Andrew D. Bowser

PHILADELPHIA – A prognostic score for acute ischemic stroke that incorporates copeptin levels, age, recanalization, and National Institutes of Health Stroke Scale score has been externally validated and accurately predicts unfavorable outcome, according to research presented at the annual meeting of the American Academy of Neurology.

Although the four-item score could not be validated for mortality prediction, it had reasonable accuracy for predicting unfavorable functional outcome, defined as disability or mortality 3 months after ischemic stroke, Gian Marco De Marchis, MD, of the department of neurology and the stroke center at University Hospital Basel (Switzerland), said in a presentation.

“The use of a biomarker increases prognostic accuracy, allowing us to personalize prognosis in the frame of individualized, precision medicine,” Dr. De Marchis said.

Copeptin has been linked to disability and mortality at 3 months in two independent, large cohort studies of patients with ischemic stroke, he said.

The four-item prognostic score devised by Dr. De Marchis and his coinvestigators, which they call the CoRisk score, was developed based on a derivation cohort of 319 acute ischemic stroke patients and a validation cohort including another 783 patients in the Copeptin for Risk Stratification in Acute Stroke Patients (CoRisk) Study.

Diagnostic accuracy was 82% for the endpoint of unfavorable functional outcome at 3 months, according to Dr. De Marchis.

“The observed outcomes matched well with the expected outcomes,” he said in his presentation.

Further analyses demonstrated that the addition of copeptin indeed contributed to the diagnostic accuracy of the score, improving the classification for 46%; in other words, about half of the patients were reclassified based on addition of the biomarker data.

By contrast, the score is not well suited to predict mortality alone at 3 months, the results of the analyses showed.

The algorithm used to calculate the score based on its four variables is somewhat complex, but available as a free app and online calculator, Dr. De Marchis said.

Dr. De Marchis and his coauthors had nothing to disclose related to their study. A full report on the study was published ahead of print on March 1 in Neurology.

SOURCE: De Marchis GM et al. AAN 2019, Abstract S47.001.

PHILADELPHIA – A prognostic score for acute ischemic stroke that incorporates copeptin levels, age, recanalization, and National Institutes of Health Stroke Scale score has been externally validated and accurately predicts unfavorable outcome, according to research presented at the annual meeting of the American Academy of Neurology.

Although the four-item score could not be validated for mortality prediction, it had reasonable accuracy for predicting unfavorable functional outcome, defined as disability or mortality 3 months after ischemic stroke, Gian Marco De Marchis, MD, of the department of neurology and the stroke center at University Hospital Basel (Switzerland), said in a presentation.

“The use of a biomarker increases prognostic accuracy, allowing us to personalize prognosis in the frame of individualized, precision medicine,” Dr. De Marchis said.

Copeptin has been linked to disability and mortality at 3 months in two independent, large cohort studies of patients with ischemic stroke, he said.

The four-item prognostic score devised by Dr. De Marchis and his coinvestigators, which they call the CoRisk score, was developed based on a derivation cohort of 319 acute ischemic stroke patients and a validation cohort including another 783 patients in the Copeptin for Risk Stratification in Acute Stroke Patients (CoRisk) Study.

Diagnostic accuracy was 82% for the endpoint of unfavorable functional outcome at 3 months, according to Dr. De Marchis.

“The observed outcomes matched well with the expected outcomes,” he said in his presentation.

Further analyses demonstrated that the addition of copeptin indeed contributed to the diagnostic accuracy of the score, improving the classification for 46%; in other words, about half of the patients were reclassified based on addition of the biomarker data.

By contrast, the score is not well suited to predict mortality alone at 3 months, the results of the analyses showed.

The algorithm used to calculate the score based on its four variables is somewhat complex, but available as a free app and online calculator, Dr. De Marchis said.

Dr. De Marchis and his coauthors had nothing to disclose related to their study. A full report on the study was published ahead of print on March 1 in Neurology.

SOURCE: De Marchis GM et al. AAN 2019, Abstract S47.001.

PHILADELPHIA – A prognostic score for acute ischemic stroke that incorporates copeptin levels, age, recanalization, and National Institutes of Health Stroke Scale score has been externally validated and accurately predicts unfavorable outcome, according to research presented at the annual meeting of the American Academy of Neurology.

Although the four-item score could not be validated for mortality prediction, it had reasonable accuracy for predicting unfavorable functional outcome, defined as disability or mortality 3 months after ischemic stroke, Gian Marco De Marchis, MD, of the department of neurology and the stroke center at University Hospital Basel (Switzerland), said in a presentation.

“The use of a biomarker increases prognostic accuracy, allowing us to personalize prognosis in the frame of individualized, precision medicine,” Dr. De Marchis said.

Copeptin has been linked to disability and mortality at 3 months in two independent, large cohort studies of patients with ischemic stroke, he said.

The four-item prognostic score devised by Dr. De Marchis and his coinvestigators, which they call the CoRisk score, was developed based on a derivation cohort of 319 acute ischemic stroke patients and a validation cohort including another 783 patients in the Copeptin for Risk Stratification in Acute Stroke Patients (CoRisk) Study.

Diagnostic accuracy was 82% for the endpoint of unfavorable functional outcome at 3 months, according to Dr. De Marchis.

“The observed outcomes matched well with the expected outcomes,” he said in his presentation.

Further analyses demonstrated that the addition of copeptin indeed contributed to the diagnostic accuracy of the score, improving the classification for 46%; in other words, about half of the patients were reclassified based on addition of the biomarker data.

By contrast, the score is not well suited to predict mortality alone at 3 months, the results of the analyses showed.

The algorithm used to calculate the score based on its four variables is somewhat complex, but available as a free app and online calculator, Dr. De Marchis said.

Dr. De Marchis and his coauthors had nothing to disclose related to their study. A full report on the study was published ahead of print on March 1 in Neurology.

SOURCE: De Marchis GM et al. AAN 2019, Abstract S47.001.

PHILADELPHIA – Incoherent text messages may be the first or even the only clue to an underlying stroke, according to two case reports described at the annual meeting of the American Academy of Neurology. The phenomenon, dubbed “dystextia” and characterized by confusing interpersonal electronic communications, is not new but is increasingly relevant to clinical practice now that smartphones are essentially ubiquitous, said the case report authors.

In fact, time to intervention may be positively impacted if access to a patient’s texts and emails can be obtained, said lead author Taylor R. Anderson, a medical student at Wayne State University, Detroit.

The findings sparked interest in further research into the underlying causes and implications of dystextia: “It will be interesting to see if there are specific regions of the brain that are responsible for texting, and how they relate to other forms of communication such as handwriting and typing,” the authors said in their poster presentation.

Mr. Anderson and colleagues described two patients evaluated at Ascension St. John Hospital and Medical Center in Detroit who had stroke presenting as difficulty in typing text messages.

One case was a 43-year-old woman who experienced headache consistent with her usual migraine and spelling errors in her texts and posts on Facebook. She had visuospatial anomalies and left facial droop on evaluation. A brain MRI revealed acute embolic infarcts in the parietal and right frontal lobes, according to Mr. Anderson and coauthors.

The second case was a 66-year-old woman who had difficulty writing texts and typed notes. A head CT done in an urgent care facility showed a left frontal subacute infarct, which, according to the authors, was likely related to risk factors including hypertension, diabetes, and dyslipidemia.

These cases show that dystextia can arise after lesions in either hemisphere, the authors said. However, they emphasized that both cases involved the dominant cerebral hemisphere, while by contrast, there have not been previous reports of dystextia due to nondominant hemispheric infarct.

It stands to reason that stroke would affect the ability to text, a multipurpose task that involves use of motor, language, and vision skills, the authors said. Strokes could affect not only skills needed to type, read, and express thoughts, but also visuospatial memory mapping to letters on the device’s keyboard, they noted.

The left frontal and superior parietal regions have been implicated in handwriting in neuroimaging experiments, the authors said, while the operculum and left second frontal convolution are involved in typing.

The authors had nothing to disclose.

SOURCE: Anderson T et al. AAN 2019. Abstract P5.3-062.

PHILADELPHIA – Incoherent text messages may be the first or even the only clue to an underlying stroke, according to two case reports described at the annual meeting of the American Academy of Neurology. The phenomenon, dubbed “dystextia” and characterized by confusing interpersonal electronic communications, is not new but is increasingly relevant to clinical practice now that smartphones are essentially ubiquitous, said the case report authors.

In fact, time to intervention may be positively impacted if access to a patient’s texts and emails can be obtained, said lead author Taylor R. Anderson, a medical student at Wayne State University, Detroit.

The findings sparked interest in further research into the underlying causes and implications of dystextia: “It will be interesting to see if there are specific regions of the brain that are responsible for texting, and how they relate to other forms of communication such as handwriting and typing,” the authors said in their poster presentation.

Mr. Anderson and colleagues described two patients evaluated at Ascension St. John Hospital and Medical Center in Detroit who had stroke presenting as difficulty in typing text messages.

One case was a 43-year-old woman who experienced headache consistent with her usual migraine and spelling errors in her texts and posts on Facebook. She had visuospatial anomalies and left facial droop on evaluation. A brain MRI revealed acute embolic infarcts in the parietal and right frontal lobes, according to Mr. Anderson and coauthors.

The second case was a 66-year-old woman who had difficulty writing texts and typed notes. A head CT done in an urgent care facility showed a left frontal subacute infarct, which, according to the authors, was likely related to risk factors including hypertension, diabetes, and dyslipidemia.

These cases show that dystextia can arise after lesions in either hemisphere, the authors said. However, they emphasized that both cases involved the dominant cerebral hemisphere, while by contrast, there have not been previous reports of dystextia due to nondominant hemispheric infarct.

It stands to reason that stroke would affect the ability to text, a multipurpose task that involves use of motor, language, and vision skills, the authors said. Strokes could affect not only skills needed to type, read, and express thoughts, but also visuospatial memory mapping to letters on the device’s keyboard, they noted.

The left frontal and superior parietal regions have been implicated in handwriting in neuroimaging experiments, the authors said, while the operculum and left second frontal convolution are involved in typing.

The authors had nothing to disclose.

SOURCE: Anderson T et al. AAN 2019. Abstract P5.3-062.

PHILADELPHIA – Incoherent text messages may be the first or even the only clue to an underlying stroke, according to two case reports described at the annual meeting of the American Academy of Neurology. The phenomenon, dubbed “dystextia” and characterized by confusing interpersonal electronic communications, is not new but is increasingly relevant to clinical practice now that smartphones are essentially ubiquitous, said the case report authors.

In fact, time to intervention may be positively impacted if access to a patient’s texts and emails can be obtained, said lead author Taylor R. Anderson, a medical student at Wayne State University, Detroit.

The findings sparked interest in further research into the underlying causes and implications of dystextia: “It will be interesting to see if there are specific regions of the brain that are responsible for texting, and how they relate to other forms of communication such as handwriting and typing,” the authors said in their poster presentation.

Mr. Anderson and colleagues described two patients evaluated at Ascension St. John Hospital and Medical Center in Detroit who had stroke presenting as difficulty in typing text messages.

One case was a 43-year-old woman who experienced headache consistent with her usual migraine and spelling errors in her texts and posts on Facebook. She had visuospatial anomalies and left facial droop on evaluation. A brain MRI revealed acute embolic infarcts in the parietal and right frontal lobes, according to Mr. Anderson and coauthors.

The second case was a 66-year-old woman who had difficulty writing texts and typed notes. A head CT done in an urgent care facility showed a left frontal subacute infarct, which, according to the authors, was likely related to risk factors including hypertension, diabetes, and dyslipidemia.

These cases show that dystextia can arise after lesions in either hemisphere, the authors said. However, they emphasized that both cases involved the dominant cerebral hemisphere, while by contrast, there have not been previous reports of dystextia due to nondominant hemispheric infarct.

It stands to reason that stroke would affect the ability to text, a multipurpose task that involves use of motor, language, and vision skills, the authors said. Strokes could affect not only skills needed to type, read, and express thoughts, but also visuospatial memory mapping to letters on the device’s keyboard, they noted.

The left frontal and superior parietal regions have been implicated in handwriting in neuroimaging experiments, the authors said, while the operculum and left second frontal convolution are involved in typing.

The authors had nothing to disclose.

SOURCE: Anderson T et al. AAN 2019. Abstract P5.3-062.

Oral rotavirus vaccination had a strong protective effect against laboratory-confirmed rotavirus infection in the first 2 years of the U.K. infant immunization program, investigators are reporting.

CDC/Dr. Erskine Palmer

The estimated effectiveness was 77% for all infants with confirmed infection, and greater than 80% for those under 12 months of age, according to the report. The vaccine did not demonstrate efficacy against all-cause acute gastroenteritis, although this was likely because of high, sustained vaccine coverage coupled with the “substantial impact” of the rotavirus vaccine, wrote investigators led by Sara L. Thomas, MB BS, PhD, of the London School of Hygiene & Tropical Medicine.

Taken together, these findings provide “reassurance” that rotavirus vaccine is effective in a real-world setting and set the stage for future analyses of cost effectiveness, Dr. Thomas and coauthors said in a report on the study appearing in Vaccine: X, the open access mirror journal of Vaccine.

“As data accumulate in the post-vaccination era, more detailed assessment of waning of effectiveness over time can be undertaken, and investigation of rotavirus strain-specific protection,” they wrote.

Oral live-attenuated rotavirus vaccine (Rotarix) was introduced in the U.K. in 2013 as a two-dose schedule at 2 and 3 months of age. Vaccine uptake by the age of 25 weeks was rapid and sustained, exceeding 90%, according to previous reports. Declines in hospital admissions and primary care for all-cause acute gastroenteritis were substantial, associated with an estimated reduction of £12.5 million in health care costs in the first year of the program for children 5 years of age and younger.

To assess rotavirus vaccine effectiveness in the public health setting, Dr. Thomas and colleagues conducted a pair of studies: one designed to evaluate vaccine effectiveness against laboratory-confirmed rotavirus infections using laboratory surveillance data for 1,869 children and 1,032 controls and another to estimate vaccine effectiveness against all-cause acute gastroenteritis using electronic health data on 40,723 children.

In U.K. children with confirmed wild-type rotavirus infection aged 5 years and under, vaccine effectiveness was 69% for one dose and 77% for two doses. Stratified by age, the data showed that vaccine effectiveness was 85% in those younger than 12 months, and 54% for older children.

By contrast, they found no evidence that the rotavirus vaccine protected against all-cause acute gastroenteritis in an analysis that adjusted for age and other factors. Analysis also suggested a lack of effectiveness against hospitalized acute gastroenteritis, according to the study authors.

In prelicensure trials, oral live-attenuated rotavirus vaccine in middle- and high-income settings had efficacy against severe rotavirus-confirmed gastroenteritis of greater than 85% and efficacy against severe all-cause gastroenteritis up to 40%, investigators noted.

The lack of vaccine efficacy on all-cause acute gastroenteritis is likely because of “highly effective implementation” of the vaccine program and rapid attainment of coverage, plus high vaccine effectiveness against rotavirus-specific acute gastroenteritis, the investigators said.

“As a result, almost all AGE in the study population in the post-vaccine era was likely to have been due to nonrotavirus organisms or non-infectious causes,” said Dr. Thomas and coauthors.

This highlights the importance of choosing “specific outcomes” to study when vaccine coverage and effectiveness are both high, they concluded.

Funding for this research came from the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England. The Immunisation and Countermeasures Division of Public Health England provided vaccine manufacturers with postmarketing surveillance reports, according to the article’s disclosure section.

SOURCE: Walker JL et al. Vaccine: X. 2019 Apr 11. doi: 10.1016/j.jvacx.2019.100005.
 

Oral rotavirus vaccination had a strong protective effect against laboratory-confirmed rotavirus infection in the first 2 years of the U.K. infant immunization program, investigators are reporting.

CDC/Dr. Erskine Palmer

The estimated effectiveness was 77% for all infants with confirmed infection, and greater than 80% for those under 12 months of age, according to the report. The vaccine did not demonstrate efficacy against all-cause acute gastroenteritis, although this was likely because of high, sustained vaccine coverage coupled with the “substantial impact” of the rotavirus vaccine, wrote investigators led by Sara L. Thomas, MB BS, PhD, of the London School of Hygiene & Tropical Medicine.

Taken together, these findings provide “reassurance” that rotavirus vaccine is effective in a real-world setting and set the stage for future analyses of cost effectiveness, Dr. Thomas and coauthors said in a report on the study appearing in Vaccine: X, the open access mirror journal of Vaccine.

“As data accumulate in the post-vaccination era, more detailed assessment of waning of effectiveness over time can be undertaken, and investigation of rotavirus strain-specific protection,” they wrote.

Oral live-attenuated rotavirus vaccine (Rotarix) was introduced in the U.K. in 2013 as a two-dose schedule at 2 and 3 months of age. Vaccine uptake by the age of 25 weeks was rapid and sustained, exceeding 90%, according to previous reports. Declines in hospital admissions and primary care for all-cause acute gastroenteritis were substantial, associated with an estimated reduction of £12.5 million in health care costs in the first year of the program for children 5 years of age and younger.

To assess rotavirus vaccine effectiveness in the public health setting, Dr. Thomas and colleagues conducted a pair of studies: one designed to evaluate vaccine effectiveness against laboratory-confirmed rotavirus infections using laboratory surveillance data for 1,869 children and 1,032 controls and another to estimate vaccine effectiveness against all-cause acute gastroenteritis using electronic health data on 40,723 children.

In U.K. children with confirmed wild-type rotavirus infection aged 5 years and under, vaccine effectiveness was 69% for one dose and 77% for two doses. Stratified by age, the data showed that vaccine effectiveness was 85% in those younger than 12 months, and 54% for older children.

By contrast, they found no evidence that the rotavirus vaccine protected against all-cause acute gastroenteritis in an analysis that adjusted for age and other factors. Analysis also suggested a lack of effectiveness against hospitalized acute gastroenteritis, according to the study authors.

In prelicensure trials, oral live-attenuated rotavirus vaccine in middle- and high-income settings had efficacy against severe rotavirus-confirmed gastroenteritis of greater than 85% and efficacy against severe all-cause gastroenteritis up to 40%, investigators noted.

The lack of vaccine efficacy on all-cause acute gastroenteritis is likely because of “highly effective implementation” of the vaccine program and rapid attainment of coverage, plus high vaccine effectiveness against rotavirus-specific acute gastroenteritis, the investigators said.

“As a result, almost all AGE in the study population in the post-vaccine era was likely to have been due to nonrotavirus organisms or non-infectious causes,” said Dr. Thomas and coauthors.

This highlights the importance of choosing “specific outcomes” to study when vaccine coverage and effectiveness are both high, they concluded.

Funding for this research came from the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England. The Immunisation and Countermeasures Division of Public Health England provided vaccine manufacturers with postmarketing surveillance reports, according to the article’s disclosure section.

SOURCE: Walker JL et al. Vaccine: X. 2019 Apr 11. doi: 10.1016/j.jvacx.2019.100005.
 

Oral rotavirus vaccination had a strong protective effect against laboratory-confirmed rotavirus infection in the first 2 years of the U.K. infant immunization program, investigators are reporting.

CDC/Dr. Erskine Palmer

The estimated effectiveness was 77% for all infants with confirmed infection, and greater than 80% for those under 12 months of age, according to the report. The vaccine did not demonstrate efficacy against all-cause acute gastroenteritis, although this was likely because of high, sustained vaccine coverage coupled with the “substantial impact” of the rotavirus vaccine, wrote investigators led by Sara L. Thomas, MB BS, PhD, of the London School of Hygiene & Tropical Medicine.

Taken together, these findings provide “reassurance” that rotavirus vaccine is effective in a real-world setting and set the stage for future analyses of cost effectiveness, Dr. Thomas and coauthors said in a report on the study appearing in Vaccine: X, the open access mirror journal of Vaccine.

“As data accumulate in the post-vaccination era, more detailed assessment of waning of effectiveness over time can be undertaken, and investigation of rotavirus strain-specific protection,” they wrote.

Oral live-attenuated rotavirus vaccine (Rotarix) was introduced in the U.K. in 2013 as a two-dose schedule at 2 and 3 months of age. Vaccine uptake by the age of 25 weeks was rapid and sustained, exceeding 90%, according to previous reports. Declines in hospital admissions and primary care for all-cause acute gastroenteritis were substantial, associated with an estimated reduction of £12.5 million in health care costs in the first year of the program for children 5 years of age and younger.

To assess rotavirus vaccine effectiveness in the public health setting, Dr. Thomas and colleagues conducted a pair of studies: one designed to evaluate vaccine effectiveness against laboratory-confirmed rotavirus infections using laboratory surveillance data for 1,869 children and 1,032 controls and another to estimate vaccine effectiveness against all-cause acute gastroenteritis using electronic health data on 40,723 children.

In U.K. children with confirmed wild-type rotavirus infection aged 5 years and under, vaccine effectiveness was 69% for one dose and 77% for two doses. Stratified by age, the data showed that vaccine effectiveness was 85% in those younger than 12 months, and 54% for older children.

By contrast, they found no evidence that the rotavirus vaccine protected against all-cause acute gastroenteritis in an analysis that adjusted for age and other factors. Analysis also suggested a lack of effectiveness against hospitalized acute gastroenteritis, according to the study authors.

In prelicensure trials, oral live-attenuated rotavirus vaccine in middle- and high-income settings had efficacy against severe rotavirus-confirmed gastroenteritis of greater than 85% and efficacy against severe all-cause gastroenteritis up to 40%, investigators noted.

The lack of vaccine efficacy on all-cause acute gastroenteritis is likely because of “highly effective implementation” of the vaccine program and rapid attainment of coverage, plus high vaccine effectiveness against rotavirus-specific acute gastroenteritis, the investigators said.

“As a result, almost all AGE in the study population in the post-vaccine era was likely to have been due to nonrotavirus organisms or non-infectious causes,” said Dr. Thomas and coauthors.

This highlights the importance of choosing “specific outcomes” to study when vaccine coverage and effectiveness are both high, they concluded.

Funding for this research came from the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England. The Immunisation and Countermeasures Division of Public Health England provided vaccine manufacturers with postmarketing surveillance reports, according to the article’s disclosure section.

SOURCE: Walker JL et al. Vaccine: X. 2019 Apr 11. doi: 10.1016/j.jvacx.2019.100005.
 

PHILADELPHIA – Treatment with the monoclonal antibody eculizumab substantially reduced the risk of relapse versus placebo in patients with aquaporin-4 positive neuromyelitis optica (NMO) spectrum disorder, according to the results of a phase 3 trial reported at the annual meeting of the American Academy of Neurology. Nearly 98% of patients with this autoimmune inflammatory CNS disorder were relapse-free at 48 weeks in the PREVENT trial, according to principal investigator Sean J. Pittock, MD, director of the Mayo Clinic’s Center for Multiple Sclerosis and Autoimmune Neurology in Rochester, Minn.

“This was a dramatic result, I think, really showing a significant amount of hope for people with this disease,” Dr. Pittock said in a press conference.

Most cases of NMO are associated with aquaporin-4 antibodies and complement-mediated CNS damage, and eculizumab (Soliris) is an inhibitor of complement protein C5 shown to reduce relapse frequency in a previous, small open-label study, according to Dr. Pittock.

In the current global phase 3 trial, conducted at 70 centers in 18 countries, 143 adult patients with aquaporin-4 positive NMO spectrum disorder were randomized to eculizumab every 2 weeks or placebo. The trial allowed for supportive immunosuppressive therapy and excluded patients who had received rituximab in the past 3 months. A total of 124 patients completed the study, which was stopped after 23 adjudicated relapses had occurred.

Time to first adjudicated relapse on trial, the primary endpoint of the study, showed a significant effect (P less than .0001) in favor of monoclonal antibody treatment over placebo, with a 94.2% reduction in risk of relapse, according to Dr. Pittock and coinvestigators.

At 48 weeks, 97.9% of patients were relapse free in the eculizumab group, versus 63.2% in the placebo group, they added in their report, which was published May 3 online ahead of print in the New England Journal of Medicine (doi: 10.1056/NEJMoa1900866).

Longer-term follow-up showed that, at 144 weeks, 96% of eculizumab-treated patients remained relapse free, while 45% of the placebo group were relapse free, Dr. Pittock said in the press conference.

Most adverse events seen on treatment were mild to moderate, and no meningococcal infections were observed.

One death occurred in the study from pulmonary empyema in an eculizumab-treated patient, but the associated cultures yielded microorganisms not associated with complement deficiency, investigators said in their published report.

“The concept that you can discover a target, understand the immunopathology of a disease, identify a novel mechanism, then identify a precision drug that targets that mechanism, and essentially turn off, or switch off, the disease is very, very exciting,” Dr. Pittock said in the press conference.

The study was supported by Alexion Pharmaceuticals. Dr. Pittock provided disclosures related to Alexion Pharmaceuticals, MedImmune, and Grifols, along with patents related to administration of eculizumab and cancer markers in neuromyelitis optica.

SOURCE: Pittock SJ et al. AAN 2019, Emerging Science Abstract 009.

PHILADELPHIA – Treatment with the monoclonal antibody eculizumab substantially reduced the risk of relapse versus placebo in patients with aquaporin-4 positive neuromyelitis optica (NMO) spectrum disorder, according to the results of a phase 3 trial reported at the annual meeting of the American Academy of Neurology. Nearly 98% of patients with this autoimmune inflammatory CNS disorder were relapse-free at 48 weeks in the PREVENT trial, according to principal investigator Sean J. Pittock, MD, director of the Mayo Clinic’s Center for Multiple Sclerosis and Autoimmune Neurology in Rochester, Minn.

“This was a dramatic result, I think, really showing a significant amount of hope for people with this disease,” Dr. Pittock said in a press conference.

Most cases of NMO are associated with aquaporin-4 antibodies and complement-mediated CNS damage, and eculizumab (Soliris) is an inhibitor of complement protein C5 shown to reduce relapse frequency in a previous, small open-label study, according to Dr. Pittock.

In the current global phase 3 trial, conducted at 70 centers in 18 countries, 143 adult patients with aquaporin-4 positive NMO spectrum disorder were randomized to eculizumab every 2 weeks or placebo. The trial allowed for supportive immunosuppressive therapy and excluded patients who had received rituximab in the past 3 months. A total of 124 patients completed the study, which was stopped after 23 adjudicated relapses had occurred.

Time to first adjudicated relapse on trial, the primary endpoint of the study, showed a significant effect (P less than .0001) in favor of monoclonal antibody treatment over placebo, with a 94.2% reduction in risk of relapse, according to Dr. Pittock and coinvestigators.

At 48 weeks, 97.9% of patients were relapse free in the eculizumab group, versus 63.2% in the placebo group, they added in their report, which was published May 3 online ahead of print in the New England Journal of Medicine (doi: 10.1056/NEJMoa1900866).

Longer-term follow-up showed that, at 144 weeks, 96% of eculizumab-treated patients remained relapse free, while 45% of the placebo group were relapse free, Dr. Pittock said in the press conference.

Most adverse events seen on treatment were mild to moderate, and no meningococcal infections were observed.

One death occurred in the study from pulmonary empyema in an eculizumab-treated patient, but the associated cultures yielded microorganisms not associated with complement deficiency, investigators said in their published report.

“The concept that you can discover a target, understand the immunopathology of a disease, identify a novel mechanism, then identify a precision drug that targets that mechanism, and essentially turn off, or switch off, the disease is very, very exciting,” Dr. Pittock said in the press conference.

The study was supported by Alexion Pharmaceuticals. Dr. Pittock provided disclosures related to Alexion Pharmaceuticals, MedImmune, and Grifols, along with patents related to administration of eculizumab and cancer markers in neuromyelitis optica.

SOURCE: Pittock SJ et al. AAN 2019, Emerging Science Abstract 009.

PHILADELPHIA – Treatment with the monoclonal antibody eculizumab substantially reduced the risk of relapse versus placebo in patients with aquaporin-4 positive neuromyelitis optica (NMO) spectrum disorder, according to the results of a phase 3 trial reported at the annual meeting of the American Academy of Neurology. Nearly 98% of patients with this autoimmune inflammatory CNS disorder were relapse-free at 48 weeks in the PREVENT trial, according to principal investigator Sean J. Pittock, MD, director of the Mayo Clinic’s Center for Multiple Sclerosis and Autoimmune Neurology in Rochester, Minn.

“This was a dramatic result, I think, really showing a significant amount of hope for people with this disease,” Dr. Pittock said in a press conference.

Most cases of NMO are associated with aquaporin-4 antibodies and complement-mediated CNS damage, and eculizumab (Soliris) is an inhibitor of complement protein C5 shown to reduce relapse frequency in a previous, small open-label study, according to Dr. Pittock.

In the current global phase 3 trial, conducted at 70 centers in 18 countries, 143 adult patients with aquaporin-4 positive NMO spectrum disorder were randomized to eculizumab every 2 weeks or placebo. The trial allowed for supportive immunosuppressive therapy and excluded patients who had received rituximab in the past 3 months. A total of 124 patients completed the study, which was stopped after 23 adjudicated relapses had occurred.

Time to first adjudicated relapse on trial, the primary endpoint of the study, showed a significant effect (P less than .0001) in favor of monoclonal antibody treatment over placebo, with a 94.2% reduction in risk of relapse, according to Dr. Pittock and coinvestigators.

At 48 weeks, 97.9% of patients were relapse free in the eculizumab group, versus 63.2% in the placebo group, they added in their report, which was published May 3 online ahead of print in the New England Journal of Medicine (doi: 10.1056/NEJMoa1900866).

Longer-term follow-up showed that, at 144 weeks, 96% of eculizumab-treated patients remained relapse free, while 45% of the placebo group were relapse free, Dr. Pittock said in the press conference.

Most adverse events seen on treatment were mild to moderate, and no meningococcal infections were observed.

One death occurred in the study from pulmonary empyema in an eculizumab-treated patient, but the associated cultures yielded microorganisms not associated with complement deficiency, investigators said in their published report.

“The concept that you can discover a target, understand the immunopathology of a disease, identify a novel mechanism, then identify a precision drug that targets that mechanism, and essentially turn off, or switch off, the disease is very, very exciting,” Dr. Pittock said in the press conference.

The study was supported by Alexion Pharmaceuticals. Dr. Pittock provided disclosures related to Alexion Pharmaceuticals, MedImmune, and Grifols, along with patents related to administration of eculizumab and cancer markers in neuromyelitis optica.

SOURCE: Pittock SJ et al. AAN 2019, Emerging Science Abstract 009.

The number of reported cases of Fourier gangrene in patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors has surged since the US Food and Drug Administration (FDA) issued a 2018 warning about this rare but serious infection, researchers say.

Health care providers prescribing SGLT2 inhibitors to patients with diabetes should have a high index of suspicion for the signs and symptoms of Fournier gangrene, given its substantial morbidity and mortality, according to Susan J. Bersoff-Matcha, MD, and her colleagues at the FDA.

“Although the risk for [Fournier gangrene] is low, serious infection should be considered and weighed against the benefits of SGLT2 inhibitor therapy,” said Dr. Bersoff-Matcha and co-authors in their recent report published in the Annals of Internal Medicine (2019 May 6. doi: 10.7326/M19-0085).

In the previous warning, FDA officials said 12 cases of Fournier gangrene in patients taking an SGLT2 inhibitor had been reported to the agency or in medical literature from March 2013, when the first such inhibitor was approved, and May 2018.

In this latest report, a total of 55 Fournier gangrene cases had been reported in patients receiving SGLT2 inhibitors from March 2, 2013 through January 31, 2019.

The influx of reports may have been prompted by growing awareness of the safety issue, investigators said, but could also reflect the increasing prevalence of diabetes combined with SGLT2 inhibitor use. The researchers also noted that diabetes is a comorbidity in 32% to 66% of cases of Fournier gangrene.

But the likliehood that diabetes mellitus alone causes Fournier gangrene seems unlikley, given that Dr. Bersoff-Matcha and co-authors only found 19 Fournier gangrene cases associated with other classes of antiglycemic agents reported to the FDA or in the literature over a 35-year time frame.

“If Fournier gangrene were associated only with diabetes mellitus and not SGLT2 inhibitors, we would expect far more cases reported with the other antiglycemic agents, considering the 35-year timeframe and the large number of agents,” they said in their report.

Cases were reported for all FDA-approved SGLT2 inhibitors besides ertugliflozin, an agent approved for use in the U.S. in December 2017. The lack of cases reported for this drug could be related to its limited time on the market, the investigators said.

Fournier gangrene, marked by rapidly progressing necrotizing infection of the genitalia, perineum, and perianal region, requires antibiotics and immediate surgery, according to Dr. Bersoff-Matcha and colleagues.

“Serious complications and death are likely if Fournier gangrene is not recognized immediately and surgical intervention is not carried out within the first few hours of diagnosis,” they said in the report.

Of the 55 cases reported in patients receiving SGLT2 inhibitors, 39 were men and 16 were women, with an average of 9 months from the start of treatment to the event, investigators said.

At least 25 patients required multiple surgeries, including one patient who had 17 trips to the operating room, they said. A total of 8 patients had a fecal diversion procedure, and 4 patients had skin grafting.

Six patients had multiple encounters with a provider before being diagnosed, suggesting that the provider may have not recognized the infection due to its nonspecific symptoms, which include fatigue, fever, and malaise.

“Pain that seems out of proportion to findings on physical examination is a strong clinical indicator of necrotizing fasciitis and may be the most important diagnostic clue,” Dr. Bersoff-Matcha and co-authors said in their report.

The incidence of Fournier gangrene in patients taking SGLT2 inhibitors can’t be established by these cases reported to the FDA, which are spontaneously provided by health care providers and patients, investigators said.

“We suspect that our numbers underestimate the true burden,” they said in their report.

Dr. Bersoff-Matcha and co-authors disclosed no conflicts of interest related to their report.

SOURCE: Bersoff-Matcha SJ, et al. Ann Intern Med. 2019 May 6. Doi: doi:10.7326/M19-0085.

This article was updated May 9, 2019.

The number of reported cases of Fourier gangrene in patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors has surged since the US Food and Drug Administration (FDA) issued a 2018 warning about this rare but serious infection, researchers say.

Health care providers prescribing SGLT2 inhibitors to patients with diabetes should have a high index of suspicion for the signs and symptoms of Fournier gangrene, given its substantial morbidity and mortality, according to Susan J. Bersoff-Matcha, MD, and her colleagues at the FDA.

“Although the risk for [Fournier gangrene] is low, serious infection should be considered and weighed against the benefits of SGLT2 inhibitor therapy,” said Dr. Bersoff-Matcha and co-authors in their recent report published in the Annals of Internal Medicine (2019 May 6. doi: 10.7326/M19-0085).

In the previous warning, FDA officials said 12 cases of Fournier gangrene in patients taking an SGLT2 inhibitor had been reported to the agency or in medical literature from March 2013, when the first such inhibitor was approved, and May 2018.

In this latest report, a total of 55 Fournier gangrene cases had been reported in patients receiving SGLT2 inhibitors from March 2, 2013 through January 31, 2019.

The influx of reports may have been prompted by growing awareness of the safety issue, investigators said, but could also reflect the increasing prevalence of diabetes combined with SGLT2 inhibitor use. The researchers also noted that diabetes is a comorbidity in 32% to 66% of cases of Fournier gangrene.

But the likliehood that diabetes mellitus alone causes Fournier gangrene seems unlikley, given that Dr. Bersoff-Matcha and co-authors only found 19 Fournier gangrene cases associated with other classes of antiglycemic agents reported to the FDA or in the literature over a 35-year time frame.

“If Fournier gangrene were associated only with diabetes mellitus and not SGLT2 inhibitors, we would expect far more cases reported with the other antiglycemic agents, considering the 35-year timeframe and the large number of agents,” they said in their report.

Cases were reported for all FDA-approved SGLT2 inhibitors besides ertugliflozin, an agent approved for use in the U.S. in December 2017. The lack of cases reported for this drug could be related to its limited time on the market, the investigators said.

Fournier gangrene, marked by rapidly progressing necrotizing infection of the genitalia, perineum, and perianal region, requires antibiotics and immediate surgery, according to Dr. Bersoff-Matcha and colleagues.

“Serious complications and death are likely if Fournier gangrene is not recognized immediately and surgical intervention is not carried out within the first few hours of diagnosis,” they said in the report.

Of the 55 cases reported in patients receiving SGLT2 inhibitors, 39 were men and 16 were women, with an average of 9 months from the start of treatment to the event, investigators said.

At least 25 patients required multiple surgeries, including one patient who had 17 trips to the operating room, they said. A total of 8 patients had a fecal diversion procedure, and 4 patients had skin grafting.

Six patients had multiple encounters with a provider before being diagnosed, suggesting that the provider may have not recognized the infection due to its nonspecific symptoms, which include fatigue, fever, and malaise.

“Pain that seems out of proportion to findings on physical examination is a strong clinical indicator of necrotizing fasciitis and may be the most important diagnostic clue,” Dr. Bersoff-Matcha and co-authors said in their report.

The incidence of Fournier gangrene in patients taking SGLT2 inhibitors can’t be established by these cases reported to the FDA, which are spontaneously provided by health care providers and patients, investigators said.

“We suspect that our numbers underestimate the true burden,” they said in their report.

Dr. Bersoff-Matcha and co-authors disclosed no conflicts of interest related to their report.

SOURCE: Bersoff-Matcha SJ, et al. Ann Intern Med. 2019 May 6. Doi: doi:10.7326/M19-0085.

This article was updated May 9, 2019.

The number of reported cases of Fourier gangrene in patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors has surged since the US Food and Drug Administration (FDA) issued a 2018 warning about this rare but serious infection, researchers say.

Health care providers prescribing SGLT2 inhibitors to patients with diabetes should have a high index of suspicion for the signs and symptoms of Fournier gangrene, given its substantial morbidity and mortality, according to Susan J. Bersoff-Matcha, MD, and her colleagues at the FDA.

“Although the risk for [Fournier gangrene] is low, serious infection should be considered and weighed against the benefits of SGLT2 inhibitor therapy,” said Dr. Bersoff-Matcha and co-authors in their recent report published in the Annals of Internal Medicine (2019 May 6. doi: 10.7326/M19-0085).

In the previous warning, FDA officials said 12 cases of Fournier gangrene in patients taking an SGLT2 inhibitor had been reported to the agency or in medical literature from March 2013, when the first such inhibitor was approved, and May 2018.

In this latest report, a total of 55 Fournier gangrene cases had been reported in patients receiving SGLT2 inhibitors from March 2, 2013 through January 31, 2019.

The influx of reports may have been prompted by growing awareness of the safety issue, investigators said, but could also reflect the increasing prevalence of diabetes combined with SGLT2 inhibitor use. The researchers also noted that diabetes is a comorbidity in 32% to 66% of cases of Fournier gangrene.

But the likliehood that diabetes mellitus alone causes Fournier gangrene seems unlikley, given that Dr. Bersoff-Matcha and co-authors only found 19 Fournier gangrene cases associated with other classes of antiglycemic agents reported to the FDA or in the literature over a 35-year time frame.

“If Fournier gangrene were associated only with diabetes mellitus and not SGLT2 inhibitors, we would expect far more cases reported with the other antiglycemic agents, considering the 35-year timeframe and the large number of agents,” they said in their report.

Cases were reported for all FDA-approved SGLT2 inhibitors besides ertugliflozin, an agent approved for use in the U.S. in December 2017. The lack of cases reported for this drug could be related to its limited time on the market, the investigators said.

Fournier gangrene, marked by rapidly progressing necrotizing infection of the genitalia, perineum, and perianal region, requires antibiotics and immediate surgery, according to Dr. Bersoff-Matcha and colleagues.

“Serious complications and death are likely if Fournier gangrene is not recognized immediately and surgical intervention is not carried out within the first few hours of diagnosis,” they said in the report.

Of the 55 cases reported in patients receiving SGLT2 inhibitors, 39 were men and 16 were women, with an average of 9 months from the start of treatment to the event, investigators said.

At least 25 patients required multiple surgeries, including one patient who had 17 trips to the operating room, they said. A total of 8 patients had a fecal diversion procedure, and 4 patients had skin grafting.

Six patients had multiple encounters with a provider before being diagnosed, suggesting that the provider may have not recognized the infection due to its nonspecific symptoms, which include fatigue, fever, and malaise.

“Pain that seems out of proportion to findings on physical examination is a strong clinical indicator of necrotizing fasciitis and may be the most important diagnostic clue,” Dr. Bersoff-Matcha and co-authors said in their report.

The incidence of Fournier gangrene in patients taking SGLT2 inhibitors can’t be established by these cases reported to the FDA, which are spontaneously provided by health care providers and patients, investigators said.

“We suspect that our numbers underestimate the true burden,” they said in their report.

Dr. Bersoff-Matcha and co-authors disclosed no conflicts of interest related to their report.

SOURCE: Bersoff-Matcha SJ, et al. Ann Intern Med. 2019 May 6. Doi: doi:10.7326/M19-0085.

This article was updated May 9, 2019.

PHILADELPHIA – A disproportionate number of breakthrough strokes were observed among patients receiving rivaroxaban for nonvalvular atrial fibrillation in a stroke unit, according to a small, single-center, retrospective study presented at the annual meeting of the American Academy of Neurology.

The researchers reviewed all patients presenting to a tertiary care stroke unit in Australia from January 2015 to June 2018.

A total of 56 patients (median age was 74 years; 61% were male) had received direct oral anticoagulant (DOAC) therapy and then had an ischemic stroke. Of those patients, 37 (66%) had strokes while receiving the treatment; 14 patients (25%) had a stroke after recently stopping a DOAC, often prior to a medical procedure; and 5 patients (9%) were not adherent to their DOAC regimen.

Of the 37 patients who had strokes during DOAC treatment, 48% were on rivaroxaban, 9% were on dabigatran, and 9% were on apixaban, Fiona Chan, MD, of The Princess Alexandra Hospital, Brisbane, Australia, and coinvestigators reported in a poster presentation.

While these findings need to be replicated in a larger study, they do “raise concern for inadequate stroke prevention within this cohort,” they said.

Moreover, the findings illustrate the importance of bridging anticoagulation prior to procedures, when appropriate, to minimize stroke risk, they added, as 25% of the strokes had occurred in patients who recently stopped the DOACs due to procedures.

To determine which DOAC was most often associated with breakthrough ischemic strokes in patients with nonvalvular atrial fibrillation, the investigators compared the proportion of DOACs prescribed in Australia to the proportion of observed strokes in their cohort.

Despite accounting for about 51% of Australian DOAC prescriptions, rivaroxaban represented nearly 73% of breakthrough strokes among the patients who had strokes while receiving the treatment (P = .001), the investigators reported.

Conversely, apixaban accounted for about 35% of prescriptions but 14% of the breakthrough strokes (P = .0007), while dabigatran accounted for 14% of prescriptions and 14% of the strokes (P = 0.99), the investigators said in their poster.

One limitation of this retrospective study is that the patient cohort came from a single specialized center, and may not reflect the true incidence of nonvalvular atrial fibrillation across Australia, the researchers noted.

Dr. Chan and coinvestigators reported that they had no relevant financial disclosures.

SOURCE: Chan F et al. AAN 2019. P1.3-001.

PHILADELPHIA – A disproportionate number of breakthrough strokes were observed among patients receiving rivaroxaban for nonvalvular atrial fibrillation in a stroke unit, according to a small, single-center, retrospective study presented at the annual meeting of the American Academy of Neurology.

The researchers reviewed all patients presenting to a tertiary care stroke unit in Australia from January 2015 to June 2018.

A total of 56 patients (median age was 74 years; 61% were male) had received direct oral anticoagulant (DOAC) therapy and then had an ischemic stroke. Of those patients, 37 (66%) had strokes while receiving the treatment; 14 patients (25%) had a stroke after recently stopping a DOAC, often prior to a medical procedure; and 5 patients (9%) were not adherent to their DOAC regimen.

Of the 37 patients who had strokes during DOAC treatment, 48% were on rivaroxaban, 9% were on dabigatran, and 9% were on apixaban, Fiona Chan, MD, of The Princess Alexandra Hospital, Brisbane, Australia, and coinvestigators reported in a poster presentation.

While these findings need to be replicated in a larger study, they do “raise concern for inadequate stroke prevention within this cohort,” they said.

Moreover, the findings illustrate the importance of bridging anticoagulation prior to procedures, when appropriate, to minimize stroke risk, they added, as 25% of the strokes had occurred in patients who recently stopped the DOACs due to procedures.

To determine which DOAC was most often associated with breakthrough ischemic strokes in patients with nonvalvular atrial fibrillation, the investigators compared the proportion of DOACs prescribed in Australia to the proportion of observed strokes in their cohort.

Despite accounting for about 51% of Australian DOAC prescriptions, rivaroxaban represented nearly 73% of breakthrough strokes among the patients who had strokes while receiving the treatment (P = .001), the investigators reported.

Conversely, apixaban accounted for about 35% of prescriptions but 14% of the breakthrough strokes (P = .0007), while dabigatran accounted for 14% of prescriptions and 14% of the strokes (P = 0.99), the investigators said in their poster.

One limitation of this retrospective study is that the patient cohort came from a single specialized center, and may not reflect the true incidence of nonvalvular atrial fibrillation across Australia, the researchers noted.

Dr. Chan and coinvestigators reported that they had no relevant financial disclosures.

SOURCE: Chan F et al. AAN 2019. P1.3-001.

PHILADELPHIA – A disproportionate number of breakthrough strokes were observed among patients receiving rivaroxaban for nonvalvular atrial fibrillation in a stroke unit, according to a small, single-center, retrospective study presented at the annual meeting of the American Academy of Neurology.

The researchers reviewed all patients presenting to a tertiary care stroke unit in Australia from January 2015 to June 2018.

A total of 56 patients (median age was 74 years; 61% were male) had received direct oral anticoagulant (DOAC) therapy and then had an ischemic stroke. Of those patients, 37 (66%) had strokes while receiving the treatment; 14 patients (25%) had a stroke after recently stopping a DOAC, often prior to a medical procedure; and 5 patients (9%) were not adherent to their DOAC regimen.

Of the 37 patients who had strokes during DOAC treatment, 48% were on rivaroxaban, 9% were on dabigatran, and 9% were on apixaban, Fiona Chan, MD, of The Princess Alexandra Hospital, Brisbane, Australia, and coinvestigators reported in a poster presentation.

While these findings need to be replicated in a larger study, they do “raise concern for inadequate stroke prevention within this cohort,” they said.

Moreover, the findings illustrate the importance of bridging anticoagulation prior to procedures, when appropriate, to minimize stroke risk, they added, as 25% of the strokes had occurred in patients who recently stopped the DOACs due to procedures.

To determine which DOAC was most often associated with breakthrough ischemic strokes in patients with nonvalvular atrial fibrillation, the investigators compared the proportion of DOACs prescribed in Australia to the proportion of observed strokes in their cohort.

Despite accounting for about 51% of Australian DOAC prescriptions, rivaroxaban represented nearly 73% of breakthrough strokes among the patients who had strokes while receiving the treatment (P = .001), the investigators reported.

Conversely, apixaban accounted for about 35% of prescriptions but 14% of the breakthrough strokes (P = .0007), while dabigatran accounted for 14% of prescriptions and 14% of the strokes (P = 0.99), the investigators said in their poster.

One limitation of this retrospective study is that the patient cohort came from a single specialized center, and may not reflect the true incidence of nonvalvular atrial fibrillation across Australia, the researchers noted.

Dr. Chan and coinvestigators reported that they had no relevant financial disclosures.

SOURCE: Chan F et al. AAN 2019. P1.3-001.

Philadelphia – Adoptive transfer of donor-derived T cells represents a potentially life-saving treatment of severely immunocompromised patients with progressive multifocal leukoencephalopathy (PML).

Courtesy NIH/NINDS

“We think this strategy has real potential to be one of the first effective treatments for PML,” Erin Beck, MD, PhD, said during a press conference at the annual meeting of the American Academy of Neurology.

In a pilot study including 12 patients with PML, the 7 who survived had substantial neurological improvement after treatment with this immunotherapeutic approach, said Dr. Beck of the National Institute of Neurological Disorders and Stroke.

“This was very encouraging to us because these patients were worsening at the time of their treatment and we did not expect them to do well,” she said.

There were no serious adverse events related to treatment, which suggests the approach is safe for patients with PML, according to Dr. Beck.

“This is a phenomenal breakthrough,” Natalia S. Rost, MD, MPH, chair of the meeting’s science committee, said at the press conference. “Giving a diagnosis of PML to a patient is basically giving them a death sentence, and it’s one of the most dreaded scenarios in our clinical practice.”

PML, an opportunistic infection of the central nervous system caused by JC polyomavirus, is usually fatal unless adaptive immunity to JC polyomavirus can be restored, Dr. Beck said.

Cases of PML surged in the 1980s and 1990s as a result of the HIV/AIDS epidemic, she said, and an increase in cases has been observed more recently related to new immunosuppressive treatments for cancer and autoimmune diseases.

The pilot study described by Dr. Beck included 12 patients with refractory PML who underwent adoptive transfer of polyomavirus-specific T cells (PyVSTs) that were generated from partially matched first-degree relatives of the patients. Up to three infusions were given at least 28 days apart.

Although five patients died of PML, the remaining seven patients stabilized and in some cases experienced significant neurological improvement, according to the investigators. Two of the seven died of PML a year after their final infusion.

No overt immune reconstitution inflammatory syndrome (IRIS) was observed in treated patients.

It’s not clear to date which PML patients may be most likely to benefit from this treatment approach because there were no differences in age, sex, baseline leukocyte count numbers, or time since their initial diagnosis between responders and nonresponders, Dr. Beck said.

However, patients who died tended to have much higher JC virus copy numbers in their spinal fluid, as did some patients who were enrolled but died before they could receive any treatment, she added.

“That high range, I think, is a very bad prognostic sign,” Dr. Beck said. “A number in the lower range doesn’t mean a good prognosis, but it means potentially that you could respond to a treatment such as this one.”

The study was funded by National Institute of Neurological Disorders and Stroke. The investigators disclosed no conflicts related to the study.

SOURCE: Cortese I et al. AAN 2019, Abstract Plen01.002.

Philadelphia – Adoptive transfer of donor-derived T cells represents a potentially life-saving treatment of severely immunocompromised patients with progressive multifocal leukoencephalopathy (PML).

Courtesy NIH/NINDS

“We think this strategy has real potential to be one of the first effective treatments for PML,” Erin Beck, MD, PhD, said during a press conference at the annual meeting of the American Academy of Neurology.

In a pilot study including 12 patients with PML, the 7 who survived had substantial neurological improvement after treatment with this immunotherapeutic approach, said Dr. Beck of the National Institute of Neurological Disorders and Stroke.

“This was very encouraging to us because these patients were worsening at the time of their treatment and we did not expect them to do well,” she said.

There were no serious adverse events related to treatment, which suggests the approach is safe for patients with PML, according to Dr. Beck.

“This is a phenomenal breakthrough,” Natalia S. Rost, MD, MPH, chair of the meeting’s science committee, said at the press conference. “Giving a diagnosis of PML to a patient is basically giving them a death sentence, and it’s one of the most dreaded scenarios in our clinical practice.”

PML, an opportunistic infection of the central nervous system caused by JC polyomavirus, is usually fatal unless adaptive immunity to JC polyomavirus can be restored, Dr. Beck said.

Cases of PML surged in the 1980s and 1990s as a result of the HIV/AIDS epidemic, she said, and an increase in cases has been observed more recently related to new immunosuppressive treatments for cancer and autoimmune diseases.

The pilot study described by Dr. Beck included 12 patients with refractory PML who underwent adoptive transfer of polyomavirus-specific T cells (PyVSTs) that were generated from partially matched first-degree relatives of the patients. Up to three infusions were given at least 28 days apart.

Although five patients died of PML, the remaining seven patients stabilized and in some cases experienced significant neurological improvement, according to the investigators. Two of the seven died of PML a year after their final infusion.

No overt immune reconstitution inflammatory syndrome (IRIS) was observed in treated patients.

It’s not clear to date which PML patients may be most likely to benefit from this treatment approach because there were no differences in age, sex, baseline leukocyte count numbers, or time since their initial diagnosis between responders and nonresponders, Dr. Beck said.

However, patients who died tended to have much higher JC virus copy numbers in their spinal fluid, as did some patients who were enrolled but died before they could receive any treatment, she added.

“That high range, I think, is a very bad prognostic sign,” Dr. Beck said. “A number in the lower range doesn’t mean a good prognosis, but it means potentially that you could respond to a treatment such as this one.”

The study was funded by National Institute of Neurological Disorders and Stroke. The investigators disclosed no conflicts related to the study.

SOURCE: Cortese I et al. AAN 2019, Abstract Plen01.002.

Philadelphia – Adoptive transfer of donor-derived T cells represents a potentially life-saving treatment of severely immunocompromised patients with progressive multifocal leukoencephalopathy (PML).

Courtesy NIH/NINDS

“We think this strategy has real potential to be one of the first effective treatments for PML,” Erin Beck, MD, PhD, said during a press conference at the annual meeting of the American Academy of Neurology.

In a pilot study including 12 patients with PML, the 7 who survived had substantial neurological improvement after treatment with this immunotherapeutic approach, said Dr. Beck of the National Institute of Neurological Disorders and Stroke.

“This was very encouraging to us because these patients were worsening at the time of their treatment and we did not expect them to do well,” she said.

There were no serious adverse events related to treatment, which suggests the approach is safe for patients with PML, according to Dr. Beck.

“This is a phenomenal breakthrough,” Natalia S. Rost, MD, MPH, chair of the meeting’s science committee, said at the press conference. “Giving a diagnosis of PML to a patient is basically giving them a death sentence, and it’s one of the most dreaded scenarios in our clinical practice.”

PML, an opportunistic infection of the central nervous system caused by JC polyomavirus, is usually fatal unless adaptive immunity to JC polyomavirus can be restored, Dr. Beck said.

Cases of PML surged in the 1980s and 1990s as a result of the HIV/AIDS epidemic, she said, and an increase in cases has been observed more recently related to new immunosuppressive treatments for cancer and autoimmune diseases.

The pilot study described by Dr. Beck included 12 patients with refractory PML who underwent adoptive transfer of polyomavirus-specific T cells (PyVSTs) that were generated from partially matched first-degree relatives of the patients. Up to three infusions were given at least 28 days apart.

Although five patients died of PML, the remaining seven patients stabilized and in some cases experienced significant neurological improvement, according to the investigators. Two of the seven died of PML a year after their final infusion.

No overt immune reconstitution inflammatory syndrome (IRIS) was observed in treated patients.

It’s not clear to date which PML patients may be most likely to benefit from this treatment approach because there were no differences in age, sex, baseline leukocyte count numbers, or time since their initial diagnosis between responders and nonresponders, Dr. Beck said.

However, patients who died tended to have much higher JC virus copy numbers in their spinal fluid, as did some patients who were enrolled but died before they could receive any treatment, she added.

“That high range, I think, is a very bad prognostic sign,” Dr. Beck said. “A number in the lower range doesn’t mean a good prognosis, but it means potentially that you could respond to a treatment such as this one.”

The study was funded by National Institute of Neurological Disorders and Stroke. The investigators disclosed no conflicts related to the study.

SOURCE: Cortese I et al. AAN 2019, Abstract Plen01.002.

Philadelphia – OV101 (gaboxadol), a type A gamma-aminobutyric acid receptor agonist, was safe, well tolerated, and improved clinical outcomes in a phase 2 trial of adults and adolescents with Angelman syndrome, according to results of a study presented at the annual meeting of the American Academy of Neurology.

Clinician-rated clinical global impressions of improvement (CGI-I) were improved versus placebo in the randomized study, as were other outcomes in post hoc analyses, including measures of sleep and motor function, said Alexander Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, New York.

This study of OV101 was a genetics-driven trial for the rare genetic disorder, which is caused by mutations in UBE3A and characterized by seizures, speech impairments, profound intellectual disability, gait problems, and anxiety, Dr. Kolevzon said in a press conference.

“The only treatments that exist are really very symptomatically driven,” Dr. Kolevzon said. “Here, we are taking a genetics-first approach. Having identified the gene, there is some understanding of what the underlying biology is, and it seems to relate to deficits in tonic inhibition.”

OV101 is a delta-selective type A gamma-aminobutyric acid receptor agonist that may potentially normalize the tonic inhibition that is decreased in Angelman syndrome. “What we think this compound is doing is actually reversing the deficits of tonic inhibition, and sort of restoring that state to these patients,” Dr. Kolevzon said in the press conference.

A total of 78 patients completed the phase 2, randomized study, known as STARS, which had a primary endpoint of safety and tolerability over 12 weeks of treatment with OV101 once daily, twice daily, or placebo. The mean age of the 87 patients who enrolled and had at least one dose of study drug was 22.6 years.

Most adverse events were mild, and frequencies of specific adverse events were similar for OV101 and placebo treatment groups, according to Dr. Kolevzon and his coinvestigators.

Improvements in motor function, sleep, and behavior were seen in a series of exploratory analyses, including global improvement at week 12, as captured by CGI-I, which was significantly improved for daily OV101 versus placebo (P = .0006).

These phase 2 results have informed discussions of which specific endpoints might be incorporated into the design of a planned phase 3 trial in pediatric patients. The CGI-I may be especially useful to measure clinical improvement in Angelman syndrome, which is a very “heterogeneous” disorder, Dr. Kolevzon said in the press conference.

“Every child has a different composite of symptoms, so that is the big challenge,” Dr. Kolevzon said. “I do not think we are going to have one singular outcome. The idea is to have a global measure that really captures heterogeneity across each trial and allows for children to be compared to their baseline, and each as their own control, in essence, but with specific domains in mind.”

Funding for the study came from Ovid Therapeutics. Dr. Kolevzon reported disclosures related to Ovid Therapeutics, as well as Coronis Neurosciences, 5AM Ventures, SEMA4, LabCorp, and AMO Pharma.

Philadelphia – OV101 (gaboxadol), a type A gamma-aminobutyric acid receptor agonist, was safe, well tolerated, and improved clinical outcomes in a phase 2 trial of adults and adolescents with Angelman syndrome, according to results of a study presented at the annual meeting of the American Academy of Neurology.

Clinician-rated clinical global impressions of improvement (CGI-I) were improved versus placebo in the randomized study, as were other outcomes in post hoc analyses, including measures of sleep and motor function, said Alexander Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, New York.

This study of OV101 was a genetics-driven trial for the rare genetic disorder, which is caused by mutations in UBE3A and characterized by seizures, speech impairments, profound intellectual disability, gait problems, and anxiety, Dr. Kolevzon said in a press conference.

“The only treatments that exist are really very symptomatically driven,” Dr. Kolevzon said. “Here, we are taking a genetics-first approach. Having identified the gene, there is some understanding of what the underlying biology is, and it seems to relate to deficits in tonic inhibition.”

OV101 is a delta-selective type A gamma-aminobutyric acid receptor agonist that may potentially normalize the tonic inhibition that is decreased in Angelman syndrome. “What we think this compound is doing is actually reversing the deficits of tonic inhibition, and sort of restoring that state to these patients,” Dr. Kolevzon said in the press conference.

A total of 78 patients completed the phase 2, randomized study, known as STARS, which had a primary endpoint of safety and tolerability over 12 weeks of treatment with OV101 once daily, twice daily, or placebo. The mean age of the 87 patients who enrolled and had at least one dose of study drug was 22.6 years.

Most adverse events were mild, and frequencies of specific adverse events were similar for OV101 and placebo treatment groups, according to Dr. Kolevzon and his coinvestigators.

Improvements in motor function, sleep, and behavior were seen in a series of exploratory analyses, including global improvement at week 12, as captured by CGI-I, which was significantly improved for daily OV101 versus placebo (P = .0006).

These phase 2 results have informed discussions of which specific endpoints might be incorporated into the design of a planned phase 3 trial in pediatric patients. The CGI-I may be especially useful to measure clinical improvement in Angelman syndrome, which is a very “heterogeneous” disorder, Dr. Kolevzon said in the press conference.

“Every child has a different composite of symptoms, so that is the big challenge,” Dr. Kolevzon said. “I do not think we are going to have one singular outcome. The idea is to have a global measure that really captures heterogeneity across each trial and allows for children to be compared to their baseline, and each as their own control, in essence, but with specific domains in mind.”

Funding for the study came from Ovid Therapeutics. Dr. Kolevzon reported disclosures related to Ovid Therapeutics, as well as Coronis Neurosciences, 5AM Ventures, SEMA4, LabCorp, and AMO Pharma.

Philadelphia – OV101 (gaboxadol), a type A gamma-aminobutyric acid receptor agonist, was safe, well tolerated, and improved clinical outcomes in a phase 2 trial of adults and adolescents with Angelman syndrome, according to results of a study presented at the annual meeting of the American Academy of Neurology.

Clinician-rated clinical global impressions of improvement (CGI-I) were improved versus placebo in the randomized study, as were other outcomes in post hoc analyses, including measures of sleep and motor function, said Alexander Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, New York.

This study of OV101 was a genetics-driven trial for the rare genetic disorder, which is caused by mutations in UBE3A and characterized by seizures, speech impairments, profound intellectual disability, gait problems, and anxiety, Dr. Kolevzon said in a press conference.

“The only treatments that exist are really very symptomatically driven,” Dr. Kolevzon said. “Here, we are taking a genetics-first approach. Having identified the gene, there is some understanding of what the underlying biology is, and it seems to relate to deficits in tonic inhibition.”

OV101 is a delta-selective type A gamma-aminobutyric acid receptor agonist that may potentially normalize the tonic inhibition that is decreased in Angelman syndrome. “What we think this compound is doing is actually reversing the deficits of tonic inhibition, and sort of restoring that state to these patients,” Dr. Kolevzon said in the press conference.

A total of 78 patients completed the phase 2, randomized study, known as STARS, which had a primary endpoint of safety and tolerability over 12 weeks of treatment with OV101 once daily, twice daily, or placebo. The mean age of the 87 patients who enrolled and had at least one dose of study drug was 22.6 years.

Most adverse events were mild, and frequencies of specific adverse events were similar for OV101 and placebo treatment groups, according to Dr. Kolevzon and his coinvestigators.

Improvements in motor function, sleep, and behavior were seen in a series of exploratory analyses, including global improvement at week 12, as captured by CGI-I, which was significantly improved for daily OV101 versus placebo (P = .0006).

These phase 2 results have informed discussions of which specific endpoints might be incorporated into the design of a planned phase 3 trial in pediatric patients. The CGI-I may be especially useful to measure clinical improvement in Angelman syndrome, which is a very “heterogeneous” disorder, Dr. Kolevzon said in the press conference.

“Every child has a different composite of symptoms, so that is the big challenge,” Dr. Kolevzon said. “I do not think we are going to have one singular outcome. The idea is to have a global measure that really captures heterogeneity across each trial and allows for children to be compared to their baseline, and each as their own control, in essence, but with specific domains in mind.”

Funding for the study came from Ovid Therapeutics. Dr. Kolevzon reported disclosures related to Ovid Therapeutics, as well as Coronis Neurosciences, 5AM Ventures, SEMA4, LabCorp, and AMO Pharma.

State laws that give pharmacists direct authority to dispense naloxone are linked to significant drops in opioid-related fatal overdoses, investigators reported.

By contrast, state laws that stopped short of allowing pharmacists to directly dispense the opioid antagonist did not appear to impact mortality, according to the report, which appears in JAMA Internal Medicine (2019 May 6. doi: 10.1001/jamainternmed.2019.0272).

The report, based on state-level trends tracked from 2005 to 2016, indicates that fatal opioid overdoses fell by nearly one-third in states that adopted direct dispensing laws as compared with states that adopted other naloxone laws.

That finding suggests that the policy type determines whether a naloxone law is useful in combating fatal opioid overdoses, said Rahi Abouk, PhD, of William Paterson University, Wayne, N.J. and co-authors of the paper.

“Enabling distribution through various sources, or requiring gatekeepers, will not be as beneficial,” Dr. Abouk and co-authors said in their report.

The current rate of deaths from fentanyl, heroin, and prescription analgesic overdose has outpaced all previous drug epidemics on record, and even surpasses the number of deaths in the peak year of the HIV epidemic of the 1980s, Dr. Abouk and colleagues wrote in their paper.

The number of states with naloxone access laws grew from just 2 in 2005 to 47 by 2016, including 9 states that granted direct authority to pharmacists and 38 that granted indirect authority, according to the researchers.

The analysis of overdose trends from 2005 to 2016 was based on naloxone distribution data from state Medicaid agencies and opioid-related mortality data from a national statistics system. Forty percent of nonelderly adults with an opioid addiction are covered by Medicaid, the researchers said.

They found that naloxone laws granting pharmacists direct dispensing authority were linked to a drop in opioid deaths that increased in magnitude over time, according to researchers. The mean number of opioid deaths dropped by 27% in the second year after adoption of direct authority laws, relative to opioid deaths in states with indirect access laws, while in subsequent years, deaths dropped by 34%.

Emergency department visits related to opioids increased by 15% in direct authority states 3 or more years after adoption, as compared to states that did not adopt direct authority laws. According to investigators, that translated into 15 additional opioid-related emergency department visits each month.

That increase suggests that, alongside direct dispensing laws, “useful interventions” and connections to treatment are needed for the emergency department, according to Dr. Abouk and colleagues.

“This is the location where such programs may be the most effective,” they said in their report.

Future research should be done to determine whether removing gatekeepers increases the value of naloxone distribution policies, they concluded in the report.

Dr. Abouk had no disclosures. Co-authors on the study reported funding and conflict of interest disclosures related to the National Institute on Drug Abuse and the Centers for Disease Control and Prevention.

SOURCE: Abouk R, et al. JAMA Intern Med. 2019 May 6. doi:10.1001/jamainternmed.2019.0272.

State laws that give pharmacists direct authority to dispense naloxone are linked to significant drops in opioid-related fatal overdoses, investigators reported.

By contrast, state laws that stopped short of allowing pharmacists to directly dispense the opioid antagonist did not appear to impact mortality, according to the report, which appears in JAMA Internal Medicine (2019 May 6. doi: 10.1001/jamainternmed.2019.0272).

The report, based on state-level trends tracked from 2005 to 2016, indicates that fatal opioid overdoses fell by nearly one-third in states that adopted direct dispensing laws as compared with states that adopted other naloxone laws.

That finding suggests that the policy type determines whether a naloxone law is useful in combating fatal opioid overdoses, said Rahi Abouk, PhD, of William Paterson University, Wayne, N.J. and co-authors of the paper.

“Enabling distribution through various sources, or requiring gatekeepers, will not be as beneficial,” Dr. Abouk and co-authors said in their report.

The current rate of deaths from fentanyl, heroin, and prescription analgesic overdose has outpaced all previous drug epidemics on record, and even surpasses the number of deaths in the peak year of the HIV epidemic of the 1980s, Dr. Abouk and colleagues wrote in their paper.

The number of states with naloxone access laws grew from just 2 in 2005 to 47 by 2016, including 9 states that granted direct authority to pharmacists and 38 that granted indirect authority, according to the researchers.

The analysis of overdose trends from 2005 to 2016 was based on naloxone distribution data from state Medicaid agencies and opioid-related mortality data from a national statistics system. Forty percent of nonelderly adults with an opioid addiction are covered by Medicaid, the researchers said.

They found that naloxone laws granting pharmacists direct dispensing authority were linked to a drop in opioid deaths that increased in magnitude over time, according to researchers. The mean number of opioid deaths dropped by 27% in the second year after adoption of direct authority laws, relative to opioid deaths in states with indirect access laws, while in subsequent years, deaths dropped by 34%.

Emergency department visits related to opioids increased by 15% in direct authority states 3 or more years after adoption, as compared to states that did not adopt direct authority laws. According to investigators, that translated into 15 additional opioid-related emergency department visits each month.

That increase suggests that, alongside direct dispensing laws, “useful interventions” and connections to treatment are needed for the emergency department, according to Dr. Abouk and colleagues.

“This is the location where such programs may be the most effective,” they said in their report.

Future research should be done to determine whether removing gatekeepers increases the value of naloxone distribution policies, they concluded in the report.

Dr. Abouk had no disclosures. Co-authors on the study reported funding and conflict of interest disclosures related to the National Institute on Drug Abuse and the Centers for Disease Control and Prevention.

SOURCE: Abouk R, et al. JAMA Intern Med. 2019 May 6. doi:10.1001/jamainternmed.2019.0272.

State laws that give pharmacists direct authority to dispense naloxone are linked to significant drops in opioid-related fatal overdoses, investigators reported.

By contrast, state laws that stopped short of allowing pharmacists to directly dispense the opioid antagonist did not appear to impact mortality, according to the report, which appears in JAMA Internal Medicine (2019 May 6. doi: 10.1001/jamainternmed.2019.0272).

The report, based on state-level trends tracked from 2005 to 2016, indicates that fatal opioid overdoses fell by nearly one-third in states that adopted direct dispensing laws as compared with states that adopted other naloxone laws.

That finding suggests that the policy type determines whether a naloxone law is useful in combating fatal opioid overdoses, said Rahi Abouk, PhD, of William Paterson University, Wayne, N.J. and co-authors of the paper.

“Enabling distribution through various sources, or requiring gatekeepers, will not be as beneficial,” Dr. Abouk and co-authors said in their report.

The current rate of deaths from fentanyl, heroin, and prescription analgesic overdose has outpaced all previous drug epidemics on record, and even surpasses the number of deaths in the peak year of the HIV epidemic of the 1980s, Dr. Abouk and colleagues wrote in their paper.

The number of states with naloxone access laws grew from just 2 in 2005 to 47 by 2016, including 9 states that granted direct authority to pharmacists and 38 that granted indirect authority, according to the researchers.

The analysis of overdose trends from 2005 to 2016 was based on naloxone distribution data from state Medicaid agencies and opioid-related mortality data from a national statistics system. Forty percent of nonelderly adults with an opioid addiction are covered by Medicaid, the researchers said.

They found that naloxone laws granting pharmacists direct dispensing authority were linked to a drop in opioid deaths that increased in magnitude over time, according to researchers. The mean number of opioid deaths dropped by 27% in the second year after adoption of direct authority laws, relative to opioid deaths in states with indirect access laws, while in subsequent years, deaths dropped by 34%.

Emergency department visits related to opioids increased by 15% in direct authority states 3 or more years after adoption, as compared to states that did not adopt direct authority laws. According to investigators, that translated into 15 additional opioid-related emergency department visits each month.

That increase suggests that, alongside direct dispensing laws, “useful interventions” and connections to treatment are needed for the emergency department, according to Dr. Abouk and colleagues.

“This is the location where such programs may be the most effective,” they said in their report.

Future research should be done to determine whether removing gatekeepers increases the value of naloxone distribution policies, they concluded in the report.

Dr. Abouk had no disclosures. Co-authors on the study reported funding and conflict of interest disclosures related to the National Institute on Drug Abuse and the Centers for Disease Control and Prevention.

SOURCE: Abouk R, et al. JAMA Intern Med. 2019 May 6. doi:10.1001/jamainternmed.2019.0272.

Hepatologists and gastroenterologists see multiple and substantial barriers to the use of palliative care in patients with end-stage liver disease, results of a recent survey show.

©Lighthaunter/Thinkstock

Cultural factors, unrealistic expectations of the patient, lack of reimbursement, and competing demands for physicians’ time were some of the barriers to palliative care cited most frequently in the survey, said the researchers, in their report on the survey results that appears in Clinical Gastroenterology and Hepatology.

Moreover, most responding physicians said they felt end-of-life advance care planning discussions take place too late in the course of illness, according to Nneka N. Ufere, MD, of the Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, and co-authors of the report.

“Multiple interventions targeted at patients, caregivers, institutions, and clinicians are needed to overcome barriers to improve the delivery of high-quality palliative and end-of-life care for patients with end-stage liver disease,” the researchers said.

Specialty palliative care can improve quality of life for patients with life-limiting conditions such as end-stage liver disease, which is associated with poor quality of life and a median survival of just two years without liver transplant, the authors said.

Advance care planning, in which patients discuss goals and care preferences in light of the expected course of illness, was a “critical component” of palliative care that can improve the quality of end-of-life care, Dr. Ufere and co-authors said.

Unfortunately, palliative care planning services are underutilized in end-stage liver disease, studies show, while rates of timely advance care planning discussions are low.

To find out why, Dr. Ufere and colleagues asked 1,238 physicians to fill out a web-based questionnaire designed to assess their perceptions of barriers to use of palliative care and barriers to timely advance care planning discussions. A total of 396 physicians (32%) completed the survey between February and April 2018.

Sixty percent were transplant hepatologists, and 79% of the survey participants said they worked in a teaching hospital, according to Dr. Ufere and co-authors, who added that no respondents had formal palliative care training.

Almost all respondents (95%) agreed that centers providing care for end-stage liver disease patients should have palliative care services, and most (86%) said they thought such patients would benefit from palliative care earlier in the course of disease.

While most (84%) agreed that a hepatologist was the best provider to discuss advance care planning with the patient, only about one-quarter (27%) said the hepatologist was best suited to provide palliative care, while most (88%) said the palliative care specialist was best for that role.

When asked about patient and caregiver barriers, nearly all respondents (95%) agreed that cultural factors that influenced palliative care perception was an issue, while 93% said patients’ unrealistic expectations was an issue.

Clinician barriers that respondents perceived included competing demands for clinicians’ time, cited by 91%, fear that palliative care might destroy the patient’s hope, cited by 82%, and the misperception that palliative care starts when active treatment ends, cited by 81%.

One potential solution to the competing demands on clinicians’ time would be development of “collaborative care models” between palliative care and hepatology services, according to Dr. Ufere and co-authors.

“Outpatient specialty palliative care visits, ideally temporally coordinated with the hepatology visits, can play a role not only in attending to symptom assessment and ACP, but also in addressing important psychosocial aspects of care, such as patient coping and well-being,” they said in their report on the survey.

Institutional barriers of note included limited reimbursement for time spent providing palliative care, cited by 76% and lack of a palliative care service, cited by nearly half (46%).

Some of the most commonly affirmed barriers to timely advance care planning discussions included insufficient training in end-of-life communication issues, and insufficient training in cultural competency issues related to the discussions.

In terms of timeliness, only 17% said advance care planning discussions happen at the right time, while 81% said they happen too late, investigators found.

Funding for the research came from the National Institutes of Health. The authors had no disclosures or conflicts of interest related to the report.

SOURCE: Ufere NN, et al. Clin Gastroenterol Hepatol. 2019 Mar 15. doi: 10.1016/j.cgh.2019.03.022.

Hepatologists and gastroenterologists see multiple and substantial barriers to the use of palliative care in patients with end-stage liver disease, results of a recent survey show.

©Lighthaunter/Thinkstock

Cultural factors, unrealistic expectations of the patient, lack of reimbursement, and competing demands for physicians’ time were some of the barriers to palliative care cited most frequently in the survey, said the researchers, in their report on the survey results that appears in Clinical Gastroenterology and Hepatology.

Moreover, most responding physicians said they felt end-of-life advance care planning discussions take place too late in the course of illness, according to Nneka N. Ufere, MD, of the Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, and co-authors of the report.

“Multiple interventions targeted at patients, caregivers, institutions, and clinicians are needed to overcome barriers to improve the delivery of high-quality palliative and end-of-life care for patients with end-stage liver disease,” the researchers said.

Specialty palliative care can improve quality of life for patients with life-limiting conditions such as end-stage liver disease, which is associated with poor quality of life and a median survival of just two years without liver transplant, the authors said.

Advance care planning, in which patients discuss goals and care preferences in light of the expected course of illness, was a “critical component” of palliative care that can improve the quality of end-of-life care, Dr. Ufere and co-authors said.

Unfortunately, palliative care planning services are underutilized in end-stage liver disease, studies show, while rates of timely advance care planning discussions are low.

To find out why, Dr. Ufere and colleagues asked 1,238 physicians to fill out a web-based questionnaire designed to assess their perceptions of barriers to use of palliative care and barriers to timely advance care planning discussions. A total of 396 physicians (32%) completed the survey between February and April 2018.

Sixty percent were transplant hepatologists, and 79% of the survey participants said they worked in a teaching hospital, according to Dr. Ufere and co-authors, who added that no respondents had formal palliative care training.

Almost all respondents (95%) agreed that centers providing care for end-stage liver disease patients should have palliative care services, and most (86%) said they thought such patients would benefit from palliative care earlier in the course of disease.

While most (84%) agreed that a hepatologist was the best provider to discuss advance care planning with the patient, only about one-quarter (27%) said the hepatologist was best suited to provide palliative care, while most (88%) said the palliative care specialist was best for that role.

When asked about patient and caregiver barriers, nearly all respondents (95%) agreed that cultural factors that influenced palliative care perception was an issue, while 93% said patients’ unrealistic expectations was an issue.

Clinician barriers that respondents perceived included competing demands for clinicians’ time, cited by 91%, fear that palliative care might destroy the patient’s hope, cited by 82%, and the misperception that palliative care starts when active treatment ends, cited by 81%.

One potential solution to the competing demands on clinicians’ time would be development of “collaborative care models” between palliative care and hepatology services, according to Dr. Ufere and co-authors.

“Outpatient specialty palliative care visits, ideally temporally coordinated with the hepatology visits, can play a role not only in attending to symptom assessment and ACP, but also in addressing important psychosocial aspects of care, such as patient coping and well-being,” they said in their report on the survey.

Institutional barriers of note included limited reimbursement for time spent providing palliative care, cited by 76% and lack of a palliative care service, cited by nearly half (46%).

Some of the most commonly affirmed barriers to timely advance care planning discussions included insufficient training in end-of-life communication issues, and insufficient training in cultural competency issues related to the discussions.

In terms of timeliness, only 17% said advance care planning discussions happen at the right time, while 81% said they happen too late, investigators found.

Funding for the research came from the National Institutes of Health. The authors had no disclosures or conflicts of interest related to the report.

SOURCE: Ufere NN, et al. Clin Gastroenterol Hepatol. 2019 Mar 15. doi: 10.1016/j.cgh.2019.03.022.

Hepatologists and gastroenterologists see multiple and substantial barriers to the use of palliative care in patients with end-stage liver disease, results of a recent survey show.

©Lighthaunter/Thinkstock

Cultural factors, unrealistic expectations of the patient, lack of reimbursement, and competing demands for physicians’ time were some of the barriers to palliative care cited most frequently in the survey, said the researchers, in their report on the survey results that appears in Clinical Gastroenterology and Hepatology.

Moreover, most responding physicians said they felt end-of-life advance care planning discussions take place too late in the course of illness, according to Nneka N. Ufere, MD, of the Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, and co-authors of the report.

“Multiple interventions targeted at patients, caregivers, institutions, and clinicians are needed to overcome barriers to improve the delivery of high-quality palliative and end-of-life care for patients with end-stage liver disease,” the researchers said.

Specialty palliative care can improve quality of life for patients with life-limiting conditions such as end-stage liver disease, which is associated with poor quality of life and a median survival of just two years without liver transplant, the authors said.

Advance care planning, in which patients discuss goals and care preferences in light of the expected course of illness, was a “critical component” of palliative care that can improve the quality of end-of-life care, Dr. Ufere and co-authors said.

Unfortunately, palliative care planning services are underutilized in end-stage liver disease, studies show, while rates of timely advance care planning discussions are low.

To find out why, Dr. Ufere and colleagues asked 1,238 physicians to fill out a web-based questionnaire designed to assess their perceptions of barriers to use of palliative care and barriers to timely advance care planning discussions. A total of 396 physicians (32%) completed the survey between February and April 2018.

Sixty percent were transplant hepatologists, and 79% of the survey participants said they worked in a teaching hospital, according to Dr. Ufere and co-authors, who added that no respondents had formal palliative care training.

Almost all respondents (95%) agreed that centers providing care for end-stage liver disease patients should have palliative care services, and most (86%) said they thought such patients would benefit from palliative care earlier in the course of disease.

While most (84%) agreed that a hepatologist was the best provider to discuss advance care planning with the patient, only about one-quarter (27%) said the hepatologist was best suited to provide palliative care, while most (88%) said the palliative care specialist was best for that role.

When asked about patient and caregiver barriers, nearly all respondents (95%) agreed that cultural factors that influenced palliative care perception was an issue, while 93% said patients’ unrealistic expectations was an issue.

Clinician barriers that respondents perceived included competing demands for clinicians’ time, cited by 91%, fear that palliative care might destroy the patient’s hope, cited by 82%, and the misperception that palliative care starts when active treatment ends, cited by 81%.

One potential solution to the competing demands on clinicians’ time would be development of “collaborative care models” between palliative care and hepatology services, according to Dr. Ufere and co-authors.

“Outpatient specialty palliative care visits, ideally temporally coordinated with the hepatology visits, can play a role not only in attending to symptom assessment and ACP, but also in addressing important psychosocial aspects of care, such as patient coping and well-being,” they said in their report on the survey.

Institutional barriers of note included limited reimbursement for time spent providing palliative care, cited by 76% and lack of a palliative care service, cited by nearly half (46%).

Some of the most commonly affirmed barriers to timely advance care planning discussions included insufficient training in end-of-life communication issues, and insufficient training in cultural competency issues related to the discussions.

In terms of timeliness, only 17% said advance care planning discussions happen at the right time, while 81% said they happen too late, investigators found.

Funding for the research came from the National Institutes of Health. The authors had no disclosures or conflicts of interest related to the report.

SOURCE: Ufere NN, et al. Clin Gastroenterol Hepatol. 2019 Mar 15. doi: 10.1016/j.cgh.2019.03.022.