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Oligoclonal bands, initial seizures increase risk of post-ADEM epilepsy in children
BERLIN – Children with acute disseminated encephalomyelitis have a significantly increased risk of subsequent epilepsy when it occurs with oligoclonal bands in cerebrospinal fluid and seizures at presentation, Thomas Rossor, MD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
But fortunately, the seizures of postacute disseminated encephalomyelitis (post-ADEM) epilepsy are relatively easy to control and not clinically devastating, said Dr. Rossor of Great Ormond Street Hospital, London.
Of the 12 who developed epilepsy in Dr. Rossor’s retrospective, multicenter review of 74 children with ADEM, 11 were well controlled on one drug and 1 on two drugs.
Pediatric ADEM is usually monophasic with good clinical outcome, he said. But a benign course is not set in stone: Up to 40% of children experience seizures during the acute presentation. “In contrast,” Dr. Rossor said, “adult patients with relapsing-remitting multiple sclerosis have the same risk of developing epilepsy as the general population.” Among adults with cortical encephalitis, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been associated with seizures and the need for antiepileptic medications, he added.
That finding was part of what spurred Dr. Rossor’s study, which aimed to identify predictors of relapse and post-ADEM epilepsy in children. The patients in the review had a median age of 4.5 years. All were tested for anti-MOG antibodies, and most (about 68%) were positive. Oligoclonal bands in cerebrospinal fluid (CSF) occurred in 22%. The median follow-up period was 5 years.
A total of 41% (n = 31) relapsed after the initial acute phase. Among these, the final diagnosis included multiphasic disseminated encephalomyelitis (n = 19); ADEM-optic neuritis (n = 3); and neuromyelitis optica spectrum disorder (n = 6).
Of the 74 patients, 16 (22%) had seizures during the acute phase, and 12 (16%) developed post-ADEM epilepsy at a median of 3 months. The most common clinical characteristics with post-ADEM epilepsy included oligoclonal bands (57% vs. 13%), anti-MOG antibodies (92% vs. 16%), and seizures at presentation (50% vs. 16%). When these were entered into a regression model, oligoclonal bands and initial seizures significantly predicted epilepsy, increasing the risk by 20.7 and 13.5 times, respectively.
Since relapse is known to be associated with post-ADEM epilepsy, Dr. Rossor first looked at relapse risk. He conducted a multivariate analysis that included several clinical characteristics: age, prodrome, increased CSF white cells and protein, oligoclonal bands, anti-MOG antibodies, and seizures both at presentation and after the acute phase.
Anti-MOG antibodies were significantly more common among the relapsed patients than among the monophasic patients (87% vs. 53%). Seizures at presentation also were more common among the relapsed patients (32% vs. 14%). These two factors were entered into a binary regression analysis; only anti-MOG antibodies remained significantly associated with relapse, increasing the risk fivefold (odds ratio = 5.4; P = .007).
Anti-MOG antibodies also were associated with both earlier and more relapses. Overall, 40% of anti–MOG-antibody–positive patients relapsed by 24 months. In contrast, only 20% of anti–MOG-antibody–negative patients had relapsed by 24 months, and this number remained steady throughout the follow-up period.
By 96 months, almost all the anti–MOG-antibody–positive patients had relapsed, and some experienced many relapses. “In the antibody-negative group, four patients did relapse, but they had relatively few relapses. In the antibody-positive group, some had relatively few relapses, but several had 15, 20, or 25 clinical relapses in the follow-up period,” he said.
Dr. Rossor and his coauthors had no financial disclosures.
SOURCE: Rossor T et al. Mult Scler. 2018;24(Suppl 2):27. Abstract 62.
BERLIN – Children with acute disseminated encephalomyelitis have a significantly increased risk of subsequent epilepsy when it occurs with oligoclonal bands in cerebrospinal fluid and seizures at presentation, Thomas Rossor, MD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
But fortunately, the seizures of postacute disseminated encephalomyelitis (post-ADEM) epilepsy are relatively easy to control and not clinically devastating, said Dr. Rossor of Great Ormond Street Hospital, London.
Of the 12 who developed epilepsy in Dr. Rossor’s retrospective, multicenter review of 74 children with ADEM, 11 were well controlled on one drug and 1 on two drugs.
Pediatric ADEM is usually monophasic with good clinical outcome, he said. But a benign course is not set in stone: Up to 40% of children experience seizures during the acute presentation. “In contrast,” Dr. Rossor said, “adult patients with relapsing-remitting multiple sclerosis have the same risk of developing epilepsy as the general population.” Among adults with cortical encephalitis, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been associated with seizures and the need for antiepileptic medications, he added.
That finding was part of what spurred Dr. Rossor’s study, which aimed to identify predictors of relapse and post-ADEM epilepsy in children. The patients in the review had a median age of 4.5 years. All were tested for anti-MOG antibodies, and most (about 68%) were positive. Oligoclonal bands in cerebrospinal fluid (CSF) occurred in 22%. The median follow-up period was 5 years.
A total of 41% (n = 31) relapsed after the initial acute phase. Among these, the final diagnosis included multiphasic disseminated encephalomyelitis (n = 19); ADEM-optic neuritis (n = 3); and neuromyelitis optica spectrum disorder (n = 6).
Of the 74 patients, 16 (22%) had seizures during the acute phase, and 12 (16%) developed post-ADEM epilepsy at a median of 3 months. The most common clinical characteristics with post-ADEM epilepsy included oligoclonal bands (57% vs. 13%), anti-MOG antibodies (92% vs. 16%), and seizures at presentation (50% vs. 16%). When these were entered into a regression model, oligoclonal bands and initial seizures significantly predicted epilepsy, increasing the risk by 20.7 and 13.5 times, respectively.
Since relapse is known to be associated with post-ADEM epilepsy, Dr. Rossor first looked at relapse risk. He conducted a multivariate analysis that included several clinical characteristics: age, prodrome, increased CSF white cells and protein, oligoclonal bands, anti-MOG antibodies, and seizures both at presentation and after the acute phase.
Anti-MOG antibodies were significantly more common among the relapsed patients than among the monophasic patients (87% vs. 53%). Seizures at presentation also were more common among the relapsed patients (32% vs. 14%). These two factors were entered into a binary regression analysis; only anti-MOG antibodies remained significantly associated with relapse, increasing the risk fivefold (odds ratio = 5.4; P = .007).
Anti-MOG antibodies also were associated with both earlier and more relapses. Overall, 40% of anti–MOG-antibody–positive patients relapsed by 24 months. In contrast, only 20% of anti–MOG-antibody–negative patients had relapsed by 24 months, and this number remained steady throughout the follow-up period.
By 96 months, almost all the anti–MOG-antibody–positive patients had relapsed, and some experienced many relapses. “In the antibody-negative group, four patients did relapse, but they had relatively few relapses. In the antibody-positive group, some had relatively few relapses, but several had 15, 20, or 25 clinical relapses in the follow-up period,” he said.
Dr. Rossor and his coauthors had no financial disclosures.
SOURCE: Rossor T et al. Mult Scler. 2018;24(Suppl 2):27. Abstract 62.
BERLIN – Children with acute disseminated encephalomyelitis have a significantly increased risk of subsequent epilepsy when it occurs with oligoclonal bands in cerebrospinal fluid and seizures at presentation, Thomas Rossor, MD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
But fortunately, the seizures of postacute disseminated encephalomyelitis (post-ADEM) epilepsy are relatively easy to control and not clinically devastating, said Dr. Rossor of Great Ormond Street Hospital, London.
Of the 12 who developed epilepsy in Dr. Rossor’s retrospective, multicenter review of 74 children with ADEM, 11 were well controlled on one drug and 1 on two drugs.
Pediatric ADEM is usually monophasic with good clinical outcome, he said. But a benign course is not set in stone: Up to 40% of children experience seizures during the acute presentation. “In contrast,” Dr. Rossor said, “adult patients with relapsing-remitting multiple sclerosis have the same risk of developing epilepsy as the general population.” Among adults with cortical encephalitis, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been associated with seizures and the need for antiepileptic medications, he added.
That finding was part of what spurred Dr. Rossor’s study, which aimed to identify predictors of relapse and post-ADEM epilepsy in children. The patients in the review had a median age of 4.5 years. All were tested for anti-MOG antibodies, and most (about 68%) were positive. Oligoclonal bands in cerebrospinal fluid (CSF) occurred in 22%. The median follow-up period was 5 years.
A total of 41% (n = 31) relapsed after the initial acute phase. Among these, the final diagnosis included multiphasic disseminated encephalomyelitis (n = 19); ADEM-optic neuritis (n = 3); and neuromyelitis optica spectrum disorder (n = 6).
Of the 74 patients, 16 (22%) had seizures during the acute phase, and 12 (16%) developed post-ADEM epilepsy at a median of 3 months. The most common clinical characteristics with post-ADEM epilepsy included oligoclonal bands (57% vs. 13%), anti-MOG antibodies (92% vs. 16%), and seizures at presentation (50% vs. 16%). When these were entered into a regression model, oligoclonal bands and initial seizures significantly predicted epilepsy, increasing the risk by 20.7 and 13.5 times, respectively.
Since relapse is known to be associated with post-ADEM epilepsy, Dr. Rossor first looked at relapse risk. He conducted a multivariate analysis that included several clinical characteristics: age, prodrome, increased CSF white cells and protein, oligoclonal bands, anti-MOG antibodies, and seizures both at presentation and after the acute phase.
Anti-MOG antibodies were significantly more common among the relapsed patients than among the monophasic patients (87% vs. 53%). Seizures at presentation also were more common among the relapsed patients (32% vs. 14%). These two factors were entered into a binary regression analysis; only anti-MOG antibodies remained significantly associated with relapse, increasing the risk fivefold (odds ratio = 5.4; P = .007).
Anti-MOG antibodies also were associated with both earlier and more relapses. Overall, 40% of anti–MOG-antibody–positive patients relapsed by 24 months. In contrast, only 20% of anti–MOG-antibody–negative patients had relapsed by 24 months, and this number remained steady throughout the follow-up period.
By 96 months, almost all the anti–MOG-antibody–positive patients had relapsed, and some experienced many relapses. “In the antibody-negative group, four patients did relapse, but they had relatively few relapses. In the antibody-positive group, some had relatively few relapses, but several had 15, 20, or 25 clinical relapses in the follow-up period,” he said.
Dr. Rossor and his coauthors had no financial disclosures.
SOURCE: Rossor T et al. Mult Scler. 2018;24(Suppl 2):27. Abstract 62.
REPORTING FROM ECTRIMS 2018
Key clinical point: .
Major finding: Oligoclonal bands in CSF increased the risk of post-ADEM epilepsy by more than 20 times.
Study details: The retrospective cohort review comprised 74 children.
Disclosures: Dr. Rossor and his coauthors had no financial disclosures.
Source: Rossor T et al. Mult Scler. 2018;24(Suppl 2):27. Abstract 62.
Revamped MS criteria boost pediatric diagnoses
BERLIN –
The increased accuracy largely hinged on a positive finding of oligoclonal bands in cerebrospinal fluid – a diagnostic hallmark that was not included in the earlier criteria, Georgina Arrambide, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“Application to children of the new diagnostic criteria is limited,” said Dr. Arrambide, of the University Hospital Vall d’Hebron Multiple Sclerosis Centre of Catalonia, Barcelona. “And there are still some uncertainties with regard to fluid biomarkers and how they predict or confirm a diagnosis of MS in children, and also their relationship to the disease evolution.”
The updated McDonald criteria are intended to boost early, definitive MS diagnosis, leading to earlier initiation of therapy. They are intended primarily for patients aged 11 years and older who present with a typical clinically isolated syndrome and high probability of MS (Lancet Neurol. 2018;17[2]:162-73).
Dr. Arrambide and her colleagues used the revamped criteria to reassess MS diagnoses in a prospective Spanish cohort of children who experienced an acute first demyelinating event and were diagnosed with the 2010 criteria. The Kids-METOMS-MOGBCN Study enrolls children aged younger than 18 years within 1 year of a first acute demyelinating episode. It includes demographic, clinical, and imaging data, as well as data on oligoclonal bands and antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MoG). Of these fluid biomarkers, only oligoclonal bands are included in the new McDonald criteria.
The 55 children in Dr. Arrambide’s analysis were followed for a mean of 16 months. They included 25 (45%) girls with an overall median age of 6 years at the first acute event. Oligoclonal bands were present in 56%, and both anti-MoG and anti–aquaporin-4 antibodies in 82%.
All children had abnormal brain MRI at baseline, with about 33% having gadolinium-enhancing brain lesions. Spinal cord MRI was abnormal in 50%, with 39% having gadolinium-enhancing lesions. According to the 2010 criteria, only three had a definitive MS diagnosis at baseline. The diagnosis was acute disseminated encephalomyelitis in 51%, clinically isolated syndrome in 31%, radiologically isolated syndrome in 2%, and nonencephalopathic disseminated encephalomyelitis in the remainder.
At baseline, three of those had a definitive MS diagnosis, displaying dissemination in both space and time as required by both the 2010 and 2017 criteria. The addition of oligoclonal band positivity added one more patient over the 2010 criteria, and assessing the cohort with the complete 2017 criteria added three more definitive diagnoses. This was a significant increase in definitive MS diagnoses when compared against the earlier criteria (70% vs. 30%).
Diagnoses changed in 10 other patients during follow-up. The single patient with radiologically isolated syndrome was definitively diagnosed with MS. Of the seven with clinically isolated syndrome, six were diagnosed with MS and one with a relapsing optic neuritis. Of the 28 with a nonencephalopathic encephalitis, 2 were diagnosed with optic neuritis.
The study also confirmed the benefit of adding oligoclonal bands as a diagnostic marker in children. Of those with an MS diagnosis at last follow-up, 71% were positive for the cerebrospinal fluid finding, compared with just 4% of those with a non-MS diagnosis. However, none of those children had anti-MoG antibodies, compared with 58% of those with a non-MS diagnosis. None of the patients were positive for anti–aquaporin-4, regardless of diagnosis.
That finding does not necessarily mean that the absence of anti-MoG antibodies can rule out an MS diagnosis in children, Dr. Arrambide cautioned. Nevertheless, the finding is a useful clinical marker during a diagnostic work-up.
“The presence of oligoclonal bands and the absence of MOG-IgG are both useful biomarkers when evaluating the risk of MS in children with a first demyelinating event,” she said.
She disclosed financial relationships with several pharmaceutical companies.
SOURCE: Arrambide G et al. ECTRIMS 2018, Abstract 64
BERLIN –
The increased accuracy largely hinged on a positive finding of oligoclonal bands in cerebrospinal fluid – a diagnostic hallmark that was not included in the earlier criteria, Georgina Arrambide, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“Application to children of the new diagnostic criteria is limited,” said Dr. Arrambide, of the University Hospital Vall d’Hebron Multiple Sclerosis Centre of Catalonia, Barcelona. “And there are still some uncertainties with regard to fluid biomarkers and how they predict or confirm a diagnosis of MS in children, and also their relationship to the disease evolution.”
The updated McDonald criteria are intended to boost early, definitive MS diagnosis, leading to earlier initiation of therapy. They are intended primarily for patients aged 11 years and older who present with a typical clinically isolated syndrome and high probability of MS (Lancet Neurol. 2018;17[2]:162-73).
Dr. Arrambide and her colleagues used the revamped criteria to reassess MS diagnoses in a prospective Spanish cohort of children who experienced an acute first demyelinating event and were diagnosed with the 2010 criteria. The Kids-METOMS-MOGBCN Study enrolls children aged younger than 18 years within 1 year of a first acute demyelinating episode. It includes demographic, clinical, and imaging data, as well as data on oligoclonal bands and antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MoG). Of these fluid biomarkers, only oligoclonal bands are included in the new McDonald criteria.
The 55 children in Dr. Arrambide’s analysis were followed for a mean of 16 months. They included 25 (45%) girls with an overall median age of 6 years at the first acute event. Oligoclonal bands were present in 56%, and both anti-MoG and anti–aquaporin-4 antibodies in 82%.
All children had abnormal brain MRI at baseline, with about 33% having gadolinium-enhancing brain lesions. Spinal cord MRI was abnormal in 50%, with 39% having gadolinium-enhancing lesions. According to the 2010 criteria, only three had a definitive MS diagnosis at baseline. The diagnosis was acute disseminated encephalomyelitis in 51%, clinically isolated syndrome in 31%, radiologically isolated syndrome in 2%, and nonencephalopathic disseminated encephalomyelitis in the remainder.
At baseline, three of those had a definitive MS diagnosis, displaying dissemination in both space and time as required by both the 2010 and 2017 criteria. The addition of oligoclonal band positivity added one more patient over the 2010 criteria, and assessing the cohort with the complete 2017 criteria added three more definitive diagnoses. This was a significant increase in definitive MS diagnoses when compared against the earlier criteria (70% vs. 30%).
Diagnoses changed in 10 other patients during follow-up. The single patient with radiologically isolated syndrome was definitively diagnosed with MS. Of the seven with clinically isolated syndrome, six were diagnosed with MS and one with a relapsing optic neuritis. Of the 28 with a nonencephalopathic encephalitis, 2 were diagnosed with optic neuritis.
The study also confirmed the benefit of adding oligoclonal bands as a diagnostic marker in children. Of those with an MS diagnosis at last follow-up, 71% were positive for the cerebrospinal fluid finding, compared with just 4% of those with a non-MS diagnosis. However, none of those children had anti-MoG antibodies, compared with 58% of those with a non-MS diagnosis. None of the patients were positive for anti–aquaporin-4, regardless of diagnosis.
That finding does not necessarily mean that the absence of anti-MoG antibodies can rule out an MS diagnosis in children, Dr. Arrambide cautioned. Nevertheless, the finding is a useful clinical marker during a diagnostic work-up.
“The presence of oligoclonal bands and the absence of MOG-IgG are both useful biomarkers when evaluating the risk of MS in children with a first demyelinating event,” she said.
She disclosed financial relationships with several pharmaceutical companies.
SOURCE: Arrambide G et al. ECTRIMS 2018, Abstract 64
BERLIN –
The increased accuracy largely hinged on a positive finding of oligoclonal bands in cerebrospinal fluid – a diagnostic hallmark that was not included in the earlier criteria, Georgina Arrambide, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
“Application to children of the new diagnostic criteria is limited,” said Dr. Arrambide, of the University Hospital Vall d’Hebron Multiple Sclerosis Centre of Catalonia, Barcelona. “And there are still some uncertainties with regard to fluid biomarkers and how they predict or confirm a diagnosis of MS in children, and also their relationship to the disease evolution.”
The updated McDonald criteria are intended to boost early, definitive MS diagnosis, leading to earlier initiation of therapy. They are intended primarily for patients aged 11 years and older who present with a typical clinically isolated syndrome and high probability of MS (Lancet Neurol. 2018;17[2]:162-73).
Dr. Arrambide and her colleagues used the revamped criteria to reassess MS diagnoses in a prospective Spanish cohort of children who experienced an acute first demyelinating event and were diagnosed with the 2010 criteria. The Kids-METOMS-MOGBCN Study enrolls children aged younger than 18 years within 1 year of a first acute demyelinating episode. It includes demographic, clinical, and imaging data, as well as data on oligoclonal bands and antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein (MoG). Of these fluid biomarkers, only oligoclonal bands are included in the new McDonald criteria.
The 55 children in Dr. Arrambide’s analysis were followed for a mean of 16 months. They included 25 (45%) girls with an overall median age of 6 years at the first acute event. Oligoclonal bands were present in 56%, and both anti-MoG and anti–aquaporin-4 antibodies in 82%.
All children had abnormal brain MRI at baseline, with about 33% having gadolinium-enhancing brain lesions. Spinal cord MRI was abnormal in 50%, with 39% having gadolinium-enhancing lesions. According to the 2010 criteria, only three had a definitive MS diagnosis at baseline. The diagnosis was acute disseminated encephalomyelitis in 51%, clinically isolated syndrome in 31%, radiologically isolated syndrome in 2%, and nonencephalopathic disseminated encephalomyelitis in the remainder.
At baseline, three of those had a definitive MS diagnosis, displaying dissemination in both space and time as required by both the 2010 and 2017 criteria. The addition of oligoclonal band positivity added one more patient over the 2010 criteria, and assessing the cohort with the complete 2017 criteria added three more definitive diagnoses. This was a significant increase in definitive MS diagnoses when compared against the earlier criteria (70% vs. 30%).
Diagnoses changed in 10 other patients during follow-up. The single patient with radiologically isolated syndrome was definitively diagnosed with MS. Of the seven with clinically isolated syndrome, six were diagnosed with MS and one with a relapsing optic neuritis. Of the 28 with a nonencephalopathic encephalitis, 2 were diagnosed with optic neuritis.
The study also confirmed the benefit of adding oligoclonal bands as a diagnostic marker in children. Of those with an MS diagnosis at last follow-up, 71% were positive for the cerebrospinal fluid finding, compared with just 4% of those with a non-MS diagnosis. However, none of those children had anti-MoG antibodies, compared with 58% of those with a non-MS diagnosis. None of the patients were positive for anti–aquaporin-4, regardless of diagnosis.
That finding does not necessarily mean that the absence of anti-MoG antibodies can rule out an MS diagnosis in children, Dr. Arrambide cautioned. Nevertheless, the finding is a useful clinical marker during a diagnostic work-up.
“The presence of oligoclonal bands and the absence of MOG-IgG are both useful biomarkers when evaluating the risk of MS in children with a first demyelinating event,” she said.
She disclosed financial relationships with several pharmaceutical companies.
SOURCE: Arrambide G et al. ECTRIMS 2018, Abstract 64
REPORTING FROM ECTRIMS 2018
Key clinical point: The revised McDonald criteria increased definitive multiple sclerosis diagnoses in children.
Major finding: The 2017 criteria boosted pediatric diagnostic accuracy by 40%.
Study details: The prospective cohort study comprised 55 patients.
Disclosures: Dr. Arrambide disclosed relationships with several pharmaceutical companies.
Source: Arrambide G et al. ECTRIMS 2018, Abstract 64.
For surgeons, 1 on-call night equals 3 sleep-disrupted nights
SAN DIEGO – Almost 70% of surgeons who pull in-house call duty may be sleep deprived, Jamie Jones Coleman, MD, said at the annual meeting of the American Association for the Surgery of Trauma.
Even extra sleep the night after call doesn’t even things out, said Dr. Coleman of the University of Colorado, Denver. Her prospective study found that it takes 3 nights for sleep patterns to return to normal – a potential problem for surgeons who have frequent on-call nights.
“Sleep deprivation slows reaction time, decreases fine motor coordination, and increases the risk of chronic disease,” said Dr. Coleman. “A single period of 24 hours without sleep results in a neurocognitive performance that’s similar to having a blood alcohol content of 0.1%. It’s also associated with decreased empathy and increased depression. We need to take this issue seriously.”
Dr. Coleman measured sleep hours and architecture on 17 surgeons over 3 months, collecting data on 1,421 nights. Each surgeon wore a biometric measuring device called “Whoop” for the entire study. Worn on the wrist, the device measures heart rate, heart rate variability, and movement 100 times per second. It also records sleep onset and termination and can determine stages of sleep (light, slow wave, and REM).
In addition to wearing the device, the subjects also recorded all of their call schedules. The study compared sleep patterns on pre-call day 1 to those on post-call days 1, 2, and 3. Acute sleep deprivation was defined as two or more cycles of slow-wave sleep before REM; chronic sleep deprivation was one or more cycles of REM before slow-wave sleep onset.
Most of the subjects (65%) were men; the mean age was 45 years. Of the 1,421 nights recorded, 227 were on-call. Surgeons were already getting fewer hours of sleep than generally recommended, averaging 6.5 hours excluding call nights.
Subjects tried to “catch up” on sleep the day after call, Dr. Coleman said. On the day before call, they recorded an average of 6.4 hours of sleep; that increased to about 7 hours on post-call day 1. On post-call day 2, the average sleep time was about 6.3 hours, and increased to 6.5 hours by the third day.
Most of these recovery nights (70%) had abnormal amounts of REM sleep; 56% had abnormal amounts of slow-wave sleep. The majority of subjects (65%) showed patterns that qualified as either acute or chronic sleep deprivation.
“A recent study of football players found that correcting sleep issues was associated with both decreased alcohol consumption and decreased injuries,” Dr. Coleman said. “Well, we are being injured too. Shouldn’t surgeons take this as seriously as people who throw a ball for a living?”
She had no financial disclosures.
[email protected]
SOURCE: Coleman JJ et al. AAST 2018, Abstract 29.
SAN DIEGO – Almost 70% of surgeons who pull in-house call duty may be sleep deprived, Jamie Jones Coleman, MD, said at the annual meeting of the American Association for the Surgery of Trauma.
Even extra sleep the night after call doesn’t even things out, said Dr. Coleman of the University of Colorado, Denver. Her prospective study found that it takes 3 nights for sleep patterns to return to normal – a potential problem for surgeons who have frequent on-call nights.
“Sleep deprivation slows reaction time, decreases fine motor coordination, and increases the risk of chronic disease,” said Dr. Coleman. “A single period of 24 hours without sleep results in a neurocognitive performance that’s similar to having a blood alcohol content of 0.1%. It’s also associated with decreased empathy and increased depression. We need to take this issue seriously.”
Dr. Coleman measured sleep hours and architecture on 17 surgeons over 3 months, collecting data on 1,421 nights. Each surgeon wore a biometric measuring device called “Whoop” for the entire study. Worn on the wrist, the device measures heart rate, heart rate variability, and movement 100 times per second. It also records sleep onset and termination and can determine stages of sleep (light, slow wave, and REM).
In addition to wearing the device, the subjects also recorded all of their call schedules. The study compared sleep patterns on pre-call day 1 to those on post-call days 1, 2, and 3. Acute sleep deprivation was defined as two or more cycles of slow-wave sleep before REM; chronic sleep deprivation was one or more cycles of REM before slow-wave sleep onset.
Most of the subjects (65%) were men; the mean age was 45 years. Of the 1,421 nights recorded, 227 were on-call. Surgeons were already getting fewer hours of sleep than generally recommended, averaging 6.5 hours excluding call nights.
Subjects tried to “catch up” on sleep the day after call, Dr. Coleman said. On the day before call, they recorded an average of 6.4 hours of sleep; that increased to about 7 hours on post-call day 1. On post-call day 2, the average sleep time was about 6.3 hours, and increased to 6.5 hours by the third day.
Most of these recovery nights (70%) had abnormal amounts of REM sleep; 56% had abnormal amounts of slow-wave sleep. The majority of subjects (65%) showed patterns that qualified as either acute or chronic sleep deprivation.
“A recent study of football players found that correcting sleep issues was associated with both decreased alcohol consumption and decreased injuries,” Dr. Coleman said. “Well, we are being injured too. Shouldn’t surgeons take this as seriously as people who throw a ball for a living?”
She had no financial disclosures.
[email protected]
SOURCE: Coleman JJ et al. AAST 2018, Abstract 29.
SAN DIEGO – Almost 70% of surgeons who pull in-house call duty may be sleep deprived, Jamie Jones Coleman, MD, said at the annual meeting of the American Association for the Surgery of Trauma.
Even extra sleep the night after call doesn’t even things out, said Dr. Coleman of the University of Colorado, Denver. Her prospective study found that it takes 3 nights for sleep patterns to return to normal – a potential problem for surgeons who have frequent on-call nights.
“Sleep deprivation slows reaction time, decreases fine motor coordination, and increases the risk of chronic disease,” said Dr. Coleman. “A single period of 24 hours without sleep results in a neurocognitive performance that’s similar to having a blood alcohol content of 0.1%. It’s also associated with decreased empathy and increased depression. We need to take this issue seriously.”
Dr. Coleman measured sleep hours and architecture on 17 surgeons over 3 months, collecting data on 1,421 nights. Each surgeon wore a biometric measuring device called “Whoop” for the entire study. Worn on the wrist, the device measures heart rate, heart rate variability, and movement 100 times per second. It also records sleep onset and termination and can determine stages of sleep (light, slow wave, and REM).
In addition to wearing the device, the subjects also recorded all of their call schedules. The study compared sleep patterns on pre-call day 1 to those on post-call days 1, 2, and 3. Acute sleep deprivation was defined as two or more cycles of slow-wave sleep before REM; chronic sleep deprivation was one or more cycles of REM before slow-wave sleep onset.
Most of the subjects (65%) were men; the mean age was 45 years. Of the 1,421 nights recorded, 227 were on-call. Surgeons were already getting fewer hours of sleep than generally recommended, averaging 6.5 hours excluding call nights.
Subjects tried to “catch up” on sleep the day after call, Dr. Coleman said. On the day before call, they recorded an average of 6.4 hours of sleep; that increased to about 7 hours on post-call day 1. On post-call day 2, the average sleep time was about 6.3 hours, and increased to 6.5 hours by the third day.
Most of these recovery nights (70%) had abnormal amounts of REM sleep; 56% had abnormal amounts of slow-wave sleep. The majority of subjects (65%) showed patterns that qualified as either acute or chronic sleep deprivation.
“A recent study of football players found that correcting sleep issues was associated with both decreased alcohol consumption and decreased injuries,” Dr. Coleman said. “Well, we are being injured too. Shouldn’t surgeons take this as seriously as people who throw a ball for a living?”
She had no financial disclosures.
[email protected]
SOURCE: Coleman JJ et al. AAST 2018, Abstract 29.
REPORTING FROM THE AAST ANNUAL MEETING
Key clinical point: On-call duty disrupts sleep for many surgeons.
Major finding: About 65% qualify as having acute or chronic sleep deprivation.
Study details: The prospective study involved 17 surgeons.
Disclosures: Dr. Coleman had no relevant financial disclosures.
Source: Coleman JJ et al. AAST 2018, Abstract 29.
The hidden cost of excellence
SAN DIEGO – Readiness and excellence in trauma services come at a high cost.
Level I trauma centers in Georgia lay out an average of $10 million each year to maintain the essential services necessary to operate at full throttle 24 hours a day, 7 days a week. At the Medical Center of Central Georgia, Macon, that amounts to about $4,480 per patient, Dennis W. Ashley, MD, said at the annual meeting of American Association for the Surgery of Trauma. The yearly tab comes to about $5 million for level II centers.
Medical staff pay was the biggest single driver of that cost, accounting for an average $5.5 million annually for level I centers and $3 million for level II centers.
“These readiness costs are incurred well before the first patient is even treated,” said Dr. Ashley, director of trauma and adult critical care at the Medical Center of Central Georgia. “These are costs required by trauma center regulations to maintain essential infrastructure – nonpatient care costs that the hospital would not have to pay if it were not a trauma center.”
Hospitals incur these costs to comply with standards outlined in “Resources for Optimal Care of the Injured Patient,” otherwise known as the “Orange Book.”
To assess these by center, the Georgia Trauma Commission created a cost-reporting survey that was distributed to the state’s 6 level I centers and 10 level II centers in 2017. The surveys examined 2016 costs, and were carried out in conjunction with independent financial reviews to guarantee accurate reporting. Data were gathered in four general areas: administrative/program support staff, clinical medical staff, in-house operating room, and outreach and education.
During 2016, the 16 centers treated a total of 24,488 trauma patients: 15,660 in level I centers and 8,828 in level II centers.
Overall, the six level I centers spent a total of about $60.5 million in 2017 on resource readiness expense. The 10 level II centers spent a total of about $51 million. In all, trauma center status costs these institutions more than $112 million that year.
Salary and benefits for clinical and medical staff were the biggest cost driver for both types of trauma centers. Level I centers laid out a total of $33.2 million – about $5.5 million for each center. Level II centers paid a total of $31.7 million – about $3.1 million each.
Administrative and program support staff comprised the next largest expense. Level I centers paid abut $21.6 million altogether – $3.6 million each. Level II centers paid $13.9 million – about $1.4 million each.
The cost of maintaining constant operating room coverage accounted for $4.9 million in the level I centers ($830,000 each), and $2.5 million in level II centers (about $252,000 each).
Outreach and education comprised the smallest portion of spending. This accounted for a total of about $700,000 for level I centers and $1 million for level II centers ($115,000 and $109,000, respectively).
Dr. Ashley further broke down each general category. In the administrative and program support bucket, trauma program managers and trauma coordinators were the main cost drivers for both types of center. Trauma managers cost a grand total of $1.56 million: $113,000 for each level I center and $88,169 for level II centers. Trauma coordinators cost a grand total of $921,800 and senior administrative support accounted for a total of about $590,000.
Program support staff consisted of physical, occupational, and speech therapists, as well as research coordinators and others. The big-ticket items here were case managers, and staff providing physical, occupational, and speech therapy. Each of those services cost a total of about $6 million for all centers (around $600,000 for each level I center and $240,000 for each level II center).
Staffing trauma surgery made up the bulk of costs for clinical medical staff (a total of almost $19 million), followed by orthopedics ($13.8 million) and neurosurgery ($6.5 million).
Education and outreach were comparatively poorly funded, Dr. Ashley said. “We should do a better job on this,” he noted. All the centers combined spent about $340,000 on injury prevention, for example. Educational programs for emergency department staff made up about $590,000, and for intensive care unit staff, the total tab was about $174,000.
The survey plainly shows the financial commitment necessary to maintain high-quality trauma care, he said. “The significant cost of trauma center readiness highlights the need for additional trauma funding.”
He had no financial disclosures.
[email protected]
SAN DIEGO – Readiness and excellence in trauma services come at a high cost.
Level I trauma centers in Georgia lay out an average of $10 million each year to maintain the essential services necessary to operate at full throttle 24 hours a day, 7 days a week. At the Medical Center of Central Georgia, Macon, that amounts to about $4,480 per patient, Dennis W. Ashley, MD, said at the annual meeting of American Association for the Surgery of Trauma. The yearly tab comes to about $5 million for level II centers.
Medical staff pay was the biggest single driver of that cost, accounting for an average $5.5 million annually for level I centers and $3 million for level II centers.
“These readiness costs are incurred well before the first patient is even treated,” said Dr. Ashley, director of trauma and adult critical care at the Medical Center of Central Georgia. “These are costs required by trauma center regulations to maintain essential infrastructure – nonpatient care costs that the hospital would not have to pay if it were not a trauma center.”
Hospitals incur these costs to comply with standards outlined in “Resources for Optimal Care of the Injured Patient,” otherwise known as the “Orange Book.”
To assess these by center, the Georgia Trauma Commission created a cost-reporting survey that was distributed to the state’s 6 level I centers and 10 level II centers in 2017. The surveys examined 2016 costs, and were carried out in conjunction with independent financial reviews to guarantee accurate reporting. Data were gathered in four general areas: administrative/program support staff, clinical medical staff, in-house operating room, and outreach and education.
During 2016, the 16 centers treated a total of 24,488 trauma patients: 15,660 in level I centers and 8,828 in level II centers.
Overall, the six level I centers spent a total of about $60.5 million in 2017 on resource readiness expense. The 10 level II centers spent a total of about $51 million. In all, trauma center status costs these institutions more than $112 million that year.
Salary and benefits for clinical and medical staff were the biggest cost driver for both types of trauma centers. Level I centers laid out a total of $33.2 million – about $5.5 million for each center. Level II centers paid a total of $31.7 million – about $3.1 million each.
Administrative and program support staff comprised the next largest expense. Level I centers paid abut $21.6 million altogether – $3.6 million each. Level II centers paid $13.9 million – about $1.4 million each.
The cost of maintaining constant operating room coverage accounted for $4.9 million in the level I centers ($830,000 each), and $2.5 million in level II centers (about $252,000 each).
Outreach and education comprised the smallest portion of spending. This accounted for a total of about $700,000 for level I centers and $1 million for level II centers ($115,000 and $109,000, respectively).
Dr. Ashley further broke down each general category. In the administrative and program support bucket, trauma program managers and trauma coordinators were the main cost drivers for both types of center. Trauma managers cost a grand total of $1.56 million: $113,000 for each level I center and $88,169 for level II centers. Trauma coordinators cost a grand total of $921,800 and senior administrative support accounted for a total of about $590,000.
Program support staff consisted of physical, occupational, and speech therapists, as well as research coordinators and others. The big-ticket items here were case managers, and staff providing physical, occupational, and speech therapy. Each of those services cost a total of about $6 million for all centers (around $600,000 for each level I center and $240,000 for each level II center).
Staffing trauma surgery made up the bulk of costs for clinical medical staff (a total of almost $19 million), followed by orthopedics ($13.8 million) and neurosurgery ($6.5 million).
Education and outreach were comparatively poorly funded, Dr. Ashley said. “We should do a better job on this,” he noted. All the centers combined spent about $340,000 on injury prevention, for example. Educational programs for emergency department staff made up about $590,000, and for intensive care unit staff, the total tab was about $174,000.
The survey plainly shows the financial commitment necessary to maintain high-quality trauma care, he said. “The significant cost of trauma center readiness highlights the need for additional trauma funding.”
He had no financial disclosures.
[email protected]
SAN DIEGO – Readiness and excellence in trauma services come at a high cost.
Level I trauma centers in Georgia lay out an average of $10 million each year to maintain the essential services necessary to operate at full throttle 24 hours a day, 7 days a week. At the Medical Center of Central Georgia, Macon, that amounts to about $4,480 per patient, Dennis W. Ashley, MD, said at the annual meeting of American Association for the Surgery of Trauma. The yearly tab comes to about $5 million for level II centers.
Medical staff pay was the biggest single driver of that cost, accounting for an average $5.5 million annually for level I centers and $3 million for level II centers.
“These readiness costs are incurred well before the first patient is even treated,” said Dr. Ashley, director of trauma and adult critical care at the Medical Center of Central Georgia. “These are costs required by trauma center regulations to maintain essential infrastructure – nonpatient care costs that the hospital would not have to pay if it were not a trauma center.”
Hospitals incur these costs to comply with standards outlined in “Resources for Optimal Care of the Injured Patient,” otherwise known as the “Orange Book.”
To assess these by center, the Georgia Trauma Commission created a cost-reporting survey that was distributed to the state’s 6 level I centers and 10 level II centers in 2017. The surveys examined 2016 costs, and were carried out in conjunction with independent financial reviews to guarantee accurate reporting. Data were gathered in four general areas: administrative/program support staff, clinical medical staff, in-house operating room, and outreach and education.
During 2016, the 16 centers treated a total of 24,488 trauma patients: 15,660 in level I centers and 8,828 in level II centers.
Overall, the six level I centers spent a total of about $60.5 million in 2017 on resource readiness expense. The 10 level II centers spent a total of about $51 million. In all, trauma center status costs these institutions more than $112 million that year.
Salary and benefits for clinical and medical staff were the biggest cost driver for both types of trauma centers. Level I centers laid out a total of $33.2 million – about $5.5 million for each center. Level II centers paid a total of $31.7 million – about $3.1 million each.
Administrative and program support staff comprised the next largest expense. Level I centers paid abut $21.6 million altogether – $3.6 million each. Level II centers paid $13.9 million – about $1.4 million each.
The cost of maintaining constant operating room coverage accounted for $4.9 million in the level I centers ($830,000 each), and $2.5 million in level II centers (about $252,000 each).
Outreach and education comprised the smallest portion of spending. This accounted for a total of about $700,000 for level I centers and $1 million for level II centers ($115,000 and $109,000, respectively).
Dr. Ashley further broke down each general category. In the administrative and program support bucket, trauma program managers and trauma coordinators were the main cost drivers for both types of center. Trauma managers cost a grand total of $1.56 million: $113,000 for each level I center and $88,169 for level II centers. Trauma coordinators cost a grand total of $921,800 and senior administrative support accounted for a total of about $590,000.
Program support staff consisted of physical, occupational, and speech therapists, as well as research coordinators and others. The big-ticket items here were case managers, and staff providing physical, occupational, and speech therapy. Each of those services cost a total of about $6 million for all centers (around $600,000 for each level I center and $240,000 for each level II center).
Staffing trauma surgery made up the bulk of costs for clinical medical staff (a total of almost $19 million), followed by orthopedics ($13.8 million) and neurosurgery ($6.5 million).
Education and outreach were comparatively poorly funded, Dr. Ashley said. “We should do a better job on this,” he noted. All the centers combined spent about $340,000 on injury prevention, for example. Educational programs for emergency department staff made up about $590,000, and for intensive care unit staff, the total tab was about $174,000.
The survey plainly shows the financial commitment necessary to maintain high-quality trauma care, he said. “The significant cost of trauma center readiness highlights the need for additional trauma funding.”
He had no financial disclosures.
[email protected]
REPORTING FROM THE AAST ANNUAL MEETING
Key clinical point: Meeting excellence requirements costs trauma centers millions of dollars.
Major finding: A level I center invests about $10 million annually to meet readiness requirements.
Study details: The Georgia survey queried six level I centers and 10 level II centers.
Disclosures: Dr. Ashley had no financial disclosures.
Source: Ashely DW et al. AAST 2018. Abstract 18.
Low-dose ketamine controls pain from severe chest injury, while sparing opioid consumption
SAN DIEGO – while reducing opioid consumption.
The anesthetic didn’t make much difference in pain control or opioid use overall in a randomized study of 93 patients with thoracic injury Nathan Kugler, MD, said at the annual meeting of the American Association for the Surgery of Trauma. But among severely injured patients, it cut the opioid mean equivalency dose by about 164 mg over the 48-hour infusion and by 328 mg over a mean hospital stay while maintaining pain control, said Dr. Kugler, a surgical resident at the Medical College of Wisconsin, Milwaukee.
“With increasing focus on multimodal pain strategies, opioid-based regimens continue to be the backbone of pain control,” he said. “We have used ketamine effectively for failure of maximum therapy and demonstrated an opioid-sparing effect.” This new research shows that the drug can be an effective adjunct for acute pain control for severely injured patients in the emergency setting.
The study recruited 93 patients with thoracic injury; they had a mean of six broken ribs, mostly caused by motor vehicle accidents. Most of the patients were male (75%), and their mean age was 46 years. The mean Injury Severity Score was about 15; about 30% had flail chest.
All patients received a standardized acute pain medication regime comprising acetaminophen, nonsteroidal anti-inflammatories, methocarbamol (Robaxin), and intravenous opioids. Regional therapies included rib block with an epidural catheter. In addition, they were randomized to placebo infusions or to 48 hours of IV ketamine at 2.5 mcg/kg per minute. “To put this in perspective, for a 70-kg patient, that is a mean of 10.5 mg/hour,” Dr. Kugler said.
The primary endpoint was a reduction of at least 2 points on an 11-point pain scale. Secondary endpoints included opioid use in oral morphine equivalents (OME); respiratory complications; and psychoactive events. The primary outcome was assessed with an area under the curve model.
In the overall group, there was no significant between-group difference in pain score. Nor were there differences in the total OME at 12-24 hours (184 mg ketamine vs. 230 mg placebo), or at 48 hours (86 vs. 113 mg).
Dr. Kugler also looked at these outcomes in patients who had only rib fractures independent of other chest injury. He saw no significant differences in pain scores or OME at 24 or 48 hours.
However, significant differences did emerge in the group of severely injured patients with an Injury Severity Score of more than 15. There were no differences in pain scores at either time point. However, ketamine allowed patients to achieve the same level of pain control with significantly less opioid medication. The OME at 12-24 hours was 50.5 mg vs 94 mg. At 24-48 hours, it was 87 mg vs. 64 mg.
This worked out to a mean OME savings of 148 mg over a patient’s entire hospitalization.
“We saw a very nice separation of opioid consumption that began early and continued to separate over the 48-hour infusion and even after it was discontinued,” Dr. Kugler said.
This benefit was achieved without any additional adverse events, he added. There were no significant differences in confusion; epidural placement; length of stay; respiratory event, sedation, hallucinations, delusions or disturbing dreams; or unplanned transfers to the ICU.
Dr. Kugler disclosed that he and primary investigator Thomas Carver, MD, also of the Medical College of Wisconsin, Milwaukee, are both paid consultants for InnoVital Systems.
SAN DIEGO – while reducing opioid consumption.
The anesthetic didn’t make much difference in pain control or opioid use overall in a randomized study of 93 patients with thoracic injury Nathan Kugler, MD, said at the annual meeting of the American Association for the Surgery of Trauma. But among severely injured patients, it cut the opioid mean equivalency dose by about 164 mg over the 48-hour infusion and by 328 mg over a mean hospital stay while maintaining pain control, said Dr. Kugler, a surgical resident at the Medical College of Wisconsin, Milwaukee.
“With increasing focus on multimodal pain strategies, opioid-based regimens continue to be the backbone of pain control,” he said. “We have used ketamine effectively for failure of maximum therapy and demonstrated an opioid-sparing effect.” This new research shows that the drug can be an effective adjunct for acute pain control for severely injured patients in the emergency setting.
The study recruited 93 patients with thoracic injury; they had a mean of six broken ribs, mostly caused by motor vehicle accidents. Most of the patients were male (75%), and their mean age was 46 years. The mean Injury Severity Score was about 15; about 30% had flail chest.
All patients received a standardized acute pain medication regime comprising acetaminophen, nonsteroidal anti-inflammatories, methocarbamol (Robaxin), and intravenous opioids. Regional therapies included rib block with an epidural catheter. In addition, they were randomized to placebo infusions or to 48 hours of IV ketamine at 2.5 mcg/kg per minute. “To put this in perspective, for a 70-kg patient, that is a mean of 10.5 mg/hour,” Dr. Kugler said.
The primary endpoint was a reduction of at least 2 points on an 11-point pain scale. Secondary endpoints included opioid use in oral morphine equivalents (OME); respiratory complications; and psychoactive events. The primary outcome was assessed with an area under the curve model.
In the overall group, there was no significant between-group difference in pain score. Nor were there differences in the total OME at 12-24 hours (184 mg ketamine vs. 230 mg placebo), or at 48 hours (86 vs. 113 mg).
Dr. Kugler also looked at these outcomes in patients who had only rib fractures independent of other chest injury. He saw no significant differences in pain scores or OME at 24 or 48 hours.
However, significant differences did emerge in the group of severely injured patients with an Injury Severity Score of more than 15. There were no differences in pain scores at either time point. However, ketamine allowed patients to achieve the same level of pain control with significantly less opioid medication. The OME at 12-24 hours was 50.5 mg vs 94 mg. At 24-48 hours, it was 87 mg vs. 64 mg.
This worked out to a mean OME savings of 148 mg over a patient’s entire hospitalization.
“We saw a very nice separation of opioid consumption that began early and continued to separate over the 48-hour infusion and even after it was discontinued,” Dr. Kugler said.
This benefit was achieved without any additional adverse events, he added. There were no significant differences in confusion; epidural placement; length of stay; respiratory event, sedation, hallucinations, delusions or disturbing dreams; or unplanned transfers to the ICU.
Dr. Kugler disclosed that he and primary investigator Thomas Carver, MD, also of the Medical College of Wisconsin, Milwaukee, are both paid consultants for InnoVital Systems.
SAN DIEGO – while reducing opioid consumption.
The anesthetic didn’t make much difference in pain control or opioid use overall in a randomized study of 93 patients with thoracic injury Nathan Kugler, MD, said at the annual meeting of the American Association for the Surgery of Trauma. But among severely injured patients, it cut the opioid mean equivalency dose by about 164 mg over the 48-hour infusion and by 328 mg over a mean hospital stay while maintaining pain control, said Dr. Kugler, a surgical resident at the Medical College of Wisconsin, Milwaukee.
“With increasing focus on multimodal pain strategies, opioid-based regimens continue to be the backbone of pain control,” he said. “We have used ketamine effectively for failure of maximum therapy and demonstrated an opioid-sparing effect.” This new research shows that the drug can be an effective adjunct for acute pain control for severely injured patients in the emergency setting.
The study recruited 93 patients with thoracic injury; they had a mean of six broken ribs, mostly caused by motor vehicle accidents. Most of the patients were male (75%), and their mean age was 46 years. The mean Injury Severity Score was about 15; about 30% had flail chest.
All patients received a standardized acute pain medication regime comprising acetaminophen, nonsteroidal anti-inflammatories, methocarbamol (Robaxin), and intravenous opioids. Regional therapies included rib block with an epidural catheter. In addition, they were randomized to placebo infusions or to 48 hours of IV ketamine at 2.5 mcg/kg per minute. “To put this in perspective, for a 70-kg patient, that is a mean of 10.5 mg/hour,” Dr. Kugler said.
The primary endpoint was a reduction of at least 2 points on an 11-point pain scale. Secondary endpoints included opioid use in oral morphine equivalents (OME); respiratory complications; and psychoactive events. The primary outcome was assessed with an area under the curve model.
In the overall group, there was no significant between-group difference in pain score. Nor were there differences in the total OME at 12-24 hours (184 mg ketamine vs. 230 mg placebo), or at 48 hours (86 vs. 113 mg).
Dr. Kugler also looked at these outcomes in patients who had only rib fractures independent of other chest injury. He saw no significant differences in pain scores or OME at 24 or 48 hours.
However, significant differences did emerge in the group of severely injured patients with an Injury Severity Score of more than 15. There were no differences in pain scores at either time point. However, ketamine allowed patients to achieve the same level of pain control with significantly less opioid medication. The OME at 12-24 hours was 50.5 mg vs 94 mg. At 24-48 hours, it was 87 mg vs. 64 mg.
This worked out to a mean OME savings of 148 mg over a patient’s entire hospitalization.
“We saw a very nice separation of opioid consumption that began early and continued to separate over the 48-hour infusion and even after it was discontinued,” Dr. Kugler said.
This benefit was achieved without any additional adverse events, he added. There were no significant differences in confusion; epidural placement; length of stay; respiratory event, sedation, hallucinations, delusions or disturbing dreams; or unplanned transfers to the ICU.
Dr. Kugler disclosed that he and primary investigator Thomas Carver, MD, also of the Medical College of Wisconsin, Milwaukee, are both paid consultants for InnoVital Systems.
REPORTING FROM THE AAST ANNUAL MEETING
Key clinical point: Low-dose ketamine controlled pain while reducing opioid use among patients with severe thoracic injury.
Major finding: Compared with placebo, ketamine reduced opioids conferred OME savings of 148 mg over a patient’s entire hospitalization.
Study details: The randomized study comprised 93 patients with thoracic injury.
Disclosures: Dr. Kugler disclosed that he and primary investigator Thomas Carver, MD, are both paid consultants for InnoVital Systems.
Source: Carver T et al. AAST 2018, Oral abstract 2
It may be time to rethink damage-control laparotomy
SAN ANTONIO – A , but it can cost fewer resources: fewer days in intensive care, fewer days on a ventilator, and a shorter overall length of stay.
Among damage-control abdominal trauma cases that could have been closed, definitive laparotomy (DEF) was associated with a 56% probability of major abdominal complications – very close to the probability associated with damage-control closure, John Harvin, MD, said at the annual meeting of the American Association for the Surgery of Trauma.
Definitive closure was also associated with about a 72% chance of more ventilator- and hospital-free days and a 77% chance of more ICU-free days than damage-control closure, said Dr. Harvin of the University of Texas, Austin.
“Our analysis tells us that there’s a minimal chance of reducing complications with a definitive laparotomy, compared to leaving them open, but this also comes with more than a 70% chance of having a shorter hospital staying and getting off the ventilator faster.”
The data from a 2-year quality review process reaffirms what trauma surgeons have been seeing, and reporting, since damage-control closure became more popular in the past decade, said Peter Rhee, MD, commenting on the study.
“There are three congregations in this faith of damage-control laparotomy,” said Dr. Rhee, a surgeon in Atlanta, Ga. “The first believes it should be the default for all these types of operations and that being preemptive is better than anything. The second believes that it doesn’t hurt the patient too much, and that it can be done when absolutely needed to save a life. The third belief is that there’s minimal data to support it, that it should rarely be used, and that it’s always costly. We all know that the pendulum of damage-control laparotomy is finally swinging back to the center.”
The study arose from an effort at the Red Duke Trauma Institute, Austin, Tex., to reduce its rate of damage-control laparotomy (DCL). Surgeons examined all emergent trauma laparotomies conducted from 2013 to 2015. They discussed each case and compared morbidity and mortality rates to a published control group. This work was published last year in the Journal of the American College of Surgeons.
By adopting this review procedure, the hospital was able to decrease its 39% DCL rate to 23% over 2 years (an absolute reduction of 68 cases) without any change in infection rates, fascial dehiscence, unplanned reoperation, or mortality. The improvements continued, Dr. Harvin noted, with a farther 17% reduction in DCL after the project concluded.
Dr. Harvin’s analysis looked at 44 of these procedures which, according to the adjudication panel, could have been managed by DEF. Each was matched to a DEF case, and the outcomes were calculated with a Bayesian statistical model.
The primary outcome was major abdominal complication, a composite measure of fascial dehiscence, organ or space surgical-site infection, reopening of fascia, and enteric suture line failure. Secondary outcomes were days off the ventilator and out of the ICU and hospital.
Of the 872 patients in the study, most (639; 73%) were managed by DEF; the rest (209; 24%) were managed by DCL. Of these, the panel agreed that 44 (22%) could have been safely closed at the time of surgery and survived at least 5 days. The propensity-matching scheme comprised 39 of these cases matched with 39 DEF cases.
Most were male (74%); the mean age was 38 years. Penetrating injuries were most common (54%). The abdominal Abbreviated Injury Score was 3. The mean Injury Severity Score was 22 in the DEF cases and 25 in the DCL cases, but this was not a significant difference. There were no differences in blood pressure at presentation or at the end of the surgery, no differences in blood transfusion needs, and no differences in body temperature.
A major abdominal complication occurred in 31% of the DEF cases and 21% of the DCL cases, a relative risk of 0.99. This amounted to a 56% posterior probability of a complication associated with DEF.
Comparing DCL cases with DEF cases, the mean number of hospital-free days was 15 vs.13; ICU-free days, 26 vs. 21; and ventilator-free days, 29 vs. 26. These differences amount to a 72% chance that DEL would result in more hospital-free days and more ventilator-free days, and a 77% chance that DEL would result in more ICU-free days.
The numbers underscore the need to rethink DCL for abdominal trauma, Dr. Rhee said.
“I too once believed in this procedure and used to do it all the time. After 2 decades, we now know that it contributed to the frozen bellies, abdominal wound hernias, fascial dehiscence, missed complications, and to the never-ending enteroatmospheric fistulas. If we want to reduce fistulas, we must first reduce damage-control laparotomy. Nurses will love you for not creating the narcotic-addicted, total parenteral nutrition–dependent patient with a fragrant open belly and a fistula.”
Neither Dr. Harvin nor Dr Rhee had any relevant financial disclosures.
SAN ANTONIO – A , but it can cost fewer resources: fewer days in intensive care, fewer days on a ventilator, and a shorter overall length of stay.
Among damage-control abdominal trauma cases that could have been closed, definitive laparotomy (DEF) was associated with a 56% probability of major abdominal complications – very close to the probability associated with damage-control closure, John Harvin, MD, said at the annual meeting of the American Association for the Surgery of Trauma.
Definitive closure was also associated with about a 72% chance of more ventilator- and hospital-free days and a 77% chance of more ICU-free days than damage-control closure, said Dr. Harvin of the University of Texas, Austin.
“Our analysis tells us that there’s a minimal chance of reducing complications with a definitive laparotomy, compared to leaving them open, but this also comes with more than a 70% chance of having a shorter hospital staying and getting off the ventilator faster.”
The data from a 2-year quality review process reaffirms what trauma surgeons have been seeing, and reporting, since damage-control closure became more popular in the past decade, said Peter Rhee, MD, commenting on the study.
“There are three congregations in this faith of damage-control laparotomy,” said Dr. Rhee, a surgeon in Atlanta, Ga. “The first believes it should be the default for all these types of operations and that being preemptive is better than anything. The second believes that it doesn’t hurt the patient too much, and that it can be done when absolutely needed to save a life. The third belief is that there’s minimal data to support it, that it should rarely be used, and that it’s always costly. We all know that the pendulum of damage-control laparotomy is finally swinging back to the center.”
The study arose from an effort at the Red Duke Trauma Institute, Austin, Tex., to reduce its rate of damage-control laparotomy (DCL). Surgeons examined all emergent trauma laparotomies conducted from 2013 to 2015. They discussed each case and compared morbidity and mortality rates to a published control group. This work was published last year in the Journal of the American College of Surgeons.
By adopting this review procedure, the hospital was able to decrease its 39% DCL rate to 23% over 2 years (an absolute reduction of 68 cases) without any change in infection rates, fascial dehiscence, unplanned reoperation, or mortality. The improvements continued, Dr. Harvin noted, with a farther 17% reduction in DCL after the project concluded.
Dr. Harvin’s analysis looked at 44 of these procedures which, according to the adjudication panel, could have been managed by DEF. Each was matched to a DEF case, and the outcomes were calculated with a Bayesian statistical model.
The primary outcome was major abdominal complication, a composite measure of fascial dehiscence, organ or space surgical-site infection, reopening of fascia, and enteric suture line failure. Secondary outcomes were days off the ventilator and out of the ICU and hospital.
Of the 872 patients in the study, most (639; 73%) were managed by DEF; the rest (209; 24%) were managed by DCL. Of these, the panel agreed that 44 (22%) could have been safely closed at the time of surgery and survived at least 5 days. The propensity-matching scheme comprised 39 of these cases matched with 39 DEF cases.
Most were male (74%); the mean age was 38 years. Penetrating injuries were most common (54%). The abdominal Abbreviated Injury Score was 3. The mean Injury Severity Score was 22 in the DEF cases and 25 in the DCL cases, but this was not a significant difference. There were no differences in blood pressure at presentation or at the end of the surgery, no differences in blood transfusion needs, and no differences in body temperature.
A major abdominal complication occurred in 31% of the DEF cases and 21% of the DCL cases, a relative risk of 0.99. This amounted to a 56% posterior probability of a complication associated with DEF.
Comparing DCL cases with DEF cases, the mean number of hospital-free days was 15 vs.13; ICU-free days, 26 vs. 21; and ventilator-free days, 29 vs. 26. These differences amount to a 72% chance that DEL would result in more hospital-free days and more ventilator-free days, and a 77% chance that DEL would result in more ICU-free days.
The numbers underscore the need to rethink DCL for abdominal trauma, Dr. Rhee said.
“I too once believed in this procedure and used to do it all the time. After 2 decades, we now know that it contributed to the frozen bellies, abdominal wound hernias, fascial dehiscence, missed complications, and to the never-ending enteroatmospheric fistulas. If we want to reduce fistulas, we must first reduce damage-control laparotomy. Nurses will love you for not creating the narcotic-addicted, total parenteral nutrition–dependent patient with a fragrant open belly and a fistula.”
Neither Dr. Harvin nor Dr Rhee had any relevant financial disclosures.
SAN ANTONIO – A , but it can cost fewer resources: fewer days in intensive care, fewer days on a ventilator, and a shorter overall length of stay.
Among damage-control abdominal trauma cases that could have been closed, definitive laparotomy (DEF) was associated with a 56% probability of major abdominal complications – very close to the probability associated with damage-control closure, John Harvin, MD, said at the annual meeting of the American Association for the Surgery of Trauma.
Definitive closure was also associated with about a 72% chance of more ventilator- and hospital-free days and a 77% chance of more ICU-free days than damage-control closure, said Dr. Harvin of the University of Texas, Austin.
“Our analysis tells us that there’s a minimal chance of reducing complications with a definitive laparotomy, compared to leaving them open, but this also comes with more than a 70% chance of having a shorter hospital staying and getting off the ventilator faster.”
The data from a 2-year quality review process reaffirms what trauma surgeons have been seeing, and reporting, since damage-control closure became more popular in the past decade, said Peter Rhee, MD, commenting on the study.
“There are three congregations in this faith of damage-control laparotomy,” said Dr. Rhee, a surgeon in Atlanta, Ga. “The first believes it should be the default for all these types of operations and that being preemptive is better than anything. The second believes that it doesn’t hurt the patient too much, and that it can be done when absolutely needed to save a life. The third belief is that there’s minimal data to support it, that it should rarely be used, and that it’s always costly. We all know that the pendulum of damage-control laparotomy is finally swinging back to the center.”
The study arose from an effort at the Red Duke Trauma Institute, Austin, Tex., to reduce its rate of damage-control laparotomy (DCL). Surgeons examined all emergent trauma laparotomies conducted from 2013 to 2015. They discussed each case and compared morbidity and mortality rates to a published control group. This work was published last year in the Journal of the American College of Surgeons.
By adopting this review procedure, the hospital was able to decrease its 39% DCL rate to 23% over 2 years (an absolute reduction of 68 cases) without any change in infection rates, fascial dehiscence, unplanned reoperation, or mortality. The improvements continued, Dr. Harvin noted, with a farther 17% reduction in DCL after the project concluded.
Dr. Harvin’s analysis looked at 44 of these procedures which, according to the adjudication panel, could have been managed by DEF. Each was matched to a DEF case, and the outcomes were calculated with a Bayesian statistical model.
The primary outcome was major abdominal complication, a composite measure of fascial dehiscence, organ or space surgical-site infection, reopening of fascia, and enteric suture line failure. Secondary outcomes were days off the ventilator and out of the ICU and hospital.
Of the 872 patients in the study, most (639; 73%) were managed by DEF; the rest (209; 24%) were managed by DCL. Of these, the panel agreed that 44 (22%) could have been safely closed at the time of surgery and survived at least 5 days. The propensity-matching scheme comprised 39 of these cases matched with 39 DEF cases.
Most were male (74%); the mean age was 38 years. Penetrating injuries were most common (54%). The abdominal Abbreviated Injury Score was 3. The mean Injury Severity Score was 22 in the DEF cases and 25 in the DCL cases, but this was not a significant difference. There were no differences in blood pressure at presentation or at the end of the surgery, no differences in blood transfusion needs, and no differences in body temperature.
A major abdominal complication occurred in 31% of the DEF cases and 21% of the DCL cases, a relative risk of 0.99. This amounted to a 56% posterior probability of a complication associated with DEF.
Comparing DCL cases with DEF cases, the mean number of hospital-free days was 15 vs.13; ICU-free days, 26 vs. 21; and ventilator-free days, 29 vs. 26. These differences amount to a 72% chance that DEL would result in more hospital-free days and more ventilator-free days, and a 77% chance that DEL would result in more ICU-free days.
The numbers underscore the need to rethink DCL for abdominal trauma, Dr. Rhee said.
“I too once believed in this procedure and used to do it all the time. After 2 decades, we now know that it contributed to the frozen bellies, abdominal wound hernias, fascial dehiscence, missed complications, and to the never-ending enteroatmospheric fistulas. If we want to reduce fistulas, we must first reduce damage-control laparotomy. Nurses will love you for not creating the narcotic-addicted, total parenteral nutrition–dependent patient with a fragrant open belly and a fistula.”
Neither Dr. Harvin nor Dr Rhee had any relevant financial disclosures.
AT THE AAST ANNUAL MEETING
Key clinical point: Definitive laparotomy for abdominal trauma added little risk of complications but shortened ventilator and ICU days.
Major finding: Definitive closure was associated with a 72% chance of more ventilator- and hospital-free days and a 77% chance of more ICU-free days than damage-control closure.
Study details: The Bayseian analysis comprised 39 definitive and 39 damage-control laparotomy patients.
Disclosures: Neither Dr. Harvin nor Dr. Rhee had any financial disclosures.
Source: Harvin J et al. AAST 2018, Oral paper 12.
Opioid use in OA may mean more activity-limiting pain
LAS VEGAS – Patients with OA pain who used opioids persistently were more likely to report worse pain interference with daily activities and more functional limitations than nonopioid users in a nationally representative survey, Drishti Shah and her colleagues reported at the annual PAINWeek.
“These findings suggest an unmet need and calls for better patient management, including consideration of alternative treatment strategies,” said Ms. Shah, a graduate student at West Virginia University, Morgantown.
The authors examined data from 4,172 adults with OA aged 18 years and older who took part in the nationally representative Medical Expenditure Panel Survey during 2010-2015.
Each respondent was followed for up to 2 years, with five rounds of surveys. The primary outcomes were longitudinal changes in pain interference with daily activities (PIA) as measured by the bodily pain item of the Short Form Health Survey scale and functional limitations in social, physical, work, and cognitive activities.
Opioid use was considered persistent when reported in at least two consecutive rounds and intermittent use was opioid use reported in any one or alternative rounds of the panel. Multivariate regression analyses were conducted, controlling for baseline sociodemographics, clinical characteristics, and prescription NSAID use.
Most of the patients were female (66%), and the mean age was 62 years. The majority (83%) were aged 50 years or older. About 45% were employed at baseline.
About one-third of patients reported opioid use in each round, and 25% reported prescription NSAID use. About 15% of patients reported persistent opioid use and 19% disclosed intermittent use.
At the end of follow-up, persistent opioid users were nearly three times more likely to report extreme or severe PIA when compared with nonopioid users (odds ratio, 2.91) and twice as likely to report moderate PIA (OR, 2.04). No significant differences were observed for intermittent opioid users.
Regardless of baseline functional status, persistent opioid users had a significantly higher likelihood of reporting functional limitation at end of follow-up when compared against nonopioid users. Similar results were observed for intermittent opioid users who reported no functional limitations at baseline. However, intermittent opioid users who reported functional limitation at baseline were less likely to report social and cognitive limitations at end of follow-up than were nonopioid users.
Regeneron and Teva Pharmaceuticals supported the study. Ms. Shah was a paid consultant for both companies and has no other personal financial relationships with either company.
LAS VEGAS – Patients with OA pain who used opioids persistently were more likely to report worse pain interference with daily activities and more functional limitations than nonopioid users in a nationally representative survey, Drishti Shah and her colleagues reported at the annual PAINWeek.
“These findings suggest an unmet need and calls for better patient management, including consideration of alternative treatment strategies,” said Ms. Shah, a graduate student at West Virginia University, Morgantown.
The authors examined data from 4,172 adults with OA aged 18 years and older who took part in the nationally representative Medical Expenditure Panel Survey during 2010-2015.
Each respondent was followed for up to 2 years, with five rounds of surveys. The primary outcomes were longitudinal changes in pain interference with daily activities (PIA) as measured by the bodily pain item of the Short Form Health Survey scale and functional limitations in social, physical, work, and cognitive activities.
Opioid use was considered persistent when reported in at least two consecutive rounds and intermittent use was opioid use reported in any one or alternative rounds of the panel. Multivariate regression analyses were conducted, controlling for baseline sociodemographics, clinical characteristics, and prescription NSAID use.
Most of the patients were female (66%), and the mean age was 62 years. The majority (83%) were aged 50 years or older. About 45% were employed at baseline.
About one-third of patients reported opioid use in each round, and 25% reported prescription NSAID use. About 15% of patients reported persistent opioid use and 19% disclosed intermittent use.
At the end of follow-up, persistent opioid users were nearly three times more likely to report extreme or severe PIA when compared with nonopioid users (odds ratio, 2.91) and twice as likely to report moderate PIA (OR, 2.04). No significant differences were observed for intermittent opioid users.
Regardless of baseline functional status, persistent opioid users had a significantly higher likelihood of reporting functional limitation at end of follow-up when compared against nonopioid users. Similar results were observed for intermittent opioid users who reported no functional limitations at baseline. However, intermittent opioid users who reported functional limitation at baseline were less likely to report social and cognitive limitations at end of follow-up than were nonopioid users.
Regeneron and Teva Pharmaceuticals supported the study. Ms. Shah was a paid consultant for both companies and has no other personal financial relationships with either company.
LAS VEGAS – Patients with OA pain who used opioids persistently were more likely to report worse pain interference with daily activities and more functional limitations than nonopioid users in a nationally representative survey, Drishti Shah and her colleagues reported at the annual PAINWeek.
“These findings suggest an unmet need and calls for better patient management, including consideration of alternative treatment strategies,” said Ms. Shah, a graduate student at West Virginia University, Morgantown.
The authors examined data from 4,172 adults with OA aged 18 years and older who took part in the nationally representative Medical Expenditure Panel Survey during 2010-2015.
Each respondent was followed for up to 2 years, with five rounds of surveys. The primary outcomes were longitudinal changes in pain interference with daily activities (PIA) as measured by the bodily pain item of the Short Form Health Survey scale and functional limitations in social, physical, work, and cognitive activities.
Opioid use was considered persistent when reported in at least two consecutive rounds and intermittent use was opioid use reported in any one or alternative rounds of the panel. Multivariate regression analyses were conducted, controlling for baseline sociodemographics, clinical characteristics, and prescription NSAID use.
Most of the patients were female (66%), and the mean age was 62 years. The majority (83%) were aged 50 years or older. About 45% were employed at baseline.
About one-third of patients reported opioid use in each round, and 25% reported prescription NSAID use. About 15% of patients reported persistent opioid use and 19% disclosed intermittent use.
At the end of follow-up, persistent opioid users were nearly three times more likely to report extreme or severe PIA when compared with nonopioid users (odds ratio, 2.91) and twice as likely to report moderate PIA (OR, 2.04). No significant differences were observed for intermittent opioid users.
Regardless of baseline functional status, persistent opioid users had a significantly higher likelihood of reporting functional limitation at end of follow-up when compared against nonopioid users. Similar results were observed for intermittent opioid users who reported no functional limitations at baseline. However, intermittent opioid users who reported functional limitation at baseline were less likely to report social and cognitive limitations at end of follow-up than were nonopioid users.
Regeneron and Teva Pharmaceuticals supported the study. Ms. Shah was a paid consultant for both companies and has no other personal financial relationships with either company.
REPORTING FROM PAINWEEK 2018
Key clinical point:
Major finding: Compared with intermittent opioid users, persistent opioid users were three times more likely to report extreme or severe pain interfering with daily activities.
Study details: A group of 4,172 adults with OA from the 2010-2015 Medical Expenditure Panel Surveys
Disclosures: Regeneron and Teva Pharmaceuticals supported the study. Ms. Shah was a paid consultant for both companies and has no other personal financial relationships with either company.
Signs point to growing abuse of gabapentinoids in the U.S.
LAS VEGAS – Up to 22% of opioid abusers also abuse gabapentin, taking high doses of the antiepileptic for its psychoactive effects, or to potentiate the effect of opioids.
The drug – the 10th most commonly prescribed in the United States – is increasingly implicated in overdose deaths. In response, several states have recently reclassified the antiepileptic as a Schedule V controlled substance. Other states have declined to go that far, but have added gabapentin (Neurontin and others) to the drugs that must be reported to state prescription monitoring programs.
“Gabapentin and pregabalin [Lyrica] are versatile and important drugs that are widely prescribed and used off label for a number of conditions from seizure disorder to fibromyalgia,” said Joseph Pergolizzi Jr., MD, who discussed the issue during the annual PAINWeek. “Abuse patterns differ somewhat from abuse patterns with prescription opioids. People who misuse gabapentinoids tend to already use other drugs inappropriately. It’s rare to find a person who only takes them recreationally, but it is increasingly common to find polydrug abusers who take gabapentinoids.”
Gabapentin abuse appears to be more common in Europe than in the United States, where it’s just beginning to emerge, Dr. Pergolizzi said. And the picture is more nuanced than it might first appear: Many of those who are misusing the drug are using it as a “do-it-yourself” opioid withdrawal aid, he said in an interview.
At the meeting, he presented a literature review comprising 46 papers on pregabalin abuse and 263 on gabapentin abuse. Several important themes arose from these papers, said Dr. Pergolizzi, cofounder and chief operating officer of NEMA Research Inc., Naples, Fla.:
- Gabapentin and pregabalin are being prescribed off label for numerous conditions, including bipolar disorder, neuropathic pain, diabetic neuropathy, complex regional pain syndrome, attention deficit disorder, restless leg syndrome, trigeminal neuralgia, periodic limb movement disorder of sleep, migraine, drug and alcohol withdrawal seizures, chronic low back pain, and even menopausal symptoms.
- About a one-third of users experience withdrawal symptoms with sudden discontinuation. Symptoms include disorientation, anxiety, insomnia, heart palpitations, diaphoresis, and abdominal cramps.
- Risk factors for abuse are emerging. These include opioid use disorders, mental illnesses, and a history of taking supratherapeutic doses of the drugs. Age and sex don’t seem to be a consistent risk factor for abuse.
- Abusers can obtain nonprescription gabapentinoids more easily each year, including street sales and online orders, Dr. Pergolizzi said. “A Google search conducted in July for ‘buy gabapentin without a prescription’ yielded 4.48 million results and ‘buy pregabalin without a prescription,’ 622,000. A similar search conducted in September 2017 yielded 1.19 million and 352,000 results, respectively.”
- Few urine drug assays screen for gabapentinoids, which makes them easy to conceal in random drug testing.
Reports of gabapentin-involved drug overdoses and even deaths have recently emerged in the United States, particularly in the opioid abuse-plagued Appalachian states. An article in May in Drug and Alcohol Dependence examined the prevalence of gabapentin in postmortem toxicology in drug overdose deaths in four Appalachian states in 2015 (Drug Alcohol Depend. 2018;186:80-5). Rates were 4% in eastern Tennessee, 15% in West Virginia, 20% in North Carolina, and 41% in Kentucky.
Three states have now added gabapentin to their list of Schedule V controlled substances: Kentucky in 2017, West Virginia this May, and Tennessee in July.
Ohio, Minnesota, Virginia, and Massachusetts have taken a different tack to controlling dispensing. In those states, all pharmacies, prescribers, and wholesalers must report all dispensing and sales of gabapentin to their prescription monitoring databases.
Dr. Pergolizzi disclosed financial relationships with numerous pharmaceutical companies.
LAS VEGAS – Up to 22% of opioid abusers also abuse gabapentin, taking high doses of the antiepileptic for its psychoactive effects, or to potentiate the effect of opioids.
The drug – the 10th most commonly prescribed in the United States – is increasingly implicated in overdose deaths. In response, several states have recently reclassified the antiepileptic as a Schedule V controlled substance. Other states have declined to go that far, but have added gabapentin (Neurontin and others) to the drugs that must be reported to state prescription monitoring programs.
“Gabapentin and pregabalin [Lyrica] are versatile and important drugs that are widely prescribed and used off label for a number of conditions from seizure disorder to fibromyalgia,” said Joseph Pergolizzi Jr., MD, who discussed the issue during the annual PAINWeek. “Abuse patterns differ somewhat from abuse patterns with prescription opioids. People who misuse gabapentinoids tend to already use other drugs inappropriately. It’s rare to find a person who only takes them recreationally, but it is increasingly common to find polydrug abusers who take gabapentinoids.”
Gabapentin abuse appears to be more common in Europe than in the United States, where it’s just beginning to emerge, Dr. Pergolizzi said. And the picture is more nuanced than it might first appear: Many of those who are misusing the drug are using it as a “do-it-yourself” opioid withdrawal aid, he said in an interview.
At the meeting, he presented a literature review comprising 46 papers on pregabalin abuse and 263 on gabapentin abuse. Several important themes arose from these papers, said Dr. Pergolizzi, cofounder and chief operating officer of NEMA Research Inc., Naples, Fla.:
- Gabapentin and pregabalin are being prescribed off label for numerous conditions, including bipolar disorder, neuropathic pain, diabetic neuropathy, complex regional pain syndrome, attention deficit disorder, restless leg syndrome, trigeminal neuralgia, periodic limb movement disorder of sleep, migraine, drug and alcohol withdrawal seizures, chronic low back pain, and even menopausal symptoms.
- About a one-third of users experience withdrawal symptoms with sudden discontinuation. Symptoms include disorientation, anxiety, insomnia, heart palpitations, diaphoresis, and abdominal cramps.
- Risk factors for abuse are emerging. These include opioid use disorders, mental illnesses, and a history of taking supratherapeutic doses of the drugs. Age and sex don’t seem to be a consistent risk factor for abuse.
- Abusers can obtain nonprescription gabapentinoids more easily each year, including street sales and online orders, Dr. Pergolizzi said. “A Google search conducted in July for ‘buy gabapentin without a prescription’ yielded 4.48 million results and ‘buy pregabalin without a prescription,’ 622,000. A similar search conducted in September 2017 yielded 1.19 million and 352,000 results, respectively.”
- Few urine drug assays screen for gabapentinoids, which makes them easy to conceal in random drug testing.
Reports of gabapentin-involved drug overdoses and even deaths have recently emerged in the United States, particularly in the opioid abuse-plagued Appalachian states. An article in May in Drug and Alcohol Dependence examined the prevalence of gabapentin in postmortem toxicology in drug overdose deaths in four Appalachian states in 2015 (Drug Alcohol Depend. 2018;186:80-5). Rates were 4% in eastern Tennessee, 15% in West Virginia, 20% in North Carolina, and 41% in Kentucky.
Three states have now added gabapentin to their list of Schedule V controlled substances: Kentucky in 2017, West Virginia this May, and Tennessee in July.
Ohio, Minnesota, Virginia, and Massachusetts have taken a different tack to controlling dispensing. In those states, all pharmacies, prescribers, and wholesalers must report all dispensing and sales of gabapentin to their prescription monitoring databases.
Dr. Pergolizzi disclosed financial relationships with numerous pharmaceutical companies.
LAS VEGAS – Up to 22% of opioid abusers also abuse gabapentin, taking high doses of the antiepileptic for its psychoactive effects, or to potentiate the effect of opioids.
The drug – the 10th most commonly prescribed in the United States – is increasingly implicated in overdose deaths. In response, several states have recently reclassified the antiepileptic as a Schedule V controlled substance. Other states have declined to go that far, but have added gabapentin (Neurontin and others) to the drugs that must be reported to state prescription monitoring programs.
“Gabapentin and pregabalin [Lyrica] are versatile and important drugs that are widely prescribed and used off label for a number of conditions from seizure disorder to fibromyalgia,” said Joseph Pergolizzi Jr., MD, who discussed the issue during the annual PAINWeek. “Abuse patterns differ somewhat from abuse patterns with prescription opioids. People who misuse gabapentinoids tend to already use other drugs inappropriately. It’s rare to find a person who only takes them recreationally, but it is increasingly common to find polydrug abusers who take gabapentinoids.”
Gabapentin abuse appears to be more common in Europe than in the United States, where it’s just beginning to emerge, Dr. Pergolizzi said. And the picture is more nuanced than it might first appear: Many of those who are misusing the drug are using it as a “do-it-yourself” opioid withdrawal aid, he said in an interview.
At the meeting, he presented a literature review comprising 46 papers on pregabalin abuse and 263 on gabapentin abuse. Several important themes arose from these papers, said Dr. Pergolizzi, cofounder and chief operating officer of NEMA Research Inc., Naples, Fla.:
- Gabapentin and pregabalin are being prescribed off label for numerous conditions, including bipolar disorder, neuropathic pain, diabetic neuropathy, complex regional pain syndrome, attention deficit disorder, restless leg syndrome, trigeminal neuralgia, periodic limb movement disorder of sleep, migraine, drug and alcohol withdrawal seizures, chronic low back pain, and even menopausal symptoms.
- About a one-third of users experience withdrawal symptoms with sudden discontinuation. Symptoms include disorientation, anxiety, insomnia, heart palpitations, diaphoresis, and abdominal cramps.
- Risk factors for abuse are emerging. These include opioid use disorders, mental illnesses, and a history of taking supratherapeutic doses of the drugs. Age and sex don’t seem to be a consistent risk factor for abuse.
- Abusers can obtain nonprescription gabapentinoids more easily each year, including street sales and online orders, Dr. Pergolizzi said. “A Google search conducted in July for ‘buy gabapentin without a prescription’ yielded 4.48 million results and ‘buy pregabalin without a prescription,’ 622,000. A similar search conducted in September 2017 yielded 1.19 million and 352,000 results, respectively.”
- Few urine drug assays screen for gabapentinoids, which makes them easy to conceal in random drug testing.
Reports of gabapentin-involved drug overdoses and even deaths have recently emerged in the United States, particularly in the opioid abuse-plagued Appalachian states. An article in May in Drug and Alcohol Dependence examined the prevalence of gabapentin in postmortem toxicology in drug overdose deaths in four Appalachian states in 2015 (Drug Alcohol Depend. 2018;186:80-5). Rates were 4% in eastern Tennessee, 15% in West Virginia, 20% in North Carolina, and 41% in Kentucky.
Three states have now added gabapentin to their list of Schedule V controlled substances: Kentucky in 2017, West Virginia this May, and Tennessee in July.
Ohio, Minnesota, Virginia, and Massachusetts have taken a different tack to controlling dispensing. In those states, all pharmacies, prescribers, and wholesalers must report all dispensing and sales of gabapentin to their prescription monitoring databases.
Dr. Pergolizzi disclosed financial relationships with numerous pharmaceutical companies.
REPORTING FROM PAINWEEK 2018
Key clinical point:
Major finding: Up to 22% of opioid users are also using gabapentin.
Study details: A literature review of 46 papers on pregabalin abuse and 263 on gabapentin abuse.
Disclosures: Dr. Pergolizzi disclosed financial relationships with numerous pharmaceutical companies.
Source: Pergolizzi J et al. PAINWeek 2018, Poster 55.
Decision aid aims to make lupus nephritis treatment decisions more understandable
A computer-based decision aid aims to facilitate the complex discussions and decisions that face patients with lupus nephritis.
Under development at the University of Alabama at Birmingham, the Shared Decision-Making in Lupus Electronic tool (SMILE) describes in easy-to-understand modules the pathology of the disease, and what can happen if it progresses untreated. The tool also identifies treatment options and discusses the potential benefits of each one, as well as the risks. It can be folded into office visits, accessed during waiting times, or viewed at the patient’s leisure. Its creators hope that patients will experience more fruitful discussions with their physicians by learning more about these complicated concepts as they co-navigate the difficult decisions both must make.
“Our intent was to figure out how best to offer the education about lupus and its treatments that women need when coming into a busy clinic,” said Jasvinder Singh, MD, who is leading the developmental team. “Everyone’s time is limited, and patients want information delivered quickly, but in a way they can understand.”
SMILE is the first tool of its kind for patients with lupus nephritis, said Alexa Meara, MD, one of the rheumatologists investigating it.
“There is just nothing out there like this for either lupus, or lupus nephritis,” said Dr. Meara, a rheumatologist at Ohio State University, Columbus. “Lupus nephritis is a heterogeneous relapsing-remitting disease with complex medical regimens. It can have cognitive impacts and affect fertility, but these are things that may happen over decades. Patients may not be ready to talk about them early on, but they must understand them. We would like to enable the conversation between physician and patient, so they’re on the same page with everyone’s values and concerns addressed on both sides.”
But getting everyone on the same page at the same time is challenging, said Dr. Singh, a rheumatologist and professor of medicine and epidemiology at the University of Alabama at Birmingham. “This is a bit of a dilemma and a challenge. What’s great about the lupus decision aid is that it is culturally and linguistically appropriate for patients of all backgrounds, races, ages, literacy levels, and socioeconomic statuses. This levels the playing field for patients who are trying to understand their diagnosis and options to the best of their abilities.”
Three years in the making, SMILE comprises several modules addressing different facets of lupus nephritis. In simple words and concepts, the tool informs patients about what lupus is and what it can do to the kidneys, the information gleaned from blood and urine tests and what it means, and the potential consequences of not treating lupus kidney disease. The heart of the program is its breakdown of treatment options.
“It helps patients understand why they may be getting these cancer medications, and what their side effects are,” Dr. Singh said. “The tool also walks them through a comparison of the medications, with one slide on each medication and its risks and benefits. We really focus on that – about 60%-70% of the tool is comparing the drugs.”
The decision aid also contains optional modules that patients can bypass or explore. “There are separate sections on the risks and benefits of corticosteroids, on pregnancy and lactation, and on preserving fertility.”
A complete click-through of the basic information takes about 20 minutes, Dr. Singh said. An ideal time for a patient to do so would be before the initial visit to discuss treatment options, which can be an overwhelming experience. The tool could be presented in several ways. In the office, preloaded iPads could be one vehicle. These could be standalone, or linked to the patient’s electronic health record, so that any entered information could be directly transferred. At home, patients could navigate to a web link for an online version.
The first visit is a crucial moment, he said, where patients can evolve into management partners, or leave even more confused than when they arrived.
“We aim to motivate and provide tools to the patient, so that the conversation isn’t just, ‘You have the disease and we can put you on this or that drug,’ ” Dr. Singh said. “You can lose the patient right away in this scenario, while you’re talking about so many things the patient isn’t even hearing you, because she’s thinking about other issues that are important in her life, completely overwhelmed with the shock of the diagnosis and with fear.”
The Patient-Centered Outcomes Research Institute (PCORI) has funded much of the work getting SMILE up and running, including a soon-to-be-published trial that favorably compared it against the educational standard: a paper pamphlet on lupus nephritis prepared by the American College of Rheumatology.
In this study, 301 high‐risk women with lupus kidney disease, including racial/ethnic minorities with low socioeconomic status, either received the pamphlet or the SMILE tool. The group was demographically diverse: 47% black, 26% Hispanic, 15% white, and 7% Asian. Other groups made up the remainder.
More patients rated the information in the decision aid to be excellent for understanding the impact of lupus (49% vs. 33%), risk factors (43% vs. 27%), medication options (50% vs. 33%), and evidence about medications (47% vs. 24%). About half of the tool users rated the ease of use of materials as excellent (51% vs. 38%). Women who used the tool also reported much less decisional conflict for immunosuppressive drugs and were much more likely to choose the treatment option most consistent with their values, having viewed information that mattered the most for the treatment decision.
PCORI continues to support the project, too. Dr. Singh just received a $2.2 million grant to investigate the tool in 16 clinics. The 2-year observational study has three aims:
• Identify physician attitudes and patient barriers toward the tool, to guide decisions about how to best implement it in its final form.
• Track changes in subjective and objective measures of implementation effectiveness.
• Identify opportunities for disseminating the tool and develop a step‐by‐step implementation guide for incorporating the decision aid tool into regular lupus clinic visits and care pathways.
The study will also look at some patient‐centered outcomes, including decision conflict, emergency department and inpatient visits, patient‐physician communication, and implementation success. Some practice-level outcomes will be assessed, including potential barriers to implementation. “The team will focus on context and strategy as facilitators and barriers to effective implementation of the lupus decision aid in busy, clinical practices of various types – for example, private versus academic, urban versus suburban, large versus small group practice,” according to the PCORI study description.
“This study can’t solve the entire problem about patients choosing treatment or no treatment, but it can provide a start to the conversation,” Dr. Singh said. “And my hope is that once it’s available, people will modify it to fit their needs, make adaptations and modifications to keep it relevant and valuable.”
A computer-based decision aid aims to facilitate the complex discussions and decisions that face patients with lupus nephritis.
Under development at the University of Alabama at Birmingham, the Shared Decision-Making in Lupus Electronic tool (SMILE) describes in easy-to-understand modules the pathology of the disease, and what can happen if it progresses untreated. The tool also identifies treatment options and discusses the potential benefits of each one, as well as the risks. It can be folded into office visits, accessed during waiting times, or viewed at the patient’s leisure. Its creators hope that patients will experience more fruitful discussions with their physicians by learning more about these complicated concepts as they co-navigate the difficult decisions both must make.
“Our intent was to figure out how best to offer the education about lupus and its treatments that women need when coming into a busy clinic,” said Jasvinder Singh, MD, who is leading the developmental team. “Everyone’s time is limited, and patients want information delivered quickly, but in a way they can understand.”
SMILE is the first tool of its kind for patients with lupus nephritis, said Alexa Meara, MD, one of the rheumatologists investigating it.
“There is just nothing out there like this for either lupus, or lupus nephritis,” said Dr. Meara, a rheumatologist at Ohio State University, Columbus. “Lupus nephritis is a heterogeneous relapsing-remitting disease with complex medical regimens. It can have cognitive impacts and affect fertility, but these are things that may happen over decades. Patients may not be ready to talk about them early on, but they must understand them. We would like to enable the conversation between physician and patient, so they’re on the same page with everyone’s values and concerns addressed on both sides.”
But getting everyone on the same page at the same time is challenging, said Dr. Singh, a rheumatologist and professor of medicine and epidemiology at the University of Alabama at Birmingham. “This is a bit of a dilemma and a challenge. What’s great about the lupus decision aid is that it is culturally and linguistically appropriate for patients of all backgrounds, races, ages, literacy levels, and socioeconomic statuses. This levels the playing field for patients who are trying to understand their diagnosis and options to the best of their abilities.”
Three years in the making, SMILE comprises several modules addressing different facets of lupus nephritis. In simple words and concepts, the tool informs patients about what lupus is and what it can do to the kidneys, the information gleaned from blood and urine tests and what it means, and the potential consequences of not treating lupus kidney disease. The heart of the program is its breakdown of treatment options.
“It helps patients understand why they may be getting these cancer medications, and what their side effects are,” Dr. Singh said. “The tool also walks them through a comparison of the medications, with one slide on each medication and its risks and benefits. We really focus on that – about 60%-70% of the tool is comparing the drugs.”
The decision aid also contains optional modules that patients can bypass or explore. “There are separate sections on the risks and benefits of corticosteroids, on pregnancy and lactation, and on preserving fertility.”
A complete click-through of the basic information takes about 20 minutes, Dr. Singh said. An ideal time for a patient to do so would be before the initial visit to discuss treatment options, which can be an overwhelming experience. The tool could be presented in several ways. In the office, preloaded iPads could be one vehicle. These could be standalone, or linked to the patient’s electronic health record, so that any entered information could be directly transferred. At home, patients could navigate to a web link for an online version.
The first visit is a crucial moment, he said, where patients can evolve into management partners, or leave even more confused than when they arrived.
“We aim to motivate and provide tools to the patient, so that the conversation isn’t just, ‘You have the disease and we can put you on this or that drug,’ ” Dr. Singh said. “You can lose the patient right away in this scenario, while you’re talking about so many things the patient isn’t even hearing you, because she’s thinking about other issues that are important in her life, completely overwhelmed with the shock of the diagnosis and with fear.”
The Patient-Centered Outcomes Research Institute (PCORI) has funded much of the work getting SMILE up and running, including a soon-to-be-published trial that favorably compared it against the educational standard: a paper pamphlet on lupus nephritis prepared by the American College of Rheumatology.
In this study, 301 high‐risk women with lupus kidney disease, including racial/ethnic minorities with low socioeconomic status, either received the pamphlet or the SMILE tool. The group was demographically diverse: 47% black, 26% Hispanic, 15% white, and 7% Asian. Other groups made up the remainder.
More patients rated the information in the decision aid to be excellent for understanding the impact of lupus (49% vs. 33%), risk factors (43% vs. 27%), medication options (50% vs. 33%), and evidence about medications (47% vs. 24%). About half of the tool users rated the ease of use of materials as excellent (51% vs. 38%). Women who used the tool also reported much less decisional conflict for immunosuppressive drugs and were much more likely to choose the treatment option most consistent with their values, having viewed information that mattered the most for the treatment decision.
PCORI continues to support the project, too. Dr. Singh just received a $2.2 million grant to investigate the tool in 16 clinics. The 2-year observational study has three aims:
• Identify physician attitudes and patient barriers toward the tool, to guide decisions about how to best implement it in its final form.
• Track changes in subjective and objective measures of implementation effectiveness.
• Identify opportunities for disseminating the tool and develop a step‐by‐step implementation guide for incorporating the decision aid tool into regular lupus clinic visits and care pathways.
The study will also look at some patient‐centered outcomes, including decision conflict, emergency department and inpatient visits, patient‐physician communication, and implementation success. Some practice-level outcomes will be assessed, including potential barriers to implementation. “The team will focus on context and strategy as facilitators and barriers to effective implementation of the lupus decision aid in busy, clinical practices of various types – for example, private versus academic, urban versus suburban, large versus small group practice,” according to the PCORI study description.
“This study can’t solve the entire problem about patients choosing treatment or no treatment, but it can provide a start to the conversation,” Dr. Singh said. “And my hope is that once it’s available, people will modify it to fit their needs, make adaptations and modifications to keep it relevant and valuable.”
A computer-based decision aid aims to facilitate the complex discussions and decisions that face patients with lupus nephritis.
Under development at the University of Alabama at Birmingham, the Shared Decision-Making in Lupus Electronic tool (SMILE) describes in easy-to-understand modules the pathology of the disease, and what can happen if it progresses untreated. The tool also identifies treatment options and discusses the potential benefits of each one, as well as the risks. It can be folded into office visits, accessed during waiting times, or viewed at the patient’s leisure. Its creators hope that patients will experience more fruitful discussions with their physicians by learning more about these complicated concepts as they co-navigate the difficult decisions both must make.
“Our intent was to figure out how best to offer the education about lupus and its treatments that women need when coming into a busy clinic,” said Jasvinder Singh, MD, who is leading the developmental team. “Everyone’s time is limited, and patients want information delivered quickly, but in a way they can understand.”
SMILE is the first tool of its kind for patients with lupus nephritis, said Alexa Meara, MD, one of the rheumatologists investigating it.
“There is just nothing out there like this for either lupus, or lupus nephritis,” said Dr. Meara, a rheumatologist at Ohio State University, Columbus. “Lupus nephritis is a heterogeneous relapsing-remitting disease with complex medical regimens. It can have cognitive impacts and affect fertility, but these are things that may happen over decades. Patients may not be ready to talk about them early on, but they must understand them. We would like to enable the conversation between physician and patient, so they’re on the same page with everyone’s values and concerns addressed on both sides.”
But getting everyone on the same page at the same time is challenging, said Dr. Singh, a rheumatologist and professor of medicine and epidemiology at the University of Alabama at Birmingham. “This is a bit of a dilemma and a challenge. What’s great about the lupus decision aid is that it is culturally and linguistically appropriate for patients of all backgrounds, races, ages, literacy levels, and socioeconomic statuses. This levels the playing field for patients who are trying to understand their diagnosis and options to the best of their abilities.”
Three years in the making, SMILE comprises several modules addressing different facets of lupus nephritis. In simple words and concepts, the tool informs patients about what lupus is and what it can do to the kidneys, the information gleaned from blood and urine tests and what it means, and the potential consequences of not treating lupus kidney disease. The heart of the program is its breakdown of treatment options.
“It helps patients understand why they may be getting these cancer medications, and what their side effects are,” Dr. Singh said. “The tool also walks them through a comparison of the medications, with one slide on each medication and its risks and benefits. We really focus on that – about 60%-70% of the tool is comparing the drugs.”
The decision aid also contains optional modules that patients can bypass or explore. “There are separate sections on the risks and benefits of corticosteroids, on pregnancy and lactation, and on preserving fertility.”
A complete click-through of the basic information takes about 20 minutes, Dr. Singh said. An ideal time for a patient to do so would be before the initial visit to discuss treatment options, which can be an overwhelming experience. The tool could be presented in several ways. In the office, preloaded iPads could be one vehicle. These could be standalone, or linked to the patient’s electronic health record, so that any entered information could be directly transferred. At home, patients could navigate to a web link for an online version.
The first visit is a crucial moment, he said, where patients can evolve into management partners, or leave even more confused than when they arrived.
“We aim to motivate and provide tools to the patient, so that the conversation isn’t just, ‘You have the disease and we can put you on this or that drug,’ ” Dr. Singh said. “You can lose the patient right away in this scenario, while you’re talking about so many things the patient isn’t even hearing you, because she’s thinking about other issues that are important in her life, completely overwhelmed with the shock of the diagnosis and with fear.”
The Patient-Centered Outcomes Research Institute (PCORI) has funded much of the work getting SMILE up and running, including a soon-to-be-published trial that favorably compared it against the educational standard: a paper pamphlet on lupus nephritis prepared by the American College of Rheumatology.
In this study, 301 high‐risk women with lupus kidney disease, including racial/ethnic minorities with low socioeconomic status, either received the pamphlet or the SMILE tool. The group was demographically diverse: 47% black, 26% Hispanic, 15% white, and 7% Asian. Other groups made up the remainder.
More patients rated the information in the decision aid to be excellent for understanding the impact of lupus (49% vs. 33%), risk factors (43% vs. 27%), medication options (50% vs. 33%), and evidence about medications (47% vs. 24%). About half of the tool users rated the ease of use of materials as excellent (51% vs. 38%). Women who used the tool also reported much less decisional conflict for immunosuppressive drugs and were much more likely to choose the treatment option most consistent with their values, having viewed information that mattered the most for the treatment decision.
PCORI continues to support the project, too. Dr. Singh just received a $2.2 million grant to investigate the tool in 16 clinics. The 2-year observational study has three aims:
• Identify physician attitudes and patient barriers toward the tool, to guide decisions about how to best implement it in its final form.
• Track changes in subjective and objective measures of implementation effectiveness.
• Identify opportunities for disseminating the tool and develop a step‐by‐step implementation guide for incorporating the decision aid tool into regular lupus clinic visits and care pathways.
The study will also look at some patient‐centered outcomes, including decision conflict, emergency department and inpatient visits, patient‐physician communication, and implementation success. Some practice-level outcomes will be assessed, including potential barriers to implementation. “The team will focus on context and strategy as facilitators and barriers to effective implementation of the lupus decision aid in busy, clinical practices of various types – for example, private versus academic, urban versus suburban, large versus small group practice,” according to the PCORI study description.
“This study can’t solve the entire problem about patients choosing treatment or no treatment, but it can provide a start to the conversation,” Dr. Singh said. “And my hope is that once it’s available, people will modify it to fit their needs, make adaptations and modifications to keep it relevant and valuable.”
Peripheral opioid blocker eases opioid-induced constipation without inducing withdrawal
LAS VEGAS – .
In three placebo-controlled randomized studies, the drug increased the number of spontaneous bowel movements and improved stool consistency without inducing opioid withdrawal symptoms.
Naldemedine (Symproic) received FDA approval last year based on COMPOSE 1 and COMPOSE 2, which were published in Lancet Gastroenterology and Hepatology last year (2017 Aug 2[8]:555-64). James E. Wild, MD, of Upstate Clinical Research Associates, in Williamsville, N.Y., reported these in a poster presented at the annual PAINWeek.
The year-long COMPOSE 3 trial was not presented at the meeting, but appeared in the journal Pain (2018 May;5:987-94).
Opioids not only affect the central nervous system but also bind to mu-opioid receptors in the gut, decreasing intestinal motility. Naldemedine blocks these receptors from opioid binding but cannot cross the blood-brain barrier. Its peripheral action blocks gut opioid binding, side-stepping the motility problem without inducing any opioid withdrawal symptoms.
COMPOSE 1 (C1) and COMPOSE 2 (C2) comprised a total of 1,095 subjects with chronic, noncancer pain. They were randomized to either naldemedine 0.2 mg daily or placebo for 12 weeks.
Patients were a median of 53 years with a mean opioid use of 61 months. About 60% had a mean daily morphine equivalent of 30-100 mg, and 40% a mean dose of more than 100 mg. At baseline, they had a mean of one spontaneous bowel movement (BM) per week, with a mean of 0.4 deemed “complete.” All the BMs were accompanied by straining.
Response was defined as a patient who had at least three spontaneous BMs per week and an increase of at least one for that week, for at least 9 of the 12 treatment weeks and at least 3 of the last 4 weeks of the trial.
In both studies, the responder rate was significantly higher in the naldemedine group than in the placebo group (C1 48% vs. 34%; C2 53% vs. 33%). Those taking naldemedine had a mean of two more spontaneous BMs per week than did those taking placebo, and significantly more of those were accomplished without straining.
The most common treatment-emergent adverse effects were diarrhea (about 8% vs. 3%) and abdominal pain (about 6% vs. 1%).
Three patients in C1 experienced at least one event of opioid withdrawal (two taking the study drug and one taking placebo). There were no confirmed withdrawal events in C2, but seven patients (five taking the study drug and two taking placebo) experienced possible gastrointestinal withdrawal symptoms.
COMPOSE 3 demonstrated naldemedine’s lasting benefit in this population. It randomized 1,246 patients to 52 weeks of placebo or the 0.2 mg/day dose. Patient demographics were similar to the earlier COMPOSE studies.
The primary endpoint was treatment-emergent adverse events. Additional endpoints included opioid withdrawal, pain intensity, frequency of bowel movements, and constipation-related symptoms.
There was a significant and sustained increase from baseline in the frequency of bowel movements with naldemedine, increasing from about two to four each week. Constipation symptoms and quality of life scores both improved significantly, relative to placebo.
Again, the most common adverse event was diarrhea (11% naldemedine vs. 5% placebo). The drug was not associated with any opioid withdrawal symptoms, nor did it interfere with a patient’s pain control.
LAS VEGAS – .
In three placebo-controlled randomized studies, the drug increased the number of spontaneous bowel movements and improved stool consistency without inducing opioid withdrawal symptoms.
Naldemedine (Symproic) received FDA approval last year based on COMPOSE 1 and COMPOSE 2, which were published in Lancet Gastroenterology and Hepatology last year (2017 Aug 2[8]:555-64). James E. Wild, MD, of Upstate Clinical Research Associates, in Williamsville, N.Y., reported these in a poster presented at the annual PAINWeek.
The year-long COMPOSE 3 trial was not presented at the meeting, but appeared in the journal Pain (2018 May;5:987-94).
Opioids not only affect the central nervous system but also bind to mu-opioid receptors in the gut, decreasing intestinal motility. Naldemedine blocks these receptors from opioid binding but cannot cross the blood-brain barrier. Its peripheral action blocks gut opioid binding, side-stepping the motility problem without inducing any opioid withdrawal symptoms.
COMPOSE 1 (C1) and COMPOSE 2 (C2) comprised a total of 1,095 subjects with chronic, noncancer pain. They were randomized to either naldemedine 0.2 mg daily or placebo for 12 weeks.
Patients were a median of 53 years with a mean opioid use of 61 months. About 60% had a mean daily morphine equivalent of 30-100 mg, and 40% a mean dose of more than 100 mg. At baseline, they had a mean of one spontaneous bowel movement (BM) per week, with a mean of 0.4 deemed “complete.” All the BMs were accompanied by straining.
Response was defined as a patient who had at least three spontaneous BMs per week and an increase of at least one for that week, for at least 9 of the 12 treatment weeks and at least 3 of the last 4 weeks of the trial.
In both studies, the responder rate was significantly higher in the naldemedine group than in the placebo group (C1 48% vs. 34%; C2 53% vs. 33%). Those taking naldemedine had a mean of two more spontaneous BMs per week than did those taking placebo, and significantly more of those were accomplished without straining.
The most common treatment-emergent adverse effects were diarrhea (about 8% vs. 3%) and abdominal pain (about 6% vs. 1%).
Three patients in C1 experienced at least one event of opioid withdrawal (two taking the study drug and one taking placebo). There were no confirmed withdrawal events in C2, but seven patients (five taking the study drug and two taking placebo) experienced possible gastrointestinal withdrawal symptoms.
COMPOSE 3 demonstrated naldemedine’s lasting benefit in this population. It randomized 1,246 patients to 52 weeks of placebo or the 0.2 mg/day dose. Patient demographics were similar to the earlier COMPOSE studies.
The primary endpoint was treatment-emergent adverse events. Additional endpoints included opioid withdrawal, pain intensity, frequency of bowel movements, and constipation-related symptoms.
There was a significant and sustained increase from baseline in the frequency of bowel movements with naldemedine, increasing from about two to four each week. Constipation symptoms and quality of life scores both improved significantly, relative to placebo.
Again, the most common adverse event was diarrhea (11% naldemedine vs. 5% placebo). The drug was not associated with any opioid withdrawal symptoms, nor did it interfere with a patient’s pain control.
LAS VEGAS – .
In three placebo-controlled randomized studies, the drug increased the number of spontaneous bowel movements and improved stool consistency without inducing opioid withdrawal symptoms.
Naldemedine (Symproic) received FDA approval last year based on COMPOSE 1 and COMPOSE 2, which were published in Lancet Gastroenterology and Hepatology last year (2017 Aug 2[8]:555-64). James E. Wild, MD, of Upstate Clinical Research Associates, in Williamsville, N.Y., reported these in a poster presented at the annual PAINWeek.
The year-long COMPOSE 3 trial was not presented at the meeting, but appeared in the journal Pain (2018 May;5:987-94).
Opioids not only affect the central nervous system but also bind to mu-opioid receptors in the gut, decreasing intestinal motility. Naldemedine blocks these receptors from opioid binding but cannot cross the blood-brain barrier. Its peripheral action blocks gut opioid binding, side-stepping the motility problem without inducing any opioid withdrawal symptoms.
COMPOSE 1 (C1) and COMPOSE 2 (C2) comprised a total of 1,095 subjects with chronic, noncancer pain. They were randomized to either naldemedine 0.2 mg daily or placebo for 12 weeks.
Patients were a median of 53 years with a mean opioid use of 61 months. About 60% had a mean daily morphine equivalent of 30-100 mg, and 40% a mean dose of more than 100 mg. At baseline, they had a mean of one spontaneous bowel movement (BM) per week, with a mean of 0.4 deemed “complete.” All the BMs were accompanied by straining.
Response was defined as a patient who had at least three spontaneous BMs per week and an increase of at least one for that week, for at least 9 of the 12 treatment weeks and at least 3 of the last 4 weeks of the trial.
In both studies, the responder rate was significantly higher in the naldemedine group than in the placebo group (C1 48% vs. 34%; C2 53% vs. 33%). Those taking naldemedine had a mean of two more spontaneous BMs per week than did those taking placebo, and significantly more of those were accomplished without straining.
The most common treatment-emergent adverse effects were diarrhea (about 8% vs. 3%) and abdominal pain (about 6% vs. 1%).
Three patients in C1 experienced at least one event of opioid withdrawal (two taking the study drug and one taking placebo). There were no confirmed withdrawal events in C2, but seven patients (five taking the study drug and two taking placebo) experienced possible gastrointestinal withdrawal symptoms.
COMPOSE 3 demonstrated naldemedine’s lasting benefit in this population. It randomized 1,246 patients to 52 weeks of placebo or the 0.2 mg/day dose. Patient demographics were similar to the earlier COMPOSE studies.
The primary endpoint was treatment-emergent adverse events. Additional endpoints included opioid withdrawal, pain intensity, frequency of bowel movements, and constipation-related symptoms.
There was a significant and sustained increase from baseline in the frequency of bowel movements with naldemedine, increasing from about two to four each week. Constipation symptoms and quality of life scores both improved significantly, relative to placebo.
Again, the most common adverse event was diarrhea (11% naldemedine vs. 5% placebo). The drug was not associated with any opioid withdrawal symptoms, nor did it interfere with a patient’s pain control.
AT PAINWEEK 2018
Key clinical point: Naldemedine improves symptoms of opioid-induced constipation over 12 and 52 weeks.
Major finding: The drug doubled the frequency of bowel movements in both 12- and 52-week studies.
Study details: Altogether, COMPOSE 1, 2, and 3 randomized 2,300 patients to placebo or 0.2 mg/day naldemedine.
Disclosures: The studies were sponsored by Shionogi. Dr. Wild is a clinical trialist with Upstate Clinical Research Associates, Williamsville, N.Y.
Source: Wild JE et al. PAINWeek 2018, Abstract 34