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Abrupt behavior changes in autism? ID medical triggers first
NEW YORK – When treating children with autism spectrum disorder who develop an abrupt increase in symptoms, it is best to identify and treat the precipitating event or events – rather than intensify ASD drug therapy, an expert said.
“These acute behavior changes are almost always triggered by something,” Jeremy Veenstra-VanderWeele, MD, reported at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry. Triggers are not always identifiable, but Dr. Veenstra-VanderWeele said solutions may prove simple when they are.
In ASD patients with an acute change in behavior, caregivers typically think first of environmental triggers, including adverse interactions with peers or siblings. But Dr. Veenstra-VanderWeele emphasized that medical problems should be considered first. This makes sense because of the importance of quickly resolving health problems. However, pain and discomfort, particularly in those with difficulty verbalizing these complaints, can be overlooked.
Moreover, even highly verbal ASD patients may not volunteer physical complaints without prompting, Dr. Veenstra-VanderWeele said. Among the health issues in children, constipation and other gastrointestinal issues are “incredibly common” in ASD patients. Dr. Veenstra-VanderWeele looks for clues, such as body posturing suggesting abdominal pain or flatulence, when a history is ambiguous.
“I will order an abdominal flat plate when I hear enough symptoms to make me wonder when the family is not sure,” Dr. Veenstra-VanderWeele reported. “Almost always it comes back with evidence of constipation. We treat it, and they are less irritable like all of us would be.”
All common conditions in a pediatric population, including ear infections, dental caries, and food allergies, should be considered, according to Dr. Veenstra-VanderWeele, who recommended a practice pathway for evaluating triggers in children with ASD (Pediatrics. 2016 Feb;137 Suppl 2:S136-48). A coauthor on this pathway, Dr. Veenstra-VanderWeele emphasized the importance of pursuing a systematic approach to medical issues before considering other triggers, such as psychosocial stressors.
In adolescents, headache caused by migraine and late-onset epilepsy, often in the form of complex partial seizures, should be added to the list of potential triggers for irritation or aggression, Dr. Veenstra-VanderWeele said. Epilepsy often precedes the diagnosis of ASD in young children, and Dr. Veenstra-VanderWeele noted that a second peak incidence sometimes occurs in late adolescence.
After ruling out medical problems, helping patients recognize and verbalize stressors can serve as both diagnosis and treatment. In ASD patients with limited verbal skills who are suffering from stress, “aggression is one form of communication,” Dr. Veenstra-VanderWeele said.
However, Dr. Veenstra-VanderWeele cautioned that, even if a trigger is successfully addressed, inadvertently reinforced aggression might persist.
“Aggression can be rewarded sometimes by removing the patient from the classroom, sometimes by giving in, and then that becomes a maladaptive reinforcement pattern that needs to be broken,” Dr. Veenstra-VanderWeele said. “Even if you are treating their irritability and agitation with, say, risperidone, you still need to break the maladaptive reinforcement pattern or they will keep engaging in what has become instrumental aggression.”
Dr. Veenstra-VanderWeele reported financial relationships with Hoffmann-La Roche, Novartis, Seaside Therapeutics, and SynapDx.
NEW YORK – When treating children with autism spectrum disorder who develop an abrupt increase in symptoms, it is best to identify and treat the precipitating event or events – rather than intensify ASD drug therapy, an expert said.
“These acute behavior changes are almost always triggered by something,” Jeremy Veenstra-VanderWeele, MD, reported at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry. Triggers are not always identifiable, but Dr. Veenstra-VanderWeele said solutions may prove simple when they are.
In ASD patients with an acute change in behavior, caregivers typically think first of environmental triggers, including adverse interactions with peers or siblings. But Dr. Veenstra-VanderWeele emphasized that medical problems should be considered first. This makes sense because of the importance of quickly resolving health problems. However, pain and discomfort, particularly in those with difficulty verbalizing these complaints, can be overlooked.
Moreover, even highly verbal ASD patients may not volunteer physical complaints without prompting, Dr. Veenstra-VanderWeele said. Among the health issues in children, constipation and other gastrointestinal issues are “incredibly common” in ASD patients. Dr. Veenstra-VanderWeele looks for clues, such as body posturing suggesting abdominal pain or flatulence, when a history is ambiguous.
“I will order an abdominal flat plate when I hear enough symptoms to make me wonder when the family is not sure,” Dr. Veenstra-VanderWeele reported. “Almost always it comes back with evidence of constipation. We treat it, and they are less irritable like all of us would be.”
All common conditions in a pediatric population, including ear infections, dental caries, and food allergies, should be considered, according to Dr. Veenstra-VanderWeele, who recommended a practice pathway for evaluating triggers in children with ASD (Pediatrics. 2016 Feb;137 Suppl 2:S136-48). A coauthor on this pathway, Dr. Veenstra-VanderWeele emphasized the importance of pursuing a systematic approach to medical issues before considering other triggers, such as psychosocial stressors.
In adolescents, headache caused by migraine and late-onset epilepsy, often in the form of complex partial seizures, should be added to the list of potential triggers for irritation or aggression, Dr. Veenstra-VanderWeele said. Epilepsy often precedes the diagnosis of ASD in young children, and Dr. Veenstra-VanderWeele noted that a second peak incidence sometimes occurs in late adolescence.
After ruling out medical problems, helping patients recognize and verbalize stressors can serve as both diagnosis and treatment. In ASD patients with limited verbal skills who are suffering from stress, “aggression is one form of communication,” Dr. Veenstra-VanderWeele said.
However, Dr. Veenstra-VanderWeele cautioned that, even if a trigger is successfully addressed, inadvertently reinforced aggression might persist.
“Aggression can be rewarded sometimes by removing the patient from the classroom, sometimes by giving in, and then that becomes a maladaptive reinforcement pattern that needs to be broken,” Dr. Veenstra-VanderWeele said. “Even if you are treating their irritability and agitation with, say, risperidone, you still need to break the maladaptive reinforcement pattern or they will keep engaging in what has become instrumental aggression.”
Dr. Veenstra-VanderWeele reported financial relationships with Hoffmann-La Roche, Novartis, Seaside Therapeutics, and SynapDx.
NEW YORK – When treating children with autism spectrum disorder who develop an abrupt increase in symptoms, it is best to identify and treat the precipitating event or events – rather than intensify ASD drug therapy, an expert said.
“These acute behavior changes are almost always triggered by something,” Jeremy Veenstra-VanderWeele, MD, reported at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry. Triggers are not always identifiable, but Dr. Veenstra-VanderWeele said solutions may prove simple when they are.
In ASD patients with an acute change in behavior, caregivers typically think first of environmental triggers, including adverse interactions with peers or siblings. But Dr. Veenstra-VanderWeele emphasized that medical problems should be considered first. This makes sense because of the importance of quickly resolving health problems. However, pain and discomfort, particularly in those with difficulty verbalizing these complaints, can be overlooked.
Moreover, even highly verbal ASD patients may not volunteer physical complaints without prompting, Dr. Veenstra-VanderWeele said. Among the health issues in children, constipation and other gastrointestinal issues are “incredibly common” in ASD patients. Dr. Veenstra-VanderWeele looks for clues, such as body posturing suggesting abdominal pain or flatulence, when a history is ambiguous.
“I will order an abdominal flat plate when I hear enough symptoms to make me wonder when the family is not sure,” Dr. Veenstra-VanderWeele reported. “Almost always it comes back with evidence of constipation. We treat it, and they are less irritable like all of us would be.”
All common conditions in a pediatric population, including ear infections, dental caries, and food allergies, should be considered, according to Dr. Veenstra-VanderWeele, who recommended a practice pathway for evaluating triggers in children with ASD (Pediatrics. 2016 Feb;137 Suppl 2:S136-48). A coauthor on this pathway, Dr. Veenstra-VanderWeele emphasized the importance of pursuing a systematic approach to medical issues before considering other triggers, such as psychosocial stressors.
In adolescents, headache caused by migraine and late-onset epilepsy, often in the form of complex partial seizures, should be added to the list of potential triggers for irritation or aggression, Dr. Veenstra-VanderWeele said. Epilepsy often precedes the diagnosis of ASD in young children, and Dr. Veenstra-VanderWeele noted that a second peak incidence sometimes occurs in late adolescence.
After ruling out medical problems, helping patients recognize and verbalize stressors can serve as both diagnosis and treatment. In ASD patients with limited verbal skills who are suffering from stress, “aggression is one form of communication,” Dr. Veenstra-VanderWeele said.
However, Dr. Veenstra-VanderWeele cautioned that, even if a trigger is successfully addressed, inadvertently reinforced aggression might persist.
“Aggression can be rewarded sometimes by removing the patient from the classroom, sometimes by giving in, and then that becomes a maladaptive reinforcement pattern that needs to be broken,” Dr. Veenstra-VanderWeele said. “Even if you are treating their irritability and agitation with, say, risperidone, you still need to break the maladaptive reinforcement pattern or they will keep engaging in what has become instrumental aggression.”
Dr. Veenstra-VanderWeele reported financial relationships with Hoffmann-La Roche, Novartis, Seaside Therapeutics, and SynapDx.
EXPERT ANALYSIS FROM the PSYCHOPHARMACOLOGY UPDATE INSTITUTE
No improvement in sight for Alzheimer’s drug development
Another one bites the dust.
Yet another investigational agent joins intepirdine, verubecestat, solanezumab, bapineuzumab, latrepirdine, and many others on the scrap pile of research: The complete release of trial data on idalopirdine found the drug wasn’t of clinically significant benefit in Alzheimer’s disease (JAMA. 2018;319[2]:130-42).
The numbers are bad enough that a handful of companies, including the giant Pfizer, have decided to leave Alzheimer’s drug development entirely to focus on more promising fields. And I get that. All of us – on any exhausting, fruitless, task – will reach the point where it’s time to cut our losses and move on. I don’t blame these companies for mostly leaving the field. (Pfizer is planning to form a neuroscience venture fund to support further research.)
Optimists will argue that you still learn things from a negative trial, which is true, but nothing to date is on the immediate horizon to help. The five agents we’ve had available for the past 15-20 years are all old enough to have lost their patents, and their benefits are modest, at best.
And all this going on as the overall human population, including myself, gradually ages and dementia becomes a medical-cost time bomb on the horizon. This isn’t an American problem. Every country in the world is facing it.
Politicians love to promise hope for these things: creating fast-track programs to get drugs to market faster, finding ways to bring down costs so more people can afford them, and improving methods to treat those in need. But none of those things matter if the medications don’t work.
Many of these trials test similar molecules because the evidence to date suggests they’re targeting the cause of Alzheimer’s. But so far they aren’t working. What if, as the Firesign Theatre and others have said, everything you know is wrong?
Perhaps our greatest quality as a species is resilience. We go on because we have to. The planet keeps moving around the sun as it has for almost 5 billion years, and we face tomorrow. Caregivers wake up for another day of doing their best for a faltering parent. I wake up for another day of doing my best to help them. And the researchers go back for another day hoping to find the real answer and treatment. Without trying, no treatment for anything will ever be found. We owe our patients, and ourselves, a better future than that.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Another one bites the dust.
Yet another investigational agent joins intepirdine, verubecestat, solanezumab, bapineuzumab, latrepirdine, and many others on the scrap pile of research: The complete release of trial data on idalopirdine found the drug wasn’t of clinically significant benefit in Alzheimer’s disease (JAMA. 2018;319[2]:130-42).
The numbers are bad enough that a handful of companies, including the giant Pfizer, have decided to leave Alzheimer’s drug development entirely to focus on more promising fields. And I get that. All of us – on any exhausting, fruitless, task – will reach the point where it’s time to cut our losses and move on. I don’t blame these companies for mostly leaving the field. (Pfizer is planning to form a neuroscience venture fund to support further research.)
Optimists will argue that you still learn things from a negative trial, which is true, but nothing to date is on the immediate horizon to help. The five agents we’ve had available for the past 15-20 years are all old enough to have lost their patents, and their benefits are modest, at best.
And all this going on as the overall human population, including myself, gradually ages and dementia becomes a medical-cost time bomb on the horizon. This isn’t an American problem. Every country in the world is facing it.
Politicians love to promise hope for these things: creating fast-track programs to get drugs to market faster, finding ways to bring down costs so more people can afford them, and improving methods to treat those in need. But none of those things matter if the medications don’t work.
Many of these trials test similar molecules because the evidence to date suggests they’re targeting the cause of Alzheimer’s. But so far they aren’t working. What if, as the Firesign Theatre and others have said, everything you know is wrong?
Perhaps our greatest quality as a species is resilience. We go on because we have to. The planet keeps moving around the sun as it has for almost 5 billion years, and we face tomorrow. Caregivers wake up for another day of doing their best for a faltering parent. I wake up for another day of doing my best to help them. And the researchers go back for another day hoping to find the real answer and treatment. Without trying, no treatment for anything will ever be found. We owe our patients, and ourselves, a better future than that.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Another one bites the dust.
Yet another investigational agent joins intepirdine, verubecestat, solanezumab, bapineuzumab, latrepirdine, and many others on the scrap pile of research: The complete release of trial data on idalopirdine found the drug wasn’t of clinically significant benefit in Alzheimer’s disease (JAMA. 2018;319[2]:130-42).
The numbers are bad enough that a handful of companies, including the giant Pfizer, have decided to leave Alzheimer’s drug development entirely to focus on more promising fields. And I get that. All of us – on any exhausting, fruitless, task – will reach the point where it’s time to cut our losses and move on. I don’t blame these companies for mostly leaving the field. (Pfizer is planning to form a neuroscience venture fund to support further research.)
Optimists will argue that you still learn things from a negative trial, which is true, but nothing to date is on the immediate horizon to help. The five agents we’ve had available for the past 15-20 years are all old enough to have lost their patents, and their benefits are modest, at best.
And all this going on as the overall human population, including myself, gradually ages and dementia becomes a medical-cost time bomb on the horizon. This isn’t an American problem. Every country in the world is facing it.
Politicians love to promise hope for these things: creating fast-track programs to get drugs to market faster, finding ways to bring down costs so more people can afford them, and improving methods to treat those in need. But none of those things matter if the medications don’t work.
Many of these trials test similar molecules because the evidence to date suggests they’re targeting the cause of Alzheimer’s. But so far they aren’t working. What if, as the Firesign Theatre and others have said, everything you know is wrong?
Perhaps our greatest quality as a species is resilience. We go on because we have to. The planet keeps moving around the sun as it has for almost 5 billion years, and we face tomorrow. Caregivers wake up for another day of doing their best for a faltering parent. I wake up for another day of doing my best to help them. And the researchers go back for another day hoping to find the real answer and treatment. Without trying, no treatment for anything will ever be found. We owe our patients, and ourselves, a better future than that.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
VIDEO: Could targeting gut dysbiosis in MS prevent disease?
SAN DIEGO – Compelling findings in a genetically engineered mouse model of multiple sclerosis identify mechanisms of how adolescence and gut dysbiosis contribute to the risk of MS. In addition, disparities in gut microbiome species could explain why some people are at higher risk for developing multiple sclerosis, while others seem to enjoy a protective effect against development of this and other autoimmune diseases.
The hope is that these findings could pave the way for clinicians to potentially prevent development of multiple sclerosis in people at higher risk, perhaps through altering the gut flora and probiotic therapy, Suhayl Dhib-Jalbut, MD, said in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Dhib-Jalbut and his team discovered these findings using humanized transgenic mice – in other words, mice containing risk genes for triggering disease transferred from a patient with multiple sclerosis. The mice were more likely to develop MS-like disease at certain ages and in the presence of an altered gut microbiome or gut dysbiosis (Proc Natl Acad Sci U S A. 2017 Oct 31;114[44]:E9318-27).
Dr. Dhib-Jalbut is past president of ACTRIMS and is professor and chairman of the departments of neurology at Rutgers–Robert Wood Johnson Medical School, New Brunswick, N.J., and New Jersey Medical School, Newark. He has received research grants from Biogen and Teva, and is a consultant for Genzyme, Teva, Celgene, and, Mallinckrodt.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN DIEGO – Compelling findings in a genetically engineered mouse model of multiple sclerosis identify mechanisms of how adolescence and gut dysbiosis contribute to the risk of MS. In addition, disparities in gut microbiome species could explain why some people are at higher risk for developing multiple sclerosis, while others seem to enjoy a protective effect against development of this and other autoimmune diseases.
The hope is that these findings could pave the way for clinicians to potentially prevent development of multiple sclerosis in people at higher risk, perhaps through altering the gut flora and probiotic therapy, Suhayl Dhib-Jalbut, MD, said in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Dhib-Jalbut and his team discovered these findings using humanized transgenic mice – in other words, mice containing risk genes for triggering disease transferred from a patient with multiple sclerosis. The mice were more likely to develop MS-like disease at certain ages and in the presence of an altered gut microbiome or gut dysbiosis (Proc Natl Acad Sci U S A. 2017 Oct 31;114[44]:E9318-27).
Dr. Dhib-Jalbut is past president of ACTRIMS and is professor and chairman of the departments of neurology at Rutgers–Robert Wood Johnson Medical School, New Brunswick, N.J., and New Jersey Medical School, Newark. He has received research grants from Biogen and Teva, and is a consultant for Genzyme, Teva, Celgene, and, Mallinckrodt.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN DIEGO – Compelling findings in a genetically engineered mouse model of multiple sclerosis identify mechanisms of how adolescence and gut dysbiosis contribute to the risk of MS. In addition, disparities in gut microbiome species could explain why some people are at higher risk for developing multiple sclerosis, while others seem to enjoy a protective effect against development of this and other autoimmune diseases.
The hope is that these findings could pave the way for clinicians to potentially prevent development of multiple sclerosis in people at higher risk, perhaps through altering the gut flora and probiotic therapy, Suhayl Dhib-Jalbut, MD, said in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Dhib-Jalbut and his team discovered these findings using humanized transgenic mice – in other words, mice containing risk genes for triggering disease transferred from a patient with multiple sclerosis. The mice were more likely to develop MS-like disease at certain ages and in the presence of an altered gut microbiome or gut dysbiosis (Proc Natl Acad Sci U S A. 2017 Oct 31;114[44]:E9318-27).
Dr. Dhib-Jalbut is past president of ACTRIMS and is professor and chairman of the departments of neurology at Rutgers–Robert Wood Johnson Medical School, New Brunswick, N.J., and New Jersey Medical School, Newark. He has received research grants from Biogen and Teva, and is a consultant for Genzyme, Teva, Celgene, and, Mallinckrodt.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
EXPERT ANALYSIS FROM ACTRIMS FORUM 2018
Ticagrelor may be superior to clopidogrel in poor metabolizers
LOS ANGELES – In patients who had experienced a minor stroke or a transient ischemic attack with a moderate to high risk of stroke, the combination of ticagrelor and aspirin reduced the 90-day incidence of high on-treatment platelet reactivity, according to results from the PRINCE trial.
Although the combination outperformed clopidogrel (Plavix) plus aspirin, ticagrelor (Brilinta) was associated with higher bleeding risk.
The researchers also saw a trend toward a reduction in strokes that did not reach statistical significance, but the trial was halted following an interim analysis showing that the high on-treatment platelet reactivity (HOPR) endpoint, defined as P2Y12 reaction unit (PRU) greater than 208, showed a statistically significant difference. “To prove the clinical benefit, we will need a larger sample size,” study first author and presenter Yilong Wang, MD, PhD, of Beijing Tiantan Hospital, Capital Medical University, said in an interview at the International Stroke Conference, sponsored by the American Heart Association.
Previously, the SOCRATES trial found no advantage to treatment with ticagrelor over aspirin, but a prespecified exploratory analysis focusing on Asian patients (Stroke. 2017;48:167-73) found a trend toward reducing vascular events in the ticagrelor group, compared with patients taking aspirin.
In the Platelet Reactivity in Acute Stroke or Transient Ischemic Attack (PRINCE) trial, the researchers sought to examine the safety and efficacy of ticagrelor when compared with clopidogrel in 675 Asian patients (mean age 61 years, one-quarter of whom were female) from 26 centers in China and randomized them to ticagrelor plus aspirin (Tica) or clopidogrel plus aspirin (Clop). Within 24 hours of symptom onset, patients received 180 mg ticagrelor or 300 mg clopidogrel plus 100-300 mg aspirin. During days 1-21, they received 90 mg ticagrelor twice per day or 75 mg clopidogrel once per day. Both groups received 100 mg aspirin once per day. From day 21 to day 90, they received 90 mg ticagrelor twice per day or 75 mg clopidogrel once per day, with no aspirin.
At 90 days, the mean PRU value was 175.44 in the Clop group, compared with 69.24 in the Tica group. Overall, 27.7% of the Clop group experienced HOPR in the first 7 days, compared with 3.9% of the Tica group. At 90 days, 29.7% of the Clop group had experienced HOPR, compared with 12.5% of the Tica group (odds ratio, 0.33; 95% confidence interval, 0.21-0.51; P less than .001).
Ticagrelor was associated with greater benefit among those with impaired ability to metabolize clopidogrel. Among poor metabolizers, HOPR occurred in 10.5% in the Tica group and 42.4% of the Clop group (OR, 0.16; 95% CI, 0.05-0.56; P = .004). A similar favorable effect was seen in intermediate metabolizers in the Tica group (OR, 0.24; 95% CI, 0.12-0.49; P less than .001).
The 90-day stroke rate was no different between the Tica and Clop groups (6.3% vs. 8.8%, respectively; P = .20).
Minimal bleeding was higher in the Tica group (19.0% vs. 10.6%; hazard ratio, 1.86; P = .003), as was any bleeding (22.3% vs. 14.2%; HR, 1.65; P = .007). There were three deaths in the Tica group and two in the Clop group.
Dyspnea was the most common cause of drug discontinuation, and occurred in 4.2% of patients taking ticagrelor but none of the patients taking clopidogrel (P = .0001).
The researchers hope to demonstrate the clinical benefits of the combination in the upcoming PRINCE 2 trial. The results will have an important impact because CYP2C19 loss of function alleles are more common in Asian population. “It’s a very big problem for us,” Dr. Wang said.
The study was funded by the National Natural Science Foundation of China, the Beijing Institute for Brain, and the Beijing Municipal Science & Technology Commission of Cerebral Vascular Disease. AstraZeneca provided study drugs. Dr. Wang reported having no financial disclosures.
SOURCE: Wang Y et al. ISC 2018, abstract LB8
LOS ANGELES – In patients who had experienced a minor stroke or a transient ischemic attack with a moderate to high risk of stroke, the combination of ticagrelor and aspirin reduced the 90-day incidence of high on-treatment platelet reactivity, according to results from the PRINCE trial.
Although the combination outperformed clopidogrel (Plavix) plus aspirin, ticagrelor (Brilinta) was associated with higher bleeding risk.
The researchers also saw a trend toward a reduction in strokes that did not reach statistical significance, but the trial was halted following an interim analysis showing that the high on-treatment platelet reactivity (HOPR) endpoint, defined as P2Y12 reaction unit (PRU) greater than 208, showed a statistically significant difference. “To prove the clinical benefit, we will need a larger sample size,” study first author and presenter Yilong Wang, MD, PhD, of Beijing Tiantan Hospital, Capital Medical University, said in an interview at the International Stroke Conference, sponsored by the American Heart Association.
Previously, the SOCRATES trial found no advantage to treatment with ticagrelor over aspirin, but a prespecified exploratory analysis focusing on Asian patients (Stroke. 2017;48:167-73) found a trend toward reducing vascular events in the ticagrelor group, compared with patients taking aspirin.
In the Platelet Reactivity in Acute Stroke or Transient Ischemic Attack (PRINCE) trial, the researchers sought to examine the safety and efficacy of ticagrelor when compared with clopidogrel in 675 Asian patients (mean age 61 years, one-quarter of whom were female) from 26 centers in China and randomized them to ticagrelor plus aspirin (Tica) or clopidogrel plus aspirin (Clop). Within 24 hours of symptom onset, patients received 180 mg ticagrelor or 300 mg clopidogrel plus 100-300 mg aspirin. During days 1-21, they received 90 mg ticagrelor twice per day or 75 mg clopidogrel once per day. Both groups received 100 mg aspirin once per day. From day 21 to day 90, they received 90 mg ticagrelor twice per day or 75 mg clopidogrel once per day, with no aspirin.
At 90 days, the mean PRU value was 175.44 in the Clop group, compared with 69.24 in the Tica group. Overall, 27.7% of the Clop group experienced HOPR in the first 7 days, compared with 3.9% of the Tica group. At 90 days, 29.7% of the Clop group had experienced HOPR, compared with 12.5% of the Tica group (odds ratio, 0.33; 95% confidence interval, 0.21-0.51; P less than .001).
Ticagrelor was associated with greater benefit among those with impaired ability to metabolize clopidogrel. Among poor metabolizers, HOPR occurred in 10.5% in the Tica group and 42.4% of the Clop group (OR, 0.16; 95% CI, 0.05-0.56; P = .004). A similar favorable effect was seen in intermediate metabolizers in the Tica group (OR, 0.24; 95% CI, 0.12-0.49; P less than .001).
The 90-day stroke rate was no different between the Tica and Clop groups (6.3% vs. 8.8%, respectively; P = .20).
Minimal bleeding was higher in the Tica group (19.0% vs. 10.6%; hazard ratio, 1.86; P = .003), as was any bleeding (22.3% vs. 14.2%; HR, 1.65; P = .007). There were three deaths in the Tica group and two in the Clop group.
Dyspnea was the most common cause of drug discontinuation, and occurred in 4.2% of patients taking ticagrelor but none of the patients taking clopidogrel (P = .0001).
The researchers hope to demonstrate the clinical benefits of the combination in the upcoming PRINCE 2 trial. The results will have an important impact because CYP2C19 loss of function alleles are more common in Asian population. “It’s a very big problem for us,” Dr. Wang said.
The study was funded by the National Natural Science Foundation of China, the Beijing Institute for Brain, and the Beijing Municipal Science & Technology Commission of Cerebral Vascular Disease. AstraZeneca provided study drugs. Dr. Wang reported having no financial disclosures.
SOURCE: Wang Y et al. ISC 2018, abstract LB8
LOS ANGELES – In patients who had experienced a minor stroke or a transient ischemic attack with a moderate to high risk of stroke, the combination of ticagrelor and aspirin reduced the 90-day incidence of high on-treatment platelet reactivity, according to results from the PRINCE trial.
Although the combination outperformed clopidogrel (Plavix) plus aspirin, ticagrelor (Brilinta) was associated with higher bleeding risk.
The researchers also saw a trend toward a reduction in strokes that did not reach statistical significance, but the trial was halted following an interim analysis showing that the high on-treatment platelet reactivity (HOPR) endpoint, defined as P2Y12 reaction unit (PRU) greater than 208, showed a statistically significant difference. “To prove the clinical benefit, we will need a larger sample size,” study first author and presenter Yilong Wang, MD, PhD, of Beijing Tiantan Hospital, Capital Medical University, said in an interview at the International Stroke Conference, sponsored by the American Heart Association.
Previously, the SOCRATES trial found no advantage to treatment with ticagrelor over aspirin, but a prespecified exploratory analysis focusing on Asian patients (Stroke. 2017;48:167-73) found a trend toward reducing vascular events in the ticagrelor group, compared with patients taking aspirin.
In the Platelet Reactivity in Acute Stroke or Transient Ischemic Attack (PRINCE) trial, the researchers sought to examine the safety and efficacy of ticagrelor when compared with clopidogrel in 675 Asian patients (mean age 61 years, one-quarter of whom were female) from 26 centers in China and randomized them to ticagrelor plus aspirin (Tica) or clopidogrel plus aspirin (Clop). Within 24 hours of symptom onset, patients received 180 mg ticagrelor or 300 mg clopidogrel plus 100-300 mg aspirin. During days 1-21, they received 90 mg ticagrelor twice per day or 75 mg clopidogrel once per day. Both groups received 100 mg aspirin once per day. From day 21 to day 90, they received 90 mg ticagrelor twice per day or 75 mg clopidogrel once per day, with no aspirin.
At 90 days, the mean PRU value was 175.44 in the Clop group, compared with 69.24 in the Tica group. Overall, 27.7% of the Clop group experienced HOPR in the first 7 days, compared with 3.9% of the Tica group. At 90 days, 29.7% of the Clop group had experienced HOPR, compared with 12.5% of the Tica group (odds ratio, 0.33; 95% confidence interval, 0.21-0.51; P less than .001).
Ticagrelor was associated with greater benefit among those with impaired ability to metabolize clopidogrel. Among poor metabolizers, HOPR occurred in 10.5% in the Tica group and 42.4% of the Clop group (OR, 0.16; 95% CI, 0.05-0.56; P = .004). A similar favorable effect was seen in intermediate metabolizers in the Tica group (OR, 0.24; 95% CI, 0.12-0.49; P less than .001).
The 90-day stroke rate was no different between the Tica and Clop groups (6.3% vs. 8.8%, respectively; P = .20).
Minimal bleeding was higher in the Tica group (19.0% vs. 10.6%; hazard ratio, 1.86; P = .003), as was any bleeding (22.3% vs. 14.2%; HR, 1.65; P = .007). There were three deaths in the Tica group and two in the Clop group.
Dyspnea was the most common cause of drug discontinuation, and occurred in 4.2% of patients taking ticagrelor but none of the patients taking clopidogrel (P = .0001).
The researchers hope to demonstrate the clinical benefits of the combination in the upcoming PRINCE 2 trial. The results will have an important impact because CYP2C19 loss of function alleles are more common in Asian population. “It’s a very big problem for us,” Dr. Wang said.
The study was funded by the National Natural Science Foundation of China, the Beijing Institute for Brain, and the Beijing Municipal Science & Technology Commission of Cerebral Vascular Disease. AstraZeneca provided study drugs. Dr. Wang reported having no financial disclosures.
SOURCE: Wang Y et al. ISC 2018, abstract LB8
REPORTING FROM ISC 2018
Key clinical point: Ticagrelor may be a better option than clopidogrel in patients with loss-of-function CYP2C19 alleles.
Major finding: Patients on ticagrelor had a lower 90-day risk of high on-treatment platelet reactivity (OR, 0.33).
Data source: Randomized, open-label trial with blinded assessments (n = 675).
Disclosures: The study was funded by the National Natural Science Foundation of China, the Beijing Institute for Brain, and the Beijing Municipal Science & Technology Commission of Cerebral Vascular Disease. AstraZeneca provided study drugs. Dr. Wang reported having no financial disclosures.
Source: Wang Y et al. ISC 2018, abstract LB8
Baby boomers are the hepatitis C generation
Increases in hepatitis C–related inpatient stays for baby boomers from 2005 to 2014 far outpaced those of older adults, while younger adults saw their admissions drop over that period, according to the Agency for Healthcare Research and Quality.
For the baby boomers (adults aged 52-72 years), the rate of inpatient stays involving hepatitis C with or without hepatitis B, HIV, or alcoholic liver disease rose from 300.7 per 100,000 population in 2005 to 503.1 per 100,000 in 2014 – an increase of over 67%. For patients aged 73 years and older, that rate went from 104.4 in 2005 to 117.1 in 2014, which translates to a 12% increase, and for patients aged 18-51 years, it dropped 15%, from 182.5 to 155.4, the AHRQ said in a statistical brief.
Along with the increased hospitalizations, “acute hepatitis C cases nearly tripled from 2010 through 2015,” the report noted, which was “likely the result of increasing injection drug use due to the growing opioid epidemic.”
AGA offers tools to help you become more efficient, understand quality standards, and improve the process of care for your hepatitis C patients.
Increases in hepatitis C–related inpatient stays for baby boomers from 2005 to 2014 far outpaced those of older adults, while younger adults saw their admissions drop over that period, according to the Agency for Healthcare Research and Quality.
For the baby boomers (adults aged 52-72 years), the rate of inpatient stays involving hepatitis C with or without hepatitis B, HIV, or alcoholic liver disease rose from 300.7 per 100,000 population in 2005 to 503.1 per 100,000 in 2014 – an increase of over 67%. For patients aged 73 years and older, that rate went from 104.4 in 2005 to 117.1 in 2014, which translates to a 12% increase, and for patients aged 18-51 years, it dropped 15%, from 182.5 to 155.4, the AHRQ said in a statistical brief.
Along with the increased hospitalizations, “acute hepatitis C cases nearly tripled from 2010 through 2015,” the report noted, which was “likely the result of increasing injection drug use due to the growing opioid epidemic.”
AGA offers tools to help you become more efficient, understand quality standards, and improve the process of care for your hepatitis C patients.
Increases in hepatitis C–related inpatient stays for baby boomers from 2005 to 2014 far outpaced those of older adults, while younger adults saw their admissions drop over that period, according to the Agency for Healthcare Research and Quality.
For the baby boomers (adults aged 52-72 years), the rate of inpatient stays involving hepatitis C with or without hepatitis B, HIV, or alcoholic liver disease rose from 300.7 per 100,000 population in 2005 to 503.1 per 100,000 in 2014 – an increase of over 67%. For patients aged 73 years and older, that rate went from 104.4 in 2005 to 117.1 in 2014, which translates to a 12% increase, and for patients aged 18-51 years, it dropped 15%, from 182.5 to 155.4, the AHRQ said in a statistical brief.
Along with the increased hospitalizations, “acute hepatitis C cases nearly tripled from 2010 through 2015,” the report noted, which was “likely the result of increasing injection drug use due to the growing opioid epidemic.”
AGA offers tools to help you become more efficient, understand quality standards, and improve the process of care for your hepatitis C patients.
Tenecteplase surpasses alteplase for thrombolysing acute ischemic stroke
LOS ANGELES – Thrombolysis with tenecteplase beat alteplase on an acute imaging endpoint in patients with acute ischemic stroke who were on their way to also get thrombectomy in a randomized, multicenter study with 202 patients in Australia and New Zealand.
The results of the trial, called Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK), showed that when the patients underwent their initial angiogram after receiving thrombolysis and before their thrombectomy procedure, the percentage of patients with robust blood flow – a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3 or no retrievable thrombus – was 22% in the patients treated with tenecteplase 0.25 mg/kg and 10% among those who received alteplase 0.9 mg/kg. After adjustment, the 12% incremental change in robust reperfusion with tenecteplase calculated into a 2.6-fold higher rate of robust reperfusion, statistically significant for both noninferiority and for superiority, Bruce C. Campbell, MBBS, PhD, said at the International Stroke Conference, sponsored by the American Heart Association.
Tenecteplase is a genetically-modified tissue plasminogen activator with enhanced fibrin specificity that increases the drug’s half life and allows for bolus administration, unlike alteplase, which needs continuous infusion (CNS Drugs. 2015 Oct;29[10]:811-8). Tenecteplase also has a U.S. wholesale price that is about $3,000 cheaper per vial than alteplase, said Dr. Campbell, professor of neurology at the University of Melbourne and head of hyperacute stroke at Royal Melbourne Hospital.
But further data are needed before tenecteplase is ready for routine use, conceded Dr. Campbell, an assessment other experts agreed with. Dr. Campbell cited two studies in progress that are comparing tenecteplase with alteplase in acute ischemic stroke patients not headed for endovascular thrombectomy, as well as a study he is leading that compares the tenecteplase dose he just tested, 0.25 mg/kg, with a higher dose, 0.40 mg/kg.
Several reports have appeared in recent years suggesting that treatment with tenecteplase seems to be at least as good as alteplase in ischemic stroke patients. For example, a randomized trial with 75 ischemic stroke patients selected by imaging at three Australian centers showed that treatment with tenecteplase produced a significant 24% improvement in the rate of arterial reperfusion and an average 5-point improvement in NIH Stroke Scale score (N Engl J Med. 2012;366[12]:1099-107). And results from the NOR-TEST study recently showed that among 1,100 patients randomized at 13 Norwegian centers, the primary outcome of a 90-day modified Rankin Scale score of 0-1 was achieved by 64% of the tenecteplase patients and by 63% of those who received alteplase (Lancet Neurol. 2017 Oct;16[10]:781-8).
The EXTEND-IA TNK trial ran during 2015-2017 at 18 hospitals. All enrolled patients received their thrombolytic treatment within 4.5 hours of their stroke onset, and underwent endovascular thrombectomy within 6 hours of onset. The safety outcomes of death, symptomatic intracranial hemorrhage, and parenchymal hematoma occurred at statistically similar rates in both treatment arms.
The study was investigator initiated and funded chiefly by the Australian government. Medtronic provided an unrestricted grant for trial infrastructure but had no role in study design conduct or analysis. Dr. Campbell and Dr. Powers had no disclosures.
SOURCE: Campbell B et al. ISC 2018, abstract LB2.
In the EXTEND-IA TNK study, tenecteplase appeared to act better than alteplase and has the extra advantage of being administered as a bolus injection. Alteplase is delivered as a drip, and it’s often hard to get patients with an intravenous infusion out of the hospital quickly when you have to transport the patient. You need a nurse in the ambulance monitoring the drip. With tenecteplase you administer the bolus and can then send the patient without an intravenous line.
Jeffrey L. Saver, MD, is professor of neurology and director of the stroke unit at the University of California, Los Angeles. He has received research support and personal fees from Medtronic-Abbott and Neuravia. He made these comments in an interview.
In the EXTEND-IA TNK study, tenecteplase appeared to act better than alteplase and has the extra advantage of being administered as a bolus injection. Alteplase is delivered as a drip, and it’s often hard to get patients with an intravenous infusion out of the hospital quickly when you have to transport the patient. You need a nurse in the ambulance monitoring the drip. With tenecteplase you administer the bolus and can then send the patient without an intravenous line.
Jeffrey L. Saver, MD, is professor of neurology and director of the stroke unit at the University of California, Los Angeles. He has received research support and personal fees from Medtronic-Abbott and Neuravia. He made these comments in an interview.
In the EXTEND-IA TNK study, tenecteplase appeared to act better than alteplase and has the extra advantage of being administered as a bolus injection. Alteplase is delivered as a drip, and it’s often hard to get patients with an intravenous infusion out of the hospital quickly when you have to transport the patient. You need a nurse in the ambulance monitoring the drip. With tenecteplase you administer the bolus and can then send the patient without an intravenous line.
Jeffrey L. Saver, MD, is professor of neurology and director of the stroke unit at the University of California, Los Angeles. He has received research support and personal fees from Medtronic-Abbott and Neuravia. He made these comments in an interview.
LOS ANGELES – Thrombolysis with tenecteplase beat alteplase on an acute imaging endpoint in patients with acute ischemic stroke who were on their way to also get thrombectomy in a randomized, multicenter study with 202 patients in Australia and New Zealand.
The results of the trial, called Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK), showed that when the patients underwent their initial angiogram after receiving thrombolysis and before their thrombectomy procedure, the percentage of patients with robust blood flow – a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3 or no retrievable thrombus – was 22% in the patients treated with tenecteplase 0.25 mg/kg and 10% among those who received alteplase 0.9 mg/kg. After adjustment, the 12% incremental change in robust reperfusion with tenecteplase calculated into a 2.6-fold higher rate of robust reperfusion, statistically significant for both noninferiority and for superiority, Bruce C. Campbell, MBBS, PhD, said at the International Stroke Conference, sponsored by the American Heart Association.
Tenecteplase is a genetically-modified tissue plasminogen activator with enhanced fibrin specificity that increases the drug’s half life and allows for bolus administration, unlike alteplase, which needs continuous infusion (CNS Drugs. 2015 Oct;29[10]:811-8). Tenecteplase also has a U.S. wholesale price that is about $3,000 cheaper per vial than alteplase, said Dr. Campbell, professor of neurology at the University of Melbourne and head of hyperacute stroke at Royal Melbourne Hospital.
But further data are needed before tenecteplase is ready for routine use, conceded Dr. Campbell, an assessment other experts agreed with. Dr. Campbell cited two studies in progress that are comparing tenecteplase with alteplase in acute ischemic stroke patients not headed for endovascular thrombectomy, as well as a study he is leading that compares the tenecteplase dose he just tested, 0.25 mg/kg, with a higher dose, 0.40 mg/kg.
Several reports have appeared in recent years suggesting that treatment with tenecteplase seems to be at least as good as alteplase in ischemic stroke patients. For example, a randomized trial with 75 ischemic stroke patients selected by imaging at three Australian centers showed that treatment with tenecteplase produced a significant 24% improvement in the rate of arterial reperfusion and an average 5-point improvement in NIH Stroke Scale score (N Engl J Med. 2012;366[12]:1099-107). And results from the NOR-TEST study recently showed that among 1,100 patients randomized at 13 Norwegian centers, the primary outcome of a 90-day modified Rankin Scale score of 0-1 was achieved by 64% of the tenecteplase patients and by 63% of those who received alteplase (Lancet Neurol. 2017 Oct;16[10]:781-8).
The EXTEND-IA TNK trial ran during 2015-2017 at 18 hospitals. All enrolled patients received their thrombolytic treatment within 4.5 hours of their stroke onset, and underwent endovascular thrombectomy within 6 hours of onset. The safety outcomes of death, symptomatic intracranial hemorrhage, and parenchymal hematoma occurred at statistically similar rates in both treatment arms.
The study was investigator initiated and funded chiefly by the Australian government. Medtronic provided an unrestricted grant for trial infrastructure but had no role in study design conduct or analysis. Dr. Campbell and Dr. Powers had no disclosures.
SOURCE: Campbell B et al. ISC 2018, abstract LB2.
LOS ANGELES – Thrombolysis with tenecteplase beat alteplase on an acute imaging endpoint in patients with acute ischemic stroke who were on their way to also get thrombectomy in a randomized, multicenter study with 202 patients in Australia and New Zealand.
The results of the trial, called Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK), showed that when the patients underwent their initial angiogram after receiving thrombolysis and before their thrombectomy procedure, the percentage of patients with robust blood flow – a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3 or no retrievable thrombus – was 22% in the patients treated with tenecteplase 0.25 mg/kg and 10% among those who received alteplase 0.9 mg/kg. After adjustment, the 12% incremental change in robust reperfusion with tenecteplase calculated into a 2.6-fold higher rate of robust reperfusion, statistically significant for both noninferiority and for superiority, Bruce C. Campbell, MBBS, PhD, said at the International Stroke Conference, sponsored by the American Heart Association.
Tenecteplase is a genetically-modified tissue plasminogen activator with enhanced fibrin specificity that increases the drug’s half life and allows for bolus administration, unlike alteplase, which needs continuous infusion (CNS Drugs. 2015 Oct;29[10]:811-8). Tenecteplase also has a U.S. wholesale price that is about $3,000 cheaper per vial than alteplase, said Dr. Campbell, professor of neurology at the University of Melbourne and head of hyperacute stroke at Royal Melbourne Hospital.
But further data are needed before tenecteplase is ready for routine use, conceded Dr. Campbell, an assessment other experts agreed with. Dr. Campbell cited two studies in progress that are comparing tenecteplase with alteplase in acute ischemic stroke patients not headed for endovascular thrombectomy, as well as a study he is leading that compares the tenecteplase dose he just tested, 0.25 mg/kg, with a higher dose, 0.40 mg/kg.
Several reports have appeared in recent years suggesting that treatment with tenecteplase seems to be at least as good as alteplase in ischemic stroke patients. For example, a randomized trial with 75 ischemic stroke patients selected by imaging at three Australian centers showed that treatment with tenecteplase produced a significant 24% improvement in the rate of arterial reperfusion and an average 5-point improvement in NIH Stroke Scale score (N Engl J Med. 2012;366[12]:1099-107). And results from the NOR-TEST study recently showed that among 1,100 patients randomized at 13 Norwegian centers, the primary outcome of a 90-day modified Rankin Scale score of 0-1 was achieved by 64% of the tenecteplase patients and by 63% of those who received alteplase (Lancet Neurol. 2017 Oct;16[10]:781-8).
The EXTEND-IA TNK trial ran during 2015-2017 at 18 hospitals. All enrolled patients received their thrombolytic treatment within 4.5 hours of their stroke onset, and underwent endovascular thrombectomy within 6 hours of onset. The safety outcomes of death, symptomatic intracranial hemorrhage, and parenchymal hematoma occurred at statistically similar rates in both treatment arms.
The study was investigator initiated and funded chiefly by the Australian government. Medtronic provided an unrestricted grant for trial infrastructure but had no role in study design conduct or analysis. Dr. Campbell and Dr. Powers had no disclosures.
SOURCE: Campbell B et al. ISC 2018, abstract LB2.
REPORTING FROM ISC 2018
Key clinical point: Tenecteplase thrombolysis produced better reperfusion than did alteplase.
Major finding: Robust reperfusion occurred in 22% of tenecteplase patients and in 10% of patients who received alteplase.
Study details: EXTEND-IA TNK, a multicenter, randomized trial with 202 patients.
Disclosures: The study was investigator initiated and funded chiefly by the Australian government. Medtronic provided an unrestricted grant for trial infrastructure but had no role in study design conduct or analysis. Dr. Campbell and Dr. Powers had no disclosures.
Source: Campbell B et al. ISC 2018, abstract LB2
Joint Outpatient Experience Gets an A
The results are in: 93% of soldiers, retirees, and family members report very high overall satisfaction with their experience at Army medical treatment facilities.
Survey responses were for the DoD’s 2017 Joint Outpatient Experience Survey (JOES), which also asked about ease of access to Army providers (83% positive response) and overall experience with Army pharmacies (78% positive).
The results showed an increase in satisfaction of about 2% for those 3 questions compared with the results of 2016, the first time the Army participated in the survey, according to Melissa Gliner, senior health policy analyst with the Office of the Army Surgeon General, in an article for Defense.gov. The survey goes to about 10% of patients who have visited a military health facility.
Besides sharing the survey results with the facilities, Gliner advises them on how to improve the patient experience. For instance, she looks at civilian treatment facilities to see what works. One insight she culled was that it helps to have staff members circulate in the waiting area to chat with patients so they do not feel they are being ignored. Another was that facilities should retrain scheduling clerks to set up appointments without making the patient call back.
Gliner says the U.S. Army Medical Command also is working on a website that will help military health facilities share their ideas and “further elevate patient experience and survey scores.”
The results are in: 93% of soldiers, retirees, and family members report very high overall satisfaction with their experience at Army medical treatment facilities.
Survey responses were for the DoD’s 2017 Joint Outpatient Experience Survey (JOES), which also asked about ease of access to Army providers (83% positive response) and overall experience with Army pharmacies (78% positive).
The results showed an increase in satisfaction of about 2% for those 3 questions compared with the results of 2016, the first time the Army participated in the survey, according to Melissa Gliner, senior health policy analyst with the Office of the Army Surgeon General, in an article for Defense.gov. The survey goes to about 10% of patients who have visited a military health facility.
Besides sharing the survey results with the facilities, Gliner advises them on how to improve the patient experience. For instance, she looks at civilian treatment facilities to see what works. One insight she culled was that it helps to have staff members circulate in the waiting area to chat with patients so they do not feel they are being ignored. Another was that facilities should retrain scheduling clerks to set up appointments without making the patient call back.
Gliner says the U.S. Army Medical Command also is working on a website that will help military health facilities share their ideas and “further elevate patient experience and survey scores.”
The results are in: 93% of soldiers, retirees, and family members report very high overall satisfaction with their experience at Army medical treatment facilities.
Survey responses were for the DoD’s 2017 Joint Outpatient Experience Survey (JOES), which also asked about ease of access to Army providers (83% positive response) and overall experience with Army pharmacies (78% positive).
The results showed an increase in satisfaction of about 2% for those 3 questions compared with the results of 2016, the first time the Army participated in the survey, according to Melissa Gliner, senior health policy analyst with the Office of the Army Surgeon General, in an article for Defense.gov. The survey goes to about 10% of patients who have visited a military health facility.
Besides sharing the survey results with the facilities, Gliner advises them on how to improve the patient experience. For instance, she looks at civilian treatment facilities to see what works. One insight she culled was that it helps to have staff members circulate in the waiting area to chat with patients so they do not feel they are being ignored. Another was that facilities should retrain scheduling clerks to set up appointments without making the patient call back.
Gliner says the U.S. Army Medical Command also is working on a website that will help military health facilities share their ideas and “further elevate patient experience and survey scores.”
Best Practices in Hematology and Oncology (February 2018)
Click here to access the Best Practices in Hematology and Oncology 2018 Digital Edition.
Table of Contents
- Mohs Micrographic Surgery in the VHA
- A National WestlawNext Database Analysis of Malpractice Litigation in Radiation Oncology
- Barriers and Facilitators to the Use of Genomic-Based Targeted Therapy in the VA: Qualitative Findings
- Why Am I Being Treated Like a Female Breast Cancer Patient?
- Breast Cancer Tumor Board
- Advances in CAR T-Cell Therapies
Click here to access the Best Practices in Hematology and Oncology 2018 Digital Edition.
Table of Contents
- Mohs Micrographic Surgery in the VHA
- A National WestlawNext Database Analysis of Malpractice Litigation in Radiation Oncology
- Barriers and Facilitators to the Use of Genomic-Based Targeted Therapy in the VA: Qualitative Findings
- Why Am I Being Treated Like a Female Breast Cancer Patient?
- Breast Cancer Tumor Board
- Advances in CAR T-Cell Therapies
Click here to access the Best Practices in Hematology and Oncology 2018 Digital Edition.
Table of Contents
- Mohs Micrographic Surgery in the VHA
- A National WestlawNext Database Analysis of Malpractice Litigation in Radiation Oncology
- Barriers and Facilitators to the Use of Genomic-Based Targeted Therapy in the VA: Qualitative Findings
- Why Am I Being Treated Like a Female Breast Cancer Patient?
- Breast Cancer Tumor Board
- Advances in CAR T-Cell Therapies
Combo could treat double-hit lymphoma
Existing drugs could be combined to treat double-hit lymphoma (DHL), according to preclinical research published in Science Translational Medicine.
The drugs are tigecycline, an antibiotic, and venetoclax, a BCL2 inhibitor.
Researchers observed promising activity with these drugs in combination, both in cell lines and mouse models of DHL.
The team therefore believes the drugs could be repurposed to treat DHL, which currently has a dismal prognosis.
Study author Micol Ravà, PhD, of the European Institute of Oncology in Milan, Italy, and her colleagues noted that DHL is driven by the abnormal activation of MYC and BCL2. However, selective BCL2 inhibitors like venetoclax have failed to halt disease progression in DHL patients.
Seeking a way to sensitize DHL to BCL2 inhibitors, the researchers turned to tigecycline, which interferes with mitochondria to trigger a MYC-dependent cell death pathway.
The team found that tigecycline and venetoclax demonstrated synergy in 5 DHL cell lines. The drugs were synergistic in 3 cell lines—Karpas-422, SU-DHL-6, and DOHH-2—in which neither drug alone showed significant pro-apoptotic activity.
In 2 other cell lines—SU-DHL-4 and OCI-LY8—venetoclax was active when given alone, but its activity was enhanced by the addition of tigecycline.
In mouse models of DHL (using the human cell lines SU-DHL-6, DOHH-2, and OCI-LY8), each of the drugs alone were able to slow tumor progression somewhat.
However, combination tigecycline and venetoclax exhibited “strong antitumoral activity,” according to the researchers. In fact, the combination caused full disease regression in all 8 SU-DHL-6 mice and 3 of 9 OCI-LY8 mice.
Dr Ravà and her colleagues also found the combination produced “rapid and marked tumor regression” in mice with a patient-derived xenograft.
The researchers observed no toxicity when tigecycline and venetoclax were given at low doses. However, mice receiving more aggressive treatment had some inflammation in the liver and spleen. And some mice treated with high doses of tigecycline and venetoclax died within 1 week of treatment initiation.
Finally, Dr Ravà and her colleagues found that tigecycline and venetoclax each synergized with rituximab. The team therefore concluded that tigecycline and venetoclax “have the potential to reinforce rituximab-containing therapies in the clinic.” 
Existing drugs could be combined to treat double-hit lymphoma (DHL), according to preclinical research published in Science Translational Medicine.
The drugs are tigecycline, an antibiotic, and venetoclax, a BCL2 inhibitor.
Researchers observed promising activity with these drugs in combination, both in cell lines and mouse models of DHL.
The team therefore believes the drugs could be repurposed to treat DHL, which currently has a dismal prognosis.
Study author Micol Ravà, PhD, of the European Institute of Oncology in Milan, Italy, and her colleagues noted that DHL is driven by the abnormal activation of MYC and BCL2. However, selective BCL2 inhibitors like venetoclax have failed to halt disease progression in DHL patients.
Seeking a way to sensitize DHL to BCL2 inhibitors, the researchers turned to tigecycline, which interferes with mitochondria to trigger a MYC-dependent cell death pathway.
The team found that tigecycline and venetoclax demonstrated synergy in 5 DHL cell lines. The drugs were synergistic in 3 cell lines—Karpas-422, SU-DHL-6, and DOHH-2—in which neither drug alone showed significant pro-apoptotic activity.
In 2 other cell lines—SU-DHL-4 and OCI-LY8—venetoclax was active when given alone, but its activity was enhanced by the addition of tigecycline.
In mouse models of DHL (using the human cell lines SU-DHL-6, DOHH-2, and OCI-LY8), each of the drugs alone were able to slow tumor progression somewhat.
However, combination tigecycline and venetoclax exhibited “strong antitumoral activity,” according to the researchers. In fact, the combination caused full disease regression in all 8 SU-DHL-6 mice and 3 of 9 OCI-LY8 mice.
Dr Ravà and her colleagues also found the combination produced “rapid and marked tumor regression” in mice with a patient-derived xenograft.
The researchers observed no toxicity when tigecycline and venetoclax were given at low doses. However, mice receiving more aggressive treatment had some inflammation in the liver and spleen. And some mice treated with high doses of tigecycline and venetoclax died within 1 week of treatment initiation.
Finally, Dr Ravà and her colleagues found that tigecycline and venetoclax each synergized with rituximab. The team therefore concluded that tigecycline and venetoclax “have the potential to reinforce rituximab-containing therapies in the clinic.”
Existing drugs could be combined to treat double-hit lymphoma (DHL), according to preclinical research published in Science Translational Medicine.
The drugs are tigecycline, an antibiotic, and venetoclax, a BCL2 inhibitor.
Researchers observed promising activity with these drugs in combination, both in cell lines and mouse models of DHL.
The team therefore believes the drugs could be repurposed to treat DHL, which currently has a dismal prognosis.
Study author Micol Ravà, PhD, of the European Institute of Oncology in Milan, Italy, and her colleagues noted that DHL is driven by the abnormal activation of MYC and BCL2. However, selective BCL2 inhibitors like venetoclax have failed to halt disease progression in DHL patients.
Seeking a way to sensitize DHL to BCL2 inhibitors, the researchers turned to tigecycline, which interferes with mitochondria to trigger a MYC-dependent cell death pathway.
The team found that tigecycline and venetoclax demonstrated synergy in 5 DHL cell lines. The drugs were synergistic in 3 cell lines—Karpas-422, SU-DHL-6, and DOHH-2—in which neither drug alone showed significant pro-apoptotic activity.
In 2 other cell lines—SU-DHL-4 and OCI-LY8—venetoclax was active when given alone, but its activity was enhanced by the addition of tigecycline.
In mouse models of DHL (using the human cell lines SU-DHL-6, DOHH-2, and OCI-LY8), each of the drugs alone were able to slow tumor progression somewhat.
However, combination tigecycline and venetoclax exhibited “strong antitumoral activity,” according to the researchers. In fact, the combination caused full disease regression in all 8 SU-DHL-6 mice and 3 of 9 OCI-LY8 mice.
Dr Ravà and her colleagues also found the combination produced “rapid and marked tumor regression” in mice with a patient-derived xenograft.
The researchers observed no toxicity when tigecycline and venetoclax were given at low doses. However, mice receiving more aggressive treatment had some inflammation in the liver and spleen. And some mice treated with high doses of tigecycline and venetoclax died within 1 week of treatment initiation.
Finally, Dr Ravà and her colleagues found that tigecycline and venetoclax each synergized with rituximab. The team therefore concluded that tigecycline and venetoclax “have the potential to reinforce rituximab-containing therapies in the clinic.”
Interim trial results may be misleading
Interim results from randomized trials may be misleading at times, according to research published in JAMA.
Researchers compared interim and final publications on randomized trials and found that, 21% of the time, results changed significantly.
“Changes between interim and final publication matter because clinicians and the public could have been misled about whether an intervention was beneficial, harmful, or ineffective,” said study author Lisa Schwartz, MD, of Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire.
She and her colleagues searched PubMed for randomized trials from 2006 to 2015 with “interim,” “not mature,” or “immature” in the title or abstract.
To identify final publications, they searched PubMed, ClinicalTrials.gov, and Web of Science through 2016. The team emailed authors of interim reports when no final publication was identified.
For interim and final publications reporting the same efficacy and or safety outcome, the researchers compared trial characteristics and prominence. They also categorized abstract conclusions (not different, beneficial, or harmful) and compared changes between interim and final publications.
Findings
Interim results were reported in 613 of 1267 screened publications.
Of those publications, 72% reported on trials stopped early (for benefit, harm, futility, or other problems). The remaining 171 ongoing trials (mostly in oncology, surgery, or cardiology) reported interim efficacy or safety results.
Forty-one percent of the publications stated that the interim analysis was specified in the protocol, but half provided no reason for the interim publication.
Final results were published for 98 of the 160 trials (61%) that were more than 1 year beyond the completion date.
The researchers compared 73 interim and final publications reporting the same efficacy or safety outcome. And they found that interim and final publications had similar prominence.
In most cases (79%), the abstract conclusions did not change from the interim publication to the final publication. However, for 21% of trials, there were significant changes.
For 4 trials, the conclusions changed from “no difference” between randomized to treatments to the study treatment being “beneficial.” In 3 trials, the conclusions changed from “not different” to “harmful or possibly harmful.”
In 6 trials, the conclusions changed from “beneficial” to “not different.” One trial changed from “beneficial” to “harmful,” and another changed from “inconclusive” to “noninferior.”
Dr Schwartz and her colleagues concluded that while most interim and final publications reached similar conclusions, frequent non-publication of final results can lead to confusion or unfounded assumptions with true treatment effects remaining unknown.
To safeguard against any such confusion, the researchers recommended routinely adding the word “interim” in the title and justifying the reason in the publication. (Many interim publications reported analyses without any justification.)
“Most importantly, journals, authors, and funders should commit to making final results accessible by linking interim publications to final reports whenever available,” said study author Steven Woloshin, MD, of Dartmouth Institute for Health Policy and Clinical Practice.
Interim results from randomized trials may be misleading at times, according to research published in JAMA.
Researchers compared interim and final publications on randomized trials and found that, 21% of the time, results changed significantly.
“Changes between interim and final publication matter because clinicians and the public could have been misled about whether an intervention was beneficial, harmful, or ineffective,” said study author Lisa Schwartz, MD, of Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire.
She and her colleagues searched PubMed for randomized trials from 2006 to 2015 with “interim,” “not mature,” or “immature” in the title or abstract.
To identify final publications, they searched PubMed, ClinicalTrials.gov, and Web of Science through 2016. The team emailed authors of interim reports when no final publication was identified.
For interim and final publications reporting the same efficacy and or safety outcome, the researchers compared trial characteristics and prominence. They also categorized abstract conclusions (not different, beneficial, or harmful) and compared changes between interim and final publications.
Findings
Interim results were reported in 613 of 1267 screened publications.
Of those publications, 72% reported on trials stopped early (for benefit, harm, futility, or other problems). The remaining 171 ongoing trials (mostly in oncology, surgery, or cardiology) reported interim efficacy or safety results.
Forty-one percent of the publications stated that the interim analysis was specified in the protocol, but half provided no reason for the interim publication.
Final results were published for 98 of the 160 trials (61%) that were more than 1 year beyond the completion date.
The researchers compared 73 interim and final publications reporting the same efficacy or safety outcome. And they found that interim and final publications had similar prominence.
In most cases (79%), the abstract conclusions did not change from the interim publication to the final publication. However, for 21% of trials, there were significant changes.
For 4 trials, the conclusions changed from “no difference” between randomized to treatments to the study treatment being “beneficial.” In 3 trials, the conclusions changed from “not different” to “harmful or possibly harmful.”
In 6 trials, the conclusions changed from “beneficial” to “not different.” One trial changed from “beneficial” to “harmful,” and another changed from “inconclusive” to “noninferior.”
Dr Schwartz and her colleagues concluded that while most interim and final publications reached similar conclusions, frequent non-publication of final results can lead to confusion or unfounded assumptions with true treatment effects remaining unknown.
To safeguard against any such confusion, the researchers recommended routinely adding the word “interim” in the title and justifying the reason in the publication. (Many interim publications reported analyses without any justification.)
“Most importantly, journals, authors, and funders should commit to making final results accessible by linking interim publications to final reports whenever available,” said study author Steven Woloshin, MD, of Dartmouth Institute for Health Policy and Clinical Practice.
Interim results from randomized trials may be misleading at times, according to research published in JAMA.
Researchers compared interim and final publications on randomized trials and found that, 21% of the time, results changed significantly.
“Changes between interim and final publication matter because clinicians and the public could have been misled about whether an intervention was beneficial, harmful, or ineffective,” said study author Lisa Schwartz, MD, of Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire.
She and her colleagues searched PubMed for randomized trials from 2006 to 2015 with “interim,” “not mature,” or “immature” in the title or abstract.
To identify final publications, they searched PubMed, ClinicalTrials.gov, and Web of Science through 2016. The team emailed authors of interim reports when no final publication was identified.
For interim and final publications reporting the same efficacy and or safety outcome, the researchers compared trial characteristics and prominence. They also categorized abstract conclusions (not different, beneficial, or harmful) and compared changes between interim and final publications.
Findings
Interim results were reported in 613 of 1267 screened publications.
Of those publications, 72% reported on trials stopped early (for benefit, harm, futility, or other problems). The remaining 171 ongoing trials (mostly in oncology, surgery, or cardiology) reported interim efficacy or safety results.
Forty-one percent of the publications stated that the interim analysis was specified in the protocol, but half provided no reason for the interim publication.
Final results were published for 98 of the 160 trials (61%) that were more than 1 year beyond the completion date.
The researchers compared 73 interim and final publications reporting the same efficacy or safety outcome. And they found that interim and final publications had similar prominence.
In most cases (79%), the abstract conclusions did not change from the interim publication to the final publication. However, for 21% of trials, there were significant changes.
For 4 trials, the conclusions changed from “no difference” between randomized to treatments to the study treatment being “beneficial.” In 3 trials, the conclusions changed from “not different” to “harmful or possibly harmful.”
In 6 trials, the conclusions changed from “beneficial” to “not different.” One trial changed from “beneficial” to “harmful,” and another changed from “inconclusive” to “noninferior.”
Dr Schwartz and her colleagues concluded that while most interim and final publications reached similar conclusions, frequent non-publication of final results can lead to confusion or unfounded assumptions with true treatment effects remaining unknown.
To safeguard against any such confusion, the researchers recommended routinely adding the word “interim” in the title and justifying the reason in the publication. (Many interim publications reported analyses without any justification.)
“Most importantly, journals, authors, and funders should commit to making final results accessible by linking interim publications to final reports whenever available,” said study author Steven Woloshin, MD, of Dartmouth Institute for Health Policy and Clinical Practice.