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Epilepsy after TBI linked to worse 12-month outcomes
findings from an analysis of a large, prospective database suggest. “We found that patients essentially have a 10-times greater risk of developing posttraumatic epilepsy and seizures at 12 months [post injury] if the presenting Glasgow Coma Scale GCS) is less than 8,” said lead author John F. Burke, MD, PhD, University of California, San Francisco, in presenting the findings as part of the virtual annual meeting of the American Association of Neurological Surgeons.
Assessing risk factors
While posttraumatic epilepsy represents an estimated 20% of all cases of symptomatic epilepsy, many questions remain on those most at risk and on the long-term effects of posttraumatic epilepsy on TBI outcomes. To probe those issues, Dr. Burke and colleagues turned to the multicenter TRACK-TBI database, which has prospective, longitudinal data on more than 2,700 patients with traumatic brain injuries and is considered the largest source of prospective data on posttraumatic epilepsy.
Using the criteria of no previous epilepsy and having 12 months of follow-up, the team identified 1,493 patients with TBI. In addition, investigators identified 182 orthopedic controls (included and prospectively followed because they have injuries but not specifically head trauma) and 210 controls who are friends of the patients and who do not have injuries but allow researchers to control for socioeconomic and environmental factors.
Of the 1,493 patients with TBI, 41 (2.7%) were determined to have posttraumatic epilepsy, assessed according to a National Institute of Neurological Disorders and Stroke epilepsy screening questionnaire, which is designed to identify patients with posttraumatic epilepsy symptoms. There were no reports of epilepsy symptoms using the screening tool among the controls. Dr. Burke noted that the 2.7% was in agreement with historical reports.
In comparing patients with TBI who did and did not have posttraumatic epilepsy, no differences were observed in the groups in terms of gender, although there was a trend toward younger age among those with PTE (mean age, 35.4 years with posttraumatic injury vs. 41.5 without; P = .05).
A major risk factor for the development of posttraumatic epilepsy was presenting GCS scores. Among those with scores of less than 8, indicative of severe injury, the rate of posttraumatic epilepsy was 6% at 6 months and 12.5% at 12 months. In contrast, those with TBI presenting with GCS scores between 13 and 15, indicative of minor injury, had an incidence of posttraumatic epilepsy of 0.9% at 6 months and 1.4% at 12 months.
Imaging findings in the two groups showed that hemorrhage detected on CT imaging was associated with a significantly higher risk for posttraumatic epilepsy (P < .001).
“The main takeaway is that any hemorrhage in the brain is a major risk factor for developing seizures,” Dr. Burke said. “Whether it is subdural, epidural blood, subarachnoid or contusion, any blood confers a very [high] risk for developing seizures.”
Posttraumatic epilepsy was linked to poorer longer-term outcomes even for patients with lesser injury: Among those with TBI and GCS of 13-15, the mean Glasgow Outcome Scale Extended (GOSE) score at 12 months among those without posttraumatic epilepsy was 7, indicative of a good recovery with minor defects, whereas the mean GOSE score for those with PTE was 4.6, indicative of moderate to severe disability (P < .001).
“It was surprising to us that PTE-positive patients had a very significant decrease in GOSE, compared to PTE-negative patients,” Dr. Burke said. “There was a nearly 2-point drop in the GOSE and that was extremely significant.”
A multivariate analysis showed there was still a significant independent risk for a poor GOSE score with posttraumatic epilepsy after controlling for GCS score, head CT findings, and age (P < .001).
The authors also looked at mood outcomes using the Brief Symptom Inventory–18, which showed significant worse effect in those with posttraumatic epilepsy after multivariate adjustment (P = .01). Additionally, a highly significant worse effect in cognitive outcomes on the Rivermead cognitive metric was observed with posttraumatic epilepsy (P = .001).
“On all metrics tested, posttraumatic epilepsy worsened outcomes,” Dr. Burke said.
He noted that the study has some key limitations, including the 12-month follow-up. A previous study showed a linear increase in posttraumatic follow-up up to 30 years. “The fact that we found 41 patients at 12 months indicates there are probably more that are out there who are going to develop seizures, but because we don’t have the follow-up we can’t look at that.”
Although the screening questionnaires are effective, “the issue is these people are not being seen by an epileptologist or having scalp EEG done, and we need a more accurate way to do this,” he said. A new study, TRACK-TBI EPI, will address those limitations and a host of other issues with a 5-year follow-up.
Capturing the nuances of brain injury
Commenting on the study as a discussant, neurosurgeon Uzma Samadani, MD, PhD, of the Minneapolis Veterans Affairs Medical Center and CentraCare in Minneapolis, suggested that the future work should focus on issues including the wide-ranging mechanisms that could explain the seizure activity.
“For example, it’s known that posttraumatic epilepsy or seizures can be triggered by abnormal conductivity due to multiple different mechanisms associated with brain injury, such as endocrine dysfunction, cortical-spreading depression, and many others,” said Dr. Samadani, who has been a researcher on the TRACK-TBI study.
Factors ranging from genetic differences to comorbid conditions such as alcoholism can play a role in brain injury susceptibility, Dr. Samadani added. Furthermore, outcome measures currently available simply may not capture the unknown nuances of brain injury.
“We have to ask, are these an all-or-none phenomena, or is aberrant electrical activity after brain injury a continuum of dysfunction?” Dr. Samadani speculated.
“I would caution that we are likely underestimating the non–easily measurable consequences of brain injury,” she said. “And the better we can quantitate susceptibility, classify the nature of injury and target acute management, the less posttraumatic epilepsy/aberrant electrical activity our patients will have.”
Dr. Burke and Dr. Samadani disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
findings from an analysis of a large, prospective database suggest. “We found that patients essentially have a 10-times greater risk of developing posttraumatic epilepsy and seizures at 12 months [post injury] if the presenting Glasgow Coma Scale GCS) is less than 8,” said lead author John F. Burke, MD, PhD, University of California, San Francisco, in presenting the findings as part of the virtual annual meeting of the American Association of Neurological Surgeons.
Assessing risk factors
While posttraumatic epilepsy represents an estimated 20% of all cases of symptomatic epilepsy, many questions remain on those most at risk and on the long-term effects of posttraumatic epilepsy on TBI outcomes. To probe those issues, Dr. Burke and colleagues turned to the multicenter TRACK-TBI database, which has prospective, longitudinal data on more than 2,700 patients with traumatic brain injuries and is considered the largest source of prospective data on posttraumatic epilepsy.
Using the criteria of no previous epilepsy and having 12 months of follow-up, the team identified 1,493 patients with TBI. In addition, investigators identified 182 orthopedic controls (included and prospectively followed because they have injuries but not specifically head trauma) and 210 controls who are friends of the patients and who do not have injuries but allow researchers to control for socioeconomic and environmental factors.
Of the 1,493 patients with TBI, 41 (2.7%) were determined to have posttraumatic epilepsy, assessed according to a National Institute of Neurological Disorders and Stroke epilepsy screening questionnaire, which is designed to identify patients with posttraumatic epilepsy symptoms. There were no reports of epilepsy symptoms using the screening tool among the controls. Dr. Burke noted that the 2.7% was in agreement with historical reports.
In comparing patients with TBI who did and did not have posttraumatic epilepsy, no differences were observed in the groups in terms of gender, although there was a trend toward younger age among those with PTE (mean age, 35.4 years with posttraumatic injury vs. 41.5 without; P = .05).
A major risk factor for the development of posttraumatic epilepsy was presenting GCS scores. Among those with scores of less than 8, indicative of severe injury, the rate of posttraumatic epilepsy was 6% at 6 months and 12.5% at 12 months. In contrast, those with TBI presenting with GCS scores between 13 and 15, indicative of minor injury, had an incidence of posttraumatic epilepsy of 0.9% at 6 months and 1.4% at 12 months.
Imaging findings in the two groups showed that hemorrhage detected on CT imaging was associated with a significantly higher risk for posttraumatic epilepsy (P < .001).
“The main takeaway is that any hemorrhage in the brain is a major risk factor for developing seizures,” Dr. Burke said. “Whether it is subdural, epidural blood, subarachnoid or contusion, any blood confers a very [high] risk for developing seizures.”
Posttraumatic epilepsy was linked to poorer longer-term outcomes even for patients with lesser injury: Among those with TBI and GCS of 13-15, the mean Glasgow Outcome Scale Extended (GOSE) score at 12 months among those without posttraumatic epilepsy was 7, indicative of a good recovery with minor defects, whereas the mean GOSE score for those with PTE was 4.6, indicative of moderate to severe disability (P < .001).
“It was surprising to us that PTE-positive patients had a very significant decrease in GOSE, compared to PTE-negative patients,” Dr. Burke said. “There was a nearly 2-point drop in the GOSE and that was extremely significant.”
A multivariate analysis showed there was still a significant independent risk for a poor GOSE score with posttraumatic epilepsy after controlling for GCS score, head CT findings, and age (P < .001).
The authors also looked at mood outcomes using the Brief Symptom Inventory–18, which showed significant worse effect in those with posttraumatic epilepsy after multivariate adjustment (P = .01). Additionally, a highly significant worse effect in cognitive outcomes on the Rivermead cognitive metric was observed with posttraumatic epilepsy (P = .001).
“On all metrics tested, posttraumatic epilepsy worsened outcomes,” Dr. Burke said.
He noted that the study has some key limitations, including the 12-month follow-up. A previous study showed a linear increase in posttraumatic follow-up up to 30 years. “The fact that we found 41 patients at 12 months indicates there are probably more that are out there who are going to develop seizures, but because we don’t have the follow-up we can’t look at that.”
Although the screening questionnaires are effective, “the issue is these people are not being seen by an epileptologist or having scalp EEG done, and we need a more accurate way to do this,” he said. A new study, TRACK-TBI EPI, will address those limitations and a host of other issues with a 5-year follow-up.
Capturing the nuances of brain injury
Commenting on the study as a discussant, neurosurgeon Uzma Samadani, MD, PhD, of the Minneapolis Veterans Affairs Medical Center and CentraCare in Minneapolis, suggested that the future work should focus on issues including the wide-ranging mechanisms that could explain the seizure activity.
“For example, it’s known that posttraumatic epilepsy or seizures can be triggered by abnormal conductivity due to multiple different mechanisms associated with brain injury, such as endocrine dysfunction, cortical-spreading depression, and many others,” said Dr. Samadani, who has been a researcher on the TRACK-TBI study.
Factors ranging from genetic differences to comorbid conditions such as alcoholism can play a role in brain injury susceptibility, Dr. Samadani added. Furthermore, outcome measures currently available simply may not capture the unknown nuances of brain injury.
“We have to ask, are these an all-or-none phenomena, or is aberrant electrical activity after brain injury a continuum of dysfunction?” Dr. Samadani speculated.
“I would caution that we are likely underestimating the non–easily measurable consequences of brain injury,” she said. “And the better we can quantitate susceptibility, classify the nature of injury and target acute management, the less posttraumatic epilepsy/aberrant electrical activity our patients will have.”
Dr. Burke and Dr. Samadani disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
findings from an analysis of a large, prospective database suggest. “We found that patients essentially have a 10-times greater risk of developing posttraumatic epilepsy and seizures at 12 months [post injury] if the presenting Glasgow Coma Scale GCS) is less than 8,” said lead author John F. Burke, MD, PhD, University of California, San Francisco, in presenting the findings as part of the virtual annual meeting of the American Association of Neurological Surgeons.
Assessing risk factors
While posttraumatic epilepsy represents an estimated 20% of all cases of symptomatic epilepsy, many questions remain on those most at risk and on the long-term effects of posttraumatic epilepsy on TBI outcomes. To probe those issues, Dr. Burke and colleagues turned to the multicenter TRACK-TBI database, which has prospective, longitudinal data on more than 2,700 patients with traumatic brain injuries and is considered the largest source of prospective data on posttraumatic epilepsy.
Using the criteria of no previous epilepsy and having 12 months of follow-up, the team identified 1,493 patients with TBI. In addition, investigators identified 182 orthopedic controls (included and prospectively followed because they have injuries but not specifically head trauma) and 210 controls who are friends of the patients and who do not have injuries but allow researchers to control for socioeconomic and environmental factors.
Of the 1,493 patients with TBI, 41 (2.7%) were determined to have posttraumatic epilepsy, assessed according to a National Institute of Neurological Disorders and Stroke epilepsy screening questionnaire, which is designed to identify patients with posttraumatic epilepsy symptoms. There were no reports of epilepsy symptoms using the screening tool among the controls. Dr. Burke noted that the 2.7% was in agreement with historical reports.
In comparing patients with TBI who did and did not have posttraumatic epilepsy, no differences were observed in the groups in terms of gender, although there was a trend toward younger age among those with PTE (mean age, 35.4 years with posttraumatic injury vs. 41.5 without; P = .05).
A major risk factor for the development of posttraumatic epilepsy was presenting GCS scores. Among those with scores of less than 8, indicative of severe injury, the rate of posttraumatic epilepsy was 6% at 6 months and 12.5% at 12 months. In contrast, those with TBI presenting with GCS scores between 13 and 15, indicative of minor injury, had an incidence of posttraumatic epilepsy of 0.9% at 6 months and 1.4% at 12 months.
Imaging findings in the two groups showed that hemorrhage detected on CT imaging was associated with a significantly higher risk for posttraumatic epilepsy (P < .001).
“The main takeaway is that any hemorrhage in the brain is a major risk factor for developing seizures,” Dr. Burke said. “Whether it is subdural, epidural blood, subarachnoid or contusion, any blood confers a very [high] risk for developing seizures.”
Posttraumatic epilepsy was linked to poorer longer-term outcomes even for patients with lesser injury: Among those with TBI and GCS of 13-15, the mean Glasgow Outcome Scale Extended (GOSE) score at 12 months among those without posttraumatic epilepsy was 7, indicative of a good recovery with minor defects, whereas the mean GOSE score for those with PTE was 4.6, indicative of moderate to severe disability (P < .001).
“It was surprising to us that PTE-positive patients had a very significant decrease in GOSE, compared to PTE-negative patients,” Dr. Burke said. “There was a nearly 2-point drop in the GOSE and that was extremely significant.”
A multivariate analysis showed there was still a significant independent risk for a poor GOSE score with posttraumatic epilepsy after controlling for GCS score, head CT findings, and age (P < .001).
The authors also looked at mood outcomes using the Brief Symptom Inventory–18, which showed significant worse effect in those with posttraumatic epilepsy after multivariate adjustment (P = .01). Additionally, a highly significant worse effect in cognitive outcomes on the Rivermead cognitive metric was observed with posttraumatic epilepsy (P = .001).
“On all metrics tested, posttraumatic epilepsy worsened outcomes,” Dr. Burke said.
He noted that the study has some key limitations, including the 12-month follow-up. A previous study showed a linear increase in posttraumatic follow-up up to 30 years. “The fact that we found 41 patients at 12 months indicates there are probably more that are out there who are going to develop seizures, but because we don’t have the follow-up we can’t look at that.”
Although the screening questionnaires are effective, “the issue is these people are not being seen by an epileptologist or having scalp EEG done, and we need a more accurate way to do this,” he said. A new study, TRACK-TBI EPI, will address those limitations and a host of other issues with a 5-year follow-up.
Capturing the nuances of brain injury
Commenting on the study as a discussant, neurosurgeon Uzma Samadani, MD, PhD, of the Minneapolis Veterans Affairs Medical Center and CentraCare in Minneapolis, suggested that the future work should focus on issues including the wide-ranging mechanisms that could explain the seizure activity.
“For example, it’s known that posttraumatic epilepsy or seizures can be triggered by abnormal conductivity due to multiple different mechanisms associated with brain injury, such as endocrine dysfunction, cortical-spreading depression, and many others,” said Dr. Samadani, who has been a researcher on the TRACK-TBI study.
Factors ranging from genetic differences to comorbid conditions such as alcoholism can play a role in brain injury susceptibility, Dr. Samadani added. Furthermore, outcome measures currently available simply may not capture the unknown nuances of brain injury.
“We have to ask, are these an all-or-none phenomena, or is aberrant electrical activity after brain injury a continuum of dysfunction?” Dr. Samadani speculated.
“I would caution that we are likely underestimating the non–easily measurable consequences of brain injury,” she said. “And the better we can quantitate susceptibility, classify the nature of injury and target acute management, the less posttraumatic epilepsy/aberrant electrical activity our patients will have.”
Dr. Burke and Dr. Samadani disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AANS 2020
Beefed up inpatient/outpatient care transition is key to suicide prevention
The care transition period between inpatient psychiatric hospitalization and initiation of outpatient mental health services is a time of extraordinarily heightened suicide risk that has been woefully neglected, according to speakers from the National Action Alliance for Suicide Prevention at the virtual annual meeting of the American Association of Suicidology.
This transition period traditionally has been a time when nobody really takes responsibility for patient care. In an effort to close this potentially deadly gap in services, the alliance recently has issued a report entitled, “Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care.” The recommendations focus on specific, innovative, evidence-based strategies that health care systems can use to prevent patients from falling through the cracks in care, mainly by implementing protocols aimed at fostering interorganizational teamwork between inpatient and outpatient behavioral health services.
“I believe that improving care transitions in the United States is the area where we can likely save the most lives. It’s within our grasp if we can just do this better,” declared Richard McKeon, PhD, MPH, chief of the Suicide Prevention Branch at the Center for Mental Health Services within SAMHSA, the Substance Abuse and Mental Health Services Administration.
He cited a recent meta-analysis that concluded that the risk of suicide during the first week post discharge after psychiatric hospitalization is a staggering 300 times greater than in the general population, while in the first month, the risk is increased 200-fold. The meta-analysis included 29 studies encompassing 3,551 suicides during the first month and 24 studies reporting 1,928 suicides during the first week post discharge (BMJ Open. 2019 Mar 23;9[3]:e023883. doi: 10.1136/bmjopen-2018-023883).
Everyone in the mental health field as well as patients and their families should know those statistics, but they don’t.
“I think it’s natural for people to think someone who’s been discharged from an inpatient unit or the emergency department is not at risk, when in reality it’s still a high-risk time. Suicide risk is not like a light switch that you can just switch off,” the clinical psychologist observed.
He cited other harrowing statistics that underscore the vast problem of poor care transitions. Nationally, fully one-third of patients don’t complete a single outpatient visit within the first 30 days after discharge from inpatient behavioral health care. And one in seven people who die by suicide have had contact with inpatient mental health services in the year before they died.
“That doesn’t mean that inpatient care did not do everything that they could do. What it does reflect is the need to make sure that there’s follow-up care after inpatient discharge. Too often, people don’t get the follow-up care that they need. And the research literature is clear that intervention can save lives,” Dr. McKeon said.
Panelist Becky Stoll, LCSW, vice president for crisis and disaster management at Centerstone Health in Nashville, Tenn., noted, “We see a lot of no-shows on the outpatient side, because nobody ever asked the patients if they can actually get to the outpatient appointment that’s been made.
“We have got to figure out this care transition and do better. The road to mental health is paved with Swiss cheese. There are so many holes to fall into, even if you know how to navigate the system – and most of the people we’re serving don’t know how,” observed Ms. Stoll, who, like Dr. McKeon, was among the coauthors of the alliance’s guidelines on best practices in care transitions. Ms. Stoll also serves on the AAS board as crisis services division chair.*
The National Action Alliance for Suicide Prevention is a public/private partnership whose goal is to advance the National Strategy for Suicide Prevention, which was developed by the alliance and the U.S. Surgeon General. The alliance includes mental health professionals as well as influential leaders from the military, journalism, entertainment, railroad, health insurance, law enforcement, defense, education, technology, and other industries.
Dr. McKeon and Ms. Stall were joined by Karen Johnson, MSW, another coauthor of the guidelines. They shared highlights of the report.
Inpatient provider strategies
Discharge and crisis safety planning should begin upon admission, according to Ms. Johnson, senior vice president for clinical services and division compliance at Universal Health Services, which owns and operates more than 200 behavioral health facilities across the United States.
Inpatient and outpatient care providers need to sit down and develop collaborative protocols and negotiate a memorandum of understanding regarding expectations, which absolutely must include procedures to ensure timely electronic delivery of medical records and other key documents to the outpatient care providers. The inpatient providers need to work collaboratively with the patient, family, and community support resources to develop a safety plan – including reduced access to lethal mean – as part of predischarge planning.
Among the strategies routinely employed on the inpatient side at Universal Health Services are advance scheduling of an initial outpatient appointment within 24-72 hours post discharge. Also, someone on the inpatient team is tasked with connecting with the outpatient provider prior to discharge to develop rapport.
“If our outpatient providers are located in our facility, as many of them are, we ask them to come in and attend inpatient team meetings to identify and meet with patients who are appropriate for continuing care in outpatient settings,” she explained. “A soft, warm handoff is critical.”
At these team meetings, the appropriateness of step-down care in the form of partial hospitalization or intensive outpatient care is weighed. Someone from the inpatient side is charged with maintaining contact with the patient until after the first outpatient appointment. Ongoing caring contact in the form of brief, encouraging postcards, emails, or texts that do not require a response from the patient should be maintained for several months.
Strategies for outpatient providers
Ms. Stoll is a big believer in the guideline-recommended practice of notifying the inpatient provider that the patient kept the outpatient appointment, along with having a system for red-flagging no-shows for prompt follow-up by a crisis management team.
She and her colleagues at Centerstone Health have conducted two studies of an intensive patient outreach program designed for the first 30 days of the care transition. The program included many elements of the alliance’s best practices guidelines. The yearlong first study, funded by Blue Cross/Blue Shield of Tennessee, documented zero suicides and 92% freedom from emergency department visits during the care transition period, along with greater than $400,000 savings in health care costs, compared with usual care. The second study, funded by SAMHSA, showed much the same over a 2-year period.
She emphasized that this was not a high-tech, intensive intervention. She characterized it, instead as “high-touch follow-up.
“It’s some staff and a phone and a laptop, nothing fancy, just a person who’s competent and confident and skilled with a laptop. With that, you can do some pretty amazing stuff: Get people what they need, keep them alive, and oh, guess what? You can also save a lot of health care dollars that can be put back into the system,” Ms. Stoll said.
She recognizes that it’s a lot to ask busy outpatient providers to leave their practice during the workday to participate in inpatient team meetings addressing discharge planning, as recommended in the alliance guidelines. But in this regard, she sees a silver lining to the COVID-19 pandemic, in that it forces health professionals to rely upon newly opened channels of telemedicine.
“COVID-19 is giving us an opportunity to do things in a different way. Things don’t just have to be done in person. , where we can do things in a more innovative way,” she said.
Dr. McKeon agreed that reimbursement issues have long impeded efforts to improve the inpatient to outpatient care transition. He added that it will be really important that adequate reimbursement of remote forms of care remain in place after COVID-19 fades.
“This is exactly the kind of thing that’s needed to improve care transitions,” according to Dr. McKeon.
*This story was updated 7/9/2020.
The care transition period between inpatient psychiatric hospitalization and initiation of outpatient mental health services is a time of extraordinarily heightened suicide risk that has been woefully neglected, according to speakers from the National Action Alliance for Suicide Prevention at the virtual annual meeting of the American Association of Suicidology.
This transition period traditionally has been a time when nobody really takes responsibility for patient care. In an effort to close this potentially deadly gap in services, the alliance recently has issued a report entitled, “Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care.” The recommendations focus on specific, innovative, evidence-based strategies that health care systems can use to prevent patients from falling through the cracks in care, mainly by implementing protocols aimed at fostering interorganizational teamwork between inpatient and outpatient behavioral health services.
“I believe that improving care transitions in the United States is the area where we can likely save the most lives. It’s within our grasp if we can just do this better,” declared Richard McKeon, PhD, MPH, chief of the Suicide Prevention Branch at the Center for Mental Health Services within SAMHSA, the Substance Abuse and Mental Health Services Administration.
He cited a recent meta-analysis that concluded that the risk of suicide during the first week post discharge after psychiatric hospitalization is a staggering 300 times greater than in the general population, while in the first month, the risk is increased 200-fold. The meta-analysis included 29 studies encompassing 3,551 suicides during the first month and 24 studies reporting 1,928 suicides during the first week post discharge (BMJ Open. 2019 Mar 23;9[3]:e023883. doi: 10.1136/bmjopen-2018-023883).
Everyone in the mental health field as well as patients and their families should know those statistics, but they don’t.
“I think it’s natural for people to think someone who’s been discharged from an inpatient unit or the emergency department is not at risk, when in reality it’s still a high-risk time. Suicide risk is not like a light switch that you can just switch off,” the clinical psychologist observed.
He cited other harrowing statistics that underscore the vast problem of poor care transitions. Nationally, fully one-third of patients don’t complete a single outpatient visit within the first 30 days after discharge from inpatient behavioral health care. And one in seven people who die by suicide have had contact with inpatient mental health services in the year before they died.
“That doesn’t mean that inpatient care did not do everything that they could do. What it does reflect is the need to make sure that there’s follow-up care after inpatient discharge. Too often, people don’t get the follow-up care that they need. And the research literature is clear that intervention can save lives,” Dr. McKeon said.
Panelist Becky Stoll, LCSW, vice president for crisis and disaster management at Centerstone Health in Nashville, Tenn., noted, “We see a lot of no-shows on the outpatient side, because nobody ever asked the patients if they can actually get to the outpatient appointment that’s been made.
“We have got to figure out this care transition and do better. The road to mental health is paved with Swiss cheese. There are so many holes to fall into, even if you know how to navigate the system – and most of the people we’re serving don’t know how,” observed Ms. Stoll, who, like Dr. McKeon, was among the coauthors of the alliance’s guidelines on best practices in care transitions. Ms. Stoll also serves on the AAS board as crisis services division chair.*
The National Action Alliance for Suicide Prevention is a public/private partnership whose goal is to advance the National Strategy for Suicide Prevention, which was developed by the alliance and the U.S. Surgeon General. The alliance includes mental health professionals as well as influential leaders from the military, journalism, entertainment, railroad, health insurance, law enforcement, defense, education, technology, and other industries.
Dr. McKeon and Ms. Stall were joined by Karen Johnson, MSW, another coauthor of the guidelines. They shared highlights of the report.
Inpatient provider strategies
Discharge and crisis safety planning should begin upon admission, according to Ms. Johnson, senior vice president for clinical services and division compliance at Universal Health Services, which owns and operates more than 200 behavioral health facilities across the United States.
Inpatient and outpatient care providers need to sit down and develop collaborative protocols and negotiate a memorandum of understanding regarding expectations, which absolutely must include procedures to ensure timely electronic delivery of medical records and other key documents to the outpatient care providers. The inpatient providers need to work collaboratively with the patient, family, and community support resources to develop a safety plan – including reduced access to lethal mean – as part of predischarge planning.
Among the strategies routinely employed on the inpatient side at Universal Health Services are advance scheduling of an initial outpatient appointment within 24-72 hours post discharge. Also, someone on the inpatient team is tasked with connecting with the outpatient provider prior to discharge to develop rapport.
“If our outpatient providers are located in our facility, as many of them are, we ask them to come in and attend inpatient team meetings to identify and meet with patients who are appropriate for continuing care in outpatient settings,” she explained. “A soft, warm handoff is critical.”
At these team meetings, the appropriateness of step-down care in the form of partial hospitalization or intensive outpatient care is weighed. Someone from the inpatient side is charged with maintaining contact with the patient until after the first outpatient appointment. Ongoing caring contact in the form of brief, encouraging postcards, emails, or texts that do not require a response from the patient should be maintained for several months.
Strategies for outpatient providers
Ms. Stoll is a big believer in the guideline-recommended practice of notifying the inpatient provider that the patient kept the outpatient appointment, along with having a system for red-flagging no-shows for prompt follow-up by a crisis management team.
She and her colleagues at Centerstone Health have conducted two studies of an intensive patient outreach program designed for the first 30 days of the care transition. The program included many elements of the alliance’s best practices guidelines. The yearlong first study, funded by Blue Cross/Blue Shield of Tennessee, documented zero suicides and 92% freedom from emergency department visits during the care transition period, along with greater than $400,000 savings in health care costs, compared with usual care. The second study, funded by SAMHSA, showed much the same over a 2-year period.
She emphasized that this was not a high-tech, intensive intervention. She characterized it, instead as “high-touch follow-up.
“It’s some staff and a phone and a laptop, nothing fancy, just a person who’s competent and confident and skilled with a laptop. With that, you can do some pretty amazing stuff: Get people what they need, keep them alive, and oh, guess what? You can also save a lot of health care dollars that can be put back into the system,” Ms. Stoll said.
She recognizes that it’s a lot to ask busy outpatient providers to leave their practice during the workday to participate in inpatient team meetings addressing discharge planning, as recommended in the alliance guidelines. But in this regard, she sees a silver lining to the COVID-19 pandemic, in that it forces health professionals to rely upon newly opened channels of telemedicine.
“COVID-19 is giving us an opportunity to do things in a different way. Things don’t just have to be done in person. , where we can do things in a more innovative way,” she said.
Dr. McKeon agreed that reimbursement issues have long impeded efforts to improve the inpatient to outpatient care transition. He added that it will be really important that adequate reimbursement of remote forms of care remain in place after COVID-19 fades.
“This is exactly the kind of thing that’s needed to improve care transitions,” according to Dr. McKeon.
*This story was updated 7/9/2020.
The care transition period between inpatient psychiatric hospitalization and initiation of outpatient mental health services is a time of extraordinarily heightened suicide risk that has been woefully neglected, according to speakers from the National Action Alliance for Suicide Prevention at the virtual annual meeting of the American Association of Suicidology.
This transition period traditionally has been a time when nobody really takes responsibility for patient care. In an effort to close this potentially deadly gap in services, the alliance recently has issued a report entitled, “Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care.” The recommendations focus on specific, innovative, evidence-based strategies that health care systems can use to prevent patients from falling through the cracks in care, mainly by implementing protocols aimed at fostering interorganizational teamwork between inpatient and outpatient behavioral health services.
“I believe that improving care transitions in the United States is the area where we can likely save the most lives. It’s within our grasp if we can just do this better,” declared Richard McKeon, PhD, MPH, chief of the Suicide Prevention Branch at the Center for Mental Health Services within SAMHSA, the Substance Abuse and Mental Health Services Administration.
He cited a recent meta-analysis that concluded that the risk of suicide during the first week post discharge after psychiatric hospitalization is a staggering 300 times greater than in the general population, while in the first month, the risk is increased 200-fold. The meta-analysis included 29 studies encompassing 3,551 suicides during the first month and 24 studies reporting 1,928 suicides during the first week post discharge (BMJ Open. 2019 Mar 23;9[3]:e023883. doi: 10.1136/bmjopen-2018-023883).
Everyone in the mental health field as well as patients and their families should know those statistics, but they don’t.
“I think it’s natural for people to think someone who’s been discharged from an inpatient unit or the emergency department is not at risk, when in reality it’s still a high-risk time. Suicide risk is not like a light switch that you can just switch off,” the clinical psychologist observed.
He cited other harrowing statistics that underscore the vast problem of poor care transitions. Nationally, fully one-third of patients don’t complete a single outpatient visit within the first 30 days after discharge from inpatient behavioral health care. And one in seven people who die by suicide have had contact with inpatient mental health services in the year before they died.
“That doesn’t mean that inpatient care did not do everything that they could do. What it does reflect is the need to make sure that there’s follow-up care after inpatient discharge. Too often, people don’t get the follow-up care that they need. And the research literature is clear that intervention can save lives,” Dr. McKeon said.
Panelist Becky Stoll, LCSW, vice president for crisis and disaster management at Centerstone Health in Nashville, Tenn., noted, “We see a lot of no-shows on the outpatient side, because nobody ever asked the patients if they can actually get to the outpatient appointment that’s been made.
“We have got to figure out this care transition and do better. The road to mental health is paved with Swiss cheese. There are so many holes to fall into, even if you know how to navigate the system – and most of the people we’re serving don’t know how,” observed Ms. Stoll, who, like Dr. McKeon, was among the coauthors of the alliance’s guidelines on best practices in care transitions. Ms. Stoll also serves on the AAS board as crisis services division chair.*
The National Action Alliance for Suicide Prevention is a public/private partnership whose goal is to advance the National Strategy for Suicide Prevention, which was developed by the alliance and the U.S. Surgeon General. The alliance includes mental health professionals as well as influential leaders from the military, journalism, entertainment, railroad, health insurance, law enforcement, defense, education, technology, and other industries.
Dr. McKeon and Ms. Stall were joined by Karen Johnson, MSW, another coauthor of the guidelines. They shared highlights of the report.
Inpatient provider strategies
Discharge and crisis safety planning should begin upon admission, according to Ms. Johnson, senior vice president for clinical services and division compliance at Universal Health Services, which owns and operates more than 200 behavioral health facilities across the United States.
Inpatient and outpatient care providers need to sit down and develop collaborative protocols and negotiate a memorandum of understanding regarding expectations, which absolutely must include procedures to ensure timely electronic delivery of medical records and other key documents to the outpatient care providers. The inpatient providers need to work collaboratively with the patient, family, and community support resources to develop a safety plan – including reduced access to lethal mean – as part of predischarge planning.
Among the strategies routinely employed on the inpatient side at Universal Health Services are advance scheduling of an initial outpatient appointment within 24-72 hours post discharge. Also, someone on the inpatient team is tasked with connecting with the outpatient provider prior to discharge to develop rapport.
“If our outpatient providers are located in our facility, as many of them are, we ask them to come in and attend inpatient team meetings to identify and meet with patients who are appropriate for continuing care in outpatient settings,” she explained. “A soft, warm handoff is critical.”
At these team meetings, the appropriateness of step-down care in the form of partial hospitalization or intensive outpatient care is weighed. Someone from the inpatient side is charged with maintaining contact with the patient until after the first outpatient appointment. Ongoing caring contact in the form of brief, encouraging postcards, emails, or texts that do not require a response from the patient should be maintained for several months.
Strategies for outpatient providers
Ms. Stoll is a big believer in the guideline-recommended practice of notifying the inpatient provider that the patient kept the outpatient appointment, along with having a system for red-flagging no-shows for prompt follow-up by a crisis management team.
She and her colleagues at Centerstone Health have conducted two studies of an intensive patient outreach program designed for the first 30 days of the care transition. The program included many elements of the alliance’s best practices guidelines. The yearlong first study, funded by Blue Cross/Blue Shield of Tennessee, documented zero suicides and 92% freedom from emergency department visits during the care transition period, along with greater than $400,000 savings in health care costs, compared with usual care. The second study, funded by SAMHSA, showed much the same over a 2-year period.
She emphasized that this was not a high-tech, intensive intervention. She characterized it, instead as “high-touch follow-up.
“It’s some staff and a phone and a laptop, nothing fancy, just a person who’s competent and confident and skilled with a laptop. With that, you can do some pretty amazing stuff: Get people what they need, keep them alive, and oh, guess what? You can also save a lot of health care dollars that can be put back into the system,” Ms. Stoll said.
She recognizes that it’s a lot to ask busy outpatient providers to leave their practice during the workday to participate in inpatient team meetings addressing discharge planning, as recommended in the alliance guidelines. But in this regard, she sees a silver lining to the COVID-19 pandemic, in that it forces health professionals to rely upon newly opened channels of telemedicine.
“COVID-19 is giving us an opportunity to do things in a different way. Things don’t just have to be done in person. , where we can do things in a more innovative way,” she said.
Dr. McKeon agreed that reimbursement issues have long impeded efforts to improve the inpatient to outpatient care transition. He added that it will be really important that adequate reimbursement of remote forms of care remain in place after COVID-19 fades.
“This is exactly the kind of thing that’s needed to improve care transitions,” according to Dr. McKeon.
*This story was updated 7/9/2020.
FROM AAS20
Amid pandemic, Virginia hospital’s opioid overdoses up nearly 10-fold
Opioid overdoses have shot up by almost 10-fold at a Virginia ED since March, a new report finds. The report provides more evidence that the coronavirus pandemic is sparking a severe medical crisis among illicit drug users.
“Health care providers should closely monitor the number of overdoses coming into their hospitals and in the surrounding community during this time,” study lead author and postdoctoral research fellow Taylor Ochalek, PhD, said in an interview. “If they do notice an increasing trend of overdoses, they should spread awareness in the community to the general public, and offer resources and information for those that may be seeking help and/or may be at a high risk of overdosing.”
Dr. Ochalek presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence.
According to the report, opioid overdoses at the VCU Medical Center in Richmond, Va., grew from an average of six a month from February to December 2019 to 50, 57, and 63 in March, April, and May 2020. Of the 171 cases in the later time frame, the average age was 44 years, 72% were male, and 82% were African American.
“The steep increase in overdoses began primarily in March,” said Dr. Ochalek, of Virginia Commonwealth University in Richmond. “This timing coincides with the Virginia governor’s state of emergency declaration, stay-at-home order, and closure of nonessential businesses order.”
The researchers did not provide details about the types of opioids used, the patient outcomes, or whether the patients tested positive for COVID-19. It’s unclear whether the pandemic directly spawned a higher number of overdoses, but there are growing signs of a stark nationwide trend.
“Nationwide, federal and local officials are reporting alarming spikes in drug overdoses – a hidden epidemic within the coronavirus pandemic,” the Washington Post reported on July 1, pointing to increases in Kentucky, Virginia, and the Chicago area.
Meanwhile, the federal Overdose Detection Mapping Application Program, which tracks overdoses nationwide, issued 191% more “spike alerts” in January to April 2020 than in the same time period in 2019. However, the spike alerts began to increase in January, weeks before the pandemic began to take hold.
The findings are consistent with trends in Houston, where overdose calls were up 31% in the first 3 months of 2020, compared with 2019, said psychologist James Bray, PhD, of the University of Texas, San Antonio, in an interview. More recent data suggest that the numbers are rising even higher, said Dr. Bray, who works with Houston first responders and has analyzed data.
Dr. Bray said.
Another potential factor is the disruption in the illicit drug supply chain because of limits on crossings at the southern border, said ED physician Scott Weiner, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston. “As a result, opioids of extremely variable potency have infiltrated markets, and people using drugs may not be used to the new doses, especially if they are high-potency fentanyl analogues.”
Moving forward, Dr. Bray said, “people need continued access to treatment. Telehealth and other virtual services need to be provided so that people can continue to have access to treatment even during the pandemic.”
Dr. Weiner also emphasized the importance of treatment for patients who overdose on opioids. “In my previous work, we discovered that about 1 in 20 patients who are treated in an emergency department and survive would die within 1 year. That number will likely increase drastically during COVID,” he said. “When a patient presents after overdose, we must intervene aggressively with buprenorphine and other harm-reduction techniques to save these lives.”
The study was funded by the National Institutes of Health. Dr. Ochalek, Dr. Weiner, and Dr. Bray reported no relevant disclosures.
Opioid overdoses have shot up by almost 10-fold at a Virginia ED since March, a new report finds. The report provides more evidence that the coronavirus pandemic is sparking a severe medical crisis among illicit drug users.
“Health care providers should closely monitor the number of overdoses coming into their hospitals and in the surrounding community during this time,” study lead author and postdoctoral research fellow Taylor Ochalek, PhD, said in an interview. “If they do notice an increasing trend of overdoses, they should spread awareness in the community to the general public, and offer resources and information for those that may be seeking help and/or may be at a high risk of overdosing.”
Dr. Ochalek presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence.
According to the report, opioid overdoses at the VCU Medical Center in Richmond, Va., grew from an average of six a month from February to December 2019 to 50, 57, and 63 in March, April, and May 2020. Of the 171 cases in the later time frame, the average age was 44 years, 72% were male, and 82% were African American.
“The steep increase in overdoses began primarily in March,” said Dr. Ochalek, of Virginia Commonwealth University in Richmond. “This timing coincides with the Virginia governor’s state of emergency declaration, stay-at-home order, and closure of nonessential businesses order.”
The researchers did not provide details about the types of opioids used, the patient outcomes, or whether the patients tested positive for COVID-19. It’s unclear whether the pandemic directly spawned a higher number of overdoses, but there are growing signs of a stark nationwide trend.
“Nationwide, federal and local officials are reporting alarming spikes in drug overdoses – a hidden epidemic within the coronavirus pandemic,” the Washington Post reported on July 1, pointing to increases in Kentucky, Virginia, and the Chicago area.
Meanwhile, the federal Overdose Detection Mapping Application Program, which tracks overdoses nationwide, issued 191% more “spike alerts” in January to April 2020 than in the same time period in 2019. However, the spike alerts began to increase in January, weeks before the pandemic began to take hold.
The findings are consistent with trends in Houston, where overdose calls were up 31% in the first 3 months of 2020, compared with 2019, said psychologist James Bray, PhD, of the University of Texas, San Antonio, in an interview. More recent data suggest that the numbers are rising even higher, said Dr. Bray, who works with Houston first responders and has analyzed data.
Dr. Bray said.
Another potential factor is the disruption in the illicit drug supply chain because of limits on crossings at the southern border, said ED physician Scott Weiner, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston. “As a result, opioids of extremely variable potency have infiltrated markets, and people using drugs may not be used to the new doses, especially if they are high-potency fentanyl analogues.”
Moving forward, Dr. Bray said, “people need continued access to treatment. Telehealth and other virtual services need to be provided so that people can continue to have access to treatment even during the pandemic.”
Dr. Weiner also emphasized the importance of treatment for patients who overdose on opioids. “In my previous work, we discovered that about 1 in 20 patients who are treated in an emergency department and survive would die within 1 year. That number will likely increase drastically during COVID,” he said. “When a patient presents after overdose, we must intervene aggressively with buprenorphine and other harm-reduction techniques to save these lives.”
The study was funded by the National Institutes of Health. Dr. Ochalek, Dr. Weiner, and Dr. Bray reported no relevant disclosures.
Opioid overdoses have shot up by almost 10-fold at a Virginia ED since March, a new report finds. The report provides more evidence that the coronavirus pandemic is sparking a severe medical crisis among illicit drug users.
“Health care providers should closely monitor the number of overdoses coming into their hospitals and in the surrounding community during this time,” study lead author and postdoctoral research fellow Taylor Ochalek, PhD, said in an interview. “If they do notice an increasing trend of overdoses, they should spread awareness in the community to the general public, and offer resources and information for those that may be seeking help and/or may be at a high risk of overdosing.”
Dr. Ochalek presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence.
According to the report, opioid overdoses at the VCU Medical Center in Richmond, Va., grew from an average of six a month from February to December 2019 to 50, 57, and 63 in March, April, and May 2020. Of the 171 cases in the later time frame, the average age was 44 years, 72% were male, and 82% were African American.
“The steep increase in overdoses began primarily in March,” said Dr. Ochalek, of Virginia Commonwealth University in Richmond. “This timing coincides with the Virginia governor’s state of emergency declaration, stay-at-home order, and closure of nonessential businesses order.”
The researchers did not provide details about the types of opioids used, the patient outcomes, or whether the patients tested positive for COVID-19. It’s unclear whether the pandemic directly spawned a higher number of overdoses, but there are growing signs of a stark nationwide trend.
“Nationwide, federal and local officials are reporting alarming spikes in drug overdoses – a hidden epidemic within the coronavirus pandemic,” the Washington Post reported on July 1, pointing to increases in Kentucky, Virginia, and the Chicago area.
Meanwhile, the federal Overdose Detection Mapping Application Program, which tracks overdoses nationwide, issued 191% more “spike alerts” in January to April 2020 than in the same time period in 2019. However, the spike alerts began to increase in January, weeks before the pandemic began to take hold.
The findings are consistent with trends in Houston, where overdose calls were up 31% in the first 3 months of 2020, compared with 2019, said psychologist James Bray, PhD, of the University of Texas, San Antonio, in an interview. More recent data suggest that the numbers are rising even higher, said Dr. Bray, who works with Houston first responders and has analyzed data.
Dr. Bray said.
Another potential factor is the disruption in the illicit drug supply chain because of limits on crossings at the southern border, said ED physician Scott Weiner, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston. “As a result, opioids of extremely variable potency have infiltrated markets, and people using drugs may not be used to the new doses, especially if they are high-potency fentanyl analogues.”
Moving forward, Dr. Bray said, “people need continued access to treatment. Telehealth and other virtual services need to be provided so that people can continue to have access to treatment even during the pandemic.”
Dr. Weiner also emphasized the importance of treatment for patients who overdose on opioids. “In my previous work, we discovered that about 1 in 20 patients who are treated in an emergency department and survive would die within 1 year. That number will likely increase drastically during COVID,” he said. “When a patient presents after overdose, we must intervene aggressively with buprenorphine and other harm-reduction techniques to save these lives.”
The study was funded by the National Institutes of Health. Dr. Ochalek, Dr. Weiner, and Dr. Bray reported no relevant disclosures.
FROM CPDD 2020
Expert shares his approach to treating warts in children
In the clinical experience of Anthony J. Mancini, MD, one option for children and adolescents who present with common warts is to do nothing, since they may resolve on their own.
“Many effective treatments that we have are painful and poorly tolerated, especially in younger children,” Dr. Mancini, professor of pediatrics and dermatology at Northwestern University, Chicago, said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “However, while they’re harmless and often self-limited, warts often form a social stigma, and parents often desire therapy.”
Even though warts may spontaneously resolve in up to 65% of patients at 2 years and 80% at 4 years, the goals of treatment are to eradicate them, minimize pain, avoid scarring, and help prevent recurrence.
One effective topical therapy he highlighted is WartPEEL cream, which is a proprietary, compounded formulation of 17% salicylic acid and 2% 5-fluorouracil. “It’s in a sustained release vehicle called Remedium, and is available from a compounding pharmacy, but not FDA approved,” said Dr. Mancini, who is also head of pediatric dermatology at Lurie Children’s Hospital of Chicago. “It’s applied nightly with plastic tape occlusion and rinsed off each morning.”
WartPEEL is available through NuCara Pharmacy at 877-268-2272. It is not covered by most insurance plans and it costs around $80. “It is very effective, tends to be totally painless, and has a much quicker response than over-the-counter salicylic acid-based treatments for warts,” he said.
Another treatment option is oral cimetidine, especially in patients who have multiple or recalcitrant warts. The recommended dosing is 30-40 mg/kg per day, divided into twice-daily dosing. “You have to give it for at least 8-12 weeks to determine whether it’s working or not,” Dr. Mancini said. “In the initial report, [investigators] described an 81% complete response rate, but subsequent randomized, controlled trials were not able to confirm that data against placebo or topical treatments. I will say, though, that cimetidine is well tolerated. It’s always worth a try but, if you do use it, always consider other medications the patient may be taking and potential drug-drug interactions.”
For flat warts, verrucous papules that commonly occur on the face, Dr. Mancini recommends off-label treatment with 5% 5-fluorouracil cream (Efudex), which is normally indicated for actinic keratoses in adults. “I have patients apply this for 3 nights per week and work their way up gradually to nightly application,” he said. “It’s really important that parents and patients understand the importance of sun protection when they’re using Efudex, and they need to know that some irritation is possible. Overall, this treatment seems to be very well tolerated.”
Other treatment options for common warts, in addition to over-the-counter products that contain salicylic acid, are home cryotherapy kits that contain a mixture of diethyl ether and propane. “These can be effective for small warts,” Dr. Mancini said. “But for larger, thicker lesions, they’re not going to quite as effective.”
Treatment options best reserved for dermatologists, he continued, include in-office liquid nitrogen cryotherapy, “if it’s tolerated,” he said. “I have a no-hold policy, so if we have to hold a child down who’s flailing and crying and screaming during treatment, we’re probably not going to use liquid nitrogen.” He also mentioned topical immunotherapy with agents like squaric acid dibutylester. “This is almost like putting poison ivy on your warts to get the immune system revved up,” he said. “It can be very effective.” Other treatment options include intralesional immune therapy, topical cidofovir, and even pulsed-dye laser.
Dr. Mancini disclosed that he is a consultant to and a member of the scientific advisory board for Verrica Pharmaceuticals.
In the clinical experience of Anthony J. Mancini, MD, one option for children and adolescents who present with common warts is to do nothing, since they may resolve on their own.
“Many effective treatments that we have are painful and poorly tolerated, especially in younger children,” Dr. Mancini, professor of pediatrics and dermatology at Northwestern University, Chicago, said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “However, while they’re harmless and often self-limited, warts often form a social stigma, and parents often desire therapy.”
Even though warts may spontaneously resolve in up to 65% of patients at 2 years and 80% at 4 years, the goals of treatment are to eradicate them, minimize pain, avoid scarring, and help prevent recurrence.
One effective topical therapy he highlighted is WartPEEL cream, which is a proprietary, compounded formulation of 17% salicylic acid and 2% 5-fluorouracil. “It’s in a sustained release vehicle called Remedium, and is available from a compounding pharmacy, but not FDA approved,” said Dr. Mancini, who is also head of pediatric dermatology at Lurie Children’s Hospital of Chicago. “It’s applied nightly with plastic tape occlusion and rinsed off each morning.”
WartPEEL is available through NuCara Pharmacy at 877-268-2272. It is not covered by most insurance plans and it costs around $80. “It is very effective, tends to be totally painless, and has a much quicker response than over-the-counter salicylic acid-based treatments for warts,” he said.
Another treatment option is oral cimetidine, especially in patients who have multiple or recalcitrant warts. The recommended dosing is 30-40 mg/kg per day, divided into twice-daily dosing. “You have to give it for at least 8-12 weeks to determine whether it’s working or not,” Dr. Mancini said. “In the initial report, [investigators] described an 81% complete response rate, but subsequent randomized, controlled trials were not able to confirm that data against placebo or topical treatments. I will say, though, that cimetidine is well tolerated. It’s always worth a try but, if you do use it, always consider other medications the patient may be taking and potential drug-drug interactions.”
For flat warts, verrucous papules that commonly occur on the face, Dr. Mancini recommends off-label treatment with 5% 5-fluorouracil cream (Efudex), which is normally indicated for actinic keratoses in adults. “I have patients apply this for 3 nights per week and work their way up gradually to nightly application,” he said. “It’s really important that parents and patients understand the importance of sun protection when they’re using Efudex, and they need to know that some irritation is possible. Overall, this treatment seems to be very well tolerated.”
Other treatment options for common warts, in addition to over-the-counter products that contain salicylic acid, are home cryotherapy kits that contain a mixture of diethyl ether and propane. “These can be effective for small warts,” Dr. Mancini said. “But for larger, thicker lesions, they’re not going to quite as effective.”
Treatment options best reserved for dermatologists, he continued, include in-office liquid nitrogen cryotherapy, “if it’s tolerated,” he said. “I have a no-hold policy, so if we have to hold a child down who’s flailing and crying and screaming during treatment, we’re probably not going to use liquid nitrogen.” He also mentioned topical immunotherapy with agents like squaric acid dibutylester. “This is almost like putting poison ivy on your warts to get the immune system revved up,” he said. “It can be very effective.” Other treatment options include intralesional immune therapy, topical cidofovir, and even pulsed-dye laser.
Dr. Mancini disclosed that he is a consultant to and a member of the scientific advisory board for Verrica Pharmaceuticals.
In the clinical experience of Anthony J. Mancini, MD, one option for children and adolescents who present with common warts is to do nothing, since they may resolve on their own.
“Many effective treatments that we have are painful and poorly tolerated, especially in younger children,” Dr. Mancini, professor of pediatrics and dermatology at Northwestern University, Chicago, said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “However, while they’re harmless and often self-limited, warts often form a social stigma, and parents often desire therapy.”
Even though warts may spontaneously resolve in up to 65% of patients at 2 years and 80% at 4 years, the goals of treatment are to eradicate them, minimize pain, avoid scarring, and help prevent recurrence.
One effective topical therapy he highlighted is WartPEEL cream, which is a proprietary, compounded formulation of 17% salicylic acid and 2% 5-fluorouracil. “It’s in a sustained release vehicle called Remedium, and is available from a compounding pharmacy, but not FDA approved,” said Dr. Mancini, who is also head of pediatric dermatology at Lurie Children’s Hospital of Chicago. “It’s applied nightly with plastic tape occlusion and rinsed off each morning.”
WartPEEL is available through NuCara Pharmacy at 877-268-2272. It is not covered by most insurance plans and it costs around $80. “It is very effective, tends to be totally painless, and has a much quicker response than over-the-counter salicylic acid-based treatments for warts,” he said.
Another treatment option is oral cimetidine, especially in patients who have multiple or recalcitrant warts. The recommended dosing is 30-40 mg/kg per day, divided into twice-daily dosing. “You have to give it for at least 8-12 weeks to determine whether it’s working or not,” Dr. Mancini said. “In the initial report, [investigators] described an 81% complete response rate, but subsequent randomized, controlled trials were not able to confirm that data against placebo or topical treatments. I will say, though, that cimetidine is well tolerated. It’s always worth a try but, if you do use it, always consider other medications the patient may be taking and potential drug-drug interactions.”
For flat warts, verrucous papules that commonly occur on the face, Dr. Mancini recommends off-label treatment with 5% 5-fluorouracil cream (Efudex), which is normally indicated for actinic keratoses in adults. “I have patients apply this for 3 nights per week and work their way up gradually to nightly application,” he said. “It’s really important that parents and patients understand the importance of sun protection when they’re using Efudex, and they need to know that some irritation is possible. Overall, this treatment seems to be very well tolerated.”
Other treatment options for common warts, in addition to over-the-counter products that contain salicylic acid, are home cryotherapy kits that contain a mixture of diethyl ether and propane. “These can be effective for small warts,” Dr. Mancini said. “But for larger, thicker lesions, they’re not going to quite as effective.”
Treatment options best reserved for dermatologists, he continued, include in-office liquid nitrogen cryotherapy, “if it’s tolerated,” he said. “I have a no-hold policy, so if we have to hold a child down who’s flailing and crying and screaming during treatment, we’re probably not going to use liquid nitrogen.” He also mentioned topical immunotherapy with agents like squaric acid dibutylester. “This is almost like putting poison ivy on your warts to get the immune system revved up,” he said. “It can be very effective.” Other treatment options include intralesional immune therapy, topical cidofovir, and even pulsed-dye laser.
Dr. Mancini disclosed that he is a consultant to and a member of the scientific advisory board for Verrica Pharmaceuticals.
FROM PEDIATRIC DERMATOLOGY 2020
HIV does not appear to worsen COVID-19 outcomes
People living with HIV who are admitted to the hospital with COVID-19 are no more likely to die than those without HIV, an analysis conducted in New York City shows. This is despite the fact that comorbidities associated with worse COVID-19 outcomes were more common in the HIV group.
“We don’t see any signs that people with HIV should take extra precautions” to protect themselves from COVID-19, said Keith Sigel, MD, associate professor of medicine and infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, and the lead researcher on the study, published online June 28 in Clinical Infectious Diseases.
“We still don’t have a great explanation for why we’re seeing what we’re seeing,” he added. “But we’re glad we’re seeing it.”
The findings have changed how Dr. Sigel talks to his patients with HIV about protecting themselves from COVID-19. Some patients have so curtailed their behavior for fear of acquiring COVID-19 that they aren’t buying groceries or attending needed medical appointments. With these data, Dr. Sigel said he’s comfortable telling his patients, “COVID-19 is bad all by itself, but you don’t need to go crazy. Wear a mask, practice appropriate social distancing and hygiene, but your risk doesn’t appear to be greater.”
The findings conform with those on the lack of association between HIV and COVID-19 severity seen in a cohort study from Spain, a case study from China, and case series from New Jersey, New York City, and Spain.
One of the only regions reporting something different so far is South Africa. There, HIV is the third most common comorbidity associated with death from COVID-19, according to a cohort analysis conducted in the province of Western Cape.
Along with data from HIV prevention and treatment trials, the conference will feature updates on where the world stands in the control of HIV during the COVID-19 pandemic. And for an even more focused look, the IAS COVID-19 Conference will immediately follow that meeting.
The New York City cohort
For their study, Dr. Sigel and colleagues examined the 4402 COVID-19 cases at the Mount Sinai Health System’s five hospitals between March 12 and April 23.
They found 88 people with COVID-19 whose charts showed codes indicating they were living with HIV. All 88 were receiving treatment, and 81% of them had undetectable viral loads documented at COVID admission or in the 12 months prior to admission.
The median age was 61 years, and 40% of the cohort was black and 30% was Hispanic.
Patients in the comparison group – 405 people without HIV from the Veterans Aging Cohort Study who had been admitted to the hospital for COVID-19 – were matched in terms of age, race, and stage of COVID-19.
The study had an 80% power to detect a 15% increase in the absolute risk for death in people with COVID-19, with or without HIV.
Patients with HIV were almost three times as likely to have smoked and were more likely to have chronic obstructive pulmonary disease, cirrhosis, and a history of cancer.
“This was a group of patients that one might suspect would do worse,” Dr. Sigel said. And yet, “we didn’t see any difference in deaths. We didn’t see any difference in respiratory failure.”
In fact, people with HIV required mechanical ventilation less often than those without HIV (18% vs. 23%). And when it came to mortality, one in five people died from COVID-19 during follow-up whether they had HIV or not (21% vs. 20%).
The only factor associated with significantly worse outcomes was a history of organ transplantation, “suggesting that non-HIV causes of immunodeficiency may be more prominent risks for severe outcomes,” Dr. Sigel and colleagues explained.
A surprise association
What’s more, the researchers found a slight association between the use of nucleoside reverse-transcriptase inhibitors (NRTI) by people with HIV and better outcomes in COVID-19. That echoes findings published June 26 in Annals of Internal Medicine, which showed that people with HIV taking the combination of tenofovir disoproxil fumarate plus emtricitabine (Truvada, Gilead Sciences) were less likely to be diagnosed with COVID-19, less likely to be hospitalized, and less likely to die.
This has led some to wonder whether NRTIs have some effect on SARS-CoV-2, the virus that causes COVID-19. Dr. Sigel said he wonders that too, but right now, it’s just musings.
“These studies are not even remotely designed” to show that NRTIs are protective against COVID-19, he explained. “Ours was extremely underpowered to detect that and there was a high potential for confounding.”
“I’d be wary of any study in a subpopulation – which is what we’re dealing with here – that is looking for signals of protection with certain medications,” he added.
A “modest” increase
Using the South African data, released on June 22, public health officials estimate that people with HIV are 2.75 times more likely to die from COVID-19 than those without HIV, making it the third most common comorbidity in people who died from COVID-19, behind diabetes and hypertension. This held true regardless of whether the people with HIV were on treatment.
But when they looked at COVID-19 deaths in the sickest of the sick – those hospitalized with COVID-19 symptoms – HIV was associated with just a 28% increase in the risk for death. The South African researchers called this risk “modest.”
“While these findings may overestimate the effect of HIV on COVID-19 death due to the presence of residual confounding, people living with HIV should be considered a high-risk group for COVID-19 management, with modestly elevated risk of poor outcomes, irrespective of viral suppression,” they wrote.
Epidemiologist Gregorio Millett, MPH, has been tracking the effect of HIV on COVID-19 outcomes since the start of the pandemic in his role as vice president and head of policy at the American Foundation for AIDS Research (amFAR).
Back in April, he and his colleagues looked at rates of COVID-19 deaths and hospitalizations in counties with disproportionate levels of black residents. These areas often overlapped with the communities selected for the Ending the HIV Epidemic plan to control HIV by 2030. What they found was that there was more HIV and COVID-19 in those communities.
What they didn’t find was that people with HIV in those communities had worse outcomes with COVID-19. This remained true even when they reran the analysis after the number of cases of COVID-19 in the United States surpassed 100,000. Those data have yet to be published, Mr. Millett reported.
“HIV does not pop out,” he said. “It’s still social determinants of health. It’s still underlying conditions. It’s still age as a primary factor.”
“People living with HIV are mainly dying of underlying conditions – so all the things associated with COVID-19 – rather than the association being with HIV itself,” he added.
Although he’s not ruling out the possibility that an association like the one in South Africa could emerge, Mr. Millett, who will present a plenary on the context of the HIV epidemic at the IAS conference, said he suspects we won’t see one.
“If we didn’t see an association with the counties that are disproportionately African American, in the black belt where we see high rates of HIV, particularly where we see the social determinants of health that definitely make a difference – if we’re not seeing that association there, where we have a high proportion of African Americans who are at risk both for HIV and COVID-19 – I just don’t think it’s going to emerge,” he said.
This article first appeared on Medscape.com.
People living with HIV who are admitted to the hospital with COVID-19 are no more likely to die than those without HIV, an analysis conducted in New York City shows. This is despite the fact that comorbidities associated with worse COVID-19 outcomes were more common in the HIV group.
“We don’t see any signs that people with HIV should take extra precautions” to protect themselves from COVID-19, said Keith Sigel, MD, associate professor of medicine and infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, and the lead researcher on the study, published online June 28 in Clinical Infectious Diseases.
“We still don’t have a great explanation for why we’re seeing what we’re seeing,” he added. “But we’re glad we’re seeing it.”
The findings have changed how Dr. Sigel talks to his patients with HIV about protecting themselves from COVID-19. Some patients have so curtailed their behavior for fear of acquiring COVID-19 that they aren’t buying groceries or attending needed medical appointments. With these data, Dr. Sigel said he’s comfortable telling his patients, “COVID-19 is bad all by itself, but you don’t need to go crazy. Wear a mask, practice appropriate social distancing and hygiene, but your risk doesn’t appear to be greater.”
The findings conform with those on the lack of association between HIV and COVID-19 severity seen in a cohort study from Spain, a case study from China, and case series from New Jersey, New York City, and Spain.
One of the only regions reporting something different so far is South Africa. There, HIV is the third most common comorbidity associated with death from COVID-19, according to a cohort analysis conducted in the province of Western Cape.
Along with data from HIV prevention and treatment trials, the conference will feature updates on where the world stands in the control of HIV during the COVID-19 pandemic. And for an even more focused look, the IAS COVID-19 Conference will immediately follow that meeting.
The New York City cohort
For their study, Dr. Sigel and colleagues examined the 4402 COVID-19 cases at the Mount Sinai Health System’s five hospitals between March 12 and April 23.
They found 88 people with COVID-19 whose charts showed codes indicating they were living with HIV. All 88 were receiving treatment, and 81% of them had undetectable viral loads documented at COVID admission or in the 12 months prior to admission.
The median age was 61 years, and 40% of the cohort was black and 30% was Hispanic.
Patients in the comparison group – 405 people without HIV from the Veterans Aging Cohort Study who had been admitted to the hospital for COVID-19 – were matched in terms of age, race, and stage of COVID-19.
The study had an 80% power to detect a 15% increase in the absolute risk for death in people with COVID-19, with or without HIV.
Patients with HIV were almost three times as likely to have smoked and were more likely to have chronic obstructive pulmonary disease, cirrhosis, and a history of cancer.
“This was a group of patients that one might suspect would do worse,” Dr. Sigel said. And yet, “we didn’t see any difference in deaths. We didn’t see any difference in respiratory failure.”
In fact, people with HIV required mechanical ventilation less often than those without HIV (18% vs. 23%). And when it came to mortality, one in five people died from COVID-19 during follow-up whether they had HIV or not (21% vs. 20%).
The only factor associated with significantly worse outcomes was a history of organ transplantation, “suggesting that non-HIV causes of immunodeficiency may be more prominent risks for severe outcomes,” Dr. Sigel and colleagues explained.
A surprise association
What’s more, the researchers found a slight association between the use of nucleoside reverse-transcriptase inhibitors (NRTI) by people with HIV and better outcomes in COVID-19. That echoes findings published June 26 in Annals of Internal Medicine, which showed that people with HIV taking the combination of tenofovir disoproxil fumarate plus emtricitabine (Truvada, Gilead Sciences) were less likely to be diagnosed with COVID-19, less likely to be hospitalized, and less likely to die.
This has led some to wonder whether NRTIs have some effect on SARS-CoV-2, the virus that causes COVID-19. Dr. Sigel said he wonders that too, but right now, it’s just musings.
“These studies are not even remotely designed” to show that NRTIs are protective against COVID-19, he explained. “Ours was extremely underpowered to detect that and there was a high potential for confounding.”
“I’d be wary of any study in a subpopulation – which is what we’re dealing with here – that is looking for signals of protection with certain medications,” he added.
A “modest” increase
Using the South African data, released on June 22, public health officials estimate that people with HIV are 2.75 times more likely to die from COVID-19 than those without HIV, making it the third most common comorbidity in people who died from COVID-19, behind diabetes and hypertension. This held true regardless of whether the people with HIV were on treatment.
But when they looked at COVID-19 deaths in the sickest of the sick – those hospitalized with COVID-19 symptoms – HIV was associated with just a 28% increase in the risk for death. The South African researchers called this risk “modest.”
“While these findings may overestimate the effect of HIV on COVID-19 death due to the presence of residual confounding, people living with HIV should be considered a high-risk group for COVID-19 management, with modestly elevated risk of poor outcomes, irrespective of viral suppression,” they wrote.
Epidemiologist Gregorio Millett, MPH, has been tracking the effect of HIV on COVID-19 outcomes since the start of the pandemic in his role as vice president and head of policy at the American Foundation for AIDS Research (amFAR).
Back in April, he and his colleagues looked at rates of COVID-19 deaths and hospitalizations in counties with disproportionate levels of black residents. These areas often overlapped with the communities selected for the Ending the HIV Epidemic plan to control HIV by 2030. What they found was that there was more HIV and COVID-19 in those communities.
What they didn’t find was that people with HIV in those communities had worse outcomes with COVID-19. This remained true even when they reran the analysis after the number of cases of COVID-19 in the United States surpassed 100,000. Those data have yet to be published, Mr. Millett reported.
“HIV does not pop out,” he said. “It’s still social determinants of health. It’s still underlying conditions. It’s still age as a primary factor.”
“People living with HIV are mainly dying of underlying conditions – so all the things associated with COVID-19 – rather than the association being with HIV itself,” he added.
Although he’s not ruling out the possibility that an association like the one in South Africa could emerge, Mr. Millett, who will present a plenary on the context of the HIV epidemic at the IAS conference, said he suspects we won’t see one.
“If we didn’t see an association with the counties that are disproportionately African American, in the black belt where we see high rates of HIV, particularly where we see the social determinants of health that definitely make a difference – if we’re not seeing that association there, where we have a high proportion of African Americans who are at risk both for HIV and COVID-19 – I just don’t think it’s going to emerge,” he said.
This article first appeared on Medscape.com.
People living with HIV who are admitted to the hospital with COVID-19 are no more likely to die than those without HIV, an analysis conducted in New York City shows. This is despite the fact that comorbidities associated with worse COVID-19 outcomes were more common in the HIV group.
“We don’t see any signs that people with HIV should take extra precautions” to protect themselves from COVID-19, said Keith Sigel, MD, associate professor of medicine and infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, and the lead researcher on the study, published online June 28 in Clinical Infectious Diseases.
“We still don’t have a great explanation for why we’re seeing what we’re seeing,” he added. “But we’re glad we’re seeing it.”
The findings have changed how Dr. Sigel talks to his patients with HIV about protecting themselves from COVID-19. Some patients have so curtailed their behavior for fear of acquiring COVID-19 that they aren’t buying groceries or attending needed medical appointments. With these data, Dr. Sigel said he’s comfortable telling his patients, “COVID-19 is bad all by itself, but you don’t need to go crazy. Wear a mask, practice appropriate social distancing and hygiene, but your risk doesn’t appear to be greater.”
The findings conform with those on the lack of association between HIV and COVID-19 severity seen in a cohort study from Spain, a case study from China, and case series from New Jersey, New York City, and Spain.
One of the only regions reporting something different so far is South Africa. There, HIV is the third most common comorbidity associated with death from COVID-19, according to a cohort analysis conducted in the province of Western Cape.
Along with data from HIV prevention and treatment trials, the conference will feature updates on where the world stands in the control of HIV during the COVID-19 pandemic. And for an even more focused look, the IAS COVID-19 Conference will immediately follow that meeting.
The New York City cohort
For their study, Dr. Sigel and colleagues examined the 4402 COVID-19 cases at the Mount Sinai Health System’s five hospitals between March 12 and April 23.
They found 88 people with COVID-19 whose charts showed codes indicating they were living with HIV. All 88 were receiving treatment, and 81% of them had undetectable viral loads documented at COVID admission or in the 12 months prior to admission.
The median age was 61 years, and 40% of the cohort was black and 30% was Hispanic.
Patients in the comparison group – 405 people without HIV from the Veterans Aging Cohort Study who had been admitted to the hospital for COVID-19 – were matched in terms of age, race, and stage of COVID-19.
The study had an 80% power to detect a 15% increase in the absolute risk for death in people with COVID-19, with or without HIV.
Patients with HIV were almost three times as likely to have smoked and were more likely to have chronic obstructive pulmonary disease, cirrhosis, and a history of cancer.
“This was a group of patients that one might suspect would do worse,” Dr. Sigel said. And yet, “we didn’t see any difference in deaths. We didn’t see any difference in respiratory failure.”
In fact, people with HIV required mechanical ventilation less often than those without HIV (18% vs. 23%). And when it came to mortality, one in five people died from COVID-19 during follow-up whether they had HIV or not (21% vs. 20%).
The only factor associated with significantly worse outcomes was a history of organ transplantation, “suggesting that non-HIV causes of immunodeficiency may be more prominent risks for severe outcomes,” Dr. Sigel and colleagues explained.
A surprise association
What’s more, the researchers found a slight association between the use of nucleoside reverse-transcriptase inhibitors (NRTI) by people with HIV and better outcomes in COVID-19. That echoes findings published June 26 in Annals of Internal Medicine, which showed that people with HIV taking the combination of tenofovir disoproxil fumarate plus emtricitabine (Truvada, Gilead Sciences) were less likely to be diagnosed with COVID-19, less likely to be hospitalized, and less likely to die.
This has led some to wonder whether NRTIs have some effect on SARS-CoV-2, the virus that causes COVID-19. Dr. Sigel said he wonders that too, but right now, it’s just musings.
“These studies are not even remotely designed” to show that NRTIs are protective against COVID-19, he explained. “Ours was extremely underpowered to detect that and there was a high potential for confounding.”
“I’d be wary of any study in a subpopulation – which is what we’re dealing with here – that is looking for signals of protection with certain medications,” he added.
A “modest” increase
Using the South African data, released on June 22, public health officials estimate that people with HIV are 2.75 times more likely to die from COVID-19 than those without HIV, making it the third most common comorbidity in people who died from COVID-19, behind diabetes and hypertension. This held true regardless of whether the people with HIV were on treatment.
But when they looked at COVID-19 deaths in the sickest of the sick – those hospitalized with COVID-19 symptoms – HIV was associated with just a 28% increase in the risk for death. The South African researchers called this risk “modest.”
“While these findings may overestimate the effect of HIV on COVID-19 death due to the presence of residual confounding, people living with HIV should be considered a high-risk group for COVID-19 management, with modestly elevated risk of poor outcomes, irrespective of viral suppression,” they wrote.
Epidemiologist Gregorio Millett, MPH, has been tracking the effect of HIV on COVID-19 outcomes since the start of the pandemic in his role as vice president and head of policy at the American Foundation for AIDS Research (amFAR).
Back in April, he and his colleagues looked at rates of COVID-19 deaths and hospitalizations in counties with disproportionate levels of black residents. These areas often overlapped with the communities selected for the Ending the HIV Epidemic plan to control HIV by 2030. What they found was that there was more HIV and COVID-19 in those communities.
What they didn’t find was that people with HIV in those communities had worse outcomes with COVID-19. This remained true even when they reran the analysis after the number of cases of COVID-19 in the United States surpassed 100,000. Those data have yet to be published, Mr. Millett reported.
“HIV does not pop out,” he said. “It’s still social determinants of health. It’s still underlying conditions. It’s still age as a primary factor.”
“People living with HIV are mainly dying of underlying conditions – so all the things associated with COVID-19 – rather than the association being with HIV itself,” he added.
Although he’s not ruling out the possibility that an association like the one in South Africa could emerge, Mr. Millett, who will present a plenary on the context of the HIV epidemic at the IAS conference, said he suspects we won’t see one.
“If we didn’t see an association with the counties that are disproportionately African American, in the black belt where we see high rates of HIV, particularly where we see the social determinants of health that definitely make a difference – if we’re not seeing that association there, where we have a high proportion of African Americans who are at risk both for HIV and COVID-19 – I just don’t think it’s going to emerge,” he said.
This article first appeared on Medscape.com.
FROM AIDS 2020
Treat acne aggressively upfront, expert advises
First, determine the types of lesions they have. “Do they have comedones, papules/pustules, and nodules present?” she asked during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. Second, quantify the number of lesions that they have. Is it few? Several? Many? Third, determine the extent of their acne. “Is it limited to half the face, or is it generalized to the face, back, chest, and shoulders?” added Dr. Zaenglein, professor of dermatology and pediatrics at Penn State University, Hershey.
Fourth, identify postinflammatory changes such as erythema, hyperpigmentation, and scarring “because that’s going to influence your management,” she said. “Finally, you want to give a quick investigative global assessment of the acne severity where you quantify them as being clear, almost clear, mild, moderate, or severe. You want to do this with each patient at every visit so you can determine what their initial treatment’s going to be and what their management going forward is going to be.”
According to Dr. Zaenglein, the best acne treatments are based on the pathogenesis of the skin condition and trying to target as many pathogenic factors as possible. The four main pathogenic factors in acne include hyperkeratinization, increased sebum production, cutibacterium, and inflammation. “This is not a stepwise process; there’s an interplay between all of those factors,” she said. “All acne is inflammatory, but each of the treatments we have target specific factors. Retinoids target hyperkeratinization and inflammation, whereas the hormonal therapies will address decreased sebum production. Antimicrobial agents like benzoyl peroxide and antibiotics will work to decrease cutibacterium acnes. All of these are influenced by the exposome. This includes your genetics, external factors like pollution or changes in seasons that can affect your skin and the severity of your acne.” A state of hyperandrogenism, she added, “can definitely increase acne” and is seen in patients with polycystic ovary syndrome (PCOS).
For patients with mild acne, initial treatment should consist of a topical retinoid and, almost always, benzoyl peroxide, “unless it’s a pure comedonal form of acne,” Dr. Zaenglein said. She recommended using the combination of a topical retinoid and benzoyl peroxide, noting that while it used to be difficult to find benzoyl peroxide, “nowadays there are numerous manufacturers and different formulations of benzoyl peroxide. We also have over-the-counter adapalene now, which is great. So now we have a complete routine for patients with adapalene and benzoyl peroxide that you can combine together in a cost-effective way.”
If the initial regimen fails to improve the patient’s mild acne, a second-line treatment would be to change the retinoid and continue on the existing benzoyl peroxide formulation or to add dapsone gel if the patient is experiencing skin irritation. The four retinoids currently available include adapalene, tretinoin, tazarotene, and trifarotene. “These normalize keratinocyte differentiation, reduce keratinocyte proliferation, and decrease expression of inflammatory markers,” Dr. Zaenglein noted. “They also prevent scarring. Adapalene is considered to be the most tolerable, whereas tazarotene may have an edge on efficacy. There’s a lot of overlap; head-to-head studies may not always match them up exactly, but generally this is how it’s considered. Picking the right retinoid for your patient based on efficacy and tolerability is most important.”
The newest topical retinoid, trifarotene 50 mcg/g cream, is a fourth-generation retinoid which is retinoic acid receptor gamma selective. Pivotal trials were conducted in patients aged 9 years and older with moderate facial and truncal acne. With monotherapy there was a success rate of 36% at 12 weeks and 60% at 52 weeks based on the Investigator’s Global Assessment. Another newcomer, tazarotene 0.045% lotion, is a third-generation retinoid which is retinoic acid receptor alpha beta gamma selective. It’s approved for moderate to severe facial acne in patients 9 years and older.
To optimize tolerance to retinoids, Dr. Zaenglein asks patients about their typical skin care regimen. “I ask them what they’re washing their face with,” she said. “Are they using apricot scrubs or harsh cleansers? Make sure they’re applying it to the entire face and not spot-treating. You get less irritation when it’s applied to dry skin, so you can recommend that. Make sure that they use a bland unscented moisturizer in the morning and apply it over top of their retinoid. I always warn them that irritation usually peaks at about 2 weeks. If they can power through, the irritation will improve with continued use.”
To optimize adherence to retinoids, she asks patients how many nights per week that they apply it. If they are using it all seven nights, “they’re good at using it,” she said. “If they say three nights, then they need to work on getting it on more frequently.”
Topical dapsone gel (5% and 7.5%) is mainly used for patients with papular-pustular acne. “Its mechanism of action for acne is not known, but presumptively it’s anti-inflammatory,” Dr. Zaenglein said. “It doesn’t require G6PD [glucose-6-phosphate dehydrogenase] testing. It can cause some orange discoloration of your skin or fabrics if you use it with benzoyl peroxide, so you want to apply them at different times of the day. It’s well tolerated. I tend to use it in patients who have problems tolerating any topical retinoid or any benzoyl peroxide but have mild to moderate acne.”
For patients with moderate acne, consider combination therapy to target as many pathogenic factors as possible. “Use a topical retinoid plus benzoyl peroxide with or without a systemic antibiotic,” Dr. Zaenglein advised. “I may give them an oral antibiotic if their acne is not responsive to the routine. But you wouldn’t want to combine the systemic antibiotic with a topical antibiotic, like clindamycin with doxycycline, because you don’t need two antibiotics. Make sure that you treat aggressively up front. It can take up to 3 months to see improvement. I counsel my patients that we’ll rescue with the antibiotic and then we maintain, but we’re going to stop that antibiotic after 3 months.”
Systemic antibiotic options for acne include tetracyclines, doxycycline, minocycline, and sarecycline. “Tetracycline itself we don’t use too much because you have to take it on an empty stomach, and availability is sometimes an issue,” she said. “Primarily, we use doxycycline. You can take it with food, so that helps. The main side effects are gastrointestinal upset and photosensitivity. Alternately, you can use minocycline, which is also okay to take with food. It does have more potentially worrisome side effects, including pseudotumor cerebri, blue pigmentation, autoimmune hepatitis, and DRESS [drug reaction with eosinophilia and systemic symptoms].”
Sarecycline is the first narrow spectrum tetracycline for acne, with fewer vestibular and phototoxic side effects, compared with other tetracyclines. “It also has less effect on the GI flora,” Dr. Zaenglein said. “It’s a good alternative but it can be costly, so make sure to check the pricing for your patients.” She does not use other antibiotics such as TMP/SMX, penicillins, or cephalosporins for acne patients. “The reason is, the tetracyclines are not only antibacterial, but they’re anti-inflammatory,” she explained. “They also are lipophilic, so they will penetrate into the sebaceous unit where the heart of the acne is.”
For patients who don’t want to take an oral antibiotic, consider minocycline 4% foam, which was studied in moderate to severe acne in patients aged 9 years and older. The pooled results from the three studies showed a 47% mean improvement in inflammatory acne, compared with 37% among those in the vehicle arm. “You wouldn’t use this as monotherapy; you’d use this in combination with the topical retinoid and the benzoyl peroxide,” Dr. Zaenglein said.
Most primary care providers do not prescribe isotretinoin for patients with severe acne, but they can start patients on triple therapy with a topical retinoid, benzoyl peroxide, and a systemic antibiotic at its full dose. “The efficacy of triple therapy in patients you would typically deem as isotretinoin worthy is actually pretty good,” she said. “There have been several studies looking at this, and about 70%-80% of patients will respond to triple therapy, where they are no longer deemed isotretinoin candidates. They still may need to move on to isotretinoin, but they will be improved.”
Dr. Zaenglein disclosed that she is a consultant for Cassiopea, Novartis, and Pfizer. She has also received grants or research support from AbbVie, Incyte, and Pfizer.
First, determine the types of lesions they have. “Do they have comedones, papules/pustules, and nodules present?” she asked during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. Second, quantify the number of lesions that they have. Is it few? Several? Many? Third, determine the extent of their acne. “Is it limited to half the face, or is it generalized to the face, back, chest, and shoulders?” added Dr. Zaenglein, professor of dermatology and pediatrics at Penn State University, Hershey.
Fourth, identify postinflammatory changes such as erythema, hyperpigmentation, and scarring “because that’s going to influence your management,” she said. “Finally, you want to give a quick investigative global assessment of the acne severity where you quantify them as being clear, almost clear, mild, moderate, or severe. You want to do this with each patient at every visit so you can determine what their initial treatment’s going to be and what their management going forward is going to be.”
According to Dr. Zaenglein, the best acne treatments are based on the pathogenesis of the skin condition and trying to target as many pathogenic factors as possible. The four main pathogenic factors in acne include hyperkeratinization, increased sebum production, cutibacterium, and inflammation. “This is not a stepwise process; there’s an interplay between all of those factors,” she said. “All acne is inflammatory, but each of the treatments we have target specific factors. Retinoids target hyperkeratinization and inflammation, whereas the hormonal therapies will address decreased sebum production. Antimicrobial agents like benzoyl peroxide and antibiotics will work to decrease cutibacterium acnes. All of these are influenced by the exposome. This includes your genetics, external factors like pollution or changes in seasons that can affect your skin and the severity of your acne.” A state of hyperandrogenism, she added, “can definitely increase acne” and is seen in patients with polycystic ovary syndrome (PCOS).
For patients with mild acne, initial treatment should consist of a topical retinoid and, almost always, benzoyl peroxide, “unless it’s a pure comedonal form of acne,” Dr. Zaenglein said. She recommended using the combination of a topical retinoid and benzoyl peroxide, noting that while it used to be difficult to find benzoyl peroxide, “nowadays there are numerous manufacturers and different formulations of benzoyl peroxide. We also have over-the-counter adapalene now, which is great. So now we have a complete routine for patients with adapalene and benzoyl peroxide that you can combine together in a cost-effective way.”
If the initial regimen fails to improve the patient’s mild acne, a second-line treatment would be to change the retinoid and continue on the existing benzoyl peroxide formulation or to add dapsone gel if the patient is experiencing skin irritation. The four retinoids currently available include adapalene, tretinoin, tazarotene, and trifarotene. “These normalize keratinocyte differentiation, reduce keratinocyte proliferation, and decrease expression of inflammatory markers,” Dr. Zaenglein noted. “They also prevent scarring. Adapalene is considered to be the most tolerable, whereas tazarotene may have an edge on efficacy. There’s a lot of overlap; head-to-head studies may not always match them up exactly, but generally this is how it’s considered. Picking the right retinoid for your patient based on efficacy and tolerability is most important.”
The newest topical retinoid, trifarotene 50 mcg/g cream, is a fourth-generation retinoid which is retinoic acid receptor gamma selective. Pivotal trials were conducted in patients aged 9 years and older with moderate facial and truncal acne. With monotherapy there was a success rate of 36% at 12 weeks and 60% at 52 weeks based on the Investigator’s Global Assessment. Another newcomer, tazarotene 0.045% lotion, is a third-generation retinoid which is retinoic acid receptor alpha beta gamma selective. It’s approved for moderate to severe facial acne in patients 9 years and older.
To optimize tolerance to retinoids, Dr. Zaenglein asks patients about their typical skin care regimen. “I ask them what they’re washing their face with,” she said. “Are they using apricot scrubs or harsh cleansers? Make sure they’re applying it to the entire face and not spot-treating. You get less irritation when it’s applied to dry skin, so you can recommend that. Make sure that they use a bland unscented moisturizer in the morning and apply it over top of their retinoid. I always warn them that irritation usually peaks at about 2 weeks. If they can power through, the irritation will improve with continued use.”
To optimize adherence to retinoids, she asks patients how many nights per week that they apply it. If they are using it all seven nights, “they’re good at using it,” she said. “If they say three nights, then they need to work on getting it on more frequently.”
Topical dapsone gel (5% and 7.5%) is mainly used for patients with papular-pustular acne. “Its mechanism of action for acne is not known, but presumptively it’s anti-inflammatory,” Dr. Zaenglein said. “It doesn’t require G6PD [glucose-6-phosphate dehydrogenase] testing. It can cause some orange discoloration of your skin or fabrics if you use it with benzoyl peroxide, so you want to apply them at different times of the day. It’s well tolerated. I tend to use it in patients who have problems tolerating any topical retinoid or any benzoyl peroxide but have mild to moderate acne.”
For patients with moderate acne, consider combination therapy to target as many pathogenic factors as possible. “Use a topical retinoid plus benzoyl peroxide with or without a systemic antibiotic,” Dr. Zaenglein advised. “I may give them an oral antibiotic if their acne is not responsive to the routine. But you wouldn’t want to combine the systemic antibiotic with a topical antibiotic, like clindamycin with doxycycline, because you don’t need two antibiotics. Make sure that you treat aggressively up front. It can take up to 3 months to see improvement. I counsel my patients that we’ll rescue with the antibiotic and then we maintain, but we’re going to stop that antibiotic after 3 months.”
Systemic antibiotic options for acne include tetracyclines, doxycycline, minocycline, and sarecycline. “Tetracycline itself we don’t use too much because you have to take it on an empty stomach, and availability is sometimes an issue,” she said. “Primarily, we use doxycycline. You can take it with food, so that helps. The main side effects are gastrointestinal upset and photosensitivity. Alternately, you can use minocycline, which is also okay to take with food. It does have more potentially worrisome side effects, including pseudotumor cerebri, blue pigmentation, autoimmune hepatitis, and DRESS [drug reaction with eosinophilia and systemic symptoms].”
Sarecycline is the first narrow spectrum tetracycline for acne, with fewer vestibular and phototoxic side effects, compared with other tetracyclines. “It also has less effect on the GI flora,” Dr. Zaenglein said. “It’s a good alternative but it can be costly, so make sure to check the pricing for your patients.” She does not use other antibiotics such as TMP/SMX, penicillins, or cephalosporins for acne patients. “The reason is, the tetracyclines are not only antibacterial, but they’re anti-inflammatory,” she explained. “They also are lipophilic, so they will penetrate into the sebaceous unit where the heart of the acne is.”
For patients who don’t want to take an oral antibiotic, consider minocycline 4% foam, which was studied in moderate to severe acne in patients aged 9 years and older. The pooled results from the three studies showed a 47% mean improvement in inflammatory acne, compared with 37% among those in the vehicle arm. “You wouldn’t use this as monotherapy; you’d use this in combination with the topical retinoid and the benzoyl peroxide,” Dr. Zaenglein said.
Most primary care providers do not prescribe isotretinoin for patients with severe acne, but they can start patients on triple therapy with a topical retinoid, benzoyl peroxide, and a systemic antibiotic at its full dose. “The efficacy of triple therapy in patients you would typically deem as isotretinoin worthy is actually pretty good,” she said. “There have been several studies looking at this, and about 70%-80% of patients will respond to triple therapy, where they are no longer deemed isotretinoin candidates. They still may need to move on to isotretinoin, but they will be improved.”
Dr. Zaenglein disclosed that she is a consultant for Cassiopea, Novartis, and Pfizer. She has also received grants or research support from AbbVie, Incyte, and Pfizer.
First, determine the types of lesions they have. “Do they have comedones, papules/pustules, and nodules present?” she asked during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. Second, quantify the number of lesions that they have. Is it few? Several? Many? Third, determine the extent of their acne. “Is it limited to half the face, or is it generalized to the face, back, chest, and shoulders?” added Dr. Zaenglein, professor of dermatology and pediatrics at Penn State University, Hershey.
Fourth, identify postinflammatory changes such as erythema, hyperpigmentation, and scarring “because that’s going to influence your management,” she said. “Finally, you want to give a quick investigative global assessment of the acne severity where you quantify them as being clear, almost clear, mild, moderate, or severe. You want to do this with each patient at every visit so you can determine what their initial treatment’s going to be and what their management going forward is going to be.”
According to Dr. Zaenglein, the best acne treatments are based on the pathogenesis of the skin condition and trying to target as many pathogenic factors as possible. The four main pathogenic factors in acne include hyperkeratinization, increased sebum production, cutibacterium, and inflammation. “This is not a stepwise process; there’s an interplay between all of those factors,” she said. “All acne is inflammatory, but each of the treatments we have target specific factors. Retinoids target hyperkeratinization and inflammation, whereas the hormonal therapies will address decreased sebum production. Antimicrobial agents like benzoyl peroxide and antibiotics will work to decrease cutibacterium acnes. All of these are influenced by the exposome. This includes your genetics, external factors like pollution or changes in seasons that can affect your skin and the severity of your acne.” A state of hyperandrogenism, she added, “can definitely increase acne” and is seen in patients with polycystic ovary syndrome (PCOS).
For patients with mild acne, initial treatment should consist of a topical retinoid and, almost always, benzoyl peroxide, “unless it’s a pure comedonal form of acne,” Dr. Zaenglein said. She recommended using the combination of a topical retinoid and benzoyl peroxide, noting that while it used to be difficult to find benzoyl peroxide, “nowadays there are numerous manufacturers and different formulations of benzoyl peroxide. We also have over-the-counter adapalene now, which is great. So now we have a complete routine for patients with adapalene and benzoyl peroxide that you can combine together in a cost-effective way.”
If the initial regimen fails to improve the patient’s mild acne, a second-line treatment would be to change the retinoid and continue on the existing benzoyl peroxide formulation or to add dapsone gel if the patient is experiencing skin irritation. The four retinoids currently available include adapalene, tretinoin, tazarotene, and trifarotene. “These normalize keratinocyte differentiation, reduce keratinocyte proliferation, and decrease expression of inflammatory markers,” Dr. Zaenglein noted. “They also prevent scarring. Adapalene is considered to be the most tolerable, whereas tazarotene may have an edge on efficacy. There’s a lot of overlap; head-to-head studies may not always match them up exactly, but generally this is how it’s considered. Picking the right retinoid for your patient based on efficacy and tolerability is most important.”
The newest topical retinoid, trifarotene 50 mcg/g cream, is a fourth-generation retinoid which is retinoic acid receptor gamma selective. Pivotal trials were conducted in patients aged 9 years and older with moderate facial and truncal acne. With monotherapy there was a success rate of 36% at 12 weeks and 60% at 52 weeks based on the Investigator’s Global Assessment. Another newcomer, tazarotene 0.045% lotion, is a third-generation retinoid which is retinoic acid receptor alpha beta gamma selective. It’s approved for moderate to severe facial acne in patients 9 years and older.
To optimize tolerance to retinoids, Dr. Zaenglein asks patients about their typical skin care regimen. “I ask them what they’re washing their face with,” she said. “Are they using apricot scrubs or harsh cleansers? Make sure they’re applying it to the entire face and not spot-treating. You get less irritation when it’s applied to dry skin, so you can recommend that. Make sure that they use a bland unscented moisturizer in the morning and apply it over top of their retinoid. I always warn them that irritation usually peaks at about 2 weeks. If they can power through, the irritation will improve with continued use.”
To optimize adherence to retinoids, she asks patients how many nights per week that they apply it. If they are using it all seven nights, “they’re good at using it,” she said. “If they say three nights, then they need to work on getting it on more frequently.”
Topical dapsone gel (5% and 7.5%) is mainly used for patients with papular-pustular acne. “Its mechanism of action for acne is not known, but presumptively it’s anti-inflammatory,” Dr. Zaenglein said. “It doesn’t require G6PD [glucose-6-phosphate dehydrogenase] testing. It can cause some orange discoloration of your skin or fabrics if you use it with benzoyl peroxide, so you want to apply them at different times of the day. It’s well tolerated. I tend to use it in patients who have problems tolerating any topical retinoid or any benzoyl peroxide but have mild to moderate acne.”
For patients with moderate acne, consider combination therapy to target as many pathogenic factors as possible. “Use a topical retinoid plus benzoyl peroxide with or without a systemic antibiotic,” Dr. Zaenglein advised. “I may give them an oral antibiotic if their acne is not responsive to the routine. But you wouldn’t want to combine the systemic antibiotic with a topical antibiotic, like clindamycin with doxycycline, because you don’t need two antibiotics. Make sure that you treat aggressively up front. It can take up to 3 months to see improvement. I counsel my patients that we’ll rescue with the antibiotic and then we maintain, but we’re going to stop that antibiotic after 3 months.”
Systemic antibiotic options for acne include tetracyclines, doxycycline, minocycline, and sarecycline. “Tetracycline itself we don’t use too much because you have to take it on an empty stomach, and availability is sometimes an issue,” she said. “Primarily, we use doxycycline. You can take it with food, so that helps. The main side effects are gastrointestinal upset and photosensitivity. Alternately, you can use minocycline, which is also okay to take with food. It does have more potentially worrisome side effects, including pseudotumor cerebri, blue pigmentation, autoimmune hepatitis, and DRESS [drug reaction with eosinophilia and systemic symptoms].”
Sarecycline is the first narrow spectrum tetracycline for acne, with fewer vestibular and phototoxic side effects, compared with other tetracyclines. “It also has less effect on the GI flora,” Dr. Zaenglein said. “It’s a good alternative but it can be costly, so make sure to check the pricing for your patients.” She does not use other antibiotics such as TMP/SMX, penicillins, or cephalosporins for acne patients. “The reason is, the tetracyclines are not only antibacterial, but they’re anti-inflammatory,” she explained. “They also are lipophilic, so they will penetrate into the sebaceous unit where the heart of the acne is.”
For patients who don’t want to take an oral antibiotic, consider minocycline 4% foam, which was studied in moderate to severe acne in patients aged 9 years and older. The pooled results from the three studies showed a 47% mean improvement in inflammatory acne, compared with 37% among those in the vehicle arm. “You wouldn’t use this as monotherapy; you’d use this in combination with the topical retinoid and the benzoyl peroxide,” Dr. Zaenglein said.
Most primary care providers do not prescribe isotretinoin for patients with severe acne, but they can start patients on triple therapy with a topical retinoid, benzoyl peroxide, and a systemic antibiotic at its full dose. “The efficacy of triple therapy in patients you would typically deem as isotretinoin worthy is actually pretty good,” she said. “There have been several studies looking at this, and about 70%-80% of patients will respond to triple therapy, where they are no longer deemed isotretinoin candidates. They still may need to move on to isotretinoin, but they will be improved.”
Dr. Zaenglein disclosed that she is a consultant for Cassiopea, Novartis, and Pfizer. She has also received grants or research support from AbbVie, Incyte, and Pfizer.
FROM PEDIATRIC DERMATOLOGY 2020
High percentage of stimulant use found in opioid ED cases
Nearly 40% of hundreds of opioid abusers at several emergency departments tested positive for stimulants, and they were more likely to be white than other users, a new study finds. Reflecting national trends, patients in the Midwest and West Coast regions were more likely to show signs of stimulant use.
Stimulant/opioid users were also “younger, with unstable housing, mostly unemployed, and reported high rates of recent incarcerations,” said substance use researcher and study lead author Marek Chawarski, PhD, of Yale University, New Haven, Conn. “They also reported higher rates of injection drug use during 1 month prior to the study admission and had higher rates of HCV infection. And higher proportions of amphetamine-type stimulant (ATS)–positive patients presented in the emergency departments (EDs) for an injury or with drug overdose.”
Dr. Chawarski, who presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence, said in an interview that the study is the first to analyze stimulant use in ED patients with opioid use disorder.
The researchers analyzed data for the period 2017-2019 from EDs in Baltimore, New York, Cincinnati, and Seattle. Out of 396 patients, 150 (38%) were positive for amphetamine-type stimulants.
Patients in the Midwest and West Coast were more likely to test positive (38%).
In general, stimulant use is higher in the Midwest and West Coast, said epidemiologist Brandon Marshall, PhD, of Brown University, Providence, R.I., in an interview. “This is due to a number of supply-side, historical, and cultural reasons. New England, Appalachia, and large urban centers on the East Coast are the historical hot spots for opioid use, while states west of the Mississippi River have lower rates of opioid overdose, but a much higher prevalence of ATS use and stimulant-related morbidity and mortality.”
Those who showed signs of stimulant use were more likely to be white (69%) vs. the nonusers (46%), and were more likely to have unstable housing (67% vs. 49%).
Those who used stimulants also were more likely to be suffering from an overdose (23% vs. 13%) and to report injecting drugs in the last month (79% vs. 47%). More had unstable housing (67% vs. 49%, P < .05 for all comparisons).
Dr. Chawarski said there are many reasons why users might use more than one kind of drug. For example, they may take one drug to “alleviate problems created by the use of one substance with taking another substance and multiple other reasons,” he said. “Polysubstance use can exacerbate social and medical harms, including overdose risk. It can pose greater treatment challenges, both for the patients and treatment providers, and often is more difficult to overcome.”
Links between opioid and stimulant use are not new. Last year, a study of 2,244 opioid-related overdose deaths in Massachusetts from 2014 to 2015 found that 36% of patients also showed signs of stimulant use. “Persons older than 24 years, nonrural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone,” the researchers reported (Drug Alcohol Depend. 2019 Jul 1;200:59-63).
Dr. Marshall said the study findings are not surprising. However, he said, they do indicate “ongoing, intentional consumption of opioids. The trends and characteristics we are seeing here suggests a large population of persons who are intentionally using both stimulants and opioids, many of whom are also injecting.”
He added that the study sample is probably higher risk than the general population since they’re presenting to the emergency department, so the findings might not reflect the use of stimulants in the general opioid-misusing population.
Dr. Marshall added that “there have been several instances in modern U.S. history during which increases in stimulant use follow a rise in opioid use, so the pattern we are seeing isn’t entirely surprising.”
“What we don’t know,” he added, “is the extent to which overdoses involving both an opioid and a stimulant are due to fentanyl contamination of the methamphetamine supply or intentional concurrent use – e.g., ‘speedballing’ or ‘goof balling’ – or some other pattern of polysubstance use, such as using an opioid to come down off a methamphetamine high.”
The National Institute on Drug Abuse funded the study. The study authors reported no relevant disclosures. Dr. Marshall reported that he has collaborated frequently with two of the study coauthors.
Nearly 40% of hundreds of opioid abusers at several emergency departments tested positive for stimulants, and they were more likely to be white than other users, a new study finds. Reflecting national trends, patients in the Midwest and West Coast regions were more likely to show signs of stimulant use.
Stimulant/opioid users were also “younger, with unstable housing, mostly unemployed, and reported high rates of recent incarcerations,” said substance use researcher and study lead author Marek Chawarski, PhD, of Yale University, New Haven, Conn. “They also reported higher rates of injection drug use during 1 month prior to the study admission and had higher rates of HCV infection. And higher proportions of amphetamine-type stimulant (ATS)–positive patients presented in the emergency departments (EDs) for an injury or with drug overdose.”
Dr. Chawarski, who presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence, said in an interview that the study is the first to analyze stimulant use in ED patients with opioid use disorder.
The researchers analyzed data for the period 2017-2019 from EDs in Baltimore, New York, Cincinnati, and Seattle. Out of 396 patients, 150 (38%) were positive for amphetamine-type stimulants.
Patients in the Midwest and West Coast were more likely to test positive (38%).
In general, stimulant use is higher in the Midwest and West Coast, said epidemiologist Brandon Marshall, PhD, of Brown University, Providence, R.I., in an interview. “This is due to a number of supply-side, historical, and cultural reasons. New England, Appalachia, and large urban centers on the East Coast are the historical hot spots for opioid use, while states west of the Mississippi River have lower rates of opioid overdose, but a much higher prevalence of ATS use and stimulant-related morbidity and mortality.”
Those who showed signs of stimulant use were more likely to be white (69%) vs. the nonusers (46%), and were more likely to have unstable housing (67% vs. 49%).
Those who used stimulants also were more likely to be suffering from an overdose (23% vs. 13%) and to report injecting drugs in the last month (79% vs. 47%). More had unstable housing (67% vs. 49%, P < .05 for all comparisons).
Dr. Chawarski said there are many reasons why users might use more than one kind of drug. For example, they may take one drug to “alleviate problems created by the use of one substance with taking another substance and multiple other reasons,” he said. “Polysubstance use can exacerbate social and medical harms, including overdose risk. It can pose greater treatment challenges, both for the patients and treatment providers, and often is more difficult to overcome.”
Links between opioid and stimulant use are not new. Last year, a study of 2,244 opioid-related overdose deaths in Massachusetts from 2014 to 2015 found that 36% of patients also showed signs of stimulant use. “Persons older than 24 years, nonrural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone,” the researchers reported (Drug Alcohol Depend. 2019 Jul 1;200:59-63).
Dr. Marshall said the study findings are not surprising. However, he said, they do indicate “ongoing, intentional consumption of opioids. The trends and characteristics we are seeing here suggests a large population of persons who are intentionally using both stimulants and opioids, many of whom are also injecting.”
He added that the study sample is probably higher risk than the general population since they’re presenting to the emergency department, so the findings might not reflect the use of stimulants in the general opioid-misusing population.
Dr. Marshall added that “there have been several instances in modern U.S. history during which increases in stimulant use follow a rise in opioid use, so the pattern we are seeing isn’t entirely surprising.”
“What we don’t know,” he added, “is the extent to which overdoses involving both an opioid and a stimulant are due to fentanyl contamination of the methamphetamine supply or intentional concurrent use – e.g., ‘speedballing’ or ‘goof balling’ – or some other pattern of polysubstance use, such as using an opioid to come down off a methamphetamine high.”
The National Institute on Drug Abuse funded the study. The study authors reported no relevant disclosures. Dr. Marshall reported that he has collaborated frequently with two of the study coauthors.
Nearly 40% of hundreds of opioid abusers at several emergency departments tested positive for stimulants, and they were more likely to be white than other users, a new study finds. Reflecting national trends, patients in the Midwest and West Coast regions were more likely to show signs of stimulant use.
Stimulant/opioid users were also “younger, with unstable housing, mostly unemployed, and reported high rates of recent incarcerations,” said substance use researcher and study lead author Marek Chawarski, PhD, of Yale University, New Haven, Conn. “They also reported higher rates of injection drug use during 1 month prior to the study admission and had higher rates of HCV infection. And higher proportions of amphetamine-type stimulant (ATS)–positive patients presented in the emergency departments (EDs) for an injury or with drug overdose.”
Dr. Chawarski, who presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence, said in an interview that the study is the first to analyze stimulant use in ED patients with opioid use disorder.
The researchers analyzed data for the period 2017-2019 from EDs in Baltimore, New York, Cincinnati, and Seattle. Out of 396 patients, 150 (38%) were positive for amphetamine-type stimulants.
Patients in the Midwest and West Coast were more likely to test positive (38%).
In general, stimulant use is higher in the Midwest and West Coast, said epidemiologist Brandon Marshall, PhD, of Brown University, Providence, R.I., in an interview. “This is due to a number of supply-side, historical, and cultural reasons. New England, Appalachia, and large urban centers on the East Coast are the historical hot spots for opioid use, while states west of the Mississippi River have lower rates of opioid overdose, but a much higher prevalence of ATS use and stimulant-related morbidity and mortality.”
Those who showed signs of stimulant use were more likely to be white (69%) vs. the nonusers (46%), and were more likely to have unstable housing (67% vs. 49%).
Those who used stimulants also were more likely to be suffering from an overdose (23% vs. 13%) and to report injecting drugs in the last month (79% vs. 47%). More had unstable housing (67% vs. 49%, P < .05 for all comparisons).
Dr. Chawarski said there are many reasons why users might use more than one kind of drug. For example, they may take one drug to “alleviate problems created by the use of one substance with taking another substance and multiple other reasons,” he said. “Polysubstance use can exacerbate social and medical harms, including overdose risk. It can pose greater treatment challenges, both for the patients and treatment providers, and often is more difficult to overcome.”
Links between opioid and stimulant use are not new. Last year, a study of 2,244 opioid-related overdose deaths in Massachusetts from 2014 to 2015 found that 36% of patients also showed signs of stimulant use. “Persons older than 24 years, nonrural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone,” the researchers reported (Drug Alcohol Depend. 2019 Jul 1;200:59-63).
Dr. Marshall said the study findings are not surprising. However, he said, they do indicate “ongoing, intentional consumption of opioids. The trends and characteristics we are seeing here suggests a large population of persons who are intentionally using both stimulants and opioids, many of whom are also injecting.”
He added that the study sample is probably higher risk than the general population since they’re presenting to the emergency department, so the findings might not reflect the use of stimulants in the general opioid-misusing population.
Dr. Marshall added that “there have been several instances in modern U.S. history during which increases in stimulant use follow a rise in opioid use, so the pattern we are seeing isn’t entirely surprising.”
“What we don’t know,” he added, “is the extent to which overdoses involving both an opioid and a stimulant are due to fentanyl contamination of the methamphetamine supply or intentional concurrent use – e.g., ‘speedballing’ or ‘goof balling’ – or some other pattern of polysubstance use, such as using an opioid to come down off a methamphetamine high.”
The National Institute on Drug Abuse funded the study. The study authors reported no relevant disclosures. Dr. Marshall reported that he has collaborated frequently with two of the study coauthors.
FROM CPDD 2020
Inhaled treprostinil improves walk distance in patients with ILD-associated pulmonary hypertension
over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.
Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).
“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.
“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.
The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.
Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.
Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.
The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.
The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.
A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.
As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).
Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.
Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.
For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.
In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).
The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.
Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.
There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.
In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.
“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.
He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).
Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”
The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.
over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.
Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).
“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.
“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.
The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.
Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.
Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.
The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.
The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.
A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.
As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).
Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.
Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.
For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.
In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).
The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.
Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.
There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.
In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.
“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.
He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).
Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”
The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.
over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.
Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).
“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.
“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.
The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.
Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.
Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.
The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.
The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.
A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.
As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).
Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.
Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.
For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.
In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).
The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.
Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.
There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.
In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.
“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.
He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).
Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”
The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.
FROM ATS 2020
Oral danicamtiv improves left atrial contractility in HFrEF
Danicamtiv, a novel oral selective cardiac myosin activator, demonstrated promising beneficial effects on left ventricular systolic function coupled with marked improvements in left atrial volume and function in patients with heart failure with reduced ejection fraction in a phase 2a clinical trial, Adriaan A. Voors, MD, PhD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.
Importantly, these improvements weren’t accompanied by any unwelcome significant increase in diastolic stiffness, added Dr. Voors, a cardiologist at the University of Groningen (the Netherlands).
This is a drug whose novel mechanism of action could make it a good fit in combination with existing guideline-recommended therapies known to improve morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), none of which do what danicamtiv does: namely, activates cardiac myosin by enhancing myofibrillar adenosine triphosphatase activity, thereby boosting intrinsic myocardial contractility without any impact upon calcium homeostasis, he explained.
Dr. Voors reported on 40 patients with stable HFrEF and a left ventricular ejection fraction of 35% or less, all on background guideline-directed medical therapy. They were randomized double blind to 7 days of danicamtiv at 50, 75, or 100 mg twice daily, or placebo. A total of 489 ECGs were performed in conjunction with blood draws to measure plasma drug concentrations during the study.
Danicamtiv significantly improved left ventricular stroke volume and global longitudinal and circumferential strain in plasma drug concentration–dependent fashion, while simultaneously decreasing left ventricular end-systolic and end-diastolic diameters. Danicamtiv increased systolic ejection time from 286 milliseconds at baseline by an additional placebo-corrected 15, 36, and 48 milliseconds in patients with low, mid-range, and high drug concentrations.
The cardiac myosin activator’s concentration-dependent salutary effects on left atrial (LA) parameters in this brief study were intriguing, since LA function is often compromised in patients with heart failure and has been shown in prior observational studies to independently predict cardiovascular outcomes, the cardiologist noted. The favorable changes in response to danicamtiv included a reduction in LA minimal volume index and an increase in LA emptying fraction. Also, there were marked improvements in LA function index, by 6.1 and 5.8 points, respectively, in patients with mid- and high drug concentrations, from a baseline of 26 points.
Holter monitoring revealed no increased risk of atrial or ventricular arrhythmias in study participants.
Treatment-emergent adverse events were mild and/or unrelated to treatment and showed no particular pattern. The one serious adverse event in the study was a case of hyperkalemia deemed by investigators to be unrelated to treatment.
Seven of 30 danicamtiv-treated patients developed mild, transient, asymptomatic increases in serum cardiac troponin I and/or high-sensitivity troponin T. Dr. Voors said the significance of this must await further examination in larger clinical trials. A phase 2 clinical trial in patients with HFrEF and paroxysmal or persistent atrial fibrillation is planned in order to learn if chronic therapy with danicamtiv results in sustained LA remodeling and clinical benefits. Another planned phase 2 study will be conducted in patients with selected forms of genetic dilated cardiomyopathy.
Because danicamtiv appears to have no effects on blood pressure, renal function, or electrolytes, Dr. Voors speculated that the drug might prove to be an attractive therapeutic option in patients with advanced refractory heart failure, who often have low blood pressure, poor renal function, and a very low left ventricular ejection fraction.
Discussant Thomas Thum, MD, PhD, commented that danicamtiv has definitely earned an opportunity to show what it can do in larger, long-term clinical trials. He was impressed by the significant increase in systolic ejection time, a good marker for cardiac contractility. But he added that the troponin signal warrants careful scrutiny.
“The slight increase over baseline in the phase 2a study was not correlated with any ECG changes or clinical symptoms. However, whether this is a detrimental biomarker sign of a silent harm to the heart remains to be investigated,” said Dr. Thum, a cardiologist at the Institute of Molecular and Translational Therapeutic Strategies at Hannover (Germany) Medical School.
The phase 2a study finding of a plasma drug concentration–dependent prolongation in isovolumetric relaxation time “warrants some caution in future clinical development in patients with impaired diastolic function,” he added.
Simultaneous with Dr. Voors’ presentation, the study results were published online (Eur J Heart Fail. 2020 Jun 19. doi: 10.1002/ejhf.1933).
The danicamtiv study was sponsored by MyoKardia. Dr. Voors reported receiving research funding from and serving as a consultant to MyoKardia and numerous other companies.
Danicamtiv, a novel oral selective cardiac myosin activator, demonstrated promising beneficial effects on left ventricular systolic function coupled with marked improvements in left atrial volume and function in patients with heart failure with reduced ejection fraction in a phase 2a clinical trial, Adriaan A. Voors, MD, PhD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.
Importantly, these improvements weren’t accompanied by any unwelcome significant increase in diastolic stiffness, added Dr. Voors, a cardiologist at the University of Groningen (the Netherlands).
This is a drug whose novel mechanism of action could make it a good fit in combination with existing guideline-recommended therapies known to improve morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), none of which do what danicamtiv does: namely, activates cardiac myosin by enhancing myofibrillar adenosine triphosphatase activity, thereby boosting intrinsic myocardial contractility without any impact upon calcium homeostasis, he explained.
Dr. Voors reported on 40 patients with stable HFrEF and a left ventricular ejection fraction of 35% or less, all on background guideline-directed medical therapy. They were randomized double blind to 7 days of danicamtiv at 50, 75, or 100 mg twice daily, or placebo. A total of 489 ECGs were performed in conjunction with blood draws to measure plasma drug concentrations during the study.
Danicamtiv significantly improved left ventricular stroke volume and global longitudinal and circumferential strain in plasma drug concentration–dependent fashion, while simultaneously decreasing left ventricular end-systolic and end-diastolic diameters. Danicamtiv increased systolic ejection time from 286 milliseconds at baseline by an additional placebo-corrected 15, 36, and 48 milliseconds in patients with low, mid-range, and high drug concentrations.
The cardiac myosin activator’s concentration-dependent salutary effects on left atrial (LA) parameters in this brief study were intriguing, since LA function is often compromised in patients with heart failure and has been shown in prior observational studies to independently predict cardiovascular outcomes, the cardiologist noted. The favorable changes in response to danicamtiv included a reduction in LA minimal volume index and an increase in LA emptying fraction. Also, there were marked improvements in LA function index, by 6.1 and 5.8 points, respectively, in patients with mid- and high drug concentrations, from a baseline of 26 points.
Holter monitoring revealed no increased risk of atrial or ventricular arrhythmias in study participants.
Treatment-emergent adverse events were mild and/or unrelated to treatment and showed no particular pattern. The one serious adverse event in the study was a case of hyperkalemia deemed by investigators to be unrelated to treatment.
Seven of 30 danicamtiv-treated patients developed mild, transient, asymptomatic increases in serum cardiac troponin I and/or high-sensitivity troponin T. Dr. Voors said the significance of this must await further examination in larger clinical trials. A phase 2 clinical trial in patients with HFrEF and paroxysmal or persistent atrial fibrillation is planned in order to learn if chronic therapy with danicamtiv results in sustained LA remodeling and clinical benefits. Another planned phase 2 study will be conducted in patients with selected forms of genetic dilated cardiomyopathy.
Because danicamtiv appears to have no effects on blood pressure, renal function, or electrolytes, Dr. Voors speculated that the drug might prove to be an attractive therapeutic option in patients with advanced refractory heart failure, who often have low blood pressure, poor renal function, and a very low left ventricular ejection fraction.
Discussant Thomas Thum, MD, PhD, commented that danicamtiv has definitely earned an opportunity to show what it can do in larger, long-term clinical trials. He was impressed by the significant increase in systolic ejection time, a good marker for cardiac contractility. But he added that the troponin signal warrants careful scrutiny.
“The slight increase over baseline in the phase 2a study was not correlated with any ECG changes or clinical symptoms. However, whether this is a detrimental biomarker sign of a silent harm to the heart remains to be investigated,” said Dr. Thum, a cardiologist at the Institute of Molecular and Translational Therapeutic Strategies at Hannover (Germany) Medical School.
The phase 2a study finding of a plasma drug concentration–dependent prolongation in isovolumetric relaxation time “warrants some caution in future clinical development in patients with impaired diastolic function,” he added.
Simultaneous with Dr. Voors’ presentation, the study results were published online (Eur J Heart Fail. 2020 Jun 19. doi: 10.1002/ejhf.1933).
The danicamtiv study was sponsored by MyoKardia. Dr. Voors reported receiving research funding from and serving as a consultant to MyoKardia and numerous other companies.
Danicamtiv, a novel oral selective cardiac myosin activator, demonstrated promising beneficial effects on left ventricular systolic function coupled with marked improvements in left atrial volume and function in patients with heart failure with reduced ejection fraction in a phase 2a clinical trial, Adriaan A. Voors, MD, PhD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.
Importantly, these improvements weren’t accompanied by any unwelcome significant increase in diastolic stiffness, added Dr. Voors, a cardiologist at the University of Groningen (the Netherlands).
This is a drug whose novel mechanism of action could make it a good fit in combination with existing guideline-recommended therapies known to improve morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), none of which do what danicamtiv does: namely, activates cardiac myosin by enhancing myofibrillar adenosine triphosphatase activity, thereby boosting intrinsic myocardial contractility without any impact upon calcium homeostasis, he explained.
Dr. Voors reported on 40 patients with stable HFrEF and a left ventricular ejection fraction of 35% or less, all on background guideline-directed medical therapy. They were randomized double blind to 7 days of danicamtiv at 50, 75, or 100 mg twice daily, or placebo. A total of 489 ECGs were performed in conjunction with blood draws to measure plasma drug concentrations during the study.
Danicamtiv significantly improved left ventricular stroke volume and global longitudinal and circumferential strain in plasma drug concentration–dependent fashion, while simultaneously decreasing left ventricular end-systolic and end-diastolic diameters. Danicamtiv increased systolic ejection time from 286 milliseconds at baseline by an additional placebo-corrected 15, 36, and 48 milliseconds in patients with low, mid-range, and high drug concentrations.
The cardiac myosin activator’s concentration-dependent salutary effects on left atrial (LA) parameters in this brief study were intriguing, since LA function is often compromised in patients with heart failure and has been shown in prior observational studies to independently predict cardiovascular outcomes, the cardiologist noted. The favorable changes in response to danicamtiv included a reduction in LA minimal volume index and an increase in LA emptying fraction. Also, there were marked improvements in LA function index, by 6.1 and 5.8 points, respectively, in patients with mid- and high drug concentrations, from a baseline of 26 points.
Holter monitoring revealed no increased risk of atrial or ventricular arrhythmias in study participants.
Treatment-emergent adverse events were mild and/or unrelated to treatment and showed no particular pattern. The one serious adverse event in the study was a case of hyperkalemia deemed by investigators to be unrelated to treatment.
Seven of 30 danicamtiv-treated patients developed mild, transient, asymptomatic increases in serum cardiac troponin I and/or high-sensitivity troponin T. Dr. Voors said the significance of this must await further examination in larger clinical trials. A phase 2 clinical trial in patients with HFrEF and paroxysmal or persistent atrial fibrillation is planned in order to learn if chronic therapy with danicamtiv results in sustained LA remodeling and clinical benefits. Another planned phase 2 study will be conducted in patients with selected forms of genetic dilated cardiomyopathy.
Because danicamtiv appears to have no effects on blood pressure, renal function, or electrolytes, Dr. Voors speculated that the drug might prove to be an attractive therapeutic option in patients with advanced refractory heart failure, who often have low blood pressure, poor renal function, and a very low left ventricular ejection fraction.
Discussant Thomas Thum, MD, PhD, commented that danicamtiv has definitely earned an opportunity to show what it can do in larger, long-term clinical trials. He was impressed by the significant increase in systolic ejection time, a good marker for cardiac contractility. But he added that the troponin signal warrants careful scrutiny.
“The slight increase over baseline in the phase 2a study was not correlated with any ECG changes or clinical symptoms. However, whether this is a detrimental biomarker sign of a silent harm to the heart remains to be investigated,” said Dr. Thum, a cardiologist at the Institute of Molecular and Translational Therapeutic Strategies at Hannover (Germany) Medical School.
The phase 2a study finding of a plasma drug concentration–dependent prolongation in isovolumetric relaxation time “warrants some caution in future clinical development in patients with impaired diastolic function,” he added.
Simultaneous with Dr. Voors’ presentation, the study results were published online (Eur J Heart Fail. 2020 Jun 19. doi: 10.1002/ejhf.1933).
The danicamtiv study was sponsored by MyoKardia. Dr. Voors reported receiving research funding from and serving as a consultant to MyoKardia and numerous other companies.
FROM ESC HEART FAILURE 2020
Lipophilic statins linked to lower mortality in ovarian cancer
, findings from a large observational study suggest.
The study included 10,062 patients with epithelial ovarian cancer enrolled in the Finnish national cancer registry. There were 2,621 patients who were prescribed statins between 1995 and 2015, and 80% of them used lipophilic statins.
When compared with no statin use, any statin use was associated with a 40% reduction in ovarian cancer mortality (weighted hazard ratio, 0.60), and any use of lipophilic statins was associated with a 43% reduction in ovarian cancer mortality (wHR, 0.57).
Kala Visvanathan, MD, of Johns Hopkins University in Baltimore, and colleagues reported these findings in a poster at the AACR virtual meeting II.
Reductions in ovarian cancer mortality were observed in women who took simvastatin or atorvastatin (wHRs 0.24 and 0.20, respectively), the researchers found.
Lipophilic statin use also was associated with a reduction in ovarian cancer mortality across disease subtypes, although the magnitude of reduction varied. The hazard ratios were 0.60 for high-grade serous ovarian cancer, 0.50 for endometrioid ovarian cancer, 0.20 for clear cell ovarian cancer, 0.30 for mucinous ovarian cancer, and 0.27 for borderline disease.
Survival benefits were evident both in patients who started statins prior to their ovarian cancer diagnosis and in those who started statins after diagnosis.
Never-statin users had a median age of 62 years at baseline, and ever-statin users had a median age of 67 years. The median follow-up was 3.6 years and 5.5 years, respectively.
Data from the registry were linked to prescription claims, and a series of analyses were conducted to examine the association between pre- and postdiagnostic statin use and mortality. The findings were adjusted for age at diagnosis, stage, ovarian cancer subtype, treatments, year of diagnosis, and chronic disease medications. Adherence to statins was greater than 90%.
Implications and next steps
The idea of using statins for the treatment of ovarian cancer is appealing because of the promising survival data as well as the broad access, low cost, and tolerability of statins, Dr. Visvanathan said in a statement. About 28% of U.S. adults over age 40 routinely take statins for cholesterol control, and statins are widely used in other countries, she said.
“Our results support research to evaluate the repurposing of therapies that are well tolerated and inexpensive in order to help reduce the global cancer burden,” Dr. Visvanathan and colleagues wrote in their poster.
“Our results provide evidence in support of the evaluation of lipophilic statins, particularly atorvastatin and/or simvastatin, for the treatment of [epithelial ovarian cancer] in conjunction with existing therapies,” the researchers wrote. They added that these statins should be “evaluated in randomized clinical trials that include correlative endpoints.”
Further, the researchers argued that “the results are biologically plausible based on known mechanisms associated with statin use and highlight the fact that statins may be effective to treat more than one disease/outcome (i.e., high cholesterol, EOC [epithelial ovarian cancer], breast cancer).”
The results of this study are intriguing, according to James Yarmolinsky, MSc, of the University of Bristol, England. Mr. Yarmolinsky is the lead author of a case-control study that showed an association between genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition and lower odds of developing epithelial ovarian cancer (JAMA. 2020;323[7]:646-655).
Mr. Yarmolinsky and colleagues found that HMG-CoA reductase inhibition equivalent to a 38.7-mg/dL reduction in low-density lipoprotein cholesterol was significantly associated with lower odds of epithelial ovarian cancer in the general population (odds ratio, 0.60) and among BRCA1/2 mutation carriers (hazard ratio, 0.69). The findings raised questions about whether a similar association would be seen with medications such as statins that inhibit HMG-CoA reductase.
“These findings linking statin use to lower ovarian cancer mortality are really interesting given our own research suggesting that these drugs may also lower women’s risk of developing this disease in the first place,” Mr. Yarmolinsky said.
“The survival rate for ovarian cancer remains the lowest among all gynecological cancers in the United States, so use of these medications in either a preventive or therapeutic context could offer an important approach for reducing disease burden,” he added. “If the findings reported by Visvanathan and colleagues can be shown to replicate in other large population-based studies, testing the efficacy of statins in a randomized clinical trial could provide definitive evidence of whether these medications lower ovarian cancer mortality.”
The Department of Defense and the Breast Cancer Research Foundation funded the current study. Dr. Visvanathan and Mr. Yarmolinsky reported no disclosures.
SOURCE: Visvanathan K et al. AACR 2020, Abstract 5782.
, findings from a large observational study suggest.
The study included 10,062 patients with epithelial ovarian cancer enrolled in the Finnish national cancer registry. There were 2,621 patients who were prescribed statins between 1995 and 2015, and 80% of them used lipophilic statins.
When compared with no statin use, any statin use was associated with a 40% reduction in ovarian cancer mortality (weighted hazard ratio, 0.60), and any use of lipophilic statins was associated with a 43% reduction in ovarian cancer mortality (wHR, 0.57).
Kala Visvanathan, MD, of Johns Hopkins University in Baltimore, and colleagues reported these findings in a poster at the AACR virtual meeting II.
Reductions in ovarian cancer mortality were observed in women who took simvastatin or atorvastatin (wHRs 0.24 and 0.20, respectively), the researchers found.
Lipophilic statin use also was associated with a reduction in ovarian cancer mortality across disease subtypes, although the magnitude of reduction varied. The hazard ratios were 0.60 for high-grade serous ovarian cancer, 0.50 for endometrioid ovarian cancer, 0.20 for clear cell ovarian cancer, 0.30 for mucinous ovarian cancer, and 0.27 for borderline disease.
Survival benefits were evident both in patients who started statins prior to their ovarian cancer diagnosis and in those who started statins after diagnosis.
Never-statin users had a median age of 62 years at baseline, and ever-statin users had a median age of 67 years. The median follow-up was 3.6 years and 5.5 years, respectively.
Data from the registry were linked to prescription claims, and a series of analyses were conducted to examine the association between pre- and postdiagnostic statin use and mortality. The findings were adjusted for age at diagnosis, stage, ovarian cancer subtype, treatments, year of diagnosis, and chronic disease medications. Adherence to statins was greater than 90%.
Implications and next steps
The idea of using statins for the treatment of ovarian cancer is appealing because of the promising survival data as well as the broad access, low cost, and tolerability of statins, Dr. Visvanathan said in a statement. About 28% of U.S. adults over age 40 routinely take statins for cholesterol control, and statins are widely used in other countries, she said.
“Our results support research to evaluate the repurposing of therapies that are well tolerated and inexpensive in order to help reduce the global cancer burden,” Dr. Visvanathan and colleagues wrote in their poster.
“Our results provide evidence in support of the evaluation of lipophilic statins, particularly atorvastatin and/or simvastatin, for the treatment of [epithelial ovarian cancer] in conjunction with existing therapies,” the researchers wrote. They added that these statins should be “evaluated in randomized clinical trials that include correlative endpoints.”
Further, the researchers argued that “the results are biologically plausible based on known mechanisms associated with statin use and highlight the fact that statins may be effective to treat more than one disease/outcome (i.e., high cholesterol, EOC [epithelial ovarian cancer], breast cancer).”
The results of this study are intriguing, according to James Yarmolinsky, MSc, of the University of Bristol, England. Mr. Yarmolinsky is the lead author of a case-control study that showed an association between genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition and lower odds of developing epithelial ovarian cancer (JAMA. 2020;323[7]:646-655).
Mr. Yarmolinsky and colleagues found that HMG-CoA reductase inhibition equivalent to a 38.7-mg/dL reduction in low-density lipoprotein cholesterol was significantly associated with lower odds of epithelial ovarian cancer in the general population (odds ratio, 0.60) and among BRCA1/2 mutation carriers (hazard ratio, 0.69). The findings raised questions about whether a similar association would be seen with medications such as statins that inhibit HMG-CoA reductase.
“These findings linking statin use to lower ovarian cancer mortality are really interesting given our own research suggesting that these drugs may also lower women’s risk of developing this disease in the first place,” Mr. Yarmolinsky said.
“The survival rate for ovarian cancer remains the lowest among all gynecological cancers in the United States, so use of these medications in either a preventive or therapeutic context could offer an important approach for reducing disease burden,” he added. “If the findings reported by Visvanathan and colleagues can be shown to replicate in other large population-based studies, testing the efficacy of statins in a randomized clinical trial could provide definitive evidence of whether these medications lower ovarian cancer mortality.”
The Department of Defense and the Breast Cancer Research Foundation funded the current study. Dr. Visvanathan and Mr. Yarmolinsky reported no disclosures.
SOURCE: Visvanathan K et al. AACR 2020, Abstract 5782.
, findings from a large observational study suggest.
The study included 10,062 patients with epithelial ovarian cancer enrolled in the Finnish national cancer registry. There were 2,621 patients who were prescribed statins between 1995 and 2015, and 80% of them used lipophilic statins.
When compared with no statin use, any statin use was associated with a 40% reduction in ovarian cancer mortality (weighted hazard ratio, 0.60), and any use of lipophilic statins was associated with a 43% reduction in ovarian cancer mortality (wHR, 0.57).
Kala Visvanathan, MD, of Johns Hopkins University in Baltimore, and colleagues reported these findings in a poster at the AACR virtual meeting II.
Reductions in ovarian cancer mortality were observed in women who took simvastatin or atorvastatin (wHRs 0.24 and 0.20, respectively), the researchers found.
Lipophilic statin use also was associated with a reduction in ovarian cancer mortality across disease subtypes, although the magnitude of reduction varied. The hazard ratios were 0.60 for high-grade serous ovarian cancer, 0.50 for endometrioid ovarian cancer, 0.20 for clear cell ovarian cancer, 0.30 for mucinous ovarian cancer, and 0.27 for borderline disease.
Survival benefits were evident both in patients who started statins prior to their ovarian cancer diagnosis and in those who started statins after diagnosis.
Never-statin users had a median age of 62 years at baseline, and ever-statin users had a median age of 67 years. The median follow-up was 3.6 years and 5.5 years, respectively.
Data from the registry were linked to prescription claims, and a series of analyses were conducted to examine the association between pre- and postdiagnostic statin use and mortality. The findings were adjusted for age at diagnosis, stage, ovarian cancer subtype, treatments, year of diagnosis, and chronic disease medications. Adherence to statins was greater than 90%.
Implications and next steps
The idea of using statins for the treatment of ovarian cancer is appealing because of the promising survival data as well as the broad access, low cost, and tolerability of statins, Dr. Visvanathan said in a statement. About 28% of U.S. adults over age 40 routinely take statins for cholesterol control, and statins are widely used in other countries, she said.
“Our results support research to evaluate the repurposing of therapies that are well tolerated and inexpensive in order to help reduce the global cancer burden,” Dr. Visvanathan and colleagues wrote in their poster.
“Our results provide evidence in support of the evaluation of lipophilic statins, particularly atorvastatin and/or simvastatin, for the treatment of [epithelial ovarian cancer] in conjunction with existing therapies,” the researchers wrote. They added that these statins should be “evaluated in randomized clinical trials that include correlative endpoints.”
Further, the researchers argued that “the results are biologically plausible based on known mechanisms associated with statin use and highlight the fact that statins may be effective to treat more than one disease/outcome (i.e., high cholesterol, EOC [epithelial ovarian cancer], breast cancer).”
The results of this study are intriguing, according to James Yarmolinsky, MSc, of the University of Bristol, England. Mr. Yarmolinsky is the lead author of a case-control study that showed an association between genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition and lower odds of developing epithelial ovarian cancer (JAMA. 2020;323[7]:646-655).
Mr. Yarmolinsky and colleagues found that HMG-CoA reductase inhibition equivalent to a 38.7-mg/dL reduction in low-density lipoprotein cholesterol was significantly associated with lower odds of epithelial ovarian cancer in the general population (odds ratio, 0.60) and among BRCA1/2 mutation carriers (hazard ratio, 0.69). The findings raised questions about whether a similar association would be seen with medications such as statins that inhibit HMG-CoA reductase.
“These findings linking statin use to lower ovarian cancer mortality are really interesting given our own research suggesting that these drugs may also lower women’s risk of developing this disease in the first place,” Mr. Yarmolinsky said.
“The survival rate for ovarian cancer remains the lowest among all gynecological cancers in the United States, so use of these medications in either a preventive or therapeutic context could offer an important approach for reducing disease burden,” he added. “If the findings reported by Visvanathan and colleagues can be shown to replicate in other large population-based studies, testing the efficacy of statins in a randomized clinical trial could provide definitive evidence of whether these medications lower ovarian cancer mortality.”
The Department of Defense and the Breast Cancer Research Foundation funded the current study. Dr. Visvanathan and Mr. Yarmolinsky reported no disclosures.
SOURCE: Visvanathan K et al. AACR 2020, Abstract 5782.
FROM AACR 2020