Ted Bosworth

NEW YORK – There are numerous clinical factors and objective tools for identifying patients with Parkinson’s disease who have an increased risk of falls, according to data from a prospective study and an overview of this topic that was presented at the International Conference on Parkinson’s Disease and Movement Disorders

Ted Bosworth/MDedge News

“Identifying risk of falls, which can produce complications beyond the acute injury, is one of the most important unmet needs in Parkinson’s disease,” reported A.V. Srinivasan, MD, PhD, DSc, of the Tamil Nadu Dr. MGR Medial University, Chennai, India.

Falls pose a risk of complications beyond acute injury because of the potential domino effect, according to Dr. Srinivasan. He maintained that when aging Parkinson’s disease patients are confined to bed for an extended period of recovery, a host of adverse health consequences can follow, including such life-threatening events as aspiration pneumonia.

“A serious fall can be the start of a downward clinical slope,” according to Dr. Srinivasan, who cited data suggesting that 40%-70% of Parkinson’s disease patients will have a serious fall at advanced stages of disease.

To identify those at greatest risk, a number of objective studies were shown to be useful in a study undertaken at the Institute of Neurology of Madras (India) Medical College, according to Dr. Srinivasan, where he was a professor when the study was conducted. In this study, 112 patients were evaluated with more than 15 months of follow-up. The 57 (51%) who experienced a fall were compared with the 55 who did not.

Between these groups, there was no difference in mean age (approximately 57 years in both) or in gender (approximately 70% male in both), according to Dr. Srinivasan. However, those who fell were significantly more likely to be obese (P = .009), to be on two or more anti-Parkinson’s medication (P = .01), and to be hypertensive (P = .018). Disease duration was significantly longer and disease severity significantly greater in those who fell relative to those who did not, according to Dr. Srinivasan.

However, Dr. Srinivasan placed particular emphasis on the objective studies that predicted risk of falls.

“When we compared baseline characteristics, Tinetti balance score, episodes of freezing gait, and the Get-Up-And-Go Test [GAGT], were all significant predictors of falls [all P less than .001],” Dr. Srinivasan said.

Of clinical studies, he suggested that GAGT is particularly simple and helpful. In GAGT, the time for a patient to rise from a chair, walk 10 feet, and return to their original sitting position, is timed. According to Dr. Srinivasan, an interval of 12 seconds or greater is a measure of impaired mobility and a signal for increased risk of falls.

Other patient characteristics or disease features that predicted increased risk of falls included the presence of dyskinesias and treatment with relatively high doses of levodopa. All of these factors should be considered when conducting a comprehensive risk assessment.

“A formal evaluation should be conducted routinely in all patients because there are a number of simple and effective strategies to reduce falls in patients at high risk,” Dr. Srinivasan said. These include teaching patients to avoid abrupt movements and modifying therapies to avoid gait freezing and other symptoms associated with falls. He cited a 2014 review article by Canning et al. (Neurodegen Dis Manag. 2014;4:203-21) as one source of clinically useful approaches.

“Early prevention is important. One of the most significant risks of falls is a previous fall. Control of disease symptoms lowers risk, but motor symptoms are not the only concern,” Dr. Srinivasan said. He suggested nonmotor issues, including inadequate sleep, impaired cognitive function, and attention deficits, can all be addressed in order to prevent falls and the risks they pose to quality of life and outcome.

NEW YORK – There are numerous clinical factors and objective tools for identifying patients with Parkinson’s disease who have an increased risk of falls, according to data from a prospective study and an overview of this topic that was presented at the International Conference on Parkinson’s Disease and Movement Disorders

Ted Bosworth/MDedge News

“Identifying risk of falls, which can produce complications beyond the acute injury, is one of the most important unmet needs in Parkinson’s disease,” reported A.V. Srinivasan, MD, PhD, DSc, of the Tamil Nadu Dr. MGR Medial University, Chennai, India.

Falls pose a risk of complications beyond acute injury because of the potential domino effect, according to Dr. Srinivasan. He maintained that when aging Parkinson’s disease patients are confined to bed for an extended period of recovery, a host of adverse health consequences can follow, including such life-threatening events as aspiration pneumonia.

“A serious fall can be the start of a downward clinical slope,” according to Dr. Srinivasan, who cited data suggesting that 40%-70% of Parkinson’s disease patients will have a serious fall at advanced stages of disease.

To identify those at greatest risk, a number of objective studies were shown to be useful in a study undertaken at the Institute of Neurology of Madras (India) Medical College, according to Dr. Srinivasan, where he was a professor when the study was conducted. In this study, 112 patients were evaluated with more than 15 months of follow-up. The 57 (51%) who experienced a fall were compared with the 55 who did not.

Between these groups, there was no difference in mean age (approximately 57 years in both) or in gender (approximately 70% male in both), according to Dr. Srinivasan. However, those who fell were significantly more likely to be obese (P = .009), to be on two or more anti-Parkinson’s medication (P = .01), and to be hypertensive (P = .018). Disease duration was significantly longer and disease severity significantly greater in those who fell relative to those who did not, according to Dr. Srinivasan.

However, Dr. Srinivasan placed particular emphasis on the objective studies that predicted risk of falls.

“When we compared baseline characteristics, Tinetti balance score, episodes of freezing gait, and the Get-Up-And-Go Test [GAGT], were all significant predictors of falls [all P less than .001],” Dr. Srinivasan said.

Of clinical studies, he suggested that GAGT is particularly simple and helpful. In GAGT, the time for a patient to rise from a chair, walk 10 feet, and return to their original sitting position, is timed. According to Dr. Srinivasan, an interval of 12 seconds or greater is a measure of impaired mobility and a signal for increased risk of falls.

Other patient characteristics or disease features that predicted increased risk of falls included the presence of dyskinesias and treatment with relatively high doses of levodopa. All of these factors should be considered when conducting a comprehensive risk assessment.

“A formal evaluation should be conducted routinely in all patients because there are a number of simple and effective strategies to reduce falls in patients at high risk,” Dr. Srinivasan said. These include teaching patients to avoid abrupt movements and modifying therapies to avoid gait freezing and other symptoms associated with falls. He cited a 2014 review article by Canning et al. (Neurodegen Dis Manag. 2014;4:203-21) as one source of clinically useful approaches.

“Early prevention is important. One of the most significant risks of falls is a previous fall. Control of disease symptoms lowers risk, but motor symptoms are not the only concern,” Dr. Srinivasan said. He suggested nonmotor issues, including inadequate sleep, impaired cognitive function, and attention deficits, can all be addressed in order to prevent falls and the risks they pose to quality of life and outcome.

NEW YORK – There are numerous clinical factors and objective tools for identifying patients with Parkinson’s disease who have an increased risk of falls, according to data from a prospective study and an overview of this topic that was presented at the International Conference on Parkinson’s Disease and Movement Disorders

Ted Bosworth/MDedge News

“Identifying risk of falls, which can produce complications beyond the acute injury, is one of the most important unmet needs in Parkinson’s disease,” reported A.V. Srinivasan, MD, PhD, DSc, of the Tamil Nadu Dr. MGR Medial University, Chennai, India.

Falls pose a risk of complications beyond acute injury because of the potential domino effect, according to Dr. Srinivasan. He maintained that when aging Parkinson’s disease patients are confined to bed for an extended period of recovery, a host of adverse health consequences can follow, including such life-threatening events as aspiration pneumonia.

“A serious fall can be the start of a downward clinical slope,” according to Dr. Srinivasan, who cited data suggesting that 40%-70% of Parkinson’s disease patients will have a serious fall at advanced stages of disease.

To identify those at greatest risk, a number of objective studies were shown to be useful in a study undertaken at the Institute of Neurology of Madras (India) Medical College, according to Dr. Srinivasan, where he was a professor when the study was conducted. In this study, 112 patients were evaluated with more than 15 months of follow-up. The 57 (51%) who experienced a fall were compared with the 55 who did not.

Between these groups, there was no difference in mean age (approximately 57 years in both) or in gender (approximately 70% male in both), according to Dr. Srinivasan. However, those who fell were significantly more likely to be obese (P = .009), to be on two or more anti-Parkinson’s medication (P = .01), and to be hypertensive (P = .018). Disease duration was significantly longer and disease severity significantly greater in those who fell relative to those who did not, according to Dr. Srinivasan.

However, Dr. Srinivasan placed particular emphasis on the objective studies that predicted risk of falls.

“When we compared baseline characteristics, Tinetti balance score, episodes of freezing gait, and the Get-Up-And-Go Test [GAGT], were all significant predictors of falls [all P less than .001],” Dr. Srinivasan said.

Of clinical studies, he suggested that GAGT is particularly simple and helpful. In GAGT, the time for a patient to rise from a chair, walk 10 feet, and return to their original sitting position, is timed. According to Dr. Srinivasan, an interval of 12 seconds or greater is a measure of impaired mobility and a signal for increased risk of falls.

Other patient characteristics or disease features that predicted increased risk of falls included the presence of dyskinesias and treatment with relatively high doses of levodopa. All of these factors should be considered when conducting a comprehensive risk assessment.

“A formal evaluation should be conducted routinely in all patients because there are a number of simple and effective strategies to reduce falls in patients at high risk,” Dr. Srinivasan said. These include teaching patients to avoid abrupt movements and modifying therapies to avoid gait freezing and other symptoms associated with falls. He cited a 2014 review article by Canning et al. (Neurodegen Dis Manag. 2014;4:203-21) as one source of clinically useful approaches.

“Early prevention is important. One of the most significant risks of falls is a previous fall. Control of disease symptoms lowers risk, but motor symptoms are not the only concern,” Dr. Srinivasan said. He suggested nonmotor issues, including inadequate sleep, impaired cognitive function, and attention deficits, can all be addressed in order to prevent falls and the risks they pose to quality of life and outcome.

NEW YORK – When paraganglionic lesions are compared with isolated basal ganglionic lesions in children, important differences in clinical manifestations were identified, according to imaging-based findings presented at the International Conference on Parkinson’s Disease and Movement Disorders.

Ted Bosworth/MDedge News

“The percentage of children with impaired cognitive function, motor weakness, and disturbed level of consciousness were all significantly higher among the paraganglionic group,” reported Hamada I. Zehry, MD, of Al-Azhar University, Cairo, Egypt.

Conversely, “the incidence of abnormal movements and rigidity were significantly higher among the group with basal ganglion lesions alone,” he said.

The findings were based on comparisons made after MRI imaging differentiated the 23 children with basal ganglionic lesions alone (IG) from 11 children with paraganglionic lesions (PG). About half of the PG group also had lesions involving the basal ganglion as well. All patients were 18 years of age or younger. The mean ages were 9 years in the IG group and 5.7 years in the PG group (P less than .04). Both groups contained approximately 55% males.

Both the IG and PG groups were stratified by ischemic, infectious, metabolic, and toxic etiologies. For the IG relative to the PG group, the ischemic (34.8% vs. 36.4%), infectious (26.1% vs. 36.4%), and metabolic (30.4% vs. 27.2%) etiologies had a relatively similar distribution. However, there was no patient in the PG group with a toxic etiology versus 8.7% (P = .003) in the IG group.

Neurologic symptoms by lesion site differed. Cognitive dysfunction (55% vs. 26%), seizures (64% vs. 43%), muscle weakness (45% vs. 30%), and changes in level of consciousness (82% vs. 22%) were all more common in the PG than the IG group according to Dr. Zehry. However, abnormal movements (30% vs. 9%) and rigidity (17% vs. 0%) were more common in the IG group.

These differences were all significant by conventional statistical analysis (P less than .05), according to Dr. Zehry, although he did not provide the specific P values for each of the comparisons.

There were also differences in the frequency of neurologic symptoms within groups when stratified by etiology. Of the biggest differences in the IG group, cognitive dysfunction was observed in 57% of those with a metabolic etiology but only 17% of those with an infectious etiology and 13% of those with an ischemic etiology. None of those with a toxic etiology had cognitive dysfunction.

In the PG group, the rates of cognitive dysfunction were 25%, 50%, and 100% for the ischemic, infectious, and metabolic etiologies, respectively. Changed levels of consciousness were observed in 75%, 100%, and 67% of these etiologies, respectively, in the PG group, but in only 13%, 33%, and 0%, respectively, in the IG group. In those with a toxic etiology in the IG group, a changed level of consciousness was observed in 100%.

Laboratory findings also were compared between groups and between etiologies within groups. It is notable that liver dysfunction and cytopenias were confined to those with metabolic infectious etiologies in both the IG and PG patients. However, Dr. Zehry suggested that the significance of these and other differences in laboratory findings deserve confirmation and further study in a larger study.

In this series, which excluded patients with a history of trauma or tumors, Dr. Zehry emphasized that bilateral lesions were commonly found in both groups. Overall, he cautioned that distinguishing IG and PG “is not straightforward.” In addition to MRI, he suggested additional imaging tools – such as MR angiography, MR venography, and CT scans – might be useful for evaluating children suspected of pathology in the basal ganglion.

Because there is often bilateral involvement, “the careful assessment of imaging abnormalities occurring simultaneously with bilateral ganglionic injury is recommended,” he said. He added that the diagnosis can also be facilitated by correlating imaging features with clinical and laboratory data.”

NEW YORK – When paraganglionic lesions are compared with isolated basal ganglionic lesions in children, important differences in clinical manifestations were identified, according to imaging-based findings presented at the International Conference on Parkinson’s Disease and Movement Disorders.

Ted Bosworth/MDedge News

“The percentage of children with impaired cognitive function, motor weakness, and disturbed level of consciousness were all significantly higher among the paraganglionic group,” reported Hamada I. Zehry, MD, of Al-Azhar University, Cairo, Egypt.

Conversely, “the incidence of abnormal movements and rigidity were significantly higher among the group with basal ganglion lesions alone,” he said.

The findings were based on comparisons made after MRI imaging differentiated the 23 children with basal ganglionic lesions alone (IG) from 11 children with paraganglionic lesions (PG). About half of the PG group also had lesions involving the basal ganglion as well. All patients were 18 years of age or younger. The mean ages were 9 years in the IG group and 5.7 years in the PG group (P less than .04). Both groups contained approximately 55% males.

Both the IG and PG groups were stratified by ischemic, infectious, metabolic, and toxic etiologies. For the IG relative to the PG group, the ischemic (34.8% vs. 36.4%), infectious (26.1% vs. 36.4%), and metabolic (30.4% vs. 27.2%) etiologies had a relatively similar distribution. However, there was no patient in the PG group with a toxic etiology versus 8.7% (P = .003) in the IG group.

Neurologic symptoms by lesion site differed. Cognitive dysfunction (55% vs. 26%), seizures (64% vs. 43%), muscle weakness (45% vs. 30%), and changes in level of consciousness (82% vs. 22%) were all more common in the PG than the IG group according to Dr. Zehry. However, abnormal movements (30% vs. 9%) and rigidity (17% vs. 0%) were more common in the IG group.

These differences were all significant by conventional statistical analysis (P less than .05), according to Dr. Zehry, although he did not provide the specific P values for each of the comparisons.

There were also differences in the frequency of neurologic symptoms within groups when stratified by etiology. Of the biggest differences in the IG group, cognitive dysfunction was observed in 57% of those with a metabolic etiology but only 17% of those with an infectious etiology and 13% of those with an ischemic etiology. None of those with a toxic etiology had cognitive dysfunction.

In the PG group, the rates of cognitive dysfunction were 25%, 50%, and 100% for the ischemic, infectious, and metabolic etiologies, respectively. Changed levels of consciousness were observed in 75%, 100%, and 67% of these etiologies, respectively, in the PG group, but in only 13%, 33%, and 0%, respectively, in the IG group. In those with a toxic etiology in the IG group, a changed level of consciousness was observed in 100%.

Laboratory findings also were compared between groups and between etiologies within groups. It is notable that liver dysfunction and cytopenias were confined to those with metabolic infectious etiologies in both the IG and PG patients. However, Dr. Zehry suggested that the significance of these and other differences in laboratory findings deserve confirmation and further study in a larger study.

In this series, which excluded patients with a history of trauma or tumors, Dr. Zehry emphasized that bilateral lesions were commonly found in both groups. Overall, he cautioned that distinguishing IG and PG “is not straightforward.” In addition to MRI, he suggested additional imaging tools – such as MR angiography, MR venography, and CT scans – might be useful for evaluating children suspected of pathology in the basal ganglion.

Because there is often bilateral involvement, “the careful assessment of imaging abnormalities occurring simultaneously with bilateral ganglionic injury is recommended,” he said. He added that the diagnosis can also be facilitated by correlating imaging features with clinical and laboratory data.”

NEW YORK – When paraganglionic lesions are compared with isolated basal ganglionic lesions in children, important differences in clinical manifestations were identified, according to imaging-based findings presented at the International Conference on Parkinson’s Disease and Movement Disorders.

Ted Bosworth/MDedge News

“The percentage of children with impaired cognitive function, motor weakness, and disturbed level of consciousness were all significantly higher among the paraganglionic group,” reported Hamada I. Zehry, MD, of Al-Azhar University, Cairo, Egypt.

Conversely, “the incidence of abnormal movements and rigidity were significantly higher among the group with basal ganglion lesions alone,” he said.

The findings were based on comparisons made after MRI imaging differentiated the 23 children with basal ganglionic lesions alone (IG) from 11 children with paraganglionic lesions (PG). About half of the PG group also had lesions involving the basal ganglion as well. All patients were 18 years of age or younger. The mean ages were 9 years in the IG group and 5.7 years in the PG group (P less than .04). Both groups contained approximately 55% males.

Both the IG and PG groups were stratified by ischemic, infectious, metabolic, and toxic etiologies. For the IG relative to the PG group, the ischemic (34.8% vs. 36.4%), infectious (26.1% vs. 36.4%), and metabolic (30.4% vs. 27.2%) etiologies had a relatively similar distribution. However, there was no patient in the PG group with a toxic etiology versus 8.7% (P = .003) in the IG group.

Neurologic symptoms by lesion site differed. Cognitive dysfunction (55% vs. 26%), seizures (64% vs. 43%), muscle weakness (45% vs. 30%), and changes in level of consciousness (82% vs. 22%) were all more common in the PG than the IG group according to Dr. Zehry. However, abnormal movements (30% vs. 9%) and rigidity (17% vs. 0%) were more common in the IG group.

These differences were all significant by conventional statistical analysis (P less than .05), according to Dr. Zehry, although he did not provide the specific P values for each of the comparisons.

There were also differences in the frequency of neurologic symptoms within groups when stratified by etiology. Of the biggest differences in the IG group, cognitive dysfunction was observed in 57% of those with a metabolic etiology but only 17% of those with an infectious etiology and 13% of those with an ischemic etiology. None of those with a toxic etiology had cognitive dysfunction.

In the PG group, the rates of cognitive dysfunction were 25%, 50%, and 100% for the ischemic, infectious, and metabolic etiologies, respectively. Changed levels of consciousness were observed in 75%, 100%, and 67% of these etiologies, respectively, in the PG group, but in only 13%, 33%, and 0%, respectively, in the IG group. In those with a toxic etiology in the IG group, a changed level of consciousness was observed in 100%.

Laboratory findings also were compared between groups and between etiologies within groups. It is notable that liver dysfunction and cytopenias were confined to those with metabolic infectious etiologies in both the IG and PG patients. However, Dr. Zehry suggested that the significance of these and other differences in laboratory findings deserve confirmation and further study in a larger study.

In this series, which excluded patients with a history of trauma or tumors, Dr. Zehry emphasized that bilateral lesions were commonly found in both groups. Overall, he cautioned that distinguishing IG and PG “is not straightforward.” In addition to MRI, he suggested additional imaging tools – such as MR angiography, MR venography, and CT scans – might be useful for evaluating children suspected of pathology in the basal ganglion.

Because there is often bilateral involvement, “the careful assessment of imaging abnormalities occurring simultaneously with bilateral ganglionic injury is recommended,” he said. He added that the diagnosis can also be facilitated by correlating imaging features with clinical and laboratory data.”

SAN DIEGO – A biomarker test based on the presence of two proteins in the blood appears to be suitable for ruling out significant intracranial injuries in patients with a history of mild traumatic brain injury (TBI) without the need for a CT head scan, according to data presented at the annual meeting of the American College of Emergency Physicians.

Ted Bosworth/MDedge News

A biomarker suitable for ruling out significant brain injury could save substantial resources because only about 10% of patients with mild TBI have a positive CT head scan, according to Jeffrey J. Bazarian, MD, professor of emergency medicine, University of Rochester (New York).

In the ALERT-TBI study, which evaluated the biomarker test, 1,959 patients with suspected TBI at 22 participating EDs in the United States and Europe were enrolled and available for analysis. All had mild TBI as defined as a Glasgow Coma Scale (GCS) score of 13-15.

The treating ED physician’s decision to order a head CT scan was the major criterion for study entry. All enrolled patients had their blood drawn within 12 hours in order to quantify two biomarkers, C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP).

The biomarker test for TBI was negative when the UCH-L1 value was less than 327 pg/mL and the GFAP was less than 22 pg/mL; the test was positive if either value was at this threshold or higher. To evaluate the sensitivity and specificity of this dual-biomarker test, results were correlated with head CT scans read by two neurologists blinded to the biomarker values.

The mean age of the study population was 48.8 years and slightly more than half were male. About half of the suspected TBI in these patients was attributed to falls and about one third to motor vehicle accidents.

Typical of TBI with GCS scores in the mild range, only 6% of the patients had a positive CT head scan. Of the 125 positive CT scans, the most common injury detected on CT scan was subarachnoid hemorrhage followed by subdural hematoma.

Of the 671 negative biomarker tests, 668 had normal head CT scans. Of the three false positives, one included a cavernous malformation that may have been present prior to the TBI. The others were a small subarachnoid hemorrhage and a small subdural hematoma. Overall the negative predictive value was 99.6% and the sensitivity was 97.6%.

Although the biomarker specificity was only 36% with an even-lower positive predictive value, the goal of the test was to rule out significant TBI to avoid the need for CT scan. On this basis, the biomarker test, which is being developed under the proprietary name Banyan BTI, appears to be promising. The data, according to Dr. Bazarian, have been submitted to the Food and Drug Administration.

“Head CT scans are the current standard for evaluating intracranial injuries after TBI, but they are overused, based on the high proportion that do not show an injury,” said Dr. Bazarian. Although he does not know the disposition of the FDA application, he said, based on these data, “I would definitely be using this test if it were available.”

SAN DIEGO – A biomarker test based on the presence of two proteins in the blood appears to be suitable for ruling out significant intracranial injuries in patients with a history of mild traumatic brain injury (TBI) without the need for a CT head scan, according to data presented at the annual meeting of the American College of Emergency Physicians.

Ted Bosworth/MDedge News

A biomarker suitable for ruling out significant brain injury could save substantial resources because only about 10% of patients with mild TBI have a positive CT head scan, according to Jeffrey J. Bazarian, MD, professor of emergency medicine, University of Rochester (New York).

In the ALERT-TBI study, which evaluated the biomarker test, 1,959 patients with suspected TBI at 22 participating EDs in the United States and Europe were enrolled and available for analysis. All had mild TBI as defined as a Glasgow Coma Scale (GCS) score of 13-15.

The treating ED physician’s decision to order a head CT scan was the major criterion for study entry. All enrolled patients had their blood drawn within 12 hours in order to quantify two biomarkers, C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP).

The biomarker test for TBI was negative when the UCH-L1 value was less than 327 pg/mL and the GFAP was less than 22 pg/mL; the test was positive if either value was at this threshold or higher. To evaluate the sensitivity and specificity of this dual-biomarker test, results were correlated with head CT scans read by two neurologists blinded to the biomarker values.

The mean age of the study population was 48.8 years and slightly more than half were male. About half of the suspected TBI in these patients was attributed to falls and about one third to motor vehicle accidents.

Typical of TBI with GCS scores in the mild range, only 6% of the patients had a positive CT head scan. Of the 125 positive CT scans, the most common injury detected on CT scan was subarachnoid hemorrhage followed by subdural hematoma.

Of the 671 negative biomarker tests, 668 had normal head CT scans. Of the three false positives, one included a cavernous malformation that may have been present prior to the TBI. The others were a small subarachnoid hemorrhage and a small subdural hematoma. Overall the negative predictive value was 99.6% and the sensitivity was 97.6%.

Although the biomarker specificity was only 36% with an even-lower positive predictive value, the goal of the test was to rule out significant TBI to avoid the need for CT scan. On this basis, the biomarker test, which is being developed under the proprietary name Banyan BTI, appears to be promising. The data, according to Dr. Bazarian, have been submitted to the Food and Drug Administration.

“Head CT scans are the current standard for evaluating intracranial injuries after TBI, but they are overused, based on the high proportion that do not show an injury,” said Dr. Bazarian. Although he does not know the disposition of the FDA application, he said, based on these data, “I would definitely be using this test if it were available.”

SAN DIEGO – A biomarker test based on the presence of two proteins in the blood appears to be suitable for ruling out significant intracranial injuries in patients with a history of mild traumatic brain injury (TBI) without the need for a CT head scan, according to data presented at the annual meeting of the American College of Emergency Physicians.

Ted Bosworth/MDedge News

A biomarker suitable for ruling out significant brain injury could save substantial resources because only about 10% of patients with mild TBI have a positive CT head scan, according to Jeffrey J. Bazarian, MD, professor of emergency medicine, University of Rochester (New York).

In the ALERT-TBI study, which evaluated the biomarker test, 1,959 patients with suspected TBI at 22 participating EDs in the United States and Europe were enrolled and available for analysis. All had mild TBI as defined as a Glasgow Coma Scale (GCS) score of 13-15.

The treating ED physician’s decision to order a head CT scan was the major criterion for study entry. All enrolled patients had their blood drawn within 12 hours in order to quantify two biomarkers, C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP).

The biomarker test for TBI was negative when the UCH-L1 value was less than 327 pg/mL and the GFAP was less than 22 pg/mL; the test was positive if either value was at this threshold or higher. To evaluate the sensitivity and specificity of this dual-biomarker test, results were correlated with head CT scans read by two neurologists blinded to the biomarker values.

The mean age of the study population was 48.8 years and slightly more than half were male. About half of the suspected TBI in these patients was attributed to falls and about one third to motor vehicle accidents.

Typical of TBI with GCS scores in the mild range, only 6% of the patients had a positive CT head scan. Of the 125 positive CT scans, the most common injury detected on CT scan was subarachnoid hemorrhage followed by subdural hematoma.

Of the 671 negative biomarker tests, 668 had normal head CT scans. Of the three false positives, one included a cavernous malformation that may have been present prior to the TBI. The others were a small subarachnoid hemorrhage and a small subdural hematoma. Overall the negative predictive value was 99.6% and the sensitivity was 97.6%.

Although the biomarker specificity was only 36% with an even-lower positive predictive value, the goal of the test was to rule out significant TBI to avoid the need for CT scan. On this basis, the biomarker test, which is being developed under the proprietary name Banyan BTI, appears to be promising. The data, according to Dr. Bazarian, have been submitted to the Food and Drug Administration.

“Head CT scans are the current standard for evaluating intracranial injuries after TBI, but they are overused, based on the high proportion that do not show an injury,” said Dr. Bazarian. Although he does not know the disposition of the FDA application, he said, based on these data, “I would definitely be using this test if it were available.”

NEW YORK – One reason to pursue a multimodality strategy to control the symptoms as well as the underlying pathophysiology of Parkinson’s disease (PD) is that a small but substantial proportion of patients with PD-like symptoms have a different diagnosis, according to an expert overview at the International Conference on Parkinson’s Disease and Movement Disorders.

Ted Bosworth/MDedge News

“Fifteen to 20% of patients treated for Parkinson’s disease, even in the most established centers of excellence, do not have Parkinson’s disease on necropsy,” said A.V. Srinivasan, MD, PhD, DSc, of The Tamil Nadu Dr. M.G.R. Medical University, Chennai, India.

This does not preclude benefit from antiparkinson drugs in those patients with PD-like symptoms but a different etiology. Many can benefit from increased dopamine availability, even in the absence of PD, but it emphasizes the complexity of clinical diseases associated with diminished dopamine function, according to Dr. Srinivasan. He characterized this complexity as a reason to avoid a regimented approach to PD management.

“You can just imagine how much this influences our data analysis,” said Dr. Srinivasan, referring to clinical trials designed to generate evidence-based treatment. “We should remember that we should not be too statistically oriented,” he added, citing the adage that “statistics can cause paralysis in your analysis.”

PD is associated with a vast array of neurologic and physical symptoms attributable to PD that overlap with other neurologic disorders, which is the reason that a definitive diagnosis is challenging, according to Dr. Srinivasan. Listing symptoms that should prompt consideration of an alternative diagnosis, Dr. Srinivasan said hallucinations suggest diffuse Lewy body disease, myoclonus suggests corticobasal degeneration, and amyotrophy suggests multiple system atrophy.

“These are only clues, however,” said Dr. Srinivasan, suggesting their presence should prompt consideration of alternative diagnoses, but their absence does not confirm PD.

In some cases, further work-up with one or more of the array of increasingly sophisticated imaging strategies, such as the combination of SPECT and PET, might help clinicians reach a more definitive diagnosis of the underlying pathology, a step that might guide use of dopaminergic therapies. However, effective treatment of PD symptoms does not depend on a definitive diagnosis.

Rather, Dr. Srinivasan advocated an open mind to the management of symptoms, which he indicated are best addressed empirically. As PD or other progressive movement disorders advance, the goal is to keep patients functional and comfortable.

This includes managing patients beyond prescription drugs to address such complications as dysphagia or impaired balance. He advocated practical solutions for causes of impaired quality of life such as soft foods to facilitate swallowing or walkers to keep patients ambulatory. No option that leads to symptom relief should be discounted, including alternative therapies.

“Some clinicians are strongly opposed to nontraditional therapies, such as naturopathy and homeopathy, but these have all been used in Parkinson’s,” Dr. Srinivasan said. Although he did not present data to show efficacy, he indicated that relief of symptoms and improvement of quality of life is the point of any treatment, which should be individualized by response in every patient.

And individualized therapy – in relationship to patient age – is particularly important, according to Dr. Srinivasan. While younger patients typically tolerate relatively aggressive therapies aimed at both PD and its specific symptoms, older patients may accept less ambitious functional improvements to achieve an adequate quality of life.

“After 70 years of age, every additional year is a bonus. After 80 years, every week is a bonus. After 90 years, every minute is a bonus,” said Dr. Srinivasan, in emphasizing an appropriate clinical perspective.

NEW YORK – One reason to pursue a multimodality strategy to control the symptoms as well as the underlying pathophysiology of Parkinson’s disease (PD) is that a small but substantial proportion of patients with PD-like symptoms have a different diagnosis, according to an expert overview at the International Conference on Parkinson’s Disease and Movement Disorders.

Ted Bosworth/MDedge News

“Fifteen to 20% of patients treated for Parkinson’s disease, even in the most established centers of excellence, do not have Parkinson’s disease on necropsy,” said A.V. Srinivasan, MD, PhD, DSc, of The Tamil Nadu Dr. M.G.R. Medical University, Chennai, India.

This does not preclude benefit from antiparkinson drugs in those patients with PD-like symptoms but a different etiology. Many can benefit from increased dopamine availability, even in the absence of PD, but it emphasizes the complexity of clinical diseases associated with diminished dopamine function, according to Dr. Srinivasan. He characterized this complexity as a reason to avoid a regimented approach to PD management.

“You can just imagine how much this influences our data analysis,” said Dr. Srinivasan, referring to clinical trials designed to generate evidence-based treatment. “We should remember that we should not be too statistically oriented,” he added, citing the adage that “statistics can cause paralysis in your analysis.”

PD is associated with a vast array of neurologic and physical symptoms attributable to PD that overlap with other neurologic disorders, which is the reason that a definitive diagnosis is challenging, according to Dr. Srinivasan. Listing symptoms that should prompt consideration of an alternative diagnosis, Dr. Srinivasan said hallucinations suggest diffuse Lewy body disease, myoclonus suggests corticobasal degeneration, and amyotrophy suggests multiple system atrophy.

“These are only clues, however,” said Dr. Srinivasan, suggesting their presence should prompt consideration of alternative diagnoses, but their absence does not confirm PD.

In some cases, further work-up with one or more of the array of increasingly sophisticated imaging strategies, such as the combination of SPECT and PET, might help clinicians reach a more definitive diagnosis of the underlying pathology, a step that might guide use of dopaminergic therapies. However, effective treatment of PD symptoms does not depend on a definitive diagnosis.

Rather, Dr. Srinivasan advocated an open mind to the management of symptoms, which he indicated are best addressed empirically. As PD or other progressive movement disorders advance, the goal is to keep patients functional and comfortable.

This includes managing patients beyond prescription drugs to address such complications as dysphagia or impaired balance. He advocated practical solutions for causes of impaired quality of life such as soft foods to facilitate swallowing or walkers to keep patients ambulatory. No option that leads to symptom relief should be discounted, including alternative therapies.

“Some clinicians are strongly opposed to nontraditional therapies, such as naturopathy and homeopathy, but these have all been used in Parkinson’s,” Dr. Srinivasan said. Although he did not present data to show efficacy, he indicated that relief of symptoms and improvement of quality of life is the point of any treatment, which should be individualized by response in every patient.

And individualized therapy – in relationship to patient age – is particularly important, according to Dr. Srinivasan. While younger patients typically tolerate relatively aggressive therapies aimed at both PD and its specific symptoms, older patients may accept less ambitious functional improvements to achieve an adequate quality of life.

“After 70 years of age, every additional year is a bonus. After 80 years, every week is a bonus. After 90 years, every minute is a bonus,” said Dr. Srinivasan, in emphasizing an appropriate clinical perspective.

NEW YORK – One reason to pursue a multimodality strategy to control the symptoms as well as the underlying pathophysiology of Parkinson’s disease (PD) is that a small but substantial proportion of patients with PD-like symptoms have a different diagnosis, according to an expert overview at the International Conference on Parkinson’s Disease and Movement Disorders.

Ted Bosworth/MDedge News

“Fifteen to 20% of patients treated for Parkinson’s disease, even in the most established centers of excellence, do not have Parkinson’s disease on necropsy,” said A.V. Srinivasan, MD, PhD, DSc, of The Tamil Nadu Dr. M.G.R. Medical University, Chennai, India.

This does not preclude benefit from antiparkinson drugs in those patients with PD-like symptoms but a different etiology. Many can benefit from increased dopamine availability, even in the absence of PD, but it emphasizes the complexity of clinical diseases associated with diminished dopamine function, according to Dr. Srinivasan. He characterized this complexity as a reason to avoid a regimented approach to PD management.

“You can just imagine how much this influences our data analysis,” said Dr. Srinivasan, referring to clinical trials designed to generate evidence-based treatment. “We should remember that we should not be too statistically oriented,” he added, citing the adage that “statistics can cause paralysis in your analysis.”

PD is associated with a vast array of neurologic and physical symptoms attributable to PD that overlap with other neurologic disorders, which is the reason that a definitive diagnosis is challenging, according to Dr. Srinivasan. Listing symptoms that should prompt consideration of an alternative diagnosis, Dr. Srinivasan said hallucinations suggest diffuse Lewy body disease, myoclonus suggests corticobasal degeneration, and amyotrophy suggests multiple system atrophy.

“These are only clues, however,” said Dr. Srinivasan, suggesting their presence should prompt consideration of alternative diagnoses, but their absence does not confirm PD.

In some cases, further work-up with one or more of the array of increasingly sophisticated imaging strategies, such as the combination of SPECT and PET, might help clinicians reach a more definitive diagnosis of the underlying pathology, a step that might guide use of dopaminergic therapies. However, effective treatment of PD symptoms does not depend on a definitive diagnosis.

Rather, Dr. Srinivasan advocated an open mind to the management of symptoms, which he indicated are best addressed empirically. As PD or other progressive movement disorders advance, the goal is to keep patients functional and comfortable.

This includes managing patients beyond prescription drugs to address such complications as dysphagia or impaired balance. He advocated practical solutions for causes of impaired quality of life such as soft foods to facilitate swallowing or walkers to keep patients ambulatory. No option that leads to symptom relief should be discounted, including alternative therapies.

“Some clinicians are strongly opposed to nontraditional therapies, such as naturopathy and homeopathy, but these have all been used in Parkinson’s,” Dr. Srinivasan said. Although he did not present data to show efficacy, he indicated that relief of symptoms and improvement of quality of life is the point of any treatment, which should be individualized by response in every patient.

And individualized therapy – in relationship to patient age – is particularly important, according to Dr. Srinivasan. While younger patients typically tolerate relatively aggressive therapies aimed at both PD and its specific symptoms, older patients may accept less ambitious functional improvements to achieve an adequate quality of life.

“After 70 years of age, every additional year is a bonus. After 80 years, every week is a bonus. After 90 years, every minute is a bonus,” said Dr. Srinivasan, in emphasizing an appropriate clinical perspective.

PARIS – Bronchiectasis responds to mepolizumab if the clinical profile includes eosinophilia, according to a small case series of patients presented as a late-breaking study at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge Newws

“The message is that it is important to think of all of the etiologies and treatable traits in patients with bronchiectasis, and do not forget eosinophilia, because this can be treated,” reported Jessica Rademacher, MD, of the Clinic for Pulmonology at Hannover (Germany) Medical School.

Mepolizumab is a monoclonal antibody that targets interleukin-5, an important signaling protein for eosinophil recruitment, and is approved for use in asthma with eosinophilia. Larger, controlled trials are needed to confirm its efficacy in bronchiectasis, but the clinical improvements after 6 months of treatment in a series of 12 patients at Dr. Rademacher’s center were impressive.

Bronchiectasis patients were selected for treatment with mepolizumab if they had been poorly controlled on conventional therapies and they had an eosinophil count of greater than 300 cells/mm³. Of 328 patients with bronchiectasis that are being followed at Dr. Rademacher’s center, 7% met these criteria. Dr. Rademacher presented data on 12 who had been followed for at least 6 months.

In these patients, the median eosinophil count fell from a median baseline of 1,000 cells/mm³ to 100 cells/mm³ at 6 months (P = .0012). The median annualized rate of exacerbations fell from three per year to one per year, and the median Modified Medical Research Council Dyspnea Scale score fell from 2 to 0 (P = .004).

“There was a steroid-sparing effect in all seven patients who were taking oral corticosteroids at baseline. Five stopped oral steroids completely,” Dr. Rademacher reported.

A visual analog scale ranging from 1 to 10 with higher scores representing improvement showed patient-rated quality of life improved from 4 to 6.5 (P = .01). Dr. Rademacher emphasized this outcome because “improved quality of life is really what we are trying to achieve.”

Mepolizumab was well tolerated. In one patient who developed pneumonia, mepolizumab was discontinued, but it was restarted when the infection resolved, because the pneumonia was not considered mepolizumab related.

Although Dr. Rademacher acknowledged the possibility that at least some of the patients in this case series had overlapping asthma, she emphasized that they were selected from a referral population that had a comprehensive workup and that this overlap has been rarely reported.

There is evidence that anti–interleukin-5 therapies such as mepolizumab are effective in respiratory diseases when eosinophilia is present, according to Dr. Rademacher. For example, she cited reports of clinical improvement in chronic obstructive pulmonary disease and granulomatosis with polyangiitis patients with high eosinophil counts. In bronchiectasis, which has many causes, it may be particularly important to select relevant targets.

“There is an important variability in the presentation of bronchiectasis. Not all these patients have reduced lung function,” she said. Rather, the most significant symptoms for a patient may be sputum or cough. She suggested that the goals are to identify underlying causes of symptoms and which may be treatable.

According to these data, eosinophilia may be one of the treatable causes in a small but significant proportion of patients with bronchiectasis. A trial of mepolizumab may be reasonable in patients inadequately controlled on inhaled anti-inflammatory drugs. “If they do not profit from this therapy, then stop,” she added.

Dr. Rademacher acknowledged that data from this small case series are “not enough to say that [mepolizumab] is an option for these patients,” but she believes the consistency of benefit in this small series will encourage the trials needed to confirm that this approach is safe and effective.

Dr. Rademacher reported no disclosures relevant to the report.

PARIS – Bronchiectasis responds to mepolizumab if the clinical profile includes eosinophilia, according to a small case series of patients presented as a late-breaking study at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge Newws

“The message is that it is important to think of all of the etiologies and treatable traits in patients with bronchiectasis, and do not forget eosinophilia, because this can be treated,” reported Jessica Rademacher, MD, of the Clinic for Pulmonology at Hannover (Germany) Medical School.

Mepolizumab is a monoclonal antibody that targets interleukin-5, an important signaling protein for eosinophil recruitment, and is approved for use in asthma with eosinophilia. Larger, controlled trials are needed to confirm its efficacy in bronchiectasis, but the clinical improvements after 6 months of treatment in a series of 12 patients at Dr. Rademacher’s center were impressive.

Bronchiectasis patients were selected for treatment with mepolizumab if they had been poorly controlled on conventional therapies and they had an eosinophil count of greater than 300 cells/mm³. Of 328 patients with bronchiectasis that are being followed at Dr. Rademacher’s center, 7% met these criteria. Dr. Rademacher presented data on 12 who had been followed for at least 6 months.

In these patients, the median eosinophil count fell from a median baseline of 1,000 cells/mm³ to 100 cells/mm³ at 6 months (P = .0012). The median annualized rate of exacerbations fell from three per year to one per year, and the median Modified Medical Research Council Dyspnea Scale score fell from 2 to 0 (P = .004).

“There was a steroid-sparing effect in all seven patients who were taking oral corticosteroids at baseline. Five stopped oral steroids completely,” Dr. Rademacher reported.

A visual analog scale ranging from 1 to 10 with higher scores representing improvement showed patient-rated quality of life improved from 4 to 6.5 (P = .01). Dr. Rademacher emphasized this outcome because “improved quality of life is really what we are trying to achieve.”

Mepolizumab was well tolerated. In one patient who developed pneumonia, mepolizumab was discontinued, but it was restarted when the infection resolved, because the pneumonia was not considered mepolizumab related.

Although Dr. Rademacher acknowledged the possibility that at least some of the patients in this case series had overlapping asthma, she emphasized that they were selected from a referral population that had a comprehensive workup and that this overlap has been rarely reported.

There is evidence that anti–interleukin-5 therapies such as mepolizumab are effective in respiratory diseases when eosinophilia is present, according to Dr. Rademacher. For example, she cited reports of clinical improvement in chronic obstructive pulmonary disease and granulomatosis with polyangiitis patients with high eosinophil counts. In bronchiectasis, which has many causes, it may be particularly important to select relevant targets.

“There is an important variability in the presentation of bronchiectasis. Not all these patients have reduced lung function,” she said. Rather, the most significant symptoms for a patient may be sputum or cough. She suggested that the goals are to identify underlying causes of symptoms and which may be treatable.

According to these data, eosinophilia may be one of the treatable causes in a small but significant proportion of patients with bronchiectasis. A trial of mepolizumab may be reasonable in patients inadequately controlled on inhaled anti-inflammatory drugs. “If they do not profit from this therapy, then stop,” she added.

Dr. Rademacher acknowledged that data from this small case series are “not enough to say that [mepolizumab] is an option for these patients,” but she believes the consistency of benefit in this small series will encourage the trials needed to confirm that this approach is safe and effective.

Dr. Rademacher reported no disclosures relevant to the report.

PARIS – Bronchiectasis responds to mepolizumab if the clinical profile includes eosinophilia, according to a small case series of patients presented as a late-breaking study at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge Newws

“The message is that it is important to think of all of the etiologies and treatable traits in patients with bronchiectasis, and do not forget eosinophilia, because this can be treated,” reported Jessica Rademacher, MD, of the Clinic for Pulmonology at Hannover (Germany) Medical School.

Mepolizumab is a monoclonal antibody that targets interleukin-5, an important signaling protein for eosinophil recruitment, and is approved for use in asthma with eosinophilia. Larger, controlled trials are needed to confirm its efficacy in bronchiectasis, but the clinical improvements after 6 months of treatment in a series of 12 patients at Dr. Rademacher’s center were impressive.

Bronchiectasis patients were selected for treatment with mepolizumab if they had been poorly controlled on conventional therapies and they had an eosinophil count of greater than 300 cells/mm³. Of 328 patients with bronchiectasis that are being followed at Dr. Rademacher’s center, 7% met these criteria. Dr. Rademacher presented data on 12 who had been followed for at least 6 months.

In these patients, the median eosinophil count fell from a median baseline of 1,000 cells/mm³ to 100 cells/mm³ at 6 months (P = .0012). The median annualized rate of exacerbations fell from three per year to one per year, and the median Modified Medical Research Council Dyspnea Scale score fell from 2 to 0 (P = .004).

“There was a steroid-sparing effect in all seven patients who were taking oral corticosteroids at baseline. Five stopped oral steroids completely,” Dr. Rademacher reported.

A visual analog scale ranging from 1 to 10 with higher scores representing improvement showed patient-rated quality of life improved from 4 to 6.5 (P = .01). Dr. Rademacher emphasized this outcome because “improved quality of life is really what we are trying to achieve.”

Mepolizumab was well tolerated. In one patient who developed pneumonia, mepolizumab was discontinued, but it was restarted when the infection resolved, because the pneumonia was not considered mepolizumab related.

Although Dr. Rademacher acknowledged the possibility that at least some of the patients in this case series had overlapping asthma, she emphasized that they were selected from a referral population that had a comprehensive workup and that this overlap has been rarely reported.

There is evidence that anti–interleukin-5 therapies such as mepolizumab are effective in respiratory diseases when eosinophilia is present, according to Dr. Rademacher. For example, she cited reports of clinical improvement in chronic obstructive pulmonary disease and granulomatosis with polyangiitis patients with high eosinophil counts. In bronchiectasis, which has many causes, it may be particularly important to select relevant targets.

“There is an important variability in the presentation of bronchiectasis. Not all these patients have reduced lung function,” she said. Rather, the most significant symptoms for a patient may be sputum or cough. She suggested that the goals are to identify underlying causes of symptoms and which may be treatable.

According to these data, eosinophilia may be one of the treatable causes in a small but significant proportion of patients with bronchiectasis. A trial of mepolizumab may be reasonable in patients inadequately controlled on inhaled anti-inflammatory drugs. “If they do not profit from this therapy, then stop,” she added.

Dr. Rademacher acknowledged that data from this small case series are “not enough to say that [mepolizumab] is an option for these patients,” but she believes the consistency of benefit in this small series will encourage the trials needed to confirm that this approach is safe and effective.

Dr. Rademacher reported no disclosures relevant to the report.

PARIS – In a multicenter, placebo-controlled trial conducted in patients with portopulmonary hypertension (PoPH), macitentan, an endothelin receptor antagonist, achieved significant improvements in a number of hemodynamic measures, including the primary endpoint of pulmonary vascular resistance, according to a late-breaking presentation at the annual congress of the European Respiratory Society.

“This is the first randomized, controlled trial that enrolled only patients with PoPH, and it demonstrates that a therapy used in pulmonary arterial hypertension improves hemodynamics in PoPH,” reported Olivier Sitbon, MD, of the Centre des Maladies Vasculaires Pulmonaires, Université de Paris–Sud, Clamart, France.

PoPH, defined by accompanying portal hypertension, is a variant on pulmonary arterial hypertension (PAH). Liver dysfunction is common but not required for a diagnosis. Although patients often receive therapies known to be effective in PAH, such as drugs in the endothelin receptor antagonist class, prostanoids, or phosphodiesterase-5 inhibitors, there “are very limited data” demonstrating efficacy of any drug specifically for patients with PoPH, according to Dr. Sitbon. One reason is that PoPH has been an exclusion criterion in large PAH treatment trials.

In PORTICO, a double-blind trial presented by Dr. Sitbon, 85 PoPH patients were randomized to 10 mg macitentan or placebo. Essentially, all were in World Health Organization functional class II or III with a median 6-minute walk distance (6MWD) of about 385 meters. During the trial, patients were permitted to remain on baseline therapies, including prostanoids and phosphodiesterase-5 inhibitors when doses had been stable for at least 3 months prior to randomization.

The primary endpoint was change in pulmonary vascular resistance (PVR) at 12 weeks. Other hemodynamic changes, such as change in cardiac index and total pulmonary resistance, were included in secondary endpoints along with change in WHO class and change in 6MWD.

When compared at 12 weeks with a model-adjusted ratio of geometric means, the ratio of PVR for the treatment to experimental arms was 0.65, which was a 35% relative improvement (P less than .0001) with macitentan.

The relative reduction from baseline in total arterial pressure was also highly significant favoring macitentan (–199.8 vs. –18.3 dyne/sec per cm^–5; P less than .0001). Mean pulmonary pressure was slightly increased at the end of 12 weeks relative to baseline in the placebo group (+0.4 mm Hg) but fell 6.4 mm Hg in the treatment group (P less than .0001). In addition, cardiac index improved substantially on macitentan but not on placebo (0.6 vs. 0.1 L/min per m²; P = .0009).

However, there were no significant differences at the end of 12 weeks between groups for change from baseline in WHO functional class or 6MWD. Change in hepatic venous pressure gradient was evaluated in patients with liver disease, but macitentan was not associated with any effect on this parameter.

Macitentan was well tolerated overall. Although one patient experienced a equal to or greater than three times the upper limit of normal elevation of liver enzymes, Dr. Sitbon reported that there were no other hepatic safety concerns. Overall, he characterized the safety of macitentan in PoPH as “consistent with that previously observed in PAH.”

Larger and longer-term trials are needed to evaluate the impact of treatment on clinical events, but Dr. Sitbon indicated that these results demonstrate acceptable safety and tolerability and a favorable effect on hemodynamics. He further suggested that this randomized study provides a first step toward establishing an evidence-based treatment in this disease.

Dr. Sitbon reported financial relationships with Bayer, GlaxoSmithKline, and Actelion, the sponsor of this trial.

PARIS – In a multicenter, placebo-controlled trial conducted in patients with portopulmonary hypertension (PoPH), macitentan, an endothelin receptor antagonist, achieved significant improvements in a number of hemodynamic measures, including the primary endpoint of pulmonary vascular resistance, according to a late-breaking presentation at the annual congress of the European Respiratory Society.

“This is the first randomized, controlled trial that enrolled only patients with PoPH, and it demonstrates that a therapy used in pulmonary arterial hypertension improves hemodynamics in PoPH,” reported Olivier Sitbon, MD, of the Centre des Maladies Vasculaires Pulmonaires, Université de Paris–Sud, Clamart, France.

PoPH, defined by accompanying portal hypertension, is a variant on pulmonary arterial hypertension (PAH). Liver dysfunction is common but not required for a diagnosis. Although patients often receive therapies known to be effective in PAH, such as drugs in the endothelin receptor antagonist class, prostanoids, or phosphodiesterase-5 inhibitors, there “are very limited data” demonstrating efficacy of any drug specifically for patients with PoPH, according to Dr. Sitbon. One reason is that PoPH has been an exclusion criterion in large PAH treatment trials.

In PORTICO, a double-blind trial presented by Dr. Sitbon, 85 PoPH patients were randomized to 10 mg macitentan or placebo. Essentially, all were in World Health Organization functional class II or III with a median 6-minute walk distance (6MWD) of about 385 meters. During the trial, patients were permitted to remain on baseline therapies, including prostanoids and phosphodiesterase-5 inhibitors when doses had been stable for at least 3 months prior to randomization.

The primary endpoint was change in pulmonary vascular resistance (PVR) at 12 weeks. Other hemodynamic changes, such as change in cardiac index and total pulmonary resistance, were included in secondary endpoints along with change in WHO class and change in 6MWD.

When compared at 12 weeks with a model-adjusted ratio of geometric means, the ratio of PVR for the treatment to experimental arms was 0.65, which was a 35% relative improvement (P less than .0001) with macitentan.

The relative reduction from baseline in total arterial pressure was also highly significant favoring macitentan (–199.8 vs. –18.3 dyne/sec per cm^–5; P less than .0001). Mean pulmonary pressure was slightly increased at the end of 12 weeks relative to baseline in the placebo group (+0.4 mm Hg) but fell 6.4 mm Hg in the treatment group (P less than .0001). In addition, cardiac index improved substantially on macitentan but not on placebo (0.6 vs. 0.1 L/min per m²; P = .0009).

However, there were no significant differences at the end of 12 weeks between groups for change from baseline in WHO functional class or 6MWD. Change in hepatic venous pressure gradient was evaluated in patients with liver disease, but macitentan was not associated with any effect on this parameter.

Macitentan was well tolerated overall. Although one patient experienced a equal to or greater than three times the upper limit of normal elevation of liver enzymes, Dr. Sitbon reported that there were no other hepatic safety concerns. Overall, he characterized the safety of macitentan in PoPH as “consistent with that previously observed in PAH.”

Larger and longer-term trials are needed to evaluate the impact of treatment on clinical events, but Dr. Sitbon indicated that these results demonstrate acceptable safety and tolerability and a favorable effect on hemodynamics. He further suggested that this randomized study provides a first step toward establishing an evidence-based treatment in this disease.

Dr. Sitbon reported financial relationships with Bayer, GlaxoSmithKline, and Actelion, the sponsor of this trial.

PARIS – In a multicenter, placebo-controlled trial conducted in patients with portopulmonary hypertension (PoPH), macitentan, an endothelin receptor antagonist, achieved significant improvements in a number of hemodynamic measures, including the primary endpoint of pulmonary vascular resistance, according to a late-breaking presentation at the annual congress of the European Respiratory Society.

“This is the first randomized, controlled trial that enrolled only patients with PoPH, and it demonstrates that a therapy used in pulmonary arterial hypertension improves hemodynamics in PoPH,” reported Olivier Sitbon, MD, of the Centre des Maladies Vasculaires Pulmonaires, Université de Paris–Sud, Clamart, France.

PoPH, defined by accompanying portal hypertension, is a variant on pulmonary arterial hypertension (PAH). Liver dysfunction is common but not required for a diagnosis. Although patients often receive therapies known to be effective in PAH, such as drugs in the endothelin receptor antagonist class, prostanoids, or phosphodiesterase-5 inhibitors, there “are very limited data” demonstrating efficacy of any drug specifically for patients with PoPH, according to Dr. Sitbon. One reason is that PoPH has been an exclusion criterion in large PAH treatment trials.

In PORTICO, a double-blind trial presented by Dr. Sitbon, 85 PoPH patients were randomized to 10 mg macitentan or placebo. Essentially, all were in World Health Organization functional class II or III with a median 6-minute walk distance (6MWD) of about 385 meters. During the trial, patients were permitted to remain on baseline therapies, including prostanoids and phosphodiesterase-5 inhibitors when doses had been stable for at least 3 months prior to randomization.

The primary endpoint was change in pulmonary vascular resistance (PVR) at 12 weeks. Other hemodynamic changes, such as change in cardiac index and total pulmonary resistance, were included in secondary endpoints along with change in WHO class and change in 6MWD.

When compared at 12 weeks with a model-adjusted ratio of geometric means, the ratio of PVR for the treatment to experimental arms was 0.65, which was a 35% relative improvement (P less than .0001) with macitentan.

The relative reduction from baseline in total arterial pressure was also highly significant favoring macitentan (–199.8 vs. –18.3 dyne/sec per cm^–5; P less than .0001). Mean pulmonary pressure was slightly increased at the end of 12 weeks relative to baseline in the placebo group (+0.4 mm Hg) but fell 6.4 mm Hg in the treatment group (P less than .0001). In addition, cardiac index improved substantially on macitentan but not on placebo (0.6 vs. 0.1 L/min per m²; P = .0009).

However, there were no significant differences at the end of 12 weeks between groups for change from baseline in WHO functional class or 6MWD. Change in hepatic venous pressure gradient was evaluated in patients with liver disease, but macitentan was not associated with any effect on this parameter.

Macitentan was well tolerated overall. Although one patient experienced a equal to or greater than three times the upper limit of normal elevation of liver enzymes, Dr. Sitbon reported that there were no other hepatic safety concerns. Overall, he characterized the safety of macitentan in PoPH as “consistent with that previously observed in PAH.”

Larger and longer-term trials are needed to evaluate the impact of treatment on clinical events, but Dr. Sitbon indicated that these results demonstrate acceptable safety and tolerability and a favorable effect on hemodynamics. He further suggested that this randomized study provides a first step toward establishing an evidence-based treatment in this disease.

Dr. Sitbon reported financial relationships with Bayer, GlaxoSmithKline, and Actelion, the sponsor of this trial.

PARIS – As an alternative to noninvasive ventilator devices (NIV), a battery-powered high-flow nasal cannula delivering heated air improves exercise tolerance as measured with the 6-minute walking distance (6MWD), according to a crossover trial presented at the annual congress of the European Respiratory Society.

PARIS – As an alternative to noninvasive ventilator devices (NIV), a battery-powered high-flow nasal cannula delivering heated air improves exercise tolerance as measured with the 6-minute walking distance (6MWD), according to a crossover trial presented at the annual congress of the European Respiratory Society.

PARIS – As an alternative to noninvasive ventilator devices (NIV), a battery-powered high-flow nasal cannula delivering heated air improves exercise tolerance as measured with the 6-minute walking distance (6MWD), according to a crossover trial presented at the annual congress of the European Respiratory Society.

PARIS – A one-way endobronchial valve placed in the lungs of emphysema patients with hyperinflation provides acceptable safety and clinically significant improvement in lung function at 12 months, according to results from a multicenter trial presented as a late-breaker at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Six-month results have been presented previously, but the 12-month results suggest that lung volume reduction associated with placement of the valves provides “durable effectiveness in appropriately selected hyperinflated emphysema patients,” according to Gerard Criner, MD, chair of the thoracic medicine department at Temple University, Philadelphia.

In this randomized controlled trial, called EMPROVE, 172 emphysema patients with severe dyspnea were randomized in a 2:1 fashion to receive a proprietary endobronchial valve or medical therapy alone. The valve, marketed under the brand name Spiration Valve System (SVS), is currently indicated for the treatment of air leaks after lung surgery.

“The valve serves to block airflow from edematous lungs with the objective of blocking hyperinflation and improving lung function,” Dr. Criner explained. The valves are retrievable, if necessary, with bronchoscopy.

High resolution computed tomography (HRCT) was used to identify emphysema obstruction and target valve placement to the most diseased lobes. The average number of valves placed per patient was slightly less than four. Most of the valves (70%) were placed in an upper lobe.

When reported at 6 months, the responder rate, defined as at least 15% improvement in forced expiratory volume in 1 second (FEV₁) was 36.8% and 10% in the SVS and control groups, respectively, a difference of 25.7% that Dr. Criner reported as statistically significant although he did not provide P values. At 12 months, the rates were 37.2% and 5.1%, respectively, demonstrating a persistent effect.

Thoracic adverse events were higher at both 6 months (31% vs. 11.9%) and 12 months (21.4% vs. 10.6%) in the treatment group relative to the control group. At 6 months, pneumothorax, which Dr. Criner characterized as “a recognized marker of target lobe volume reduction,” was the only event that occurred significantly more commonly (14.2% vs. 0%) in the SVS group.

Between 6 and 12 months, there were no pneumothorax events in either arm. The higher numerical rates of thoracic adverse events in the treatment arm were acute exacerbations (13.6% vs. 8.5%) and pneumonia in nontreated lobes (7.8% vs. 2.1%), but these rates were not statistically different.

At 6 months, there was a numerically higher rate of all-cause mortality in the treatment group (5.3% vs. 1.7%) but the rate was numerically lower between 6 and 12 months (2.9% vs. 6.4%). The differences were not significantly different at either time point or overall.

A significant reduction in hyperinflation favoring valve placement was accompanied by improvement in objective measures of lung function, such as FEV₁, and dyspnea, as measured with the Modified Medical Research Council (mMRC) Dyspnea Scale, at 6 and 12 months. These improvements translated into persistent quality of life benefits as measured with the St. George Respiratory Questionnaire (SGRQ). At 12 months, the SGRQ changes from baseline were a 5.5-point reduction and a four-point gain in the treatment and control groups, respectively. This absolute difference of 9.5 points is slightly more modest than the 13-point difference at 6 months (–8 vs. +5 points), but demonstrates a durable effect, Dr. Criner reported.

According to Dr. Criner, EMPROVE reinforces the principle that HRCT is effective “for selecting the lobe for therapy and which patients may benefit,” but the most important message from the 12-month results is persistent clinical benefit.

The endobronchial values “provide statistically and clinically meaningful improvements in FEV₁, reductions in lobe volume and dyspnea, and improvements in quality of life with an acceptable safety profile,” Dr. Criner reported.

On June 29, 2018, the Food and Drug Administration approved the first endobronchial valve for treatment of emphysema. This valve, marketed under the name Zephyr, was approved on the basis of the pivotal LIBERATE trial, also led by Dr. Criner and published earlier this year (Am J Respir Crit Care Med. 2018 May 22. doi: 10.1164/rccm.201803-0590OC.). The results of EMPROVE are consistent with previous evidence that a one-way valve, by preventing air from entering diseased lobes of patients with emphysema to exacerbate hyperinflation, improves lung function and reduces clinical symptoms.

Dr. Criner reports financial relationships with Olympus, the sponsor of this trial.

PARIS – A one-way endobronchial valve placed in the lungs of emphysema patients with hyperinflation provides acceptable safety and clinically significant improvement in lung function at 12 months, according to results from a multicenter trial presented as a late-breaker at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Six-month results have been presented previously, but the 12-month results suggest that lung volume reduction associated with placement of the valves provides “durable effectiveness in appropriately selected hyperinflated emphysema patients,” according to Gerard Criner, MD, chair of the thoracic medicine department at Temple University, Philadelphia.

In this randomized controlled trial, called EMPROVE, 172 emphysema patients with severe dyspnea were randomized in a 2:1 fashion to receive a proprietary endobronchial valve or medical therapy alone. The valve, marketed under the brand name Spiration Valve System (SVS), is currently indicated for the treatment of air leaks after lung surgery.

“The valve serves to block airflow from edematous lungs with the objective of blocking hyperinflation and improving lung function,” Dr. Criner explained. The valves are retrievable, if necessary, with bronchoscopy.

High resolution computed tomography (HRCT) was used to identify emphysema obstruction and target valve placement to the most diseased lobes. The average number of valves placed per patient was slightly less than four. Most of the valves (70%) were placed in an upper lobe.

When reported at 6 months, the responder rate, defined as at least 15% improvement in forced expiratory volume in 1 second (FEV₁) was 36.8% and 10% in the SVS and control groups, respectively, a difference of 25.7% that Dr. Criner reported as statistically significant although he did not provide P values. At 12 months, the rates were 37.2% and 5.1%, respectively, demonstrating a persistent effect.

Thoracic adverse events were higher at both 6 months (31% vs. 11.9%) and 12 months (21.4% vs. 10.6%) in the treatment group relative to the control group. At 6 months, pneumothorax, which Dr. Criner characterized as “a recognized marker of target lobe volume reduction,” was the only event that occurred significantly more commonly (14.2% vs. 0%) in the SVS group.

Between 6 and 12 months, there were no pneumothorax events in either arm. The higher numerical rates of thoracic adverse events in the treatment arm were acute exacerbations (13.6% vs. 8.5%) and pneumonia in nontreated lobes (7.8% vs. 2.1%), but these rates were not statistically different.

At 6 months, there was a numerically higher rate of all-cause mortality in the treatment group (5.3% vs. 1.7%) but the rate was numerically lower between 6 and 12 months (2.9% vs. 6.4%). The differences were not significantly different at either time point or overall.

A significant reduction in hyperinflation favoring valve placement was accompanied by improvement in objective measures of lung function, such as FEV₁, and dyspnea, as measured with the Modified Medical Research Council (mMRC) Dyspnea Scale, at 6 and 12 months. These improvements translated into persistent quality of life benefits as measured with the St. George Respiratory Questionnaire (SGRQ). At 12 months, the SGRQ changes from baseline were a 5.5-point reduction and a four-point gain in the treatment and control groups, respectively. This absolute difference of 9.5 points is slightly more modest than the 13-point difference at 6 months (–8 vs. +5 points), but demonstrates a durable effect, Dr. Criner reported.

According to Dr. Criner, EMPROVE reinforces the principle that HRCT is effective “for selecting the lobe for therapy and which patients may benefit,” but the most important message from the 12-month results is persistent clinical benefit.

The endobronchial values “provide statistically and clinically meaningful improvements in FEV₁, reductions in lobe volume and dyspnea, and improvements in quality of life with an acceptable safety profile,” Dr. Criner reported.

On June 29, 2018, the Food and Drug Administration approved the first endobronchial valve for treatment of emphysema. This valve, marketed under the name Zephyr, was approved on the basis of the pivotal LIBERATE trial, also led by Dr. Criner and published earlier this year (Am J Respir Crit Care Med. 2018 May 22. doi: 10.1164/rccm.201803-0590OC.). The results of EMPROVE are consistent with previous evidence that a one-way valve, by preventing air from entering diseased lobes of patients with emphysema to exacerbate hyperinflation, improves lung function and reduces clinical symptoms.

Dr. Criner reports financial relationships with Olympus, the sponsor of this trial.

PARIS – A one-way endobronchial valve placed in the lungs of emphysema patients with hyperinflation provides acceptable safety and clinically significant improvement in lung function at 12 months, according to results from a multicenter trial presented as a late-breaker at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Six-month results have been presented previously, but the 12-month results suggest that lung volume reduction associated with placement of the valves provides “durable effectiveness in appropriately selected hyperinflated emphysema patients,” according to Gerard Criner, MD, chair of the thoracic medicine department at Temple University, Philadelphia.

In this randomized controlled trial, called EMPROVE, 172 emphysema patients with severe dyspnea were randomized in a 2:1 fashion to receive a proprietary endobronchial valve or medical therapy alone. The valve, marketed under the brand name Spiration Valve System (SVS), is currently indicated for the treatment of air leaks after lung surgery.

“The valve serves to block airflow from edematous lungs with the objective of blocking hyperinflation and improving lung function,” Dr. Criner explained. The valves are retrievable, if necessary, with bronchoscopy.

High resolution computed tomography (HRCT) was used to identify emphysema obstruction and target valve placement to the most diseased lobes. The average number of valves placed per patient was slightly less than four. Most of the valves (70%) were placed in an upper lobe.

When reported at 6 months, the responder rate, defined as at least 15% improvement in forced expiratory volume in 1 second (FEV₁) was 36.8% and 10% in the SVS and control groups, respectively, a difference of 25.7% that Dr. Criner reported as statistically significant although he did not provide P values. At 12 months, the rates were 37.2% and 5.1%, respectively, demonstrating a persistent effect.

Thoracic adverse events were higher at both 6 months (31% vs. 11.9%) and 12 months (21.4% vs. 10.6%) in the treatment group relative to the control group. At 6 months, pneumothorax, which Dr. Criner characterized as “a recognized marker of target lobe volume reduction,” was the only event that occurred significantly more commonly (14.2% vs. 0%) in the SVS group.

Between 6 and 12 months, there were no pneumothorax events in either arm. The higher numerical rates of thoracic adverse events in the treatment arm were acute exacerbations (13.6% vs. 8.5%) and pneumonia in nontreated lobes (7.8% vs. 2.1%), but these rates were not statistically different.

At 6 months, there was a numerically higher rate of all-cause mortality in the treatment group (5.3% vs. 1.7%) but the rate was numerically lower between 6 and 12 months (2.9% vs. 6.4%). The differences were not significantly different at either time point or overall.

A significant reduction in hyperinflation favoring valve placement was accompanied by improvement in objective measures of lung function, such as FEV₁, and dyspnea, as measured with the Modified Medical Research Council (mMRC) Dyspnea Scale, at 6 and 12 months. These improvements translated into persistent quality of life benefits as measured with the St. George Respiratory Questionnaire (SGRQ). At 12 months, the SGRQ changes from baseline were a 5.5-point reduction and a four-point gain in the treatment and control groups, respectively. This absolute difference of 9.5 points is slightly more modest than the 13-point difference at 6 months (–8 vs. +5 points), but demonstrates a durable effect, Dr. Criner reported.

According to Dr. Criner, EMPROVE reinforces the principle that HRCT is effective “for selecting the lobe for therapy and which patients may benefit,” but the most important message from the 12-month results is persistent clinical benefit.

The endobronchial values “provide statistically and clinically meaningful improvements in FEV₁, reductions in lobe volume and dyspnea, and improvements in quality of life with an acceptable safety profile,” Dr. Criner reported.

On June 29, 2018, the Food and Drug Administration approved the first endobronchial valve for treatment of emphysema. This valve, marketed under the name Zephyr, was approved on the basis of the pivotal LIBERATE trial, also led by Dr. Criner and published earlier this year (Am J Respir Crit Care Med. 2018 May 22. doi: 10.1164/rccm.201803-0590OC.). The results of EMPROVE are consistent with previous evidence that a one-way valve, by preventing air from entering diseased lobes of patients with emphysema to exacerbate hyperinflation, improves lung function and reduces clinical symptoms.

Dr. Criner reports financial relationships with Olympus, the sponsor of this trial.

SAN DIEGO – In the ICU, ultrasound has been shown to reduce the need for CT to evaluate potential pulmonary embolism. But in the ED, this strategy hasn’t worked out so far, according to Joseph Brown, MD, of the department of emergency medicine at the University of California, San Francisco.

Vidyard Video

Based on the data so far, the ED patients were less likely than the ICU patients to have another etiology identified on ultrasound that explained their symptoms. Further, ultrasound alone missed small subsegmental pulmonary emboli that were detected on subsequent CT scans in 2 of 11 patients.

The study is continuing, and Dr. Brown explains in this interview how ultrasound might be combined with other risk stratification measures to safely achieve reductions in CT scans.

SAN DIEGO – In the ICU, ultrasound has been shown to reduce the need for CT to evaluate potential pulmonary embolism. But in the ED, this strategy hasn’t worked out so far, according to Joseph Brown, MD, of the department of emergency medicine at the University of California, San Francisco.

Vidyard Video

Based on the data so far, the ED patients were less likely than the ICU patients to have another etiology identified on ultrasound that explained their symptoms. Further, ultrasound alone missed small subsegmental pulmonary emboli that were detected on subsequent CT scans in 2 of 11 patients.

The study is continuing, and Dr. Brown explains in this interview how ultrasound might be combined with other risk stratification measures to safely achieve reductions in CT scans.

SAN DIEGO – In the ICU, ultrasound has been shown to reduce the need for CT to evaluate potential pulmonary embolism. But in the ED, this strategy hasn’t worked out so far, according to Joseph Brown, MD, of the department of emergency medicine at the University of California, San Francisco.

Vidyard Video

Based on the data so far, the ED patients were less likely than the ICU patients to have another etiology identified on ultrasound that explained their symptoms. Further, ultrasound alone missed small subsegmental pulmonary emboli that were detected on subsequent CT scans in 2 of 11 patients.

The study is continuing, and Dr. Brown explains in this interview how ultrasound might be combined with other risk stratification measures to safely achieve reductions in CT scans.

SAN DIEGO – Unless the cause of syncope has been identified after a thorough workup in the emergency department, there is no advantage to admitting patients aged 60 years and older who complain of syncope, an ED-based study has found.

Almost 2,500 patients aged 60 or older with unexplained syncope after a thorough workup had similar 30-day outcomes whether they were admitted to the hospital or sent home from the ED, based on the results of a retrospective study presented at the annual meeting of the American College of Emergency Physicians.

Dr. Marc A. Probst of the Icahn School of Medicine at Mount Sinai, New York, who presented the data, reported that many centers admit older patients with syncope, although the benefit of this practice has not been well established.

In a video interview, Dr. Probst points out how the findings may be useful in guiding clinical decisions or counseling patients when admission is being considered.

SAN DIEGO – Unless the cause of syncope has been identified after a thorough workup in the emergency department, there is no advantage to admitting patients aged 60 years and older who complain of syncope, an ED-based study has found.

Almost 2,500 patients aged 60 or older with unexplained syncope after a thorough workup had similar 30-day outcomes whether they were admitted to the hospital or sent home from the ED, based on the results of a retrospective study presented at the annual meeting of the American College of Emergency Physicians.

Dr. Marc A. Probst of the Icahn School of Medicine at Mount Sinai, New York, who presented the data, reported that many centers admit older patients with syncope, although the benefit of this practice has not been well established.

In a video interview, Dr. Probst points out how the findings may be useful in guiding clinical decisions or counseling patients when admission is being considered.

SAN DIEGO – Unless the cause of syncope has been identified after a thorough workup in the emergency department, there is no advantage to admitting patients aged 60 years and older who complain of syncope, an ED-based study has found.

Almost 2,500 patients aged 60 or older with unexplained syncope after a thorough workup had similar 30-day outcomes whether they were admitted to the hospital or sent home from the ED, based on the results of a retrospective study presented at the annual meeting of the American College of Emergency Physicians.

Dr. Marc A. Probst of the Icahn School of Medicine at Mount Sinai, New York, who presented the data, reported that many centers admit older patients with syncope, although the benefit of this practice has not been well established.

In a video interview, Dr. Probst points out how the findings may be useful in guiding clinical decisions or counseling patients when admission is being considered.