User login
MRD may indicate relapse risk in AML
Detecting molecular minimal residual disease among patients in complete remission was a significant independent predictor of relapse and survival in acute myeloid leukemia (AML), findings from a new study suggest.
Mojca Jongen-Lavrencic, MD, PhD, of the Erasmus University in the Netherlands, and colleagues conducted targeted next-generation sequencing on bone marrow or peripheral blood samples to detect minimal residual disease in 482 newly diagnosed AML patients aged 18-65 years. The sampling was conducted at diagnosis and again after induction therapy. The study endpoints included 4-year rates of relapse, relapse-free survival, and overall survival. The findings are reported in the New England Journal of Medicine.
Overall, at least one mutation was found in 430 patients (89.2%). Persistent DTA mutations, which are associated with age-related hematopoiesis, were not significantly associated with higher 4-year relapse rates, compared with no detection of DTA mutations (P = .29). However, having a persistent DTA mutation and a coexisting persistent non-DTA mutation was a significant predictor of relapse, with a 4-year relapse rate of 66.7% versus 39.4% for no detection (P = .002).
Similarly, having a persistent non-DTA mutation at any allele frequency was linked to an increase risk of relapse at 4 years (55.7% with detection versus 34.6% without detection, P = .001). Non-DTA mutation was also significantly associated with reduced relapsed-free survival and reduced overall survival.
The study was funded by the Queen Wilhelmina Fund Foundation of the Dutch Cancer, among others. There was no commercial funding for the study.
SOURCE: Jongen-Lavrencic M et al. N Engl J Med. 2018 Mar 29;378:1189-99.
Detecting molecular minimal residual disease among patients in complete remission was a significant independent predictor of relapse and survival in acute myeloid leukemia (AML), findings from a new study suggest.
Mojca Jongen-Lavrencic, MD, PhD, of the Erasmus University in the Netherlands, and colleagues conducted targeted next-generation sequencing on bone marrow or peripheral blood samples to detect minimal residual disease in 482 newly diagnosed AML patients aged 18-65 years. The sampling was conducted at diagnosis and again after induction therapy. The study endpoints included 4-year rates of relapse, relapse-free survival, and overall survival. The findings are reported in the New England Journal of Medicine.
Overall, at least one mutation was found in 430 patients (89.2%). Persistent DTA mutations, which are associated with age-related hematopoiesis, were not significantly associated with higher 4-year relapse rates, compared with no detection of DTA mutations (P = .29). However, having a persistent DTA mutation and a coexisting persistent non-DTA mutation was a significant predictor of relapse, with a 4-year relapse rate of 66.7% versus 39.4% for no detection (P = .002).
Similarly, having a persistent non-DTA mutation at any allele frequency was linked to an increase risk of relapse at 4 years (55.7% with detection versus 34.6% without detection, P = .001). Non-DTA mutation was also significantly associated with reduced relapsed-free survival and reduced overall survival.
The study was funded by the Queen Wilhelmina Fund Foundation of the Dutch Cancer, among others. There was no commercial funding for the study.
SOURCE: Jongen-Lavrencic M et al. N Engl J Med. 2018 Mar 29;378:1189-99.
Detecting molecular minimal residual disease among patients in complete remission was a significant independent predictor of relapse and survival in acute myeloid leukemia (AML), findings from a new study suggest.
Mojca Jongen-Lavrencic, MD, PhD, of the Erasmus University in the Netherlands, and colleagues conducted targeted next-generation sequencing on bone marrow or peripheral blood samples to detect minimal residual disease in 482 newly diagnosed AML patients aged 18-65 years. The sampling was conducted at diagnosis and again after induction therapy. The study endpoints included 4-year rates of relapse, relapse-free survival, and overall survival. The findings are reported in the New England Journal of Medicine.
Overall, at least one mutation was found in 430 patients (89.2%). Persistent DTA mutations, which are associated with age-related hematopoiesis, were not significantly associated with higher 4-year relapse rates, compared with no detection of DTA mutations (P = .29). However, having a persistent DTA mutation and a coexisting persistent non-DTA mutation was a significant predictor of relapse, with a 4-year relapse rate of 66.7% versus 39.4% for no detection (P = .002).
Similarly, having a persistent non-DTA mutation at any allele frequency was linked to an increase risk of relapse at 4 years (55.7% with detection versus 34.6% without detection, P = .001). Non-DTA mutation was also significantly associated with reduced relapsed-free survival and reduced overall survival.
The study was funded by the Queen Wilhelmina Fund Foundation of the Dutch Cancer, among others. There was no commercial funding for the study.
SOURCE: Jongen-Lavrencic M et al. N Engl J Med. 2018 Mar 29;378:1189-99.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Distinguish neurogenic from nonneurogenic orthostatic hypotension
In order to may be superior to looking at heart rate alone.
A cHR/cSBP ratio of 0.492 beats per minute (bpm)/mm Hg had the best sensitivity and specificity to distinguish neurogenic from nonneurogenic causes, according to results of a prospective study published in Annals of Neurology.
“If you just look at the heart rate increase alone, of course it is blunted, but it doesn’t really give you the bigger picture that you get when you look at the heart rate in relation to the blood pressure fall,” Dr. Norcliffe-Kaufmann said in an interview.
Neurogenic orthostatic hypotension, which indicates an underlying pathology affecting autonomic neurons, has a much worse prognosis than does nonneurogenic orthostatic hypotension, according to Dr. Norcliffe-Kaufmann and her colleagues, who published the results on behalf of the Autonomic Disorders Consortium.
One key difference between the two groups, they added, is that patients with neurogenic orthostatic hypotension typically have little or no heart rate (HR) increase in the upright position, while patients with nonneurogenic orthostatic hypotension may have marked tachycardia.
Despite the importance of orthostatic HR changes in differential diagnosis, however, there has been no systematic evaluation of HR ranges that may be diagnostic, and proposed ranges have been based on expert clinical experience rather than clinical data, they said.
Accordingly, Dr. Norcliffe-Kaufmann and her colleagues conducted a study of consecutive adult patients referred for autonomic evaluation at sites of the U.S. Autonomic Consortium.
The analysis was based on 402 patients with orthostatic hypotension who had normal sinus rhythm at the time of evaluation. Of that group, 378 had neurogenic orthostatic hypotension and were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy.
Patients with neurogenic orthostatic hypotension had twice the fall in SBP versus those with nonneurogenic causes (–43 vs. –21 mm Hg; P less than .0001), yet only about a third of the HR increase (8 vs. 25 bpm; P less than .0001), researchers reported.
They found the cHR/cSBP ratio of 0.492 bpm/mm Hg had the best sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic and nonneurogenic orthostatic hypertension.
By contrast, orthostatic HR increase by itself was a poor discriminator, according to the researchers, who reported that an HR increase of less than 17 bpm had just moderate sensitivity (79%) and specificity (87%).
“Using this simple bedside test of how much the blood pressure falls and heart rate increases can help in screening these patients,” Dr. Norcliffe-Kaufmann said of the results. “Then they can be sent to an autonomic clinic to really confirm the diagnosis with a sophisticated autonomic function test.”
The researchers also sought to determine whether the differences in heart rate could distinguish between central and peripheral causes of neurogenic orthostatic hypotension. They found that heart rate increased more in patients with multiple system atrophy, but noted “considerable overlap” with patients with Lewy body disorders, according to the findings.
“It didn’t really pan out as a way to distinguish the two forms from one another with enough sensitivity or specificity,” Dr. Norcliffe-Kaufmann said.
The findings do suggest, however, that looking at the cHR/cSBP ratio could help identify neurogenic orthostatic hypotension earlier, reducing delays in treatment and decreasing the need for expensive testing, the researchers said.
“I think there will be a place for genuine, solid autonomic function tests, but many patients cannot get referred to these services, or they don’t have these specialist medical centers on their doorstep, particularly in rural communities,” Dr. Norcliffe-Kaufmann said in the interview.
The study was supported by the National institutes of Health Rare Disease Clinical Research Network. Dr. Norcliffe-Kaufmann and her coauthors reported no potential conflicts of interest.
SOURCE: Norcliffe-Kaufmann L et al. Ann Neurol. 2018 Mar;83(3):522-31.
In order to may be superior to looking at heart rate alone.
A cHR/cSBP ratio of 0.492 beats per minute (bpm)/mm Hg had the best sensitivity and specificity to distinguish neurogenic from nonneurogenic causes, according to results of a prospective study published in Annals of Neurology.
“If you just look at the heart rate increase alone, of course it is blunted, but it doesn’t really give you the bigger picture that you get when you look at the heart rate in relation to the blood pressure fall,” Dr. Norcliffe-Kaufmann said in an interview.
Neurogenic orthostatic hypotension, which indicates an underlying pathology affecting autonomic neurons, has a much worse prognosis than does nonneurogenic orthostatic hypotension, according to Dr. Norcliffe-Kaufmann and her colleagues, who published the results on behalf of the Autonomic Disorders Consortium.
One key difference between the two groups, they added, is that patients with neurogenic orthostatic hypotension typically have little or no heart rate (HR) increase in the upright position, while patients with nonneurogenic orthostatic hypotension may have marked tachycardia.
Despite the importance of orthostatic HR changes in differential diagnosis, however, there has been no systematic evaluation of HR ranges that may be diagnostic, and proposed ranges have been based on expert clinical experience rather than clinical data, they said.
Accordingly, Dr. Norcliffe-Kaufmann and her colleagues conducted a study of consecutive adult patients referred for autonomic evaluation at sites of the U.S. Autonomic Consortium.
The analysis was based on 402 patients with orthostatic hypotension who had normal sinus rhythm at the time of evaluation. Of that group, 378 had neurogenic orthostatic hypotension and were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy.
Patients with neurogenic orthostatic hypotension had twice the fall in SBP versus those with nonneurogenic causes (–43 vs. –21 mm Hg; P less than .0001), yet only about a third of the HR increase (8 vs. 25 bpm; P less than .0001), researchers reported.
They found the cHR/cSBP ratio of 0.492 bpm/mm Hg had the best sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic and nonneurogenic orthostatic hypertension.
By contrast, orthostatic HR increase by itself was a poor discriminator, according to the researchers, who reported that an HR increase of less than 17 bpm had just moderate sensitivity (79%) and specificity (87%).
“Using this simple bedside test of how much the blood pressure falls and heart rate increases can help in screening these patients,” Dr. Norcliffe-Kaufmann said of the results. “Then they can be sent to an autonomic clinic to really confirm the diagnosis with a sophisticated autonomic function test.”
The researchers also sought to determine whether the differences in heart rate could distinguish between central and peripheral causes of neurogenic orthostatic hypotension. They found that heart rate increased more in patients with multiple system atrophy, but noted “considerable overlap” with patients with Lewy body disorders, according to the findings.
“It didn’t really pan out as a way to distinguish the two forms from one another with enough sensitivity or specificity,” Dr. Norcliffe-Kaufmann said.
The findings do suggest, however, that looking at the cHR/cSBP ratio could help identify neurogenic orthostatic hypotension earlier, reducing delays in treatment and decreasing the need for expensive testing, the researchers said.
“I think there will be a place for genuine, solid autonomic function tests, but many patients cannot get referred to these services, or they don’t have these specialist medical centers on their doorstep, particularly in rural communities,” Dr. Norcliffe-Kaufmann said in the interview.
The study was supported by the National institutes of Health Rare Disease Clinical Research Network. Dr. Norcliffe-Kaufmann and her coauthors reported no potential conflicts of interest.
SOURCE: Norcliffe-Kaufmann L et al. Ann Neurol. 2018 Mar;83(3):522-31.
In order to may be superior to looking at heart rate alone.
A cHR/cSBP ratio of 0.492 beats per minute (bpm)/mm Hg had the best sensitivity and specificity to distinguish neurogenic from nonneurogenic causes, according to results of a prospective study published in Annals of Neurology.
“If you just look at the heart rate increase alone, of course it is blunted, but it doesn’t really give you the bigger picture that you get when you look at the heart rate in relation to the blood pressure fall,” Dr. Norcliffe-Kaufmann said in an interview.
Neurogenic orthostatic hypotension, which indicates an underlying pathology affecting autonomic neurons, has a much worse prognosis than does nonneurogenic orthostatic hypotension, according to Dr. Norcliffe-Kaufmann and her colleagues, who published the results on behalf of the Autonomic Disorders Consortium.
One key difference between the two groups, they added, is that patients with neurogenic orthostatic hypotension typically have little or no heart rate (HR) increase in the upright position, while patients with nonneurogenic orthostatic hypotension may have marked tachycardia.
Despite the importance of orthostatic HR changes in differential diagnosis, however, there has been no systematic evaluation of HR ranges that may be diagnostic, and proposed ranges have been based on expert clinical experience rather than clinical data, they said.
Accordingly, Dr. Norcliffe-Kaufmann and her colleagues conducted a study of consecutive adult patients referred for autonomic evaluation at sites of the U.S. Autonomic Consortium.
The analysis was based on 402 patients with orthostatic hypotension who had normal sinus rhythm at the time of evaluation. Of that group, 378 had neurogenic orthostatic hypotension and were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy.
Patients with neurogenic orthostatic hypotension had twice the fall in SBP versus those with nonneurogenic causes (–43 vs. –21 mm Hg; P less than .0001), yet only about a third of the HR increase (8 vs. 25 bpm; P less than .0001), researchers reported.
They found the cHR/cSBP ratio of 0.492 bpm/mm Hg had the best sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic and nonneurogenic orthostatic hypertension.
By contrast, orthostatic HR increase by itself was a poor discriminator, according to the researchers, who reported that an HR increase of less than 17 bpm had just moderate sensitivity (79%) and specificity (87%).
“Using this simple bedside test of how much the blood pressure falls and heart rate increases can help in screening these patients,” Dr. Norcliffe-Kaufmann said of the results. “Then they can be sent to an autonomic clinic to really confirm the diagnosis with a sophisticated autonomic function test.”
The researchers also sought to determine whether the differences in heart rate could distinguish between central and peripheral causes of neurogenic orthostatic hypotension. They found that heart rate increased more in patients with multiple system atrophy, but noted “considerable overlap” with patients with Lewy body disorders, according to the findings.
“It didn’t really pan out as a way to distinguish the two forms from one another with enough sensitivity or specificity,” Dr. Norcliffe-Kaufmann said.
The findings do suggest, however, that looking at the cHR/cSBP ratio could help identify neurogenic orthostatic hypotension earlier, reducing delays in treatment and decreasing the need for expensive testing, the researchers said.
“I think there will be a place for genuine, solid autonomic function tests, but many patients cannot get referred to these services, or they don’t have these specialist medical centers on their doorstep, particularly in rural communities,” Dr. Norcliffe-Kaufmann said in the interview.
The study was supported by the National institutes of Health Rare Disease Clinical Research Network. Dr. Norcliffe-Kaufmann and her coauthors reported no potential conflicts of interest.
SOURCE: Norcliffe-Kaufmann L et al. Ann Neurol. 2018 Mar;83(3):522-31.
FROM ANNALS OF NEUROLOGY
Key clinical point: The ratio of change in heart rate (cHR) to change in systolic blood pressure (cSBP) was better than HR increase alone in distinguishing between neurogenic and nonneurogenic causes of orthostatic hypotension.
Major finding: A cHR/cSBP ratio of 0.492 bpm/mm Hg had the best sensitivity (91.3%) and specificity (88.4%) to distinguish neurogenic from nonneurogenic causes.
Study details: A prospective study including 444 adult patients with OH referred for autonomic evaluation to sites in the U.S. Autonomic Disorders Consortium.
Disclosures: The study authors reported no potential conflicts of interest.
Source: Norcliffe-Kaufmann L et al. Ann Neurol. 2018 Mar;83(3):522-31.
MicroRNA Could Be a Biomarker of MS
SAN DIEGO—Absence of miR-219, a microRNA (miRNA), in CSF could be a biomarker of multiple sclerosis (MS), according to data presented at the ACTRIMS 2018 Forum. If confirmed, the results could provide an objective measure to improve the diagnosis of MS.
When demyelination occurs in healthy individuals, remyelination follows. In the latter process, oligodendrocyte precursor cells repopulate the demyelinated area and create new myelin. Although large numbers of these cells surround new MS lesions, the precursor cells may fail to differentiate into mature oligodendrocytes, and thus fail to remyelinate the lesions. Data suggest that miR-219 is necessary for oligodendrocyte precursor cell differentiation in mice and rats.
Brigit A. de Jong, MD, PhD, a neurologist
An Analysis of Three Cohorts
Dr. de Jong and colleagues analyzed three independent cohorts in their study. Cohort 1 included 24 participants, Cohort 2 included 115 participants, and Cohort 3 included 112 participants. Study participants included healthy controls and patients with clinically isolated syndrome (CIS), relapsing-remitting MS, secondary progressive MS, primary progressive MS, inflammatory neurologic disease, noninflammatory neurologic disease, Alzheimer’s disease, or idiopathic intracranial hypertension. In all, 148 of the participants (59%) were women.
The absence of miR-219 in CSF was consistently associated with MS. In Cohort 1, the odds ratio for a diagnosis of progressive MS was 20.8, compared with controls, if CSF miR-219 was undetectable. In Cohort 2, the odds ratio for a diagnosis of MS or CIS was 2.6, compared with controls, if CSF miR-219 was undetectable. The odds ratio for a diagnosis of progressive MS was 3.6, compared with other neurologic disorders, if CSF miR-219 was undetectable in this cohort. In Cohort 3, the odds ratio for a diagnosis of MS was 39.7, compared with controls, if CSF miR-219 was undetectable.
Advantages of miRNAs
Detecting miRNAs in CSF is difficult because of the low levels at which they are present, said the authors. Nevertheless, miRNAs could be advantageous biomarkers because they are highly stable in body fluids, and the corresponding detection assays can be developed and multiplexed easily. Assessing the performance of miR-219 as a biomarker in situations in which MS cannot be differentiated from MS mimics will require future research, they concluded.
—Erik Greb
Suggested Reading
Agah E, Zardoui A, Saghazadeh A, et al. Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis. PLoS One. 2018 Jan 18;13(1):e0190252.
Bruinsma IB, van Dijk M, Bridel C, et al. Regulator of oligodendrocyte maturation, miR-219, a potential biomarker for MS. J Neuroinflammation. 2017;14(1):235.
Puz P, Steposz A, Lasek-Bal A, et al. Diagnostic methods used in searching for markers of atrophy in patients with multiple sclerosis. Neurol Res. 2018;40(2):110-116.
SAN DIEGO—Absence of miR-219, a microRNA (miRNA), in CSF could be a biomarker of multiple sclerosis (MS), according to data presented at the ACTRIMS 2018 Forum. If confirmed, the results could provide an objective measure to improve the diagnosis of MS.
When demyelination occurs in healthy individuals, remyelination follows. In the latter process, oligodendrocyte precursor cells repopulate the demyelinated area and create new myelin. Although large numbers of these cells surround new MS lesions, the precursor cells may fail to differentiate into mature oligodendrocytes, and thus fail to remyelinate the lesions. Data suggest that miR-219 is necessary for oligodendrocyte precursor cell differentiation in mice and rats.
Brigit A. de Jong, MD, PhD, a neurologist
An Analysis of Three Cohorts
Dr. de Jong and colleagues analyzed three independent cohorts in their study. Cohort 1 included 24 participants, Cohort 2 included 115 participants, and Cohort 3 included 112 participants. Study participants included healthy controls and patients with clinically isolated syndrome (CIS), relapsing-remitting MS, secondary progressive MS, primary progressive MS, inflammatory neurologic disease, noninflammatory neurologic disease, Alzheimer’s disease, or idiopathic intracranial hypertension. In all, 148 of the participants (59%) were women.
The absence of miR-219 in CSF was consistently associated with MS. In Cohort 1, the odds ratio for a diagnosis of progressive MS was 20.8, compared with controls, if CSF miR-219 was undetectable. In Cohort 2, the odds ratio for a diagnosis of MS or CIS was 2.6, compared with controls, if CSF miR-219 was undetectable. The odds ratio for a diagnosis of progressive MS was 3.6, compared with other neurologic disorders, if CSF miR-219 was undetectable in this cohort. In Cohort 3, the odds ratio for a diagnosis of MS was 39.7, compared with controls, if CSF miR-219 was undetectable.
Advantages of miRNAs
Detecting miRNAs in CSF is difficult because of the low levels at which they are present, said the authors. Nevertheless, miRNAs could be advantageous biomarkers because they are highly stable in body fluids, and the corresponding detection assays can be developed and multiplexed easily. Assessing the performance of miR-219 as a biomarker in situations in which MS cannot be differentiated from MS mimics will require future research, they concluded.
—Erik Greb
Suggested Reading
Agah E, Zardoui A, Saghazadeh A, et al. Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis. PLoS One. 2018 Jan 18;13(1):e0190252.
Bruinsma IB, van Dijk M, Bridel C, et al. Regulator of oligodendrocyte maturation, miR-219, a potential biomarker for MS. J Neuroinflammation. 2017;14(1):235.
Puz P, Steposz A, Lasek-Bal A, et al. Diagnostic methods used in searching for markers of atrophy in patients with multiple sclerosis. Neurol Res. 2018;40(2):110-116.
SAN DIEGO—Absence of miR-219, a microRNA (miRNA), in CSF could be a biomarker of multiple sclerosis (MS), according to data presented at the ACTRIMS 2018 Forum. If confirmed, the results could provide an objective measure to improve the diagnosis of MS.
When demyelination occurs in healthy individuals, remyelination follows. In the latter process, oligodendrocyte precursor cells repopulate the demyelinated area and create new myelin. Although large numbers of these cells surround new MS lesions, the precursor cells may fail to differentiate into mature oligodendrocytes, and thus fail to remyelinate the lesions. Data suggest that miR-219 is necessary for oligodendrocyte precursor cell differentiation in mice and rats.
Brigit A. de Jong, MD, PhD, a neurologist
An Analysis of Three Cohorts
Dr. de Jong and colleagues analyzed three independent cohorts in their study. Cohort 1 included 24 participants, Cohort 2 included 115 participants, and Cohort 3 included 112 participants. Study participants included healthy controls and patients with clinically isolated syndrome (CIS), relapsing-remitting MS, secondary progressive MS, primary progressive MS, inflammatory neurologic disease, noninflammatory neurologic disease, Alzheimer’s disease, or idiopathic intracranial hypertension. In all, 148 of the participants (59%) were women.
The absence of miR-219 in CSF was consistently associated with MS. In Cohort 1, the odds ratio for a diagnosis of progressive MS was 20.8, compared with controls, if CSF miR-219 was undetectable. In Cohort 2, the odds ratio for a diagnosis of MS or CIS was 2.6, compared with controls, if CSF miR-219 was undetectable. The odds ratio for a diagnosis of progressive MS was 3.6, compared with other neurologic disorders, if CSF miR-219 was undetectable in this cohort. In Cohort 3, the odds ratio for a diagnosis of MS was 39.7, compared with controls, if CSF miR-219 was undetectable.
Advantages of miRNAs
Detecting miRNAs in CSF is difficult because of the low levels at which they are present, said the authors. Nevertheless, miRNAs could be advantageous biomarkers because they are highly stable in body fluids, and the corresponding detection assays can be developed and multiplexed easily. Assessing the performance of miR-219 as a biomarker in situations in which MS cannot be differentiated from MS mimics will require future research, they concluded.
—Erik Greb
Suggested Reading
Agah E, Zardoui A, Saghazadeh A, et al. Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis. PLoS One. 2018 Jan 18;13(1):e0190252.
Bruinsma IB, van Dijk M, Bridel C, et al. Regulator of oligodendrocyte maturation, miR-219, a potential biomarker for MS. J Neuroinflammation. 2017;14(1):235.
Puz P, Steposz A, Lasek-Bal A, et al. Diagnostic methods used in searching for markers of atrophy in patients with multiple sclerosis. Neurol Res. 2018;40(2):110-116.
Few acutely ill hospitalized patients receive VTE prophylaxis
SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.
Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.
“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.
The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.
Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.
SOURCE: Amin A et al. THSNA 2018, Poster 51.
SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.
Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.
“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.
The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.
Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.
SOURCE: Amin A et al. THSNA 2018, Poster 51.
SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.
Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.
“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.
The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.
Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.
SOURCE: Amin A et al. THSNA 2018, Poster 51.
REPORTING FROM THSNA 2018
Key clinical point: There is a significant unmet medical need for VTE prophylaxis in the continuum of care of patients hospitalized for acute medical illnesses.
Major finding: Of the overall study population, only 7% received both inpatient and outpatient VTE prophylaxis.
Study details: An analysis of national data from 17,895 acutely ill hospitalized patients.
Disclosures: The study was funded by Portola Pharmaceuticals. The presenter reported having no financial conflicts.
Source: Amin A et al. THSNA 2018, Poster 51.
Interventionalists eager for better bioresorbable stents
WASHINGTON – The published results with bioresorbable stents have been disappointing, but most interventionalists think such devices have the potential to prevail over drug-eluting stents by addressing unmet needs, judging from a debate on this topic that took place at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center..
“There is a clinical need for bioresorbable stents [BRS] unless drug-eluting stents [DES] are perfect, and I think we agree that they are not perfect,” argued Gregg Stone, MD, director of cardiovascular research and education at Columbia University Medical Center, New York.
“It does not matter what device you evaluate,” Dr. Stone said. Whether caused by late polymer sensitivity reactions, late strut fractures, or neoatherosclerosis formation, failure can occur suddenly after a decade or more in DES that were performing well up until that point, according to data cited by Dr. Stone. This is one of the key risks that BRS technology was designed to address.
“We now know that the bioresorbable scaffold is replaced by normal tissue at 3 years,” Dr. Stone said. He reported that he is encouraged by the absence of any scaffold thrombosis after 3 years in a recent series of 501 patients with a BRS that have been followed at least 4 years. “This is the first time that we have seen that,” he asserted, adding, “The concept is there.”
His debate opponent, Stephan Windecker, MD, director of invasive cardiology at the Swiss Cardiovascular Center in Bern, cited numerous studies to conclude that “there is clear inferiority” of BRS relative to DES for most important clinical outcomes, including TLF. Although he acknowledged late TLF does occur with DES devices, he contended that new design changes are at least as likely to mitigate risk in DES as improvements in BRS.
However, Dr. Stone suggested that reductions in strut thickness might be the answer for reduced TLF for both BRS and DES devices. If so, there are several reasons to believe that this would ultimately favor BRS as the dominant technology.
“We did not get there with the 150-mcm strut thickness scaffold, but now we have struts as thin as 80 mcm. I’m pretty confident that with smaller struts we will see great results,” countered Dr. Stone.
Returning to the theme that BRS devices address an unmet need, Dr. Stone contended that BRS is the preferred strategy if advances render BRS and drug-eluting stents equally safe and effective. Not least of the reasons is patient preference. “It is an undeniable fact that based on cultural, religious, or personal beliefs, many patients prefer not to live their lives with a permanently implanted device,” he said.
The audience agreed. Asked for a show of hands regarding whether bioresorbable stents technology has the potential to address an unmet need, the majority vote was overwhelmingly in favor of Dr. Stone’s position. Based on a visual vote count that seemed to clearly affirm that BRS addresses and unmet need, Dr. Stone contended that a statistical analysis would have had a P value “with about eight zeros after the decimal point.”
Dr. Stone reports a financial relationship with Reva Medical. Dr. Windecker reports financial relationships with Abbott, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, and St. Jude.
WASHINGTON – The published results with bioresorbable stents have been disappointing, but most interventionalists think such devices have the potential to prevail over drug-eluting stents by addressing unmet needs, judging from a debate on this topic that took place at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center..
“There is a clinical need for bioresorbable stents [BRS] unless drug-eluting stents [DES] are perfect, and I think we agree that they are not perfect,” argued Gregg Stone, MD, director of cardiovascular research and education at Columbia University Medical Center, New York.
“It does not matter what device you evaluate,” Dr. Stone said. Whether caused by late polymer sensitivity reactions, late strut fractures, or neoatherosclerosis formation, failure can occur suddenly after a decade or more in DES that were performing well up until that point, according to data cited by Dr. Stone. This is one of the key risks that BRS technology was designed to address.
“We now know that the bioresorbable scaffold is replaced by normal tissue at 3 years,” Dr. Stone said. He reported that he is encouraged by the absence of any scaffold thrombosis after 3 years in a recent series of 501 patients with a BRS that have been followed at least 4 years. “This is the first time that we have seen that,” he asserted, adding, “The concept is there.”
His debate opponent, Stephan Windecker, MD, director of invasive cardiology at the Swiss Cardiovascular Center in Bern, cited numerous studies to conclude that “there is clear inferiority” of BRS relative to DES for most important clinical outcomes, including TLF. Although he acknowledged late TLF does occur with DES devices, he contended that new design changes are at least as likely to mitigate risk in DES as improvements in BRS.
However, Dr. Stone suggested that reductions in strut thickness might be the answer for reduced TLF for both BRS and DES devices. If so, there are several reasons to believe that this would ultimately favor BRS as the dominant technology.
“We did not get there with the 150-mcm strut thickness scaffold, but now we have struts as thin as 80 mcm. I’m pretty confident that with smaller struts we will see great results,” countered Dr. Stone.
Returning to the theme that BRS devices address an unmet need, Dr. Stone contended that BRS is the preferred strategy if advances render BRS and drug-eluting stents equally safe and effective. Not least of the reasons is patient preference. “It is an undeniable fact that based on cultural, religious, or personal beliefs, many patients prefer not to live their lives with a permanently implanted device,” he said.
The audience agreed. Asked for a show of hands regarding whether bioresorbable stents technology has the potential to address an unmet need, the majority vote was overwhelmingly in favor of Dr. Stone’s position. Based on a visual vote count that seemed to clearly affirm that BRS addresses and unmet need, Dr. Stone contended that a statistical analysis would have had a P value “with about eight zeros after the decimal point.”
Dr. Stone reports a financial relationship with Reva Medical. Dr. Windecker reports financial relationships with Abbott, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, and St. Jude.
WASHINGTON – The published results with bioresorbable stents have been disappointing, but most interventionalists think such devices have the potential to prevail over drug-eluting stents by addressing unmet needs, judging from a debate on this topic that took place at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center..
“There is a clinical need for bioresorbable stents [BRS] unless drug-eluting stents [DES] are perfect, and I think we agree that they are not perfect,” argued Gregg Stone, MD, director of cardiovascular research and education at Columbia University Medical Center, New York.
“It does not matter what device you evaluate,” Dr. Stone said. Whether caused by late polymer sensitivity reactions, late strut fractures, or neoatherosclerosis formation, failure can occur suddenly after a decade or more in DES that were performing well up until that point, according to data cited by Dr. Stone. This is one of the key risks that BRS technology was designed to address.
“We now know that the bioresorbable scaffold is replaced by normal tissue at 3 years,” Dr. Stone said. He reported that he is encouraged by the absence of any scaffold thrombosis after 3 years in a recent series of 501 patients with a BRS that have been followed at least 4 years. “This is the first time that we have seen that,” he asserted, adding, “The concept is there.”
His debate opponent, Stephan Windecker, MD, director of invasive cardiology at the Swiss Cardiovascular Center in Bern, cited numerous studies to conclude that “there is clear inferiority” of BRS relative to DES for most important clinical outcomes, including TLF. Although he acknowledged late TLF does occur with DES devices, he contended that new design changes are at least as likely to mitigate risk in DES as improvements in BRS.
However, Dr. Stone suggested that reductions in strut thickness might be the answer for reduced TLF for both BRS and DES devices. If so, there are several reasons to believe that this would ultimately favor BRS as the dominant technology.
“We did not get there with the 150-mcm strut thickness scaffold, but now we have struts as thin as 80 mcm. I’m pretty confident that with smaller struts we will see great results,” countered Dr. Stone.
Returning to the theme that BRS devices address an unmet need, Dr. Stone contended that BRS is the preferred strategy if advances render BRS and drug-eluting stents equally safe and effective. Not least of the reasons is patient preference. “It is an undeniable fact that based on cultural, religious, or personal beliefs, many patients prefer not to live their lives with a permanently implanted device,” he said.
The audience agreed. Asked for a show of hands regarding whether bioresorbable stents technology has the potential to address an unmet need, the majority vote was overwhelmingly in favor of Dr. Stone’s position. Based on a visual vote count that seemed to clearly affirm that BRS addresses and unmet need, Dr. Stone contended that a statistical analysis would have had a P value “with about eight zeros after the decimal point.”
Dr. Stone reports a financial relationship with Reva Medical. Dr. Windecker reports financial relationships with Abbott, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, and St. Jude.
EXPERT ANALYSIS FROM CRT 2018
Most PsA patients discontinue initial biologic within 12 months
Most adult patients with psoriatic arthritis who newly initiate biologic therapy with a tumor necrosis factor (TNF) inhibitor or anti–interleukin-12/23 inhibitor discontinued the treatment before a year is up, according to a recent analysis of a U.S. claims database.
Over a 12-month follow-up period, 27% of psoriatic arthritis (PsA) patients discontinued the index biologic, 23% switched to a different biologic, and 6% discontinued the index biologic but later restarted it, according to the results, which were published in the Journal of Managed Care & Specialty Pharmacy.
“In this population of patients with PsA, additional options for concomitant therapies or alternatives to TNF inhibitors and anti–IL-12/23 inhibitors may be important,” the authors wrote.
The retrospective, observational study included administrative claims data from the Optum research database representing 1,235 adults with PsA who newly initiated a biologic therapy between Jan. 1, 2013, and Jan. 31, 2015. The patients (53% female; mean age, 50.3 years) had received biologic therapies approved for treatment of PsA at the time. These patients had commercial health coverage or Medicare Advantage, and nearly half were from the South. About half (48%) received etanercept, 24% received adalimumab, 10% received infliximab, and the rest received golimumab, ustekinumab, or certolizumab pegol.
The mean duration of persistence with a newly initiated biologic was just 246 days, the investigators reported. Infliximab had the highest 12-month persistence in this study, investigators said, with a mean of 293 days, while certolizumab pegol had the shortest, at a mean of 207 days.
Among patients who stayed on the index biologic for at least 90 days, nearly half started an adjunctive treatment, which was usually corticosteroids (22%), opioids (17%), or an NSAID (13%), Dr. Walsh and her coauthors said.
Dose escalation of the index biologic occurred in 9.6% of patients over the 12-month follow-up, they added.
“High rates of discontinuation and switching of biologic therapies, along with high rates of dose escalation, suggest a high frequency of suboptimal biologic experience in patients with PsA,” they wrote. Although the study did not address why patients discontinued or switched, previous studies suggest adverse effects and lack of efficacy are the most commonly reported reasons.
“Insufficient control of symptoms may lead patients to discontinue biologic therapy, which can contribute to disease progression,” the authors said in their conclusion.
Novartis sponsored the study. Some study authors reported disclosures related to Novartis, including consultancy and employment, and to Optum, which was commissioned to conduct the study.
SOURCE: Walsh JA et al. J Manag Care Spec Pharm. 2018 Mar 20. doi: 10.18553/jmcp.2018.17388.
Most adult patients with psoriatic arthritis who newly initiate biologic therapy with a tumor necrosis factor (TNF) inhibitor or anti–interleukin-12/23 inhibitor discontinued the treatment before a year is up, according to a recent analysis of a U.S. claims database.
Over a 12-month follow-up period, 27% of psoriatic arthritis (PsA) patients discontinued the index biologic, 23% switched to a different biologic, and 6% discontinued the index biologic but later restarted it, according to the results, which were published in the Journal of Managed Care & Specialty Pharmacy.
“In this population of patients with PsA, additional options for concomitant therapies or alternatives to TNF inhibitors and anti–IL-12/23 inhibitors may be important,” the authors wrote.
The retrospective, observational study included administrative claims data from the Optum research database representing 1,235 adults with PsA who newly initiated a biologic therapy between Jan. 1, 2013, and Jan. 31, 2015. The patients (53% female; mean age, 50.3 years) had received biologic therapies approved for treatment of PsA at the time. These patients had commercial health coverage or Medicare Advantage, and nearly half were from the South. About half (48%) received etanercept, 24% received adalimumab, 10% received infliximab, and the rest received golimumab, ustekinumab, or certolizumab pegol.
The mean duration of persistence with a newly initiated biologic was just 246 days, the investigators reported. Infliximab had the highest 12-month persistence in this study, investigators said, with a mean of 293 days, while certolizumab pegol had the shortest, at a mean of 207 days.
Among patients who stayed on the index biologic for at least 90 days, nearly half started an adjunctive treatment, which was usually corticosteroids (22%), opioids (17%), or an NSAID (13%), Dr. Walsh and her coauthors said.
Dose escalation of the index biologic occurred in 9.6% of patients over the 12-month follow-up, they added.
“High rates of discontinuation and switching of biologic therapies, along with high rates of dose escalation, suggest a high frequency of suboptimal biologic experience in patients with PsA,” they wrote. Although the study did not address why patients discontinued or switched, previous studies suggest adverse effects and lack of efficacy are the most commonly reported reasons.
“Insufficient control of symptoms may lead patients to discontinue biologic therapy, which can contribute to disease progression,” the authors said in their conclusion.
Novartis sponsored the study. Some study authors reported disclosures related to Novartis, including consultancy and employment, and to Optum, which was commissioned to conduct the study.
SOURCE: Walsh JA et al. J Manag Care Spec Pharm. 2018 Mar 20. doi: 10.18553/jmcp.2018.17388.
Most adult patients with psoriatic arthritis who newly initiate biologic therapy with a tumor necrosis factor (TNF) inhibitor or anti–interleukin-12/23 inhibitor discontinued the treatment before a year is up, according to a recent analysis of a U.S. claims database.
Over a 12-month follow-up period, 27% of psoriatic arthritis (PsA) patients discontinued the index biologic, 23% switched to a different biologic, and 6% discontinued the index biologic but later restarted it, according to the results, which were published in the Journal of Managed Care & Specialty Pharmacy.
“In this population of patients with PsA, additional options for concomitant therapies or alternatives to TNF inhibitors and anti–IL-12/23 inhibitors may be important,” the authors wrote.
The retrospective, observational study included administrative claims data from the Optum research database representing 1,235 adults with PsA who newly initiated a biologic therapy between Jan. 1, 2013, and Jan. 31, 2015. The patients (53% female; mean age, 50.3 years) had received biologic therapies approved for treatment of PsA at the time. These patients had commercial health coverage or Medicare Advantage, and nearly half were from the South. About half (48%) received etanercept, 24% received adalimumab, 10% received infliximab, and the rest received golimumab, ustekinumab, or certolizumab pegol.
The mean duration of persistence with a newly initiated biologic was just 246 days, the investigators reported. Infliximab had the highest 12-month persistence in this study, investigators said, with a mean of 293 days, while certolizumab pegol had the shortest, at a mean of 207 days.
Among patients who stayed on the index biologic for at least 90 days, nearly half started an adjunctive treatment, which was usually corticosteroids (22%), opioids (17%), or an NSAID (13%), Dr. Walsh and her coauthors said.
Dose escalation of the index biologic occurred in 9.6% of patients over the 12-month follow-up, they added.
“High rates of discontinuation and switching of biologic therapies, along with high rates of dose escalation, suggest a high frequency of suboptimal biologic experience in patients with PsA,” they wrote. Although the study did not address why patients discontinued or switched, previous studies suggest adverse effects and lack of efficacy are the most commonly reported reasons.
“Insufficient control of symptoms may lead patients to discontinue biologic therapy, which can contribute to disease progression,” the authors said in their conclusion.
Novartis sponsored the study. Some study authors reported disclosures related to Novartis, including consultancy and employment, and to Optum, which was commissioned to conduct the study.
SOURCE: Walsh JA et al. J Manag Care Spec Pharm. 2018 Mar 20. doi: 10.18553/jmcp.2018.17388.
FROM THE JOURNAL OF MANAGED CARE & SPECIALTY PHARMACY
Key clinical point: While treatment persistence is important to achieve optimal outcomes,
Major finding: Over a 12-month follow-up period, 27% of patients discontinued the index biologic, 23% switched to a different biologic, and 6% discontinued the index biologic but later restarted it.
Study details: A retrospective, observational study of U.S. administrative claims data representing 1,235 adults with PsA who newly initiated a biologic therapy between Jan. 1, 2013, and Jan. 31, 2015.
Disclosures: Novartis sponsored the study. Some study authors reported disclosures related to Novartis, including consultancy and employment, and to Optum, which was commissioned to conduct the study.
Source: Walsh JA et al. J Manag Care Spec Pharm. 2018 Mar 20. doi: 10.18553/jmcp.2018.17388.
Patients who hide. Patients who seek.
Some people are more likely to seek medical care, and some people are less likely, but which type is more common? The results of a survey of over 14,000 Medicare beneficiaries suggest that the avoid-care type may be a bit more prevalent.
In the survey, 40% of respondents said that they were more likely to keep it to themselves when they got sick, but 36% visit a physician as soon as they feel bad. Almost 29% reported that they avoid going to a physician, but 25% worry about their own health more than others, the Centers for Medicare & Medicaid Services reported based on the results of the 2015 Medicare Current Beneficiary Survey.
Race and ethnicity made a big difference for some questions: 59% of Hispanics said that they visit a doctor as soon as they feel bad, compared with 44% of non-Hispanic blacks and 31% of non-Hispanic whites. That same order was seen for “worry about your health more than others” – 54% Hispanic, 38% black, and 19% white – and for “avoid going to the doctor” – 44% Hispanic, 34% black, and 26% white, the CMS reported.
The three groups, which were the only race/ethnicities included in the report, were all around 40% for “when sick, keep it to yourself,” while two of the three were the same for “had a problem and did not seek a doctor” (blacks and Hispanics at 14% and whites at 10%) and for “ever had a prescription you did not fill” (whites and Hispanics at 7% and blacks at 10%), the report said.
The estimates on propensity to seek care did not include Medicare recipients who lived part or all of the year in a long-term care facility, which was about 4% of the Medicare population in 2015. The survey included a total of 14,068 respondents.
Some people are more likely to seek medical care, and some people are less likely, but which type is more common? The results of a survey of over 14,000 Medicare beneficiaries suggest that the avoid-care type may be a bit more prevalent.
In the survey, 40% of respondents said that they were more likely to keep it to themselves when they got sick, but 36% visit a physician as soon as they feel bad. Almost 29% reported that they avoid going to a physician, but 25% worry about their own health more than others, the Centers for Medicare & Medicaid Services reported based on the results of the 2015 Medicare Current Beneficiary Survey.
Race and ethnicity made a big difference for some questions: 59% of Hispanics said that they visit a doctor as soon as they feel bad, compared with 44% of non-Hispanic blacks and 31% of non-Hispanic whites. That same order was seen for “worry about your health more than others” – 54% Hispanic, 38% black, and 19% white – and for “avoid going to the doctor” – 44% Hispanic, 34% black, and 26% white, the CMS reported.
The three groups, which were the only race/ethnicities included in the report, were all around 40% for “when sick, keep it to yourself,” while two of the three were the same for “had a problem and did not seek a doctor” (blacks and Hispanics at 14% and whites at 10%) and for “ever had a prescription you did not fill” (whites and Hispanics at 7% and blacks at 10%), the report said.
The estimates on propensity to seek care did not include Medicare recipients who lived part or all of the year in a long-term care facility, which was about 4% of the Medicare population in 2015. The survey included a total of 14,068 respondents.
Some people are more likely to seek medical care, and some people are less likely, but which type is more common? The results of a survey of over 14,000 Medicare beneficiaries suggest that the avoid-care type may be a bit more prevalent.
In the survey, 40% of respondents said that they were more likely to keep it to themselves when they got sick, but 36% visit a physician as soon as they feel bad. Almost 29% reported that they avoid going to a physician, but 25% worry about their own health more than others, the Centers for Medicare & Medicaid Services reported based on the results of the 2015 Medicare Current Beneficiary Survey.
Race and ethnicity made a big difference for some questions: 59% of Hispanics said that they visit a doctor as soon as they feel bad, compared with 44% of non-Hispanic blacks and 31% of non-Hispanic whites. That same order was seen for “worry about your health more than others” – 54% Hispanic, 38% black, and 19% white – and for “avoid going to the doctor” – 44% Hispanic, 34% black, and 26% white, the CMS reported.
The three groups, which were the only race/ethnicities included in the report, were all around 40% for “when sick, keep it to yourself,” while two of the three were the same for “had a problem and did not seek a doctor” (blacks and Hispanics at 14% and whites at 10%) and for “ever had a prescription you did not fill” (whites and Hispanics at 7% and blacks at 10%), the report said.
The estimates on propensity to seek care did not include Medicare recipients who lived part or all of the year in a long-term care facility, which was about 4% of the Medicare population in 2015. The survey included a total of 14,068 respondents.
Certolizumab pegol: Has serious infection risk been overstated?
Contrary to prior reports, certolizumab pegol may not be associated with an increased risk of serious infections versus other biologics used in the treatment of rheumatoid arthritis, according to results of a recent U.K. registry study.
Certolizumab pegol (Cimzia) actually had a lower risk of serious infections, compared with etanercept in the primary analysis, according to a report on the study recently published in Annals of the Rheumatic Diseases.
In sensitivity analyses, though, the result in favor of certolizumab pegol was no longer significant, according to lead author Andrew I. Rutherford, MBBS, of King’s College London, and his coauthors.
“From these results, it would be wrong to conclude that certolizumab pegol has a lower rate of [serious infection] than other biologics,” Dr. Rutherford and his colleagues said in their report. “However, the risk does not appear to be significantly higher as has previously been suggested.”
The prospective, observational cohort study, based on data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), represented 19,282 patients with 46,771 years of follow-up, according to the authors.
For the entire cohort, the incidence of serious infections was 5.51 cases per 100 patient-years (95% confidence interval, 5.29-5.71), and the 30-day mortality after serious infection was 10.4% (95% CI, 9.2%-11.6%), the report said. Compared with etanercept, the risk of serious infections was lower for certolizumab pegol (adjusted hazard ratio, 0.75; 95% CI, 0.58-0.97). Etanercept was used as the reference arm for comparison since it was the most widely prescribed drug in the registry.
That finding is in “direct contradiction” to a 2011 Cochrane review finding that certolizumab pegol was associated with an infection rate three to four times higher than other anti–tumor necrosis factor (anti-TNF) drugs (Cochrane Database Syst Rev. 2011;2:Cd008794), the authors noted.
“It would seem unusual for drugs acting on the same pathway with similar efficacy to have such drastically different infection risks,” Dr. Rutherford and his coauthors observed in their report.
However, investigators noticed that in the certolizumab pegol cohort, a large number of patients had not previously been on a biologic. When those biologic-naive patients were excluded from analysis, there was no longer a difference in infection rate favoring certolizumab pegol. “This suggests that unmeasured confounders may be responsible for the difference that was observed in the primary analysis,” the investigators said in their discussion of the results.
The Cochrane review showing an increased risk of serious infections with certolizumab pegol was a large network meta-analysis, which they said relies on indirect comparisons between drugs and could be prone to error if there are differences in study design.
“In contrast, national registers use the same methodology for detecting and reporting of adverse events for each drug,” they added.
Dr. Rutherford reported no disclosures. Study coauthors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
SOURCE: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.
Contrary to prior reports, certolizumab pegol may not be associated with an increased risk of serious infections versus other biologics used in the treatment of rheumatoid arthritis, according to results of a recent U.K. registry study.
Certolizumab pegol (Cimzia) actually had a lower risk of serious infections, compared with etanercept in the primary analysis, according to a report on the study recently published in Annals of the Rheumatic Diseases.
In sensitivity analyses, though, the result in favor of certolizumab pegol was no longer significant, according to lead author Andrew I. Rutherford, MBBS, of King’s College London, and his coauthors.
“From these results, it would be wrong to conclude that certolizumab pegol has a lower rate of [serious infection] than other biologics,” Dr. Rutherford and his colleagues said in their report. “However, the risk does not appear to be significantly higher as has previously been suggested.”
The prospective, observational cohort study, based on data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), represented 19,282 patients with 46,771 years of follow-up, according to the authors.
For the entire cohort, the incidence of serious infections was 5.51 cases per 100 patient-years (95% confidence interval, 5.29-5.71), and the 30-day mortality after serious infection was 10.4% (95% CI, 9.2%-11.6%), the report said. Compared with etanercept, the risk of serious infections was lower for certolizumab pegol (adjusted hazard ratio, 0.75; 95% CI, 0.58-0.97). Etanercept was used as the reference arm for comparison since it was the most widely prescribed drug in the registry.
That finding is in “direct contradiction” to a 2011 Cochrane review finding that certolizumab pegol was associated with an infection rate three to four times higher than other anti–tumor necrosis factor (anti-TNF) drugs (Cochrane Database Syst Rev. 2011;2:Cd008794), the authors noted.
“It would seem unusual for drugs acting on the same pathway with similar efficacy to have such drastically different infection risks,” Dr. Rutherford and his coauthors observed in their report.
However, investigators noticed that in the certolizumab pegol cohort, a large number of patients had not previously been on a biologic. When those biologic-naive patients were excluded from analysis, there was no longer a difference in infection rate favoring certolizumab pegol. “This suggests that unmeasured confounders may be responsible for the difference that was observed in the primary analysis,” the investigators said in their discussion of the results.
The Cochrane review showing an increased risk of serious infections with certolizumab pegol was a large network meta-analysis, which they said relies on indirect comparisons between drugs and could be prone to error if there are differences in study design.
“In contrast, national registers use the same methodology for detecting and reporting of adverse events for each drug,” they added.
Dr. Rutherford reported no disclosures. Study coauthors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
SOURCE: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.
Contrary to prior reports, certolizumab pegol may not be associated with an increased risk of serious infections versus other biologics used in the treatment of rheumatoid arthritis, according to results of a recent U.K. registry study.
Certolizumab pegol (Cimzia) actually had a lower risk of serious infections, compared with etanercept in the primary analysis, according to a report on the study recently published in Annals of the Rheumatic Diseases.
In sensitivity analyses, though, the result in favor of certolizumab pegol was no longer significant, according to lead author Andrew I. Rutherford, MBBS, of King’s College London, and his coauthors.
“From these results, it would be wrong to conclude that certolizumab pegol has a lower rate of [serious infection] than other biologics,” Dr. Rutherford and his colleagues said in their report. “However, the risk does not appear to be significantly higher as has previously been suggested.”
The prospective, observational cohort study, based on data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), represented 19,282 patients with 46,771 years of follow-up, according to the authors.
For the entire cohort, the incidence of serious infections was 5.51 cases per 100 patient-years (95% confidence interval, 5.29-5.71), and the 30-day mortality after serious infection was 10.4% (95% CI, 9.2%-11.6%), the report said. Compared with etanercept, the risk of serious infections was lower for certolizumab pegol (adjusted hazard ratio, 0.75; 95% CI, 0.58-0.97). Etanercept was used as the reference arm for comparison since it was the most widely prescribed drug in the registry.
That finding is in “direct contradiction” to a 2011 Cochrane review finding that certolizumab pegol was associated with an infection rate three to four times higher than other anti–tumor necrosis factor (anti-TNF) drugs (Cochrane Database Syst Rev. 2011;2:Cd008794), the authors noted.
“It would seem unusual for drugs acting on the same pathway with similar efficacy to have such drastically different infection risks,” Dr. Rutherford and his coauthors observed in their report.
However, investigators noticed that in the certolizumab pegol cohort, a large number of patients had not previously been on a biologic. When those biologic-naive patients were excluded from analysis, there was no longer a difference in infection rate favoring certolizumab pegol. “This suggests that unmeasured confounders may be responsible for the difference that was observed in the primary analysis,” the investigators said in their discussion of the results.
The Cochrane review showing an increased risk of serious infections with certolizumab pegol was a large network meta-analysis, which they said relies on indirect comparisons between drugs and could be prone to error if there are differences in study design.
“In contrast, national registers use the same methodology for detecting and reporting of adverse events for each drug,” they added.
Dr. Rutherford reported no disclosures. Study coauthors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
SOURCE: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: Certolizumab pegol had a lower risk of serious infections compared to etanercept (HR, 0.75; 95% CI, 0.58-0.97), though in sensitivity analyses, the difference was no longer significant.
Study details: A prospective observational cohort study of data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) representing 19,282 patients with 46,771 years of follow-up.
Disclosures: Study authors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
Source: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.
Wound protectors lower risk of surgical site infections
particularly dual-ring devices, new research suggests.
A meta-analysis of 12 randomized, controlled trials with 3,029 participants found that the use of wound protectors during surgery was associated with 34% lower odds of surgical site infection (95% confidence interval, 0.45–0.90; P less than .01).
The study, published in the March edition of Surgical Endoscopy, also showed that dual-ring wound protectors were associated with a highly significant 69% reduction in the odds of surgical site infections (95% CI, 0.18-0.52; P less than .0001), while the benefits of single-ring wound protectors did not reach statistical significance (OR, 0.84; 95% CI, 0.67–1.04; P = .11).
Wound protectors – also known as wound guards or wound retractors – are intended to prevent the edges of a surgical wound from coming into contact with the contaminated surgical field.
The single-ring model consists of a plastic ring that sits within the wound and a protective drape that extends out from it. In the dual-ring model, one ring sits inside the wound and the other outside the wound, with the two rings joined by the protective plastic.
Of the 12 studies included in the meta-analysis, 5 involved colorectal surgery only, 5 included both colorectal and other gastrointestinal surgery, and 2 studies focused on appendectomies. All but one study involved open surgery.
“Our study is more specific in the interventions included in that we included lower gastrointestinal surgery only, which is a population that would likely benefit the most from the intervention due to the high incidence of SSIs in bowel surgery, compared to other abdominal surgeries,” wrote Lisa Zhang, MD, a general surgery resident at the department of surgery at Kingston (Ont.) General Hospital and her coauthors.
There was no difference in the effect of wound protectors based on the target organ for surgery, even with a high number of patients in one of the appendectomy trials, which the authors were concerned may have skewed the results.
Overall, the authors rated the evidence to be of moderate quality, but several studies had a high risk of bias.
The authors said that one barrier to routine use of these devices was cost. However, given that surgical site infections are estimated to cost around $3.5 billion to $10 billion annually in health care expenditures, they argued that “the use of dual-ring wound edge protectors should be considered in open lower gastrointestinal surgery, including open appendectomies.”
No funding sources or conflicts of interest were declared.
SOURCE: Zhang L et al. Surg Endosc. 2018;32:1111–22.
particularly dual-ring devices, new research suggests.
A meta-analysis of 12 randomized, controlled trials with 3,029 participants found that the use of wound protectors during surgery was associated with 34% lower odds of surgical site infection (95% confidence interval, 0.45–0.90; P less than .01).
The study, published in the March edition of Surgical Endoscopy, also showed that dual-ring wound protectors were associated with a highly significant 69% reduction in the odds of surgical site infections (95% CI, 0.18-0.52; P less than .0001), while the benefits of single-ring wound protectors did not reach statistical significance (OR, 0.84; 95% CI, 0.67–1.04; P = .11).
Wound protectors – also known as wound guards or wound retractors – are intended to prevent the edges of a surgical wound from coming into contact with the contaminated surgical field.
The single-ring model consists of a plastic ring that sits within the wound and a protective drape that extends out from it. In the dual-ring model, one ring sits inside the wound and the other outside the wound, with the two rings joined by the protective plastic.
Of the 12 studies included in the meta-analysis, 5 involved colorectal surgery only, 5 included both colorectal and other gastrointestinal surgery, and 2 studies focused on appendectomies. All but one study involved open surgery.
“Our study is more specific in the interventions included in that we included lower gastrointestinal surgery only, which is a population that would likely benefit the most from the intervention due to the high incidence of SSIs in bowel surgery, compared to other abdominal surgeries,” wrote Lisa Zhang, MD, a general surgery resident at the department of surgery at Kingston (Ont.) General Hospital and her coauthors.
There was no difference in the effect of wound protectors based on the target organ for surgery, even with a high number of patients in one of the appendectomy trials, which the authors were concerned may have skewed the results.
Overall, the authors rated the evidence to be of moderate quality, but several studies had a high risk of bias.
The authors said that one barrier to routine use of these devices was cost. However, given that surgical site infections are estimated to cost around $3.5 billion to $10 billion annually in health care expenditures, they argued that “the use of dual-ring wound edge protectors should be considered in open lower gastrointestinal surgery, including open appendectomies.”
No funding sources or conflicts of interest were declared.
SOURCE: Zhang L et al. Surg Endosc. 2018;32:1111–22.
particularly dual-ring devices, new research suggests.
A meta-analysis of 12 randomized, controlled trials with 3,029 participants found that the use of wound protectors during surgery was associated with 34% lower odds of surgical site infection (95% confidence interval, 0.45–0.90; P less than .01).
The study, published in the March edition of Surgical Endoscopy, also showed that dual-ring wound protectors were associated with a highly significant 69% reduction in the odds of surgical site infections (95% CI, 0.18-0.52; P less than .0001), while the benefits of single-ring wound protectors did not reach statistical significance (OR, 0.84; 95% CI, 0.67–1.04; P = .11).
Wound protectors – also known as wound guards or wound retractors – are intended to prevent the edges of a surgical wound from coming into contact with the contaminated surgical field.
The single-ring model consists of a plastic ring that sits within the wound and a protective drape that extends out from it. In the dual-ring model, one ring sits inside the wound and the other outside the wound, with the two rings joined by the protective plastic.
Of the 12 studies included in the meta-analysis, 5 involved colorectal surgery only, 5 included both colorectal and other gastrointestinal surgery, and 2 studies focused on appendectomies. All but one study involved open surgery.
“Our study is more specific in the interventions included in that we included lower gastrointestinal surgery only, which is a population that would likely benefit the most from the intervention due to the high incidence of SSIs in bowel surgery, compared to other abdominal surgeries,” wrote Lisa Zhang, MD, a general surgery resident at the department of surgery at Kingston (Ont.) General Hospital and her coauthors.
There was no difference in the effect of wound protectors based on the target organ for surgery, even with a high number of patients in one of the appendectomy trials, which the authors were concerned may have skewed the results.
Overall, the authors rated the evidence to be of moderate quality, but several studies had a high risk of bias.
The authors said that one barrier to routine use of these devices was cost. However, given that surgical site infections are estimated to cost around $3.5 billion to $10 billion annually in health care expenditures, they argued that “the use of dual-ring wound edge protectors should be considered in open lower gastrointestinal surgery, including open appendectomies.”
No funding sources or conflicts of interest were declared.
SOURCE: Zhang L et al. Surg Endosc. 2018;32:1111–22.
FROM SURGICAL ENDOSCOPY
Key clinical point: Dual-ring wound protectors significantly decrease the risk of gastrointestinal surgical site infections.
Major finding: Dual-ring wound protectors were associated with a 69% reduction in the odds of surgical site infections.
Study details: A meta-analysis of 12 randomized, controlled trials.
Disclosures: No funding source or conflicts of interest were declared.
Source: Zhang L et al. Surg Endosc. 2018;32:1111–22.
Clean-Surfaced Nanocrystalline Gold May Promote Remyelination
SAN DIEGO—A novel therapy designed to promote the maturation and activation of myelin-producing oligodendrocytes is moving to phase II clinical trials based on evidence of safety and efficacy in animal models and humans. The therapy, a suspension of clean-surfaced gold nanocrystals, may remyelinate multiple sclerosis (MS) lesions, according to research presented at the ACTRIMS 2018 Forum.
This agent, known as CNM-Au8, has been associated with improved behavioral function in animal models of MS, according to Michael Hotchkin, Head of Strategic Operations at Clene Nanomedicine in Salt Lake City. Clene Nanomedicine is developing CNM-Au8. Although the mechanism of action is “multifactorial,” the benefit has been linked to bioenergetic support for the differentiation and maturation of oligodendrocyte precursor cells, said Mr. Hotchkin.
In one behavioral study of fine motor kinetics in an experimental model of MS, mice treated with CNM-Au8 “were effectively indistinguishable” from animals with no demyelination, he said.
Treatment Improved Two Models of Demyelination
Following in vitro studies that suggested that CNM-Au8 can promote the differentiation of oligodendrocyte precursor cells into mature myelin-producing oligodendrocytes, a series of studies was conducted in lysolecithin and cuprizone animal models of MS demyelination.
The studies using the lysolecithin model included vehicle controls and compared CNM-Au8’s effect on remyelinated axons after inducing spinal demyelination with lysolecithin. In the cuprizone studies, the treatments were delivered before injury to test prophylactic efficacy and after injury to test treatment efficacy. Markers of remyelination, such as oligodendrocyte maturation, myelin basic protein expression, and axonal staining, were evaluated by immunohistochemistry and transmission electron microscopy in animals sacrificed at various times after injury.
CNM-Au8 produced “striking visible evidence of progressive increase in myelin,” according to Mr. Hotchkin. The treatment was associated with reductions in myelin sheath degeneration and demyelinated areas, relative to vehicle. In one analysis of the lysolecithin model, CNM-Au8 was associated with a 43% increase in myelinated axon count. Moreover, an increase in mature oligodendrocytes localized at the site of focal demyelination injury in the CNM-Au8-treated animals was consistent with stimulation of oligodendrocyte maturation, according to Mr. Hotchkin.
In both models, investigators found evidence of increased oligodendrocyte maturation and remyelination when CNM-Au8 was administered after injury, as well as when it was administered before injury. The results suggest that CNM-Au8 has important activity in the remyelination of demyelinated axons.
Researchers also conducted behavioral studies in the cuprizone model of MS. They tracked the animals’ movement with lasers and used computer software to analyze the movement. These studies included relevant controls and compared animals with no demyelination, vehicle-treated animals dosed with cuprizone, and CNM-Au8-treated animals similarly dosed with cuprizone, to determine whether delayed treatment following initial damage from the toxin would result in functional recovery in the animals.
The investigators observed protective effects of CNM-Au8 when the drug was administered in this treatment paradigm. Improvements in several behavioral end points when the drug was administered after the demyelinating insult “demonstrated that CNM-Au8 restored behavioral function following demyelination,” said Mr. Hotchkin.
Furthermore, in a behavioral study of fine motor kinetics, function improved by 78% at week 6, compared with week 3 (ie, immediately following the start of treatment) in the group treated with CMN-Au8 that was receiving cuprizone. The animals treated with vehicle and cuprizone had a 39% functional improvement at week 6, compared with week 3. Notably, there was not a statistically significant difference in function at week 6 between CNM-Au8-treated animals and the normal healthy control animals without demyelination, indicating that the functional recovery made the former and latter animals indistinguishable.
Therapy Promotes Bioenergetics Catalysis
CNM-Au8 may generate remyelination by more than one mechanism, said Mr. Hotchkin, and evidence indicates that the drug promotes bioenergetic catalysis that is important to the maturation of oligodendrocyte precursors. Published literature suggests an association between altered oligodendrocyte energy utilization and remyelination failure in the human brain. Other evidence suggests that CNM-Au8 may trigger oligodendrocytes’ remyelinating activity by improving energy sources such as adenosine triphosphate, lactate, and oxidized nicotinamide adenine dinucleotide (NAD+), said Mr. Hotchkin. For example, CNM-Au8 increased NAD+ levels in mouse hippocampal cultures by about 40%, relative to vehicle.
In response to questions about the catalytic mechanism, Mr. Hotchkin responded, “You can fill a car’s tank with gas, but if the electrical system is fouled, the car goes nowhere. CNM-Au8 is the catalytic engine driving bioenergetic improvements in the oligodendrocytes driving them to remyelinate.” Data suggest that CNM-Au8 may have applications in other neurodegenerative diseases, based on the bioenergetic failure hypothesis of neurodegeneration and aging, said Mr. Hotchkin.
Oligodendrocyte precursor cells are known to be present in the human brain in and around MS lesions even years after an MS attack. Thus, the animal studies may be relevant to clinical MS. As an oral agent, CNM-Au8 has the potential to be a major clinical advance if human trials show activity comparable to that in animal studies, said Mr. Hotchkin.
Initial phase I human clinical work and extensive animal toxicology has supported the safety of this agent. Trials in patients with MS that examine clinical end points are planned. “A phase II study in chronic optic neuropathy in relapsing-remitting MS patients will commence in 2018,” Glen Frick, MD, PhD, Chief Medical Officer of Clene Nanomedicine, told Neurology Reviews.
—Ted Bosworth
Suggested Reading
Rone
SAN DIEGO—A novel therapy designed to promote the maturation and activation of myelin-producing oligodendrocytes is moving to phase II clinical trials based on evidence of safety and efficacy in animal models and humans. The therapy, a suspension of clean-surfaced gold nanocrystals, may remyelinate multiple sclerosis (MS) lesions, according to research presented at the ACTRIMS 2018 Forum.
This agent, known as CNM-Au8, has been associated with improved behavioral function in animal models of MS, according to Michael Hotchkin, Head of Strategic Operations at Clene Nanomedicine in Salt Lake City. Clene Nanomedicine is developing CNM-Au8. Although the mechanism of action is “multifactorial,” the benefit has been linked to bioenergetic support for the differentiation and maturation of oligodendrocyte precursor cells, said Mr. Hotchkin.
In one behavioral study of fine motor kinetics in an experimental model of MS, mice treated with CNM-Au8 “were effectively indistinguishable” from animals with no demyelination, he said.
Treatment Improved Two Models of Demyelination
Following in vitro studies that suggested that CNM-Au8 can promote the differentiation of oligodendrocyte precursor cells into mature myelin-producing oligodendrocytes, a series of studies was conducted in lysolecithin and cuprizone animal models of MS demyelination.
The studies using the lysolecithin model included vehicle controls and compared CNM-Au8’s effect on remyelinated axons after inducing spinal demyelination with lysolecithin. In the cuprizone studies, the treatments were delivered before injury to test prophylactic efficacy and after injury to test treatment efficacy. Markers of remyelination, such as oligodendrocyte maturation, myelin basic protein expression, and axonal staining, were evaluated by immunohistochemistry and transmission electron microscopy in animals sacrificed at various times after injury.
CNM-Au8 produced “striking visible evidence of progressive increase in myelin,” according to Mr. Hotchkin. The treatment was associated with reductions in myelin sheath degeneration and demyelinated areas, relative to vehicle. In one analysis of the lysolecithin model, CNM-Au8 was associated with a 43% increase in myelinated axon count. Moreover, an increase in mature oligodendrocytes localized at the site of focal demyelination injury in the CNM-Au8-treated animals was consistent with stimulation of oligodendrocyte maturation, according to Mr. Hotchkin.
In both models, investigators found evidence of increased oligodendrocyte maturation and remyelination when CNM-Au8 was administered after injury, as well as when it was administered before injury. The results suggest that CNM-Au8 has important activity in the remyelination of demyelinated axons.
Researchers also conducted behavioral studies in the cuprizone model of MS. They tracked the animals’ movement with lasers and used computer software to analyze the movement. These studies included relevant controls and compared animals with no demyelination, vehicle-treated animals dosed with cuprizone, and CNM-Au8-treated animals similarly dosed with cuprizone, to determine whether delayed treatment following initial damage from the toxin would result in functional recovery in the animals.
The investigators observed protective effects of CNM-Au8 when the drug was administered in this treatment paradigm. Improvements in several behavioral end points when the drug was administered after the demyelinating insult “demonstrated that CNM-Au8 restored behavioral function following demyelination,” said Mr. Hotchkin.
Furthermore, in a behavioral study of fine motor kinetics, function improved by 78% at week 6, compared with week 3 (ie, immediately following the start of treatment) in the group treated with CMN-Au8 that was receiving cuprizone. The animals treated with vehicle and cuprizone had a 39% functional improvement at week 6, compared with week 3. Notably, there was not a statistically significant difference in function at week 6 between CNM-Au8-treated animals and the normal healthy control animals without demyelination, indicating that the functional recovery made the former and latter animals indistinguishable.
Therapy Promotes Bioenergetics Catalysis
CNM-Au8 may generate remyelination by more than one mechanism, said Mr. Hotchkin, and evidence indicates that the drug promotes bioenergetic catalysis that is important to the maturation of oligodendrocyte precursors. Published literature suggests an association between altered oligodendrocyte energy utilization and remyelination failure in the human brain. Other evidence suggests that CNM-Au8 may trigger oligodendrocytes’ remyelinating activity by improving energy sources such as adenosine triphosphate, lactate, and oxidized nicotinamide adenine dinucleotide (NAD+), said Mr. Hotchkin. For example, CNM-Au8 increased NAD+ levels in mouse hippocampal cultures by about 40%, relative to vehicle.
In response to questions about the catalytic mechanism, Mr. Hotchkin responded, “You can fill a car’s tank with gas, but if the electrical system is fouled, the car goes nowhere. CNM-Au8 is the catalytic engine driving bioenergetic improvements in the oligodendrocytes driving them to remyelinate.” Data suggest that CNM-Au8 may have applications in other neurodegenerative diseases, based on the bioenergetic failure hypothesis of neurodegeneration and aging, said Mr. Hotchkin.
Oligodendrocyte precursor cells are known to be present in the human brain in and around MS lesions even years after an MS attack. Thus, the animal studies may be relevant to clinical MS. As an oral agent, CNM-Au8 has the potential to be a major clinical advance if human trials show activity comparable to that in animal studies, said Mr. Hotchkin.
Initial phase I human clinical work and extensive animal toxicology has supported the safety of this agent. Trials in patients with MS that examine clinical end points are planned. “A phase II study in chronic optic neuropathy in relapsing-remitting MS patients will commence in 2018,” Glen Frick, MD, PhD, Chief Medical Officer of Clene Nanomedicine, told Neurology Reviews.
—Ted Bosworth
Suggested Reading
Rone
SAN DIEGO—A novel therapy designed to promote the maturation and activation of myelin-producing oligodendrocytes is moving to phase II clinical trials based on evidence of safety and efficacy in animal models and humans. The therapy, a suspension of clean-surfaced gold nanocrystals, may remyelinate multiple sclerosis (MS) lesions, according to research presented at the ACTRIMS 2018 Forum.
This agent, known as CNM-Au8, has been associated with improved behavioral function in animal models of MS, according to Michael Hotchkin, Head of Strategic Operations at Clene Nanomedicine in Salt Lake City. Clene Nanomedicine is developing CNM-Au8. Although the mechanism of action is “multifactorial,” the benefit has been linked to bioenergetic support for the differentiation and maturation of oligodendrocyte precursor cells, said Mr. Hotchkin.
In one behavioral study of fine motor kinetics in an experimental model of MS, mice treated with CNM-Au8 “were effectively indistinguishable” from animals with no demyelination, he said.
Treatment Improved Two Models of Demyelination
Following in vitro studies that suggested that CNM-Au8 can promote the differentiation of oligodendrocyte precursor cells into mature myelin-producing oligodendrocytes, a series of studies was conducted in lysolecithin and cuprizone animal models of MS demyelination.
The studies using the lysolecithin model included vehicle controls and compared CNM-Au8’s effect on remyelinated axons after inducing spinal demyelination with lysolecithin. In the cuprizone studies, the treatments were delivered before injury to test prophylactic efficacy and after injury to test treatment efficacy. Markers of remyelination, such as oligodendrocyte maturation, myelin basic protein expression, and axonal staining, were evaluated by immunohistochemistry and transmission electron microscopy in animals sacrificed at various times after injury.
CNM-Au8 produced “striking visible evidence of progressive increase in myelin,” according to Mr. Hotchkin. The treatment was associated with reductions in myelin sheath degeneration and demyelinated areas, relative to vehicle. In one analysis of the lysolecithin model, CNM-Au8 was associated with a 43% increase in myelinated axon count. Moreover, an increase in mature oligodendrocytes localized at the site of focal demyelination injury in the CNM-Au8-treated animals was consistent with stimulation of oligodendrocyte maturation, according to Mr. Hotchkin.
In both models, investigators found evidence of increased oligodendrocyte maturation and remyelination when CNM-Au8 was administered after injury, as well as when it was administered before injury. The results suggest that CNM-Au8 has important activity in the remyelination of demyelinated axons.
Researchers also conducted behavioral studies in the cuprizone model of MS. They tracked the animals’ movement with lasers and used computer software to analyze the movement. These studies included relevant controls and compared animals with no demyelination, vehicle-treated animals dosed with cuprizone, and CNM-Au8-treated animals similarly dosed with cuprizone, to determine whether delayed treatment following initial damage from the toxin would result in functional recovery in the animals.
The investigators observed protective effects of CNM-Au8 when the drug was administered in this treatment paradigm. Improvements in several behavioral end points when the drug was administered after the demyelinating insult “demonstrated that CNM-Au8 restored behavioral function following demyelination,” said Mr. Hotchkin.
Furthermore, in a behavioral study of fine motor kinetics, function improved by 78% at week 6, compared with week 3 (ie, immediately following the start of treatment) in the group treated with CMN-Au8 that was receiving cuprizone. The animals treated with vehicle and cuprizone had a 39% functional improvement at week 6, compared with week 3. Notably, there was not a statistically significant difference in function at week 6 between CNM-Au8-treated animals and the normal healthy control animals without demyelination, indicating that the functional recovery made the former and latter animals indistinguishable.
Therapy Promotes Bioenergetics Catalysis
CNM-Au8 may generate remyelination by more than one mechanism, said Mr. Hotchkin, and evidence indicates that the drug promotes bioenergetic catalysis that is important to the maturation of oligodendrocyte precursors. Published literature suggests an association between altered oligodendrocyte energy utilization and remyelination failure in the human brain. Other evidence suggests that CNM-Au8 may trigger oligodendrocytes’ remyelinating activity by improving energy sources such as adenosine triphosphate, lactate, and oxidized nicotinamide adenine dinucleotide (NAD+), said Mr. Hotchkin. For example, CNM-Au8 increased NAD+ levels in mouse hippocampal cultures by about 40%, relative to vehicle.
In response to questions about the catalytic mechanism, Mr. Hotchkin responded, “You can fill a car’s tank with gas, but if the electrical system is fouled, the car goes nowhere. CNM-Au8 is the catalytic engine driving bioenergetic improvements in the oligodendrocytes driving them to remyelinate.” Data suggest that CNM-Au8 may have applications in other neurodegenerative diseases, based on the bioenergetic failure hypothesis of neurodegeneration and aging, said Mr. Hotchkin.
Oligodendrocyte precursor cells are known to be present in the human brain in and around MS lesions even years after an MS attack. Thus, the animal studies may be relevant to clinical MS. As an oral agent, CNM-Au8 has the potential to be a major clinical advance if human trials show activity comparable to that in animal studies, said Mr. Hotchkin.
Initial phase I human clinical work and extensive animal toxicology has supported the safety of this agent. Trials in patients with MS that examine clinical end points are planned. “A phase II study in chronic optic neuropathy in relapsing-remitting MS patients will commence in 2018,” Glen Frick, MD, PhD, Chief Medical Officer of Clene Nanomedicine, told Neurology Reviews.
—Ted Bosworth
Suggested Reading
Rone