there’s no national research program for trauma of any kind, except in the military. This is a huge problem because it’s our young people who are most at risk for these injuries," which often exert a lifelong effect, he added.

Of necessity, battlegrounds have always been a theater of frontline medical research. But those findings can eventually benefit patients in any setting, Col. Hack said. "Many changes we’ve made [in trauma treatment] over the past 10 years are now being implemented in emergency rooms. It’s gratifying to come back here and see that – it’s the reward of a lifetime."

[email protected]

On Twitter @alz_gal

SAN DIEGO – In the next 5-10 years, reaching for a powdered form of plasma may become the normative first-line treatment for trauma patients who present with severe bleeding. That’s because the current standard of administering fresh frozen plasma is riddled with problems, Dr. Martin Schreiber said at the University of California, San Diego, Critical Care Summer Session.

For one thing, frozen plasma takes 35 minutes to thaw. "That’s a problem, and the clotting factor function of plasma deteriorates as you freeze it and thaw it," said Dr. Schreiber, professor of surgery at Oregon Health & Science University, Portland. "Also, you need it in large volumes and that’s not good for patients with congestive heart failure on Coumadin, and the availability is limited, especially in rural settings."

Courtesy Wikimedia Commons/DiverDave/Creative Commons

Enter lyophilized plasma (LP), a process developed by HemCon Medical Technologies in which whole blood is sterilely removed, and the plasma component is separated and turned into a powder. The powdered plasma is returned and reconstituted prior to transfusion. "You can put this stuff as a powder on a shelf in nearly any environment," Dr. Schreiber said. "It’s good for at least 3 years, it survives a broad range of temperatures, and you can restore it to plasma within a couple of minutes."

An initial study of LP showed encouraging results with the use of a freeze-dried form of plasma for resuscitation (J. Trauma 2008;65[5]:975-85). A later study by researchers including Dr. Schreiber evaluated the effects of the lyophilization process on plasma clotting factor levels in swine, by adding the antioxidant ascorbic acid (vitamin C) to the reconstitution solution, and by comparing the efficacy of LP with that of fresh frozen plasma and that of plasma and packed red blood cells in a 1:1 ratio (Arch. Surg. 2009;144[9]:829-34). "What we found was that if we gave LP with packed red blood cells in a 1:1 ratio we had 14% less blood loss than if it’s given as FFP with packed cells, which was significant," Dr. Schreiber said.

"The LP was better in terms of stopping hemorrhage. We also noticed that with the vitamin C, we suppressed inflammation and got reduced IL-6 [interleukin 6] expression. Now, the Germans, the Dutch, and the French are using LP in their military settings. Our special forces people are also using it. It’s under current development for common use in your hospital in 5-10 years. I think this stuff is good anywhere. With LP we can always maintain a 1:1 ratio and we don’t have to worry about the thawing process."

Tranexamic acid, a synthetic derivative of lysine, is another anticoagulant therapy that is likely to be used with increasing frequency, he predicted. This agent "binds plasminogen so plasminogen can’t break down fibrin so you can’t get fibrinolysis," said Dr. Schreiber, who has been deployed three times as a combat surgeon.

"This drug has been around forever and is extremely inexpensive. It’s approved by the FDA for use in tooth extraction and the oral form is approved for menorrhagia." Tranexamic acid has also been studied in 53 prospective, randomized studies involving some 3,800 subjects, mostly cardiac patients. "They show that if you use tranexamic acid, you use less blood. It reduces the amount of blood necessary for transfusing people in high-bleeding settings, but no difference in mortality, thrombotic events, myocardial infarction, or stroke. It does not seem to produce a hypercoagulable state."

One study of tranexamic acid use by British surgeons during Afghanistan combat operations found that soldiers who received tranexamic acid were seven times more likely to live, compared with those who did not receive the agent (Arch. Surg. 2012;147:113-19). "There was a survival of 85% in tranexamic acid group, compared with about 70% in those who did not receive it," said Dr. Schreiber. "This has resulted in a change in practice in civilian trauma centers where it is being used widely."

Another anticoagulant being used is the prothrombin complex concentrate known as Kcentra, which contains all four vitamin K–dependent coagulation factors. Distributed by CSL Behring, Kcentra is approved for warfarin reversal in adult patients with acute major bleeding and for those who require emergency surgery. The max dose is 50 units/kg. "That’s about $4,445 for a 70-kg person," Dr. Schreiber said. "Why is it so good? It’s rapidly available, you don’t have to give a lot of fluid, there’s no infectious risk, and you can very rapidly increase coagulation factor function. This is where we’re headed in the future for trauma patients."

Dr. Schreiber said that he had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

SAN DIEGO – In the next 5-10 years, reaching for a powdered form of plasma may become the normative first-line treatment for trauma patients who present with severe bleeding. That’s because the current standard of administering fresh frozen plasma is riddled with problems, Dr. Martin Schreiber said at the University of California, San Diego, Critical Care Summer Session.

For one thing, frozen plasma takes 35 minutes to thaw. "That’s a problem, and the clotting factor function of plasma deteriorates as you freeze it and thaw it," said Dr. Schreiber, professor of surgery at Oregon Health & Science University, Portland. "Also, you need it in large volumes and that’s not good for patients with congestive heart failure on Coumadin, and the availability is limited, especially in rural settings."

Courtesy Wikimedia Commons/DiverDave/Creative Commons

Enter lyophilized plasma (LP), a process developed by HemCon Medical Technologies in which whole blood is sterilely removed, and the plasma component is separated and turned into a powder. The powdered plasma is returned and reconstituted prior to transfusion. "You can put this stuff as a powder on a shelf in nearly any environment," Dr. Schreiber said. "It’s good for at least 3 years, it survives a broad range of temperatures, and you can restore it to plasma within a couple of minutes."

An initial study of LP showed encouraging results with the use of a freeze-dried form of plasma for resuscitation (J. Trauma 2008;65[5]:975-85). A later study by researchers including Dr. Schreiber evaluated the effects of the lyophilization process on plasma clotting factor levels in swine, by adding the antioxidant ascorbic acid (vitamin C) to the reconstitution solution, and by comparing the efficacy of LP with that of fresh frozen plasma and that of plasma and packed red blood cells in a 1:1 ratio (Arch. Surg. 2009;144[9]:829-34). "What we found was that if we gave LP with packed red blood cells in a 1:1 ratio we had 14% less blood loss than if it’s given as FFP with packed cells, which was significant," Dr. Schreiber said.

"The LP was better in terms of stopping hemorrhage. We also noticed that with the vitamin C, we suppressed inflammation and got reduced IL-6 [interleukin 6] expression. Now, the Germans, the Dutch, and the French are using LP in their military settings. Our special forces people are also using it. It’s under current development for common use in your hospital in 5-10 years. I think this stuff is good anywhere. With LP we can always maintain a 1:1 ratio and we don’t have to worry about the thawing process."

Tranexamic acid, a synthetic derivative of lysine, is another anticoagulant therapy that is likely to be used with increasing frequency, he predicted. This agent "binds plasminogen so plasminogen can’t break down fibrin so you can’t get fibrinolysis," said Dr. Schreiber, who has been deployed three times as a combat surgeon.

"This drug has been around forever and is extremely inexpensive. It’s approved by the FDA for use in tooth extraction and the oral form is approved for menorrhagia." Tranexamic acid has also been studied in 53 prospective, randomized studies involving some 3,800 subjects, mostly cardiac patients. "They show that if you use tranexamic acid, you use less blood. It reduces the amount of blood necessary for transfusing people in high-bleeding settings, but no difference in mortality, thrombotic events, myocardial infarction, or stroke. It does not seem to produce a hypercoagulable state."

One study of tranexamic acid use by British surgeons during Afghanistan combat operations found that soldiers who received tranexamic acid were seven times more likely to live, compared with those who did not receive the agent (Arch. Surg. 2012;147:113-19). "There was a survival of 85% in tranexamic acid group, compared with about 70% in those who did not receive it," said Dr. Schreiber. "This has resulted in a change in practice in civilian trauma centers where it is being used widely."

Another anticoagulant being used is the prothrombin complex concentrate known as Kcentra, which contains all four vitamin K–dependent coagulation factors. Distributed by CSL Behring, Kcentra is approved for warfarin reversal in adult patients with acute major bleeding and for those who require emergency surgery. The max dose is 50 units/kg. "That’s about $4,445 for a 70-kg person," Dr. Schreiber said. "Why is it so good? It’s rapidly available, you don’t have to give a lot of fluid, there’s no infectious risk, and you can very rapidly increase coagulation factor function. This is where we’re headed in the future for trauma patients."

Dr. Schreiber said that he had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

SAN DIEGO – In the next 5-10 years, reaching for a powdered form of plasma may become the normative first-line treatment for trauma patients who present with severe bleeding. That’s because the current standard of administering fresh frozen plasma is riddled with problems, Dr. Martin Schreiber said at the University of California, San Diego, Critical Care Summer Session.

For one thing, frozen plasma takes 35 minutes to thaw. "That’s a problem, and the clotting factor function of plasma deteriorates as you freeze it and thaw it," said Dr. Schreiber, professor of surgery at Oregon Health & Science University, Portland. "Also, you need it in large volumes and that’s not good for patients with congestive heart failure on Coumadin, and the availability is limited, especially in rural settings."

Courtesy Wikimedia Commons/DiverDave/Creative Commons

Enter lyophilized plasma (LP), a process developed by HemCon Medical Technologies in which whole blood is sterilely removed, and the plasma component is separated and turned into a powder. The powdered plasma is returned and reconstituted prior to transfusion. "You can put this stuff as a powder on a shelf in nearly any environment," Dr. Schreiber said. "It’s good for at least 3 years, it survives a broad range of temperatures, and you can restore it to plasma within a couple of minutes."

An initial study of LP showed encouraging results with the use of a freeze-dried form of plasma for resuscitation (J. Trauma 2008;65[5]:975-85). A later study by researchers including Dr. Schreiber evaluated the effects of the lyophilization process on plasma clotting factor levels in swine, by adding the antioxidant ascorbic acid (vitamin C) to the reconstitution solution, and by comparing the efficacy of LP with that of fresh frozen plasma and that of plasma and packed red blood cells in a 1:1 ratio (Arch. Surg. 2009;144[9]:829-34). "What we found was that if we gave LP with packed red blood cells in a 1:1 ratio we had 14% less blood loss than if it’s given as FFP with packed cells, which was significant," Dr. Schreiber said.

"The LP was better in terms of stopping hemorrhage. We also noticed that with the vitamin C, we suppressed inflammation and got reduced IL-6 [interleukin 6] expression. Now, the Germans, the Dutch, and the French are using LP in their military settings. Our special forces people are also using it. It’s under current development for common use in your hospital in 5-10 years. I think this stuff is good anywhere. With LP we can always maintain a 1:1 ratio and we don’t have to worry about the thawing process."

Tranexamic acid, a synthetic derivative of lysine, is another anticoagulant therapy that is likely to be used with increasing frequency, he predicted. This agent "binds plasminogen so plasminogen can’t break down fibrin so you can’t get fibrinolysis," said Dr. Schreiber, who has been deployed three times as a combat surgeon.

"This drug has been around forever and is extremely inexpensive. It’s approved by the FDA for use in tooth extraction and the oral form is approved for menorrhagia." Tranexamic acid has also been studied in 53 prospective, randomized studies involving some 3,800 subjects, mostly cardiac patients. "They show that if you use tranexamic acid, you use less blood. It reduces the amount of blood necessary for transfusing people in high-bleeding settings, but no difference in mortality, thrombotic events, myocardial infarction, or stroke. It does not seem to produce a hypercoagulable state."

One study of tranexamic acid use by British surgeons during Afghanistan combat operations found that soldiers who received tranexamic acid were seven times more likely to live, compared with those who did not receive the agent (Arch. Surg. 2012;147:113-19). "There was a survival of 85% in tranexamic acid group, compared with about 70% in those who did not receive it," said Dr. Schreiber. "This has resulted in a change in practice in civilian trauma centers where it is being used widely."

Another anticoagulant being used is the prothrombin complex concentrate known as Kcentra, which contains all four vitamin K–dependent coagulation factors. Distributed by CSL Behring, Kcentra is approved for warfarin reversal in adult patients with acute major bleeding and for those who require emergency surgery. The max dose is 50 units/kg. "That’s about $4,445 for a 70-kg person," Dr. Schreiber said. "Why is it so good? It’s rapidly available, you don’t have to give a lot of fluid, there’s no infectious risk, and you can very rapidly increase coagulation factor function. This is where we’re headed in the future for trauma patients."

Dr. Schreiber said that he had no relevant financial conflicts to disclose.

[email protected]

On Twitter @dougbrunk

Patients with certain symptoms after mild traumatic brain injury should be considered to have a form of posttraumatic stress disorder, rather than postconcussion syndrome, a prospective study of more than 1,300 patients shows.

Several published diagnostic criteria exist for postconcussion syndrome (PCS), but it is defined in the DSM-IV as a head trauma causing concussion followed by cognitive problems and at least three of eight symptoms – among them headache, dizziness, and personality change – lasting 3 months or longer. Several studies have questioned the specificity of the PCS diagnosis, finding overlap of symptoms among patients with head injuries and other types of injuries. And as traumatic brain injury is strongly associated with PTSD, researchers have suggested that certain symptoms thought to be indicative of brain injury might instead reflect stress reactions stemming from trauma.

In a study published online July 16 in JAMA Psychiatry (doi:10.1001/jamapsychiatry.2014.666), Emmanuel Lagarde, Ph.D., of the INSERM Research Center in Bordeaux, France, and colleagues, analyzed data from 1,361 patients recruited from a hospital emergency department, of whom 534 had head injuries and 827 had injuries to other parts of the body. At 3 months’ follow-up, 21.2% of the mild traumatic brain injury (MTBI) patients and 16.3% of controls without head injuries could be diagnosed with PCS based on the DSM-IV criteria.

Moreover, 8.8% of patients with head injuries fulfilled diagnostic criteria for PTSD, compared with only 2.2% of controls. In the study group as a whole, MTBI was seen as a strong predictor of PTSD (odds ratio 4.47; 95% CI 2.38-8.4) but not of PCS (OR, 1.13; 95% CI 0.82-1.55). MTBI predicted PTSD regardless of whether the injury occurred as a result of a road crash, assault, or fall.

Assault was seen as a predictor of PCS as defined by DSM-IV, while severity of injury was not, suggesting that "psychological stress, and not potential brain injury, causes these symptoms, reinforcing the idea that they should be considered part of PTSD and not PCS," the researchers wrote.

They also found that symptoms suggestive of PCS under the DSM-IV criteria clustered in a way that paralleled a group of PTSD symptoms categorized as hyperarousal.

"The rationale to define a PCS that is specific to head-trauma patients is weak," Dr. Lagarde and colleagues wrote in their analysis. "Our results also suggested that the misunderstanding related to the relevance of defining such a syndrome could be explained by the overlapping pattern with symptoms of the PTSD hyperarousal dimension."

Available evidence does not support the use of PCS, they concluded, adding that clinicians should consider PTSD risk and treatment for patients with MTBI.

Dr. Lagarde and colleagues acknowledged as limitations of their study the fact that PTSD diagnoses were not made through formal clinical exams and that researchers focused on the traumatic events that landed subjects in the emergency department without capturing information on past traumatic events.

INSERM, the REUNICA Group, and Bordeaux University Hospital funded the study. None of the authors disclosed conflicts of interest.

Patients with certain symptoms after mild traumatic brain injury should be considered to have a form of posttraumatic stress disorder, rather than postconcussion syndrome, a prospective study of more than 1,300 patients shows.

Several published diagnostic criteria exist for postconcussion syndrome (PCS), but it is defined in the DSM-IV as a head trauma causing concussion followed by cognitive problems and at least three of eight symptoms – among them headache, dizziness, and personality change – lasting 3 months or longer. Several studies have questioned the specificity of the PCS diagnosis, finding overlap of symptoms among patients with head injuries and other types of injuries. And as traumatic brain injury is strongly associated with PTSD, researchers have suggested that certain symptoms thought to be indicative of brain injury might instead reflect stress reactions stemming from trauma.

In a study published online July 16 in JAMA Psychiatry (doi:10.1001/jamapsychiatry.2014.666), Emmanuel Lagarde, Ph.D., of the INSERM Research Center in Bordeaux, France, and colleagues, analyzed data from 1,361 patients recruited from a hospital emergency department, of whom 534 had head injuries and 827 had injuries to other parts of the body. At 3 months’ follow-up, 21.2% of the mild traumatic brain injury (MTBI) patients and 16.3% of controls without head injuries could be diagnosed with PCS based on the DSM-IV criteria.

Moreover, 8.8% of patients with head injuries fulfilled diagnostic criteria for PTSD, compared with only 2.2% of controls. In the study group as a whole, MTBI was seen as a strong predictor of PTSD (odds ratio 4.47; 95% CI 2.38-8.4) but not of PCS (OR, 1.13; 95% CI 0.82-1.55). MTBI predicted PTSD regardless of whether the injury occurred as a result of a road crash, assault, or fall.

Assault was seen as a predictor of PCS as defined by DSM-IV, while severity of injury was not, suggesting that "psychological stress, and not potential brain injury, causes these symptoms, reinforcing the idea that they should be considered part of PTSD and not PCS," the researchers wrote.

They also found that symptoms suggestive of PCS under the DSM-IV criteria clustered in a way that paralleled a group of PTSD symptoms categorized as hyperarousal.

"The rationale to define a PCS that is specific to head-trauma patients is weak," Dr. Lagarde and colleagues wrote in their analysis. "Our results also suggested that the misunderstanding related to the relevance of defining such a syndrome could be explained by the overlapping pattern with symptoms of the PTSD hyperarousal dimension."

Available evidence does not support the use of PCS, they concluded, adding that clinicians should consider PTSD risk and treatment for patients with MTBI.

Dr. Lagarde and colleagues acknowledged as limitations of their study the fact that PTSD diagnoses were not made through formal clinical exams and that researchers focused on the traumatic events that landed subjects in the emergency department without capturing information on past traumatic events.

INSERM, the REUNICA Group, and Bordeaux University Hospital funded the study. None of the authors disclosed conflicts of interest.

Patients with certain symptoms after mild traumatic brain injury should be considered to have a form of posttraumatic stress disorder, rather than postconcussion syndrome, a prospective study of more than 1,300 patients shows.

Several published diagnostic criteria exist for postconcussion syndrome (PCS), but it is defined in the DSM-IV as a head trauma causing concussion followed by cognitive problems and at least three of eight symptoms – among them headache, dizziness, and personality change – lasting 3 months or longer. Several studies have questioned the specificity of the PCS diagnosis, finding overlap of symptoms among patients with head injuries and other types of injuries. And as traumatic brain injury is strongly associated with PTSD, researchers have suggested that certain symptoms thought to be indicative of brain injury might instead reflect stress reactions stemming from trauma.

In a study published online July 16 in JAMA Psychiatry (doi:10.1001/jamapsychiatry.2014.666), Emmanuel Lagarde, Ph.D., of the INSERM Research Center in Bordeaux, France, and colleagues, analyzed data from 1,361 patients recruited from a hospital emergency department, of whom 534 had head injuries and 827 had injuries to other parts of the body. At 3 months’ follow-up, 21.2% of the mild traumatic brain injury (MTBI) patients and 16.3% of controls without head injuries could be diagnosed with PCS based on the DSM-IV criteria.

Moreover, 8.8% of patients with head injuries fulfilled diagnostic criteria for PTSD, compared with only 2.2% of controls. In the study group as a whole, MTBI was seen as a strong predictor of PTSD (odds ratio 4.47; 95% CI 2.38-8.4) but not of PCS (OR, 1.13; 95% CI 0.82-1.55). MTBI predicted PTSD regardless of whether the injury occurred as a result of a road crash, assault, or fall.

Assault was seen as a predictor of PCS as defined by DSM-IV, while severity of injury was not, suggesting that "psychological stress, and not potential brain injury, causes these symptoms, reinforcing the idea that they should be considered part of PTSD and not PCS," the researchers wrote.

They also found that symptoms suggestive of PCS under the DSM-IV criteria clustered in a way that paralleled a group of PTSD symptoms categorized as hyperarousal.

"The rationale to define a PCS that is specific to head-trauma patients is weak," Dr. Lagarde and colleagues wrote in their analysis. "Our results also suggested that the misunderstanding related to the relevance of defining such a syndrome could be explained by the overlapping pattern with symptoms of the PTSD hyperarousal dimension."

Available evidence does not support the use of PCS, they concluded, adding that clinicians should consider PTSD risk and treatment for patients with MTBI.

Dr. Lagarde and colleagues acknowledged as limitations of their study the fact that PTSD diagnoses were not made through formal clinical exams and that researchers focused on the traumatic events that landed subjects in the emergency department without capturing information on past traumatic events.

INSERM, the REUNICA Group, and Bordeaux University Hospital funded the study. None of the authors disclosed conflicts of interest.