MDedge Neurology

One-year-olds who received a parent-led intervention targeting early signs of autism spectrum disorder (ASD) had significantly reduced symptoms and chances of an autism diagnosis at age 3 years, in a new study.

These findings, which were published in JAMA Pediatrics, were the first evidence worldwide that a preemptive intervention during infancy could lead to such a significant improvement in children’s social development, resulting in “three times fewer diagnoses of autism at age 3,” said lead author Andrew Whitehouse, PhD, in a statement.

“No trial of a preemptive infant intervention, applied prior to diagnosis, has to date shown such an effect to impact diagnostic outcomes – until now,” he said.
 

Study intervention is a nontraditonal approach

Dr. Whitehouse, who is professor of Autism Research at Telethon Kids and University of Western Australia, and Director of CliniKids in Perth, said the intervention is a departure from traditional approaches. “Traditionally, therapy seeks to train children to learn ‘typical’ behaviors,” he said in an email. “The difference of this therapy is that we help parents understand the unique abilities of their baby, and to use these strengths as a foundation for future development.”

Dr. Whitehouse’s study included 103 children (aged approximately 12 months), who displayed at least three of five behaviors indicating a high likelihood of ASD as defined by the Social Attention and Communication Surveillance–Revised (SACS-R) 12-month checklist. The infants were randomized to receive either usual care or the intervention, which is called the iBASIS–Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care was delivered by community physicians, whereas the intervention involved 10 sessions delivered at home by a trained therapist.

“The iBASIS-VIPP uses video-feedback as a means of helping parents recognize their baby’s communication cues so they can respond in a way that builds their social communication development,” Dr. Whitehouse explained in an interview. “The therapist then provides guidance to the parent as to how their baby is communicating with them, and they can communicate back to have back-and-forth conversations.”

“We know these back-and-forth conversations are crucial to support early social communication development, and are a precursor to more complex skills, such as verbal language,” he added.

Reassessment of the children at age 3 years showed a “small but enduring” benefit of the intervention, noted the authors. Children in the intervention group had a reduction in ASD symptom severity (P = .04), and reduced odds of ASD classification, compared with children receiving usual care (6.7% vs. 20.5%; odds ratio, 0.18; P = .02).

The findings provide “initial evidence of efficacy for a new clinical model that uses a specific developmentally focused intervention,” noted the authors. “The children falling below the diagnostic threshold still had developmental difficulties, but by working with each child’s unique differences, rather than trying to counter them, the therapy has effectively supported their development through the early childhood years,” noted Dr. Whitehouse in a statement.
 

Other research has shown benefits of new study approach

This is a “solid” study, “but, as acknowledged by the authors, the main effects are small in magnitude, and longer-term outcomes will be important to capture,” said Jessica Brian, PhD, C Psych, associate professor in the department of pediatrics at the University of Toronto, colead at the Autism Research Centre, and psychologist and clinician-investigator at Holland Bloorview Kids Rehab Hospital in Toronto.

Dr. Brian said she and her coauthors of a paper published in Autism Research and others have shown that the kind of approach used in the new study can be helpful for enhancing different areas of toddler development, but “the specific finding of reduced likelihood of a clinical ASD diagnosis is a bit different.”

The goal of reducing the likelihood of an ASD diagnosis “needs to be considered carefully, from the perspective of autism acceptance,” she added. “From an acceptance lens, the primary objective of early intervention in ASD might be better positioned as aiming to enhance or support a young child’s development, help them make developmental progress, build on their strengths, optimize outcomes, or reduce impairment. … I think the authors do a good job of balancing this perspective.”
 

New study shows value of parent-mediated interventions

Overall, Dr. Brian, who coauthored the Canadian Paediatric Society’s position statement on ASD diagnosis, lauded the findings as good news.

“It shows the value of using parent-mediated interventions, which are far less costly and are more resource-efficient than most therapist-delivered models.”

“In cases where parent-mediated approaches are made available to families prior to diagnosis, there is potential for strong effects, when the brain is most amenable to learning. Such models may also be an ideal fit before diagnosis, since they are less resource-intensive than therapist-delivered models, which may only be funded by governments once a diagnosis is confirmed,” she said.

“Finally, parent-mediated programs have the potential to support parents during what, for many families, is a particularly challenging time as they identify their child’s developmental differences or receive a diagnosis. Such programs have potential to increase parents’ confidence in parenting a young child with unique learning needs.”

What Dr. Brian thought was missing from the paper was acknowledgment that, “despite early developmental gains from parent-mediated interventions, it is likely that most children with ASD will need additional supports throughout development.”

This study was sponsored by the Telethon Kids Institute. Dr. Whitehouse reported no conflicts of interest. Dr. Brian codeveloped a parent-mediated intervention for toddlers with probable or confirmed ASD (the Social ABCs), for which she does not receive any royalties.

One-year-olds who received a parent-led intervention targeting early signs of autism spectrum disorder (ASD) had significantly reduced symptoms and chances of an autism diagnosis at age 3 years, in a new study.

These findings, which were published in JAMA Pediatrics, were the first evidence worldwide that a preemptive intervention during infancy could lead to such a significant improvement in children’s social development, resulting in “three times fewer diagnoses of autism at age 3,” said lead author Andrew Whitehouse, PhD, in a statement.

“No trial of a preemptive infant intervention, applied prior to diagnosis, has to date shown such an effect to impact diagnostic outcomes – until now,” he said.
 

Study intervention is a nontraditonal approach

Dr. Whitehouse, who is professor of Autism Research at Telethon Kids and University of Western Australia, and Director of CliniKids in Perth, said the intervention is a departure from traditional approaches. “Traditionally, therapy seeks to train children to learn ‘typical’ behaviors,” he said in an email. “The difference of this therapy is that we help parents understand the unique abilities of their baby, and to use these strengths as a foundation for future development.”

Dr. Whitehouse’s study included 103 children (aged approximately 12 months), who displayed at least three of five behaviors indicating a high likelihood of ASD as defined by the Social Attention and Communication Surveillance–Revised (SACS-R) 12-month checklist. The infants were randomized to receive either usual care or the intervention, which is called the iBASIS–Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care was delivered by community physicians, whereas the intervention involved 10 sessions delivered at home by a trained therapist.

“The iBASIS-VIPP uses video-feedback as a means of helping parents recognize their baby’s communication cues so they can respond in a way that builds their social communication development,” Dr. Whitehouse explained in an interview. “The therapist then provides guidance to the parent as to how their baby is communicating with them, and they can communicate back to have back-and-forth conversations.”

“We know these back-and-forth conversations are crucial to support early social communication development, and are a precursor to more complex skills, such as verbal language,” he added.

Reassessment of the children at age 3 years showed a “small but enduring” benefit of the intervention, noted the authors. Children in the intervention group had a reduction in ASD symptom severity (P = .04), and reduced odds of ASD classification, compared with children receiving usual care (6.7% vs. 20.5%; odds ratio, 0.18; P = .02).

The findings provide “initial evidence of efficacy for a new clinical model that uses a specific developmentally focused intervention,” noted the authors. “The children falling below the diagnostic threshold still had developmental difficulties, but by working with each child’s unique differences, rather than trying to counter them, the therapy has effectively supported their development through the early childhood years,” noted Dr. Whitehouse in a statement.
 

Other research has shown benefits of new study approach

This is a “solid” study, “but, as acknowledged by the authors, the main effects are small in magnitude, and longer-term outcomes will be important to capture,” said Jessica Brian, PhD, C Psych, associate professor in the department of pediatrics at the University of Toronto, colead at the Autism Research Centre, and psychologist and clinician-investigator at Holland Bloorview Kids Rehab Hospital in Toronto.

Dr. Brian said she and her coauthors of a paper published in Autism Research and others have shown that the kind of approach used in the new study can be helpful for enhancing different areas of toddler development, but “the specific finding of reduced likelihood of a clinical ASD diagnosis is a bit different.”

The goal of reducing the likelihood of an ASD diagnosis “needs to be considered carefully, from the perspective of autism acceptance,” she added. “From an acceptance lens, the primary objective of early intervention in ASD might be better positioned as aiming to enhance or support a young child’s development, help them make developmental progress, build on their strengths, optimize outcomes, or reduce impairment. … I think the authors do a good job of balancing this perspective.”
 

New study shows value of parent-mediated interventions

Overall, Dr. Brian, who coauthored the Canadian Paediatric Society’s position statement on ASD diagnosis, lauded the findings as good news.

“It shows the value of using parent-mediated interventions, which are far less costly and are more resource-efficient than most therapist-delivered models.”

“In cases where parent-mediated approaches are made available to families prior to diagnosis, there is potential for strong effects, when the brain is most amenable to learning. Such models may also be an ideal fit before diagnosis, since they are less resource-intensive than therapist-delivered models, which may only be funded by governments once a diagnosis is confirmed,” she said.

“Finally, parent-mediated programs have the potential to support parents during what, for many families, is a particularly challenging time as they identify their child’s developmental differences or receive a diagnosis. Such programs have potential to increase parents’ confidence in parenting a young child with unique learning needs.”

What Dr. Brian thought was missing from the paper was acknowledgment that, “despite early developmental gains from parent-mediated interventions, it is likely that most children with ASD will need additional supports throughout development.”

This study was sponsored by the Telethon Kids Institute. Dr. Whitehouse reported no conflicts of interest. Dr. Brian codeveloped a parent-mediated intervention for toddlers with probable or confirmed ASD (the Social ABCs), for which she does not receive any royalties.

One-year-olds who received a parent-led intervention targeting early signs of autism spectrum disorder (ASD) had significantly reduced symptoms and chances of an autism diagnosis at age 3 years, in a new study.

These findings, which were published in JAMA Pediatrics, were the first evidence worldwide that a preemptive intervention during infancy could lead to such a significant improvement in children’s social development, resulting in “three times fewer diagnoses of autism at age 3,” said lead author Andrew Whitehouse, PhD, in a statement.

“No trial of a preemptive infant intervention, applied prior to diagnosis, has to date shown such an effect to impact diagnostic outcomes – until now,” he said.
 

Study intervention is a nontraditonal approach

Dr. Whitehouse, who is professor of Autism Research at Telethon Kids and University of Western Australia, and Director of CliniKids in Perth, said the intervention is a departure from traditional approaches. “Traditionally, therapy seeks to train children to learn ‘typical’ behaviors,” he said in an email. “The difference of this therapy is that we help parents understand the unique abilities of their baby, and to use these strengths as a foundation for future development.”

Dr. Whitehouse’s study included 103 children (aged approximately 12 months), who displayed at least three of five behaviors indicating a high likelihood of ASD as defined by the Social Attention and Communication Surveillance–Revised (SACS-R) 12-month checklist. The infants were randomized to receive either usual care or the intervention, which is called the iBASIS–Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care was delivered by community physicians, whereas the intervention involved 10 sessions delivered at home by a trained therapist.

“The iBASIS-VIPP uses video-feedback as a means of helping parents recognize their baby’s communication cues so they can respond in a way that builds their social communication development,” Dr. Whitehouse explained in an interview. “The therapist then provides guidance to the parent as to how their baby is communicating with them, and they can communicate back to have back-and-forth conversations.”

“We know these back-and-forth conversations are crucial to support early social communication development, and are a precursor to more complex skills, such as verbal language,” he added.

Reassessment of the children at age 3 years showed a “small but enduring” benefit of the intervention, noted the authors. Children in the intervention group had a reduction in ASD symptom severity (P = .04), and reduced odds of ASD classification, compared with children receiving usual care (6.7% vs. 20.5%; odds ratio, 0.18; P = .02).

The findings provide “initial evidence of efficacy for a new clinical model that uses a specific developmentally focused intervention,” noted the authors. “The children falling below the diagnostic threshold still had developmental difficulties, but by working with each child’s unique differences, rather than trying to counter them, the therapy has effectively supported their development through the early childhood years,” noted Dr. Whitehouse in a statement.
 

Other research has shown benefits of new study approach

This is a “solid” study, “but, as acknowledged by the authors, the main effects are small in magnitude, and longer-term outcomes will be important to capture,” said Jessica Brian, PhD, C Psych, associate professor in the department of pediatrics at the University of Toronto, colead at the Autism Research Centre, and psychologist and clinician-investigator at Holland Bloorview Kids Rehab Hospital in Toronto.

Dr. Brian said she and her coauthors of a paper published in Autism Research and others have shown that the kind of approach used in the new study can be helpful for enhancing different areas of toddler development, but “the specific finding of reduced likelihood of a clinical ASD diagnosis is a bit different.”

The goal of reducing the likelihood of an ASD diagnosis “needs to be considered carefully, from the perspective of autism acceptance,” she added. “From an acceptance lens, the primary objective of early intervention in ASD might be better positioned as aiming to enhance or support a young child’s development, help them make developmental progress, build on their strengths, optimize outcomes, or reduce impairment. … I think the authors do a good job of balancing this perspective.”
 

New study shows value of parent-mediated interventions

Overall, Dr. Brian, who coauthored the Canadian Paediatric Society’s position statement on ASD diagnosis, lauded the findings as good news.

“It shows the value of using parent-mediated interventions, which are far less costly and are more resource-efficient than most therapist-delivered models.”

“In cases where parent-mediated approaches are made available to families prior to diagnosis, there is potential for strong effects, when the brain is most amenable to learning. Such models may also be an ideal fit before diagnosis, since they are less resource-intensive than therapist-delivered models, which may only be funded by governments once a diagnosis is confirmed,” she said.

“Finally, parent-mediated programs have the potential to support parents during what, for many families, is a particularly challenging time as they identify their child’s developmental differences or receive a diagnosis. Such programs have potential to increase parents’ confidence in parenting a young child with unique learning needs.”

What Dr. Brian thought was missing from the paper was acknowledgment that, “despite early developmental gains from parent-mediated interventions, it is likely that most children with ASD will need additional supports throughout development.”

This study was sponsored by the Telethon Kids Institute. Dr. Whitehouse reported no conflicts of interest. Dr. Brian codeveloped a parent-mediated intervention for toddlers with probable or confirmed ASD (the Social ABCs), for which she does not receive any royalties.

Top-line results from a phase 2 study suggest vixotrigine (BIIB074, Biogen), a nonopioid investigational oral pain medication, reduces chronic neuropathic pain caused by small fiber neuropathy (SFN) and is generally well tolerated.

“We are encouraged by the overall results of the CONVEY study, especially given the significant unmet medical need for additional agents to treat chronic painful neuropathy,” Katherine Dawson, MD, senior vice president and head of the therapeutics development unit at Biogen, said in a news release.

Vixotrigine (BIIB074) is a peripherally and centrally acting, orally administered, voltage- and use-dependent voltage-gated sodium channel blocker.

CONVEY was a phase 2, placebo-controlled, double-blind, randomized withdrawal study of 265 patients experiencing pain from confirmed idiopathic or diabetes-associated SFN.

Following a 4-week open-label run-in period, 123 responders to vixotrigine were randomly allocated to 200 mg or 350 mg vixotrigine or placebo twice daily for 12 weeks in the double-blind portion of the study.

At week 12, vixotrigine 200 mg twice daily met the primary endpoint of a statistically significant reduction from baseline in the mean average daily pain (ADP) score versus placebo (P = .0501).

A subgroup analysis showed a treatment effect in patients with diabetes-associated SFN but not in the smaller subgroup of patients with idiopathic SFN.

The 200-mg dose also led to a significant improvement over placebo in mean worst daily pain score at 12 weeks (P = .0455).

A numeric advantage of 200 mg vixotrigine over placebo was observed in additional secondary endpoints, including the proportion of patients with at least a 2-point improvement in ADP score and the proportion with at least a 30% reduction in ADP at week 12, but these failed to reach statistical significance.

Vixotrigine 350 mg twice daily did not meet the primary endpoint of mean change in ADP at 12 weeks.

However, treatment at the higher dose led to a significant increase in the proportion of patients who reported being “very much improved” or “much improved” over baseline (P = .0580), Biogen reported.

In addition, a numeric advantage of 350 mg over placebo was observed in the proportion of patients with a 2-point or greater improvement in ADP score and the proportion with at least a 30% reduction in ADP at 12 weeks, but these also did not reach statistical significance.

Both doses of vixotrigine were “generally well tolerated and the safety profile was consistent with previous studies of vixotrigine with no evidence of abuse potential,” the company said.

In the open-label period, common adverse events seen in at least 2.5% of patients were dizziness, headache, vertigo, and nausea; adverse events led 5.3% of patients to discontinue the open-label portion of the study. Across the entire study, most adverse events were mild or moderate in severity.

“The totality of data from the vixotrigine program will inform potential doses for study in future phase 3 clinical trials,” the company said.

A version of this article first appeared on Medscape.com.

Top-line results from a phase 2 study suggest vixotrigine (BIIB074, Biogen), a nonopioid investigational oral pain medication, reduces chronic neuropathic pain caused by small fiber neuropathy (SFN) and is generally well tolerated.

“We are encouraged by the overall results of the CONVEY study, especially given the significant unmet medical need for additional agents to treat chronic painful neuropathy,” Katherine Dawson, MD, senior vice president and head of the therapeutics development unit at Biogen, said in a news release.

Vixotrigine (BIIB074) is a peripherally and centrally acting, orally administered, voltage- and use-dependent voltage-gated sodium channel blocker.

CONVEY was a phase 2, placebo-controlled, double-blind, randomized withdrawal study of 265 patients experiencing pain from confirmed idiopathic or diabetes-associated SFN.

Following a 4-week open-label run-in period, 123 responders to vixotrigine were randomly allocated to 200 mg or 350 mg vixotrigine or placebo twice daily for 12 weeks in the double-blind portion of the study.

At week 12, vixotrigine 200 mg twice daily met the primary endpoint of a statistically significant reduction from baseline in the mean average daily pain (ADP) score versus placebo (P = .0501).

A subgroup analysis showed a treatment effect in patients with diabetes-associated SFN but not in the smaller subgroup of patients with idiopathic SFN.

The 200-mg dose also led to a significant improvement over placebo in mean worst daily pain score at 12 weeks (P = .0455).

A numeric advantage of 200 mg vixotrigine over placebo was observed in additional secondary endpoints, including the proportion of patients with at least a 2-point improvement in ADP score and the proportion with at least a 30% reduction in ADP at week 12, but these failed to reach statistical significance.

Vixotrigine 350 mg twice daily did not meet the primary endpoint of mean change in ADP at 12 weeks.

However, treatment at the higher dose led to a significant increase in the proportion of patients who reported being “very much improved” or “much improved” over baseline (P = .0580), Biogen reported.

In addition, a numeric advantage of 350 mg over placebo was observed in the proportion of patients with a 2-point or greater improvement in ADP score and the proportion with at least a 30% reduction in ADP at 12 weeks, but these also did not reach statistical significance.

Both doses of vixotrigine were “generally well tolerated and the safety profile was consistent with previous studies of vixotrigine with no evidence of abuse potential,” the company said.

In the open-label period, common adverse events seen in at least 2.5% of patients were dizziness, headache, vertigo, and nausea; adverse events led 5.3% of patients to discontinue the open-label portion of the study. Across the entire study, most adverse events were mild or moderate in severity.

“The totality of data from the vixotrigine program will inform potential doses for study in future phase 3 clinical trials,” the company said.

A version of this article first appeared on Medscape.com.

Top-line results from a phase 2 study suggest vixotrigine (BIIB074, Biogen), a nonopioid investigational oral pain medication, reduces chronic neuropathic pain caused by small fiber neuropathy (SFN) and is generally well tolerated.

“We are encouraged by the overall results of the CONVEY study, especially given the significant unmet medical need for additional agents to treat chronic painful neuropathy,” Katherine Dawson, MD, senior vice president and head of the therapeutics development unit at Biogen, said in a news release.

Vixotrigine (BIIB074) is a peripherally and centrally acting, orally administered, voltage- and use-dependent voltage-gated sodium channel blocker.

CONVEY was a phase 2, placebo-controlled, double-blind, randomized withdrawal study of 265 patients experiencing pain from confirmed idiopathic or diabetes-associated SFN.

Following a 4-week open-label run-in period, 123 responders to vixotrigine were randomly allocated to 200 mg or 350 mg vixotrigine or placebo twice daily for 12 weeks in the double-blind portion of the study.

At week 12, vixotrigine 200 mg twice daily met the primary endpoint of a statistically significant reduction from baseline in the mean average daily pain (ADP) score versus placebo (P = .0501).

A subgroup analysis showed a treatment effect in patients with diabetes-associated SFN but not in the smaller subgroup of patients with idiopathic SFN.

The 200-mg dose also led to a significant improvement over placebo in mean worst daily pain score at 12 weeks (P = .0455).

A numeric advantage of 200 mg vixotrigine over placebo was observed in additional secondary endpoints, including the proportion of patients with at least a 2-point improvement in ADP score and the proportion with at least a 30% reduction in ADP at week 12, but these failed to reach statistical significance.

Vixotrigine 350 mg twice daily did not meet the primary endpoint of mean change in ADP at 12 weeks.

However, treatment at the higher dose led to a significant increase in the proportion of patients who reported being “very much improved” or “much improved” over baseline (P = .0580), Biogen reported.

In addition, a numeric advantage of 350 mg over placebo was observed in the proportion of patients with a 2-point or greater improvement in ADP score and the proportion with at least a 30% reduction in ADP at 12 weeks, but these also did not reach statistical significance.

Both doses of vixotrigine were “generally well tolerated and the safety profile was consistent with previous studies of vixotrigine with no evidence of abuse potential,” the company said.

In the open-label period, common adverse events seen in at least 2.5% of patients were dizziness, headache, vertigo, and nausea; adverse events led 5.3% of patients to discontinue the open-label portion of the study. Across the entire study, most adverse events were mild or moderate in severity.

“The totality of data from the vixotrigine program will inform potential doses for study in future phase 3 clinical trials,” the company said.

A version of this article first appeared on Medscape.com.

A version of this article first appeared on Medscape.com.

A version of this article first appeared on Medscape.com.

A version of this article first appeared on Medscape.com.

Opioid-related drug overdose deaths in the United States exploded to an estimated record high of 69,031 people in 2020, topping the 49,860 deaths logged in 2019, according to a new report from the Centers for Disease Control and Prevention. Most of the deaths involved synthetic opioids such as fentanyl.

President Joe Biden has pledged more than $10 billion to expand access to prevention, treatment, and recovery services. The money is important as people receiving treatment for opioid use disorder have a high risk for relapse, and that means a high risk for opioid overdose.

Now, researchers are studying a possible bridge to successful recovery: A vaccine that could blunt the drugs’ ability to cause harm.

The first such vaccines are now entering clinical trials, raising hopes of adding another tool to the antiaddiction armamentarium. But even if the vaccines prove safe and effective, their success could generate some new problems to solve.

An advantage of vaccines is that their effects can last for several months, said trial investigator Sandra Comer, PhD, professor of neurobiology and psychiatry at Columbia University Irving Medical Center, New York. Dropout rates for existing medical therapies for opioid use disorder are as high as 50% at 6 months, and a vaccine could protect people from overdose and give them time to re-enter treatment.

“It serves as a bit of a safety net,” she said.

The first vaccine to enter a trial targets oxycodone. Volunteers are being recruited who have a diagnosis of opioid use disorder but are not being medically treated and are still using opioids. A third of them will receive a placebo vaccine, a third will receive a low-dose injection of vaccine, and the other third will receive a high-dose vaccine.
 

A shot against oxycodone

Researchers are primarily tracking the safety of the shot, but they’re also looking at whether vaccination prevents the euphoria that opioids usually produce. They expect to enroll 24 people initially but expand to 45 if results look promising.

In response to the shot, the body produces antibodies, proteins that tag oxycodone and keep it from reaching the brain. If the drug can’t reach brain cells, it can’t produce euphoria. And more important for lifesaving effects, it can’t block the brain’s signals to the body to breathe. The vaccine has already performed well in animal studies.

Previous trials of vaccines for cocaine and nicotine failed. Those vaccines made it to the last clinical trial stage, but didn’t prove effective overall. So this time, investigators plan to track antibody levels in participants, examining blood samples for signs of a good immune response to the vaccine.

But even though earlier cocaine and nicotine vaccines didn’t work for everybody, there were some people they seemed to help. This is why investigators involved in opioid vaccine trials want to track immune responses, said Marco Pravetoni, PhD, associate professor of pharmacology and medicine at the University of Minnesota, Minneapolis, whose team will be assessing the blood samples. Ultimately, a doctor might even be able to use this information to tailor vaccine selection to a specific person.

Dr. Pravetoni also said that oxycodone is one of three vaccine targets – the other two are heroin and fentanyl – that researchers hope to combine into a single shot. Recipients might need to have one shot a month for the first 3 to 4 months and then receive annual boosters.
 

Stopping the pain

The vaccines also raise some issues that need attention, said Cody Wenthur, PharmD, PhD, assistant professor of pharmacy at the University of Wisconsin–Madison, who is not involved in the vaccine trials.

“If you’re vaccinated against oxycodone, you might not have access to adequate pain control if you get into a car accident, for example,” he said.

Clinicians could use other opioids for pain management, but limiting the opioids that the vaccine targets is a “double-edged sword,” said Dr. Wenthur, because vaccinated people could just switch their opioid of choice to one that a vaccine does not inhibit.

Although these issues need to be addressed, vaccines, if successful, will have an important role. Dr. Wenthur noted a survey of pharmacists and pharmacy students that he and his group conducted showing that respondents “overwhelmingly” viewed a potential vaccine as helpful.

If the vaccines do become available, their application could extend beyond people who have opioid use disorder, said Dr. Pravetoni. He mentioned the 2002 incident when terrorists took over a theater in Moscow and Russian special forces are thought to have used an aerosolized form of fentanyl to incapacitate everyone in the room. More than 100 of the hostages died, and the episode raised the specter of opioids being used in chemical attacks.

Dr. Pravetoni said vaccination could offer protection for first responders, law enforcement or other people whose professions place them at risk for inhalation, either accidentally or through such attacks.

These or other real-world applications for people at risk for exposure are several years away. Dr. Pravetoni said it took 10 years to get to this phase and estimates that, in about 5 years, a vaccine that targets multiple opioid drugs might enter the first clinical trial.

A version of this article first appeared on WebMD.com.

Opioid-related drug overdose deaths in the United States exploded to an estimated record high of 69,031 people in 2020, topping the 49,860 deaths logged in 2019, according to a new report from the Centers for Disease Control and Prevention. Most of the deaths involved synthetic opioids such as fentanyl.

President Joe Biden has pledged more than $10 billion to expand access to prevention, treatment, and recovery services. The money is important as people receiving treatment for opioid use disorder have a high risk for relapse, and that means a high risk for opioid overdose.

Now, researchers are studying a possible bridge to successful recovery: A vaccine that could blunt the drugs’ ability to cause harm.

The first such vaccines are now entering clinical trials, raising hopes of adding another tool to the antiaddiction armamentarium. But even if the vaccines prove safe and effective, their success could generate some new problems to solve.

An advantage of vaccines is that their effects can last for several months, said trial investigator Sandra Comer, PhD, professor of neurobiology and psychiatry at Columbia University Irving Medical Center, New York. Dropout rates for existing medical therapies for opioid use disorder are as high as 50% at 6 months, and a vaccine could protect people from overdose and give them time to re-enter treatment.

“It serves as a bit of a safety net,” she said.

The first vaccine to enter a trial targets oxycodone. Volunteers are being recruited who have a diagnosis of opioid use disorder but are not being medically treated and are still using opioids. A third of them will receive a placebo vaccine, a third will receive a low-dose injection of vaccine, and the other third will receive a high-dose vaccine.
 

A shot against oxycodone

Researchers are primarily tracking the safety of the shot, but they’re also looking at whether vaccination prevents the euphoria that opioids usually produce. They expect to enroll 24 people initially but expand to 45 if results look promising.

In response to the shot, the body produces antibodies, proteins that tag oxycodone and keep it from reaching the brain. If the drug can’t reach brain cells, it can’t produce euphoria. And more important for lifesaving effects, it can’t block the brain’s signals to the body to breathe. The vaccine has already performed well in animal studies.

Previous trials of vaccines for cocaine and nicotine failed. Those vaccines made it to the last clinical trial stage, but didn’t prove effective overall. So this time, investigators plan to track antibody levels in participants, examining blood samples for signs of a good immune response to the vaccine.

But even though earlier cocaine and nicotine vaccines didn’t work for everybody, there were some people they seemed to help. This is why investigators involved in opioid vaccine trials want to track immune responses, said Marco Pravetoni, PhD, associate professor of pharmacology and medicine at the University of Minnesota, Minneapolis, whose team will be assessing the blood samples. Ultimately, a doctor might even be able to use this information to tailor vaccine selection to a specific person.

Dr. Pravetoni also said that oxycodone is one of three vaccine targets – the other two are heroin and fentanyl – that researchers hope to combine into a single shot. Recipients might need to have one shot a month for the first 3 to 4 months and then receive annual boosters.
 

Stopping the pain

The vaccines also raise some issues that need attention, said Cody Wenthur, PharmD, PhD, assistant professor of pharmacy at the University of Wisconsin–Madison, who is not involved in the vaccine trials.

“If you’re vaccinated against oxycodone, you might not have access to adequate pain control if you get into a car accident, for example,” he said.

Clinicians could use other opioids for pain management, but limiting the opioids that the vaccine targets is a “double-edged sword,” said Dr. Wenthur, because vaccinated people could just switch their opioid of choice to one that a vaccine does not inhibit.

Although these issues need to be addressed, vaccines, if successful, will have an important role. Dr. Wenthur noted a survey of pharmacists and pharmacy students that he and his group conducted showing that respondents “overwhelmingly” viewed a potential vaccine as helpful.

If the vaccines do become available, their application could extend beyond people who have opioid use disorder, said Dr. Pravetoni. He mentioned the 2002 incident when terrorists took over a theater in Moscow and Russian special forces are thought to have used an aerosolized form of fentanyl to incapacitate everyone in the room. More than 100 of the hostages died, and the episode raised the specter of opioids being used in chemical attacks.

Dr. Pravetoni said vaccination could offer protection for first responders, law enforcement or other people whose professions place them at risk for inhalation, either accidentally or through such attacks.

These or other real-world applications for people at risk for exposure are several years away. Dr. Pravetoni said it took 10 years to get to this phase and estimates that, in about 5 years, a vaccine that targets multiple opioid drugs might enter the first clinical trial.

A version of this article first appeared on WebMD.com.

Opioid-related drug overdose deaths in the United States exploded to an estimated record high of 69,031 people in 2020, topping the 49,860 deaths logged in 2019, according to a new report from the Centers for Disease Control and Prevention. Most of the deaths involved synthetic opioids such as fentanyl.

President Joe Biden has pledged more than $10 billion to expand access to prevention, treatment, and recovery services. The money is important as people receiving treatment for opioid use disorder have a high risk for relapse, and that means a high risk for opioid overdose.

Now, researchers are studying a possible bridge to successful recovery: A vaccine that could blunt the drugs’ ability to cause harm.

The first such vaccines are now entering clinical trials, raising hopes of adding another tool to the antiaddiction armamentarium. But even if the vaccines prove safe and effective, their success could generate some new problems to solve.

An advantage of vaccines is that their effects can last for several months, said trial investigator Sandra Comer, PhD, professor of neurobiology and psychiatry at Columbia University Irving Medical Center, New York. Dropout rates for existing medical therapies for opioid use disorder are as high as 50% at 6 months, and a vaccine could protect people from overdose and give them time to re-enter treatment.

“It serves as a bit of a safety net,” she said.

The first vaccine to enter a trial targets oxycodone. Volunteers are being recruited who have a diagnosis of opioid use disorder but are not being medically treated and are still using opioids. A third of them will receive a placebo vaccine, a third will receive a low-dose injection of vaccine, and the other third will receive a high-dose vaccine.
 

A shot against oxycodone

Researchers are primarily tracking the safety of the shot, but they’re also looking at whether vaccination prevents the euphoria that opioids usually produce. They expect to enroll 24 people initially but expand to 45 if results look promising.

In response to the shot, the body produces antibodies, proteins that tag oxycodone and keep it from reaching the brain. If the drug can’t reach brain cells, it can’t produce euphoria. And more important for lifesaving effects, it can’t block the brain’s signals to the body to breathe. The vaccine has already performed well in animal studies.

Previous trials of vaccines for cocaine and nicotine failed. Those vaccines made it to the last clinical trial stage, but didn’t prove effective overall. So this time, investigators plan to track antibody levels in participants, examining blood samples for signs of a good immune response to the vaccine.

But even though earlier cocaine and nicotine vaccines didn’t work for everybody, there were some people they seemed to help. This is why investigators involved in opioid vaccine trials want to track immune responses, said Marco Pravetoni, PhD, associate professor of pharmacology and medicine at the University of Minnesota, Minneapolis, whose team will be assessing the blood samples. Ultimately, a doctor might even be able to use this information to tailor vaccine selection to a specific person.

Dr. Pravetoni also said that oxycodone is one of three vaccine targets – the other two are heroin and fentanyl – that researchers hope to combine into a single shot. Recipients might need to have one shot a month for the first 3 to 4 months and then receive annual boosters.
 

Stopping the pain

The vaccines also raise some issues that need attention, said Cody Wenthur, PharmD, PhD, assistant professor of pharmacy at the University of Wisconsin–Madison, who is not involved in the vaccine trials.

“If you’re vaccinated against oxycodone, you might not have access to adequate pain control if you get into a car accident, for example,” he said.

Clinicians could use other opioids for pain management, but limiting the opioids that the vaccine targets is a “double-edged sword,” said Dr. Wenthur, because vaccinated people could just switch their opioid of choice to one that a vaccine does not inhibit.

Although these issues need to be addressed, vaccines, if successful, will have an important role. Dr. Wenthur noted a survey of pharmacists and pharmacy students that he and his group conducted showing that respondents “overwhelmingly” viewed a potential vaccine as helpful.

If the vaccines do become available, their application could extend beyond people who have opioid use disorder, said Dr. Pravetoni. He mentioned the 2002 incident when terrorists took over a theater in Moscow and Russian special forces are thought to have used an aerosolized form of fentanyl to incapacitate everyone in the room. More than 100 of the hostages died, and the episode raised the specter of opioids being used in chemical attacks.

Dr. Pravetoni said vaccination could offer protection for first responders, law enforcement or other people whose professions place them at risk for inhalation, either accidentally or through such attacks.

These or other real-world applications for people at risk for exposure are several years away. Dr. Pravetoni said it took 10 years to get to this phase and estimates that, in about 5 years, a vaccine that targets multiple opioid drugs might enter the first clinical trial.

A version of this article first appeared on WebMD.com.

Heidi Erickson, MD, is tired. As a pulmonary and critical care physician at Hennepin Healthcare in Minneapolis, she has been providing care for patients with COVID-19 since the start of the pandemic.

rclassenlayouts/Getty Images

It was exhausting from the beginning, as she and her colleagues scrambled to understand how to deal with this new disease. But lately, she has noticed a different kind of exhaustion arising from the knowledge that with vaccines widely available, the latest surge was preventable.

Her intensive care unit is currently as full as it has ever been with COVID-19 patients, many of them young adults and most of them unvaccinated. After the recent death of one patient, an unvaccinated man with teenage children, she had to face his family’s questions about why ivermectin, an antiparasitic medication that was falsely promoted as a COVID-19 treatment, was not administered.

“I’m fatigued because I’m working more than ever, but more people don’t have to die,” Dr. Erickson said in an interview . “It’s been very hard physically, mentally, emotionally.”

Amid yet another surge in COVID-19 cases around the United States, clinicians are speaking out about their growing frustration with this preventable crisis.

Some are using the terms “empathy fatigue” and “compassion fatigue” – a sense that they are losing empathy for unvaccinated individuals who are fueling the pandemic.

Dr. Erickson says she is frustrated not by individual patients but by a system that has allowed disinformation to proliferate. Experts say these types of feelings fit into a widespread pattern of physician burnout that has taken a new turn at this stage of the pandemic.

Paradoxical choices

Empathy is a cornerstone of what clinicians do, and the ability to understand and share a patient’s feelings is an essential skill for providing effective care, says Kaz Nelson, MD, a psychiatrist at the University of Minnesota, Minneapolis.

Practitioners face paradoxical situations all the time, she notes. These include individuals who break bones and go skydiving again, people who have high cholesterol but continue to eat fried foods, and those with advanced lung cancer who continue to smoke.

To treat patients with compassion, practitioners learn to set aside judgment by acknowledging the complexity of human behavior. They may lament the addictive nature of nicotine and advertising that targets children, for example, while still listening and caring.

Empathy requires high-level brain function, but as stress levels rise, brain function that drives empathy tends to shut down. It’s a survival mechanism, Dr. Nelson says.

When health care workers feel overwhelmed, trapped, or threatened by patients demanding unproven treatments or by ICUs with more patients than ventilators, they may experience a fight-or-flight response that makes them defensive, frustrated, angry, or uncaring, notes Mona Masood, DO, a Philadelphia-area psychiatrist and founder of Physician Support Line, a free mental health hotline for doctors.

Some clinicians have taken to Twitter and other social media platforms to post about these types of experiences.

These feelings, which have been brewing for months, have been exacerbated by the complexity of the current situation. Clinicians see a disconnect between what is and what could be, Dr. Nelson notes.

“Prior to vaccines, there weren’t other options, and so we had toxic stress and we had fatigue, but we could still maintain little bits of empathy by saying, ‘You know, people didn’t choose to get infected, and we are in a pandemic.’ We could kind of hate the virus. Now with access to vaccines, that last connection to empathy is removed for many people,” she says.

Self-preservation vs. empathy

Compassion fatigue or empathy fatigue is just one reaction to feeling completely maxed out and overstressed, Dr. Nelson says. Anger at society, such as what Dr. Erickson experienced, is another response.

Practitioners may also feel as if they are just going through the motions of their job, or they might disassociate, ceasing to feel that their patients are human. Plenty of doctors and nurses have cried in their cars after shifts and have posted tearful videos on social media.

Early in the pandemic, Dr. Masood says, physicians who called the support hotline expressed sadness and grief. Now, she had her colleagues hear frustration and anger, along with guilt and shame for having feelings they believe they shouldn’t be having, especially toward patients. They may feel unprofessional or worse – unworthy of being physicians, she says.

One recent caller to the hotline was a long-time ICU physician who had been told so many times by patients that ivermectin was the only medicine that would cure them that he began to doubt himself, says Dr. Masood. This caller needed to be reassured by another physician that he was doing the right thing.

Another emergency department physician told Dr. Masood about a young child who had arrived at the hospital with COVID-19 symptoms. When asked whether the family had been exposed to anyone with COVID-19, the child’s parent lied so that they could be triaged faster.

The physician, who needed to step away from the situation, reached out to Dr. Masood to express her frustration so that she wouldn’t “let it out” on the patient.

“It’s hard to have empathy for people who, for all intents and purposes, are very self-centered,” Dr. Masood says. “We’re at a place where we’re having to choose between self-preservation and empathy.”
 

How to cope

To help practitioners cope, Dr. Masood offers words that describe what they’re experiencing. She often hears clinicians say things such as, “This is a type of burnout that I feel to my bones,” or “This makes me want to quit,” or “I feel like I’m at the end of my rope.”

She encourages them to consider the terms “empathy fatigue,” and “moral injury” in order to reconcile how their sense of responsibility to take care of people is compromised by factors outside of their control.

It is not shameful to acknowledge that they experience emotions, including difficult ones such as frustration, anger, sadness, and anxiety, Dr. Masood adds.

Being frustrated with a patient doesn’t make someone a bad doctor, and admitting those emotions is the first step toward dealing with them, she says.

Dr. Nelson adds that taking breaks from work can help. She also recommends setting boundaries, seeking therapy, and acknowledging feelings early before they cause a sense of callousness or other consequences that become harder to heal from as time goes on.

“We’re trained to just go, go, go and sometimes not pause and check in,” she says. Clinicians who open up are likely to find they are not the only ones feeling tired or frustrated right now, she adds.

“Connect with peers and colleagues, because chances are, they can relate,” Dr. Nelson says.

A version of this article first appeared on Medscape.com.

Heidi Erickson, MD, is tired. As a pulmonary and critical care physician at Hennepin Healthcare in Minneapolis, she has been providing care for patients with COVID-19 since the start of the pandemic.

rclassenlayouts/Getty Images

It was exhausting from the beginning, as she and her colleagues scrambled to understand how to deal with this new disease. But lately, she has noticed a different kind of exhaustion arising from the knowledge that with vaccines widely available, the latest surge was preventable.

Her intensive care unit is currently as full as it has ever been with COVID-19 patients, many of them young adults and most of them unvaccinated. After the recent death of one patient, an unvaccinated man with teenage children, she had to face his family’s questions about why ivermectin, an antiparasitic medication that was falsely promoted as a COVID-19 treatment, was not administered.

“I’m fatigued because I’m working more than ever, but more people don’t have to die,” Dr. Erickson said in an interview . “It’s been very hard physically, mentally, emotionally.”

Amid yet another surge in COVID-19 cases around the United States, clinicians are speaking out about their growing frustration with this preventable crisis.

Some are using the terms “empathy fatigue” and “compassion fatigue” – a sense that they are losing empathy for unvaccinated individuals who are fueling the pandemic.

Dr. Erickson says she is frustrated not by individual patients but by a system that has allowed disinformation to proliferate. Experts say these types of feelings fit into a widespread pattern of physician burnout that has taken a new turn at this stage of the pandemic.

Paradoxical choices

Empathy is a cornerstone of what clinicians do, and the ability to understand and share a patient’s feelings is an essential skill for providing effective care, says Kaz Nelson, MD, a psychiatrist at the University of Minnesota, Minneapolis.

Practitioners face paradoxical situations all the time, she notes. These include individuals who break bones and go skydiving again, people who have high cholesterol but continue to eat fried foods, and those with advanced lung cancer who continue to smoke.

To treat patients with compassion, practitioners learn to set aside judgment by acknowledging the complexity of human behavior. They may lament the addictive nature of nicotine and advertising that targets children, for example, while still listening and caring.

Empathy requires high-level brain function, but as stress levels rise, brain function that drives empathy tends to shut down. It’s a survival mechanism, Dr. Nelson says.

When health care workers feel overwhelmed, trapped, or threatened by patients demanding unproven treatments or by ICUs with more patients than ventilators, they may experience a fight-or-flight response that makes them defensive, frustrated, angry, or uncaring, notes Mona Masood, DO, a Philadelphia-area psychiatrist and founder of Physician Support Line, a free mental health hotline for doctors.

Some clinicians have taken to Twitter and other social media platforms to post about these types of experiences.

These feelings, which have been brewing for months, have been exacerbated by the complexity of the current situation. Clinicians see a disconnect between what is and what could be, Dr. Nelson notes.

“Prior to vaccines, there weren’t other options, and so we had toxic stress and we had fatigue, but we could still maintain little bits of empathy by saying, ‘You know, people didn’t choose to get infected, and we are in a pandemic.’ We could kind of hate the virus. Now with access to vaccines, that last connection to empathy is removed for many people,” she says.

Self-preservation vs. empathy

Compassion fatigue or empathy fatigue is just one reaction to feeling completely maxed out and overstressed, Dr. Nelson says. Anger at society, such as what Dr. Erickson experienced, is another response.

Practitioners may also feel as if they are just going through the motions of their job, or they might disassociate, ceasing to feel that their patients are human. Plenty of doctors and nurses have cried in their cars after shifts and have posted tearful videos on social media.

Early in the pandemic, Dr. Masood says, physicians who called the support hotline expressed sadness and grief. Now, she had her colleagues hear frustration and anger, along with guilt and shame for having feelings they believe they shouldn’t be having, especially toward patients. They may feel unprofessional or worse – unworthy of being physicians, she says.

One recent caller to the hotline was a long-time ICU physician who had been told so many times by patients that ivermectin was the only medicine that would cure them that he began to doubt himself, says Dr. Masood. This caller needed to be reassured by another physician that he was doing the right thing.

Another emergency department physician told Dr. Masood about a young child who had arrived at the hospital with COVID-19 symptoms. When asked whether the family had been exposed to anyone with COVID-19, the child’s parent lied so that they could be triaged faster.

The physician, who needed to step away from the situation, reached out to Dr. Masood to express her frustration so that she wouldn’t “let it out” on the patient.

“It’s hard to have empathy for people who, for all intents and purposes, are very self-centered,” Dr. Masood says. “We’re at a place where we’re having to choose between self-preservation and empathy.”
 

How to cope

To help practitioners cope, Dr. Masood offers words that describe what they’re experiencing. She often hears clinicians say things such as, “This is a type of burnout that I feel to my bones,” or “This makes me want to quit,” or “I feel like I’m at the end of my rope.”

She encourages them to consider the terms “empathy fatigue,” and “moral injury” in order to reconcile how their sense of responsibility to take care of people is compromised by factors outside of their control.

It is not shameful to acknowledge that they experience emotions, including difficult ones such as frustration, anger, sadness, and anxiety, Dr. Masood adds.

Being frustrated with a patient doesn’t make someone a bad doctor, and admitting those emotions is the first step toward dealing with them, she says.

Dr. Nelson adds that taking breaks from work can help. She also recommends setting boundaries, seeking therapy, and acknowledging feelings early before they cause a sense of callousness or other consequences that become harder to heal from as time goes on.

“We’re trained to just go, go, go and sometimes not pause and check in,” she says. Clinicians who open up are likely to find they are not the only ones feeling tired or frustrated right now, she adds.

“Connect with peers and colleagues, because chances are, they can relate,” Dr. Nelson says.

A version of this article first appeared on Medscape.com.

Heidi Erickson, MD, is tired. As a pulmonary and critical care physician at Hennepin Healthcare in Minneapolis, she has been providing care for patients with COVID-19 since the start of the pandemic.

rclassenlayouts/Getty Images

It was exhausting from the beginning, as she and her colleagues scrambled to understand how to deal with this new disease. But lately, she has noticed a different kind of exhaustion arising from the knowledge that with vaccines widely available, the latest surge was preventable.

Her intensive care unit is currently as full as it has ever been with COVID-19 patients, many of them young adults and most of them unvaccinated. After the recent death of one patient, an unvaccinated man with teenage children, she had to face his family’s questions about why ivermectin, an antiparasitic medication that was falsely promoted as a COVID-19 treatment, was not administered.

“I’m fatigued because I’m working more than ever, but more people don’t have to die,” Dr. Erickson said in an interview . “It’s been very hard physically, mentally, emotionally.”

Amid yet another surge in COVID-19 cases around the United States, clinicians are speaking out about their growing frustration with this preventable crisis.

Some are using the terms “empathy fatigue” and “compassion fatigue” – a sense that they are losing empathy for unvaccinated individuals who are fueling the pandemic.

Dr. Erickson says she is frustrated not by individual patients but by a system that has allowed disinformation to proliferate. Experts say these types of feelings fit into a widespread pattern of physician burnout that has taken a new turn at this stage of the pandemic.

Paradoxical choices

Empathy is a cornerstone of what clinicians do, and the ability to understand and share a patient’s feelings is an essential skill for providing effective care, says Kaz Nelson, MD, a psychiatrist at the University of Minnesota, Minneapolis.

Practitioners face paradoxical situations all the time, she notes. These include individuals who break bones and go skydiving again, people who have high cholesterol but continue to eat fried foods, and those with advanced lung cancer who continue to smoke.

To treat patients with compassion, practitioners learn to set aside judgment by acknowledging the complexity of human behavior. They may lament the addictive nature of nicotine and advertising that targets children, for example, while still listening and caring.

Empathy requires high-level brain function, but as stress levels rise, brain function that drives empathy tends to shut down. It’s a survival mechanism, Dr. Nelson says.

When health care workers feel overwhelmed, trapped, or threatened by patients demanding unproven treatments or by ICUs with more patients than ventilators, they may experience a fight-or-flight response that makes them defensive, frustrated, angry, or uncaring, notes Mona Masood, DO, a Philadelphia-area psychiatrist and founder of Physician Support Line, a free mental health hotline for doctors.

Some clinicians have taken to Twitter and other social media platforms to post about these types of experiences.

These feelings, which have been brewing for months, have been exacerbated by the complexity of the current situation. Clinicians see a disconnect between what is and what could be, Dr. Nelson notes.

“Prior to vaccines, there weren’t other options, and so we had toxic stress and we had fatigue, but we could still maintain little bits of empathy by saying, ‘You know, people didn’t choose to get infected, and we are in a pandemic.’ We could kind of hate the virus. Now with access to vaccines, that last connection to empathy is removed for many people,” she says.

Self-preservation vs. empathy

Compassion fatigue or empathy fatigue is just one reaction to feeling completely maxed out and overstressed, Dr. Nelson says. Anger at society, such as what Dr. Erickson experienced, is another response.

Practitioners may also feel as if they are just going through the motions of their job, or they might disassociate, ceasing to feel that their patients are human. Plenty of doctors and nurses have cried in their cars after shifts and have posted tearful videos on social media.

Early in the pandemic, Dr. Masood says, physicians who called the support hotline expressed sadness and grief. Now, she had her colleagues hear frustration and anger, along with guilt and shame for having feelings they believe they shouldn’t be having, especially toward patients. They may feel unprofessional or worse – unworthy of being physicians, she says.

One recent caller to the hotline was a long-time ICU physician who had been told so many times by patients that ivermectin was the only medicine that would cure them that he began to doubt himself, says Dr. Masood. This caller needed to be reassured by another physician that he was doing the right thing.

Another emergency department physician told Dr. Masood about a young child who had arrived at the hospital with COVID-19 symptoms. When asked whether the family had been exposed to anyone with COVID-19, the child’s parent lied so that they could be triaged faster.

The physician, who needed to step away from the situation, reached out to Dr. Masood to express her frustration so that she wouldn’t “let it out” on the patient.

“It’s hard to have empathy for people who, for all intents and purposes, are very self-centered,” Dr. Masood says. “We’re at a place where we’re having to choose between self-preservation and empathy.”
 

How to cope

To help practitioners cope, Dr. Masood offers words that describe what they’re experiencing. She often hears clinicians say things such as, “This is a type of burnout that I feel to my bones,” or “This makes me want to quit,” or “I feel like I’m at the end of my rope.”

She encourages them to consider the terms “empathy fatigue,” and “moral injury” in order to reconcile how their sense of responsibility to take care of people is compromised by factors outside of their control.

It is not shameful to acknowledge that they experience emotions, including difficult ones such as frustration, anger, sadness, and anxiety, Dr. Masood adds.

Being frustrated with a patient doesn’t make someone a bad doctor, and admitting those emotions is the first step toward dealing with them, she says.

Dr. Nelson adds that taking breaks from work can help. She also recommends setting boundaries, seeking therapy, and acknowledging feelings early before they cause a sense of callousness or other consequences that become harder to heal from as time goes on.

“We’re trained to just go, go, go and sometimes not pause and check in,” she says. Clinicians who open up are likely to find they are not the only ones feeling tired or frustrated right now, she adds.

“Connect with peers and colleagues, because chances are, they can relate,” Dr. Nelson says.

A version of this article first appeared on Medscape.com.

Seeking novelty is central to adolescence; experimentation is how they explore their identity, exert independence, and establish deep and connected relationships outside of the family. Research over the past 2 decades has demonstrated the neurobiological changes that underpin this increase in sensation seeking. Most adolescents are very good at assessing risk but are willing to tolerate higher levels of risk than adults in the pursuit of novelty.¹ If their knowledge base is limited or inaccurate, as is often the case with drugs and alcohol, accepting higher risk becomes more dangerous. Adolescents are more likely to trust their peers than their parents, but their pediatricians still have authority and credibility.

While there is ample credible information online (from the National Institute on Drug Abuse and the Substance Abuse and Mental Health Services Administration’s excellent websites, which can be recommended to teens), marijuana and hallucinogens (LSD and psilocybin) bear special discussion here because of changing legality and their potential medical utility. There is an emerging impression of safety with both; however, policy changes and for-profit marketing may not reflect the actual scientific evidence. You have the opportunity and authority to complicate your patient’s thinking by discussing the evidence supporting their medical utility, and the emerging evidence that both types of drugs may pose special risks for their developing brains.

By June 2021, marijuana was legal for recreational use in 19 states; Washington, D.C.; and Guam, and for “medical use” in 36 states and four territories. Entrepreneurs and activists have made spectacular claims that marijuana is effective for the treatment of everything from insomnia to PTSD, but the reality is less impressive. Of course, marijuana remains a schedule I drug under the federal Controlled Substances Act (1970), which has made it difficult for researchers to perform randomized controlled studies concerning treatment or risks.

However, there are a growing number of randomized controlled trials with synthetic cannabinoids (dronabinol and nabilone) and a (legal) drug derived from cannabis (cannabidiol or CBD, as distinct from the other active ingredient, tetrahydrocannabinol). There is Food and Drug Administration approval for CBD for the treatment of epilepsy in Lennox-Gastaut or Dravet syndrome in patients aged 2 years or younger, and for the synthetic agents for the treatment of chemotherapy-related nausea and vomiting in cancer patients and for the treatment of weight loss and muscle wasting related to HIV/AIDS. That’s it. There is some evidence that these agents may be effective for the treatment of muscle spasticity in multiple sclerosis, chronic pain of many etiologies, Tourette syndrome, insomnia related to multiple sclerosis and chronic pain, and possibly PTSD. But there have been multiple studies that have failed to demonstrate efficacy (or have demonstrated exacerbation) for a host of other medical and psychiatric problems.

While the evidence for marijuana’s medicinal uses is modest, there is substantial evidence that its use in adolescence carries risks. It is an addictive substance and regular use is associated with sustained modest cognitive impairment (a loss of up to eight IQ points in the clinically dependent) and higher rates of anxiety and depressive disorders. As with other substances, use before the age of 18 substantially raises the risk (as much as sevenfold) of developing addiction than the same rate of use in adulthood. The rate of schizophrenia in adolescents with heavy marijuana use is between six and seven times greater than in the general population, whereas similar adult use does not have this association.^2,3 Studies in rats have demonstrated that use during adolescence delays and permanently changes the maturation of the prefrontal cortex, an area of the brain that is essential for complex decision-making, sustaining attention, abstract reasoning, and impulse control.⁴ While we do not fully understand the exact nature of these changes, there is good reason to believe that regular marijuana use in adolescence leads to disruption of critical brain development and cognitive or even psychotic consequences. It is worth noting that the potency of many commercially available marijuana products is much higher than those that were studied, raising the risk and uncertainty further.

Hallucinogens, or “psychedelics” (from Greek for “mind manifesting”) are a class that includes LSD and psilocybin (a chemical found in over 200 species of mushrooms). They precipitate visual and auditory “hallucinations,” a loss of sense of self, and a sense of awe that may be transcendent or frightening. While psilocybin was used by many indigenous cultures in religious ceremonies, LSD was synthesized by a chemist at Sandoz in 1938 and made widely available for study until it was classified as a schedule I drug by the 1970 Controlled Substances Act. They are not addictive. Early research demonstrated promise in the treatment of alcohol dependence and several psychiatric conditions (including other addictions and treatment-resistant depression). Research resumed in 2018, demonstrating promise in the treatment of depression related to terminal illness. Research has also concerned the nature of consciousness and spiritual experiences. Hallucinogens have become popular in certain fields (high tech) as a means of optimizing creativity and performance (“microdosing”). There is modest evidence that use in people with a family history of psychotic illness may precipitate sustained psychotic symptoms. Regular use may further increase the risk of persistent psychosis and adolescent users of multiple substances are at high risk for regular hallucinogen use. Adolescents may think that ketamine, phencyclidine , and 3,4-methylenedioxymethamphetamine are also in this category, although they are different and considerably more risky drugs. Overall, these agents show therapeutic promise, but unless your young patients are facing depression related to a terminal illness and until we learn more from studies, the potential risk to their developing brains outweighs any potential benefits.

Aware of this information, you are ready to ask your adolescent patients about their drug and alcohol use and knowledge. Using phrases like “when did you first try ...” can increase the likelihood that your patients will be forthright with you. Or start by asking about what their friends are trying and talking about. Be curious about any drug and alcohol use at home. Find out what they are curious about, whom they trust, and where they get their information. Then you can offer your information about the dramatic changes happening in their brains (just like the rest of their bodies) and the special risks of drug use during this window of brain development. Acknowledge that the risks of marijuana use in adults may very well be lower than the risks of regular alcohol use but remind them about how their brains are different than those of adults. Delaying use until they are 18 (or ideally in their mid-20s when most brain development is complete), can dramatically lower these risks. For adolescents with a family history of addiction, psychosis, or mood and anxiety disorders, discuss the additional risks that drugs may present to them. And for those adolescents who acknowledge very early (before 13) or heavy use, be curious with them about whether they might be trying to “feel better” and not just “feel good.” Screen them for depression, suicidality, and anxiety disorders. Those underlying problems are treatable, but their course will only worsen with drug and alcohol use. You are in a unique position to help your adolescent patients make wise and well-informed choices and to get them assistance if they need it.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Romer D. Dev Psychobiol. 2010 Apr;52(3):263-76.

2. Szczepanski SM and Knight TR. Neuron. 2014;83:1002-18.

3. Renard J et al. Front Psychiatry. 2018;9:281.

4. Shen H. Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):7-11.

Seeking novelty is central to adolescence; experimentation is how they explore their identity, exert independence, and establish deep and connected relationships outside of the family. Research over the past 2 decades has demonstrated the neurobiological changes that underpin this increase in sensation seeking. Most adolescents are very good at assessing risk but are willing to tolerate higher levels of risk than adults in the pursuit of novelty.¹ If their knowledge base is limited or inaccurate, as is often the case with drugs and alcohol, accepting higher risk becomes more dangerous. Adolescents are more likely to trust their peers than their parents, but their pediatricians still have authority and credibility.

While there is ample credible information online (from the National Institute on Drug Abuse and the Substance Abuse and Mental Health Services Administration’s excellent websites, which can be recommended to teens), marijuana and hallucinogens (LSD and psilocybin) bear special discussion here because of changing legality and their potential medical utility. There is an emerging impression of safety with both; however, policy changes and for-profit marketing may not reflect the actual scientific evidence. You have the opportunity and authority to complicate your patient’s thinking by discussing the evidence supporting their medical utility, and the emerging evidence that both types of drugs may pose special risks for their developing brains.

By June 2021, marijuana was legal for recreational use in 19 states; Washington, D.C.; and Guam, and for “medical use” in 36 states and four territories. Entrepreneurs and activists have made spectacular claims that marijuana is effective for the treatment of everything from insomnia to PTSD, but the reality is less impressive. Of course, marijuana remains a schedule I drug under the federal Controlled Substances Act (1970), which has made it difficult for researchers to perform randomized controlled studies concerning treatment or risks.

However, there are a growing number of randomized controlled trials with synthetic cannabinoids (dronabinol and nabilone) and a (legal) drug derived from cannabis (cannabidiol or CBD, as distinct from the other active ingredient, tetrahydrocannabinol). There is Food and Drug Administration approval for CBD for the treatment of epilepsy in Lennox-Gastaut or Dravet syndrome in patients aged 2 years or younger, and for the synthetic agents for the treatment of chemotherapy-related nausea and vomiting in cancer patients and for the treatment of weight loss and muscle wasting related to HIV/AIDS. That’s it. There is some evidence that these agents may be effective for the treatment of muscle spasticity in multiple sclerosis, chronic pain of many etiologies, Tourette syndrome, insomnia related to multiple sclerosis and chronic pain, and possibly PTSD. But there have been multiple studies that have failed to demonstrate efficacy (or have demonstrated exacerbation) for a host of other medical and psychiatric problems.

While the evidence for marijuana’s medicinal uses is modest, there is substantial evidence that its use in adolescence carries risks. It is an addictive substance and regular use is associated with sustained modest cognitive impairment (a loss of up to eight IQ points in the clinically dependent) and higher rates of anxiety and depressive disorders. As with other substances, use before the age of 18 substantially raises the risk (as much as sevenfold) of developing addiction than the same rate of use in adulthood. The rate of schizophrenia in adolescents with heavy marijuana use is between six and seven times greater than in the general population, whereas similar adult use does not have this association.^2,3 Studies in rats have demonstrated that use during adolescence delays and permanently changes the maturation of the prefrontal cortex, an area of the brain that is essential for complex decision-making, sustaining attention, abstract reasoning, and impulse control.⁴ While we do not fully understand the exact nature of these changes, there is good reason to believe that regular marijuana use in adolescence leads to disruption of critical brain development and cognitive or even psychotic consequences. It is worth noting that the potency of many commercially available marijuana products is much higher than those that were studied, raising the risk and uncertainty further.

Hallucinogens, or “psychedelics” (from Greek for “mind manifesting”) are a class that includes LSD and psilocybin (a chemical found in over 200 species of mushrooms). They precipitate visual and auditory “hallucinations,” a loss of sense of self, and a sense of awe that may be transcendent or frightening. While psilocybin was used by many indigenous cultures in religious ceremonies, LSD was synthesized by a chemist at Sandoz in 1938 and made widely available for study until it was classified as a schedule I drug by the 1970 Controlled Substances Act. They are not addictive. Early research demonstrated promise in the treatment of alcohol dependence and several psychiatric conditions (including other addictions and treatment-resistant depression). Research resumed in 2018, demonstrating promise in the treatment of depression related to terminal illness. Research has also concerned the nature of consciousness and spiritual experiences. Hallucinogens have become popular in certain fields (high tech) as a means of optimizing creativity and performance (“microdosing”). There is modest evidence that use in people with a family history of psychotic illness may precipitate sustained psychotic symptoms. Regular use may further increase the risk of persistent psychosis and adolescent users of multiple substances are at high risk for regular hallucinogen use. Adolescents may think that ketamine, phencyclidine , and 3,4-methylenedioxymethamphetamine are also in this category, although they are different and considerably more risky drugs. Overall, these agents show therapeutic promise, but unless your young patients are facing depression related to a terminal illness and until we learn more from studies, the potential risk to their developing brains outweighs any potential benefits.

Aware of this information, you are ready to ask your adolescent patients about their drug and alcohol use and knowledge. Using phrases like “when did you first try ...” can increase the likelihood that your patients will be forthright with you. Or start by asking about what their friends are trying and talking about. Be curious about any drug and alcohol use at home. Find out what they are curious about, whom they trust, and where they get their information. Then you can offer your information about the dramatic changes happening in their brains (just like the rest of their bodies) and the special risks of drug use during this window of brain development. Acknowledge that the risks of marijuana use in adults may very well be lower than the risks of regular alcohol use but remind them about how their brains are different than those of adults. Delaying use until they are 18 (or ideally in their mid-20s when most brain development is complete), can dramatically lower these risks. For adolescents with a family history of addiction, psychosis, or mood and anxiety disorders, discuss the additional risks that drugs may present to them. And for those adolescents who acknowledge very early (before 13) or heavy use, be curious with them about whether they might be trying to “feel better” and not just “feel good.” Screen them for depression, suicidality, and anxiety disorders. Those underlying problems are treatable, but their course will only worsen with drug and alcohol use. You are in a unique position to help your adolescent patients make wise and well-informed choices and to get them assistance if they need it.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Romer D. Dev Psychobiol. 2010 Apr;52(3):263-76.

2. Szczepanski SM and Knight TR. Neuron. 2014;83:1002-18.

3. Renard J et al. Front Psychiatry. 2018;9:281.

4. Shen H. Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):7-11.

Seeking novelty is central to adolescence; experimentation is how they explore their identity, exert independence, and establish deep and connected relationships outside of the family. Research over the past 2 decades has demonstrated the neurobiological changes that underpin this increase in sensation seeking. Most adolescents are very good at assessing risk but are willing to tolerate higher levels of risk than adults in the pursuit of novelty.¹ If their knowledge base is limited or inaccurate, as is often the case with drugs and alcohol, accepting higher risk becomes more dangerous. Adolescents are more likely to trust their peers than their parents, but their pediatricians still have authority and credibility.

While there is ample credible information online (from the National Institute on Drug Abuse and the Substance Abuse and Mental Health Services Administration’s excellent websites, which can be recommended to teens), marijuana and hallucinogens (LSD and psilocybin) bear special discussion here because of changing legality and their potential medical utility. There is an emerging impression of safety with both; however, policy changes and for-profit marketing may not reflect the actual scientific evidence. You have the opportunity and authority to complicate your patient’s thinking by discussing the evidence supporting their medical utility, and the emerging evidence that both types of drugs may pose special risks for their developing brains.

By June 2021, marijuana was legal for recreational use in 19 states; Washington, D.C.; and Guam, and for “medical use” in 36 states and four territories. Entrepreneurs and activists have made spectacular claims that marijuana is effective for the treatment of everything from insomnia to PTSD, but the reality is less impressive. Of course, marijuana remains a schedule I drug under the federal Controlled Substances Act (1970), which has made it difficult for researchers to perform randomized controlled studies concerning treatment or risks.

However, there are a growing number of randomized controlled trials with synthetic cannabinoids (dronabinol and nabilone) and a (legal) drug derived from cannabis (cannabidiol or CBD, as distinct from the other active ingredient, tetrahydrocannabinol). There is Food and Drug Administration approval for CBD for the treatment of epilepsy in Lennox-Gastaut or Dravet syndrome in patients aged 2 years or younger, and for the synthetic agents for the treatment of chemotherapy-related nausea and vomiting in cancer patients and for the treatment of weight loss and muscle wasting related to HIV/AIDS. That’s it. There is some evidence that these agents may be effective for the treatment of muscle spasticity in multiple sclerosis, chronic pain of many etiologies, Tourette syndrome, insomnia related to multiple sclerosis and chronic pain, and possibly PTSD. But there have been multiple studies that have failed to demonstrate efficacy (or have demonstrated exacerbation) for a host of other medical and psychiatric problems.

While the evidence for marijuana’s medicinal uses is modest, there is substantial evidence that its use in adolescence carries risks. It is an addictive substance and regular use is associated with sustained modest cognitive impairment (a loss of up to eight IQ points in the clinically dependent) and higher rates of anxiety and depressive disorders. As with other substances, use before the age of 18 substantially raises the risk (as much as sevenfold) of developing addiction than the same rate of use in adulthood. The rate of schizophrenia in adolescents with heavy marijuana use is between six and seven times greater than in the general population, whereas similar adult use does not have this association.^2,3 Studies in rats have demonstrated that use during adolescence delays and permanently changes the maturation of the prefrontal cortex, an area of the brain that is essential for complex decision-making, sustaining attention, abstract reasoning, and impulse control.⁴ While we do not fully understand the exact nature of these changes, there is good reason to believe that regular marijuana use in adolescence leads to disruption of critical brain development and cognitive or even psychotic consequences. It is worth noting that the potency of many commercially available marijuana products is much higher than those that were studied, raising the risk and uncertainty further.

Hallucinogens, or “psychedelics” (from Greek for “mind manifesting”) are a class that includes LSD and psilocybin (a chemical found in over 200 species of mushrooms). They precipitate visual and auditory “hallucinations,” a loss of sense of self, and a sense of awe that may be transcendent or frightening. While psilocybin was used by many indigenous cultures in religious ceremonies, LSD was synthesized by a chemist at Sandoz in 1938 and made widely available for study until it was classified as a schedule I drug by the 1970 Controlled Substances Act. They are not addictive. Early research demonstrated promise in the treatment of alcohol dependence and several psychiatric conditions (including other addictions and treatment-resistant depression). Research resumed in 2018, demonstrating promise in the treatment of depression related to terminal illness. Research has also concerned the nature of consciousness and spiritual experiences. Hallucinogens have become popular in certain fields (high tech) as a means of optimizing creativity and performance (“microdosing”). There is modest evidence that use in people with a family history of psychotic illness may precipitate sustained psychotic symptoms. Regular use may further increase the risk of persistent psychosis and adolescent users of multiple substances are at high risk for regular hallucinogen use. Adolescents may think that ketamine, phencyclidine , and 3,4-methylenedioxymethamphetamine are also in this category, although they are different and considerably more risky drugs. Overall, these agents show therapeutic promise, but unless your young patients are facing depression related to a terminal illness and until we learn more from studies, the potential risk to their developing brains outweighs any potential benefits.

Aware of this information, you are ready to ask your adolescent patients about their drug and alcohol use and knowledge. Using phrases like “when did you first try ...” can increase the likelihood that your patients will be forthright with you. Or start by asking about what their friends are trying and talking about. Be curious about any drug and alcohol use at home. Find out what they are curious about, whom they trust, and where they get their information. Then you can offer your information about the dramatic changes happening in their brains (just like the rest of their bodies) and the special risks of drug use during this window of brain development. Acknowledge that the risks of marijuana use in adults may very well be lower than the risks of regular alcohol use but remind them about how their brains are different than those of adults. Delaying use until they are 18 (or ideally in their mid-20s when most brain development is complete), can dramatically lower these risks. For adolescents with a family history of addiction, psychosis, or mood and anxiety disorders, discuss the additional risks that drugs may present to them. And for those adolescents who acknowledge very early (before 13) or heavy use, be curious with them about whether they might be trying to “feel better” and not just “feel good.” Screen them for depression, suicidality, and anxiety disorders. Those underlying problems are treatable, but their course will only worsen with drug and alcohol use. You are in a unique position to help your adolescent patients make wise and well-informed choices and to get them assistance if they need it.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Romer D. Dev Psychobiol. 2010 Apr;52(3):263-76.

2. Szczepanski SM and Knight TR. Neuron. 2014;83:1002-18.

3. Renard J et al. Front Psychiatry. 2018;9:281.

4. Shen H. Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):7-11.

A headache severity score compiled by assessing various migraine symptoms can help predict the likelihood of doctor visits and missed work or school, according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.

“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.

To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.

After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
 

Tracking multiple variables

“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.

“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”

He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.

“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”

The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”

The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.

A headache severity score compiled by assessing various migraine symptoms can help predict the likelihood of doctor visits and missed work or school, according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.

“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.

To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.

After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
 

Tracking multiple variables

“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.

“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”

He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.

“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”

The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”

The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.

A headache severity score compiled by assessing various migraine symptoms can help predict the likelihood of doctor visits and missed work or school, according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.

“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.

To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.

After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
 

Tracking multiple variables

“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.

“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”

He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.

“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”

The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”

The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.

Treatment with acetylsalicylic acid (ASA) or heparin is associated with an increased risk for symptomatic intracranial hemorrhage (sICH) in patients with ischemic stroke who are undergoing endovascular therapy (EVT), new data show.

In this population, ASA and heparin are each associated with an approximately doubled risk for sICH when administered during EVT.

“We did not find any evidence for a beneficial effect on functional outcome,” investigator Wouter van der Steen, MD, research physician and PhD student at Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization. The possibility that a positive effect would be observed if the trial were continued was considered negligible, he added.

The researchers stopped the trial for safety reasons and recommend avoiding the evaluated dosages of both medications during EVT for ischemic stroke, said Dr. van der Steen.

He presented the findings from the MR CLEAN-MED trial at the European Stroke Organisation Conference (ESOC) 2021, which was held online.
 

Trial stopped for safety

Previous research has supported the safety and efficacy of EVT for ischemic stroke. Still, more than 30% of patients do not recover, despite fast and complete recanalization. Incomplete microvascular reperfusion (IMR) could explain this incomplete recovery, the researchers note.

Microthrombi, which occlude distal vessels, and neutrophil extracellular traps can cause IMR. This problem can be reduced through treatment with ASA, which has an antithrombotic effect, or with heparin, which dissolves neutrophil extracellular traps, they add. Although these drugs are associated with good clinical outcomes, they entail an increased risk for sICH.

The investigators conducted the multicenter, randomized controlled MR CLEAN-MED trial to evaluate the effect of intravenous (IV) ASA and heparin, alone or in combination, during EVT for acute ischemic stroke. Treatment was open label, but outcome assessment was blinded. Eligible participants were adults with a National Institutes of Health Stroke Scale (NIHSS) score of greater than or equal to 2 and an anterior circulation large-vessel occlusion for whom EVT could be initiated in fewer than 6 hours.

Investigators randomly assigned patients to receive or not to receive ASA. Within each of these two treatment groups, patients were randomly assigned to receive no heparin, low-dose heparin, or moderate-dose heparin.

ASA was given in a loading dose of 300 mg. Patients who were given low-dose heparin received a loading dose of 5,000 IU followed by 500 IU/h for 6 hours. Patients who received moderate-dose heparin were given a loading dose of 5,000 IU followed by 1,250 IU/h for 6 hours.

The study’s primary outcome was Modified Rankin Scale (mRS) score at 90 days. Secondary outcomes were NIHSS score at 24 hours, NIHSS score at 5 to 7 days, and recanalization grade at 24 hours on CT angiography or MRI. The primary safety outcomes were sICH and death within 90 days.

An independent, unblinded data and safety monitoring board (DSMB) assessed the risk for the primary safety outcomes throughout the trial. The board performed interim analyses of safety and efficacy for every 300 patients.

After the fourth safety assessment, the DSMB recommended that enrollment in the moderate-dose heparin arm be discontinued for safety reasons. Enrollment in other arms continued.

After the second interim analysis, the DSMB advised that the trial steering committee be unblinded to decide whether to stop or continue the trial. The steering committee decided to stop the trial for reasons of safety.
 

Increased risk for sICH

In all, 628 patients were included in the study. The ASA groups included 310 patients, and the no-ASA groups included 318 patients. In all, 332 participants received heparin, and 296 received no heparin.

The demographic characteristics were well balanced between groups. The population’s median age was 73 years, and about 53% were men. The median baseline NIHSS score was approximately 15. About 74% of patients received IV thrombolysis. The median baseline Alberta Stroke Program Early CT Scan score was 9.

The investigators observed a slight shift toward worse outcome in the ASA group, compared with the no-ASA group (adjusted OR, 0.91). In addition, the ASA group had a significantly increased risk for sICH, compared with the no-ASA group (14% vs. 7.2%; aOR, 1.95).

Patients in the ASA group were less likely to have good functional outcome (mRS of 0 to 2; aOR, 0.76), and the mortality rate tended to be higher.

The researchers found a nonsignificant shift toward a worse functional outcome in the heparin group, compared with the no-heparin group (aOR, 0.81). The risk for sICH was significantly higher in the heparin group, compared with the no-heparin group (13% vs. 7.4%; aOR, 2.00).

Patients in the heparin group were also less likely to have a good functional outcome (aOR, 0.78), and there was a nonsignificant increase in risk for death among those patients.

The rate of sICH was 11% in the group that received low-dose heparin; it was 26% in the group that received moderate-dose heparin (aOR, 6.05). The mortality rate was 23% in the low-dose group and 47% in the moderate-dose group (aOR, 5.45).

There was no significant interaction between ASA and heparin on the primary outcome and on sICH occurrence.
 

‘A unique trial’

“MR CLEAN-MED is a unique trial because it investigated a widely used treatment but until now without any proof of effectiveness,” said Dr. van der Steen. The researchers expect that their findings will have a strong impact on the management of patients with acute ischemic stroke. They suggest that the administration of antithrombotic agents during EVT be avoided.

“We consider it probable that the increased risk of sICH explains at least a part of the nonsignificant shift towards a worse functional outcome,” co-investigator Bob Roozenbeek, MD, PhD, a neurologist at the Erasmus Medical Center, said in an interview. “However, to make more definite statements, we will have to do more in-depth analyses.”

It remains unclear whether the periprocedural use of lower dosages of antithrombotic agents or of a single bolus of heparin could be safe and effective, said Dr. van der Steen.

To gain insight into these questions, the investigators will evaluate the effect of the medications and dosages examined in this trial on primary hemostasis and coagulation activity in the trial population. They also plan to examine the effect of primary hemostasis and coagulation activity on risk for sICH and functional outcome.

Enhancing the effectiveness of thrombectomy for acute ischemic stroke continues to be an important goal for stroke therapy, said Mark Fisher, MD, professor of neurology and pathology and laboratory medicine at the University of California, Irvine, who commented on the findings for this news organization.

At least three strategies are available: The use of ancillary antithrombotic medications, neuroprotection, and modulation of the vasoconstrictive properties of the microcirculation.

“Results of MR CLEAN-MED argue against the antithrombotic strategy,” said Dr. Fisher. “The alternate strategies remain viable, and results of interventions using those approaches are awaited with great interest.”

The study was funded by the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative and the Brain Foundation Netherlands. Funding also was provided by Stryker, Medtronic, and Cerenovus. Dr. van der Steen and Dr. Fisher have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treatment with acetylsalicylic acid (ASA) or heparin is associated with an increased risk for symptomatic intracranial hemorrhage (sICH) in patients with ischemic stroke who are undergoing endovascular therapy (EVT), new data show.

In this population, ASA and heparin are each associated with an approximately doubled risk for sICH when administered during EVT.

“We did not find any evidence for a beneficial effect on functional outcome,” investigator Wouter van der Steen, MD, research physician and PhD student at Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization. The possibility that a positive effect would be observed if the trial were continued was considered negligible, he added.

The researchers stopped the trial for safety reasons and recommend avoiding the evaluated dosages of both medications during EVT for ischemic stroke, said Dr. van der Steen.

He presented the findings from the MR CLEAN-MED trial at the European Stroke Organisation Conference (ESOC) 2021, which was held online.
 

Trial stopped for safety

Previous research has supported the safety and efficacy of EVT for ischemic stroke. Still, more than 30% of patients do not recover, despite fast and complete recanalization. Incomplete microvascular reperfusion (IMR) could explain this incomplete recovery, the researchers note.

Microthrombi, which occlude distal vessels, and neutrophil extracellular traps can cause IMR. This problem can be reduced through treatment with ASA, which has an antithrombotic effect, or with heparin, which dissolves neutrophil extracellular traps, they add. Although these drugs are associated with good clinical outcomes, they entail an increased risk for sICH.

The investigators conducted the multicenter, randomized controlled MR CLEAN-MED trial to evaluate the effect of intravenous (IV) ASA and heparin, alone or in combination, during EVT for acute ischemic stroke. Treatment was open label, but outcome assessment was blinded. Eligible participants were adults with a National Institutes of Health Stroke Scale (NIHSS) score of greater than or equal to 2 and an anterior circulation large-vessel occlusion for whom EVT could be initiated in fewer than 6 hours.

Investigators randomly assigned patients to receive or not to receive ASA. Within each of these two treatment groups, patients were randomly assigned to receive no heparin, low-dose heparin, or moderate-dose heparin.

ASA was given in a loading dose of 300 mg. Patients who were given low-dose heparin received a loading dose of 5,000 IU followed by 500 IU/h for 6 hours. Patients who received moderate-dose heparin were given a loading dose of 5,000 IU followed by 1,250 IU/h for 6 hours.

The study’s primary outcome was Modified Rankin Scale (mRS) score at 90 days. Secondary outcomes were NIHSS score at 24 hours, NIHSS score at 5 to 7 days, and recanalization grade at 24 hours on CT angiography or MRI. The primary safety outcomes were sICH and death within 90 days.

An independent, unblinded data and safety monitoring board (DSMB) assessed the risk for the primary safety outcomes throughout the trial. The board performed interim analyses of safety and efficacy for every 300 patients.

After the fourth safety assessment, the DSMB recommended that enrollment in the moderate-dose heparin arm be discontinued for safety reasons. Enrollment in other arms continued.

After the second interim analysis, the DSMB advised that the trial steering committee be unblinded to decide whether to stop or continue the trial. The steering committee decided to stop the trial for reasons of safety.
 

Increased risk for sICH

In all, 628 patients were included in the study. The ASA groups included 310 patients, and the no-ASA groups included 318 patients. In all, 332 participants received heparin, and 296 received no heparin.

The demographic characteristics were well balanced between groups. The population’s median age was 73 years, and about 53% were men. The median baseline NIHSS score was approximately 15. About 74% of patients received IV thrombolysis. The median baseline Alberta Stroke Program Early CT Scan score was 9.

The investigators observed a slight shift toward worse outcome in the ASA group, compared with the no-ASA group (adjusted OR, 0.91). In addition, the ASA group had a significantly increased risk for sICH, compared with the no-ASA group (14% vs. 7.2%; aOR, 1.95).

Patients in the ASA group were less likely to have good functional outcome (mRS of 0 to 2; aOR, 0.76), and the mortality rate tended to be higher.

The researchers found a nonsignificant shift toward a worse functional outcome in the heparin group, compared with the no-heparin group (aOR, 0.81). The risk for sICH was significantly higher in the heparin group, compared with the no-heparin group (13% vs. 7.4%; aOR, 2.00).

Patients in the heparin group were also less likely to have a good functional outcome (aOR, 0.78), and there was a nonsignificant increase in risk for death among those patients.

The rate of sICH was 11% in the group that received low-dose heparin; it was 26% in the group that received moderate-dose heparin (aOR, 6.05). The mortality rate was 23% in the low-dose group and 47% in the moderate-dose group (aOR, 5.45).

There was no significant interaction between ASA and heparin on the primary outcome and on sICH occurrence.
 

‘A unique trial’

“MR CLEAN-MED is a unique trial because it investigated a widely used treatment but until now without any proof of effectiveness,” said Dr. van der Steen. The researchers expect that their findings will have a strong impact on the management of patients with acute ischemic stroke. They suggest that the administration of antithrombotic agents during EVT be avoided.

“We consider it probable that the increased risk of sICH explains at least a part of the nonsignificant shift towards a worse functional outcome,” co-investigator Bob Roozenbeek, MD, PhD, a neurologist at the Erasmus Medical Center, said in an interview. “However, to make more definite statements, we will have to do more in-depth analyses.”

It remains unclear whether the periprocedural use of lower dosages of antithrombotic agents or of a single bolus of heparin could be safe and effective, said Dr. van der Steen.

To gain insight into these questions, the investigators will evaluate the effect of the medications and dosages examined in this trial on primary hemostasis and coagulation activity in the trial population. They also plan to examine the effect of primary hemostasis and coagulation activity on risk for sICH and functional outcome.

Enhancing the effectiveness of thrombectomy for acute ischemic stroke continues to be an important goal for stroke therapy, said Mark Fisher, MD, professor of neurology and pathology and laboratory medicine at the University of California, Irvine, who commented on the findings for this news organization.

At least three strategies are available: The use of ancillary antithrombotic medications, neuroprotection, and modulation of the vasoconstrictive properties of the microcirculation.

“Results of MR CLEAN-MED argue against the antithrombotic strategy,” said Dr. Fisher. “The alternate strategies remain viable, and results of interventions using those approaches are awaited with great interest.”

The study was funded by the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative and the Brain Foundation Netherlands. Funding also was provided by Stryker, Medtronic, and Cerenovus. Dr. van der Steen and Dr. Fisher have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treatment with acetylsalicylic acid (ASA) or heparin is associated with an increased risk for symptomatic intracranial hemorrhage (sICH) in patients with ischemic stroke who are undergoing endovascular therapy (EVT), new data show.

In this population, ASA and heparin are each associated with an approximately doubled risk for sICH when administered during EVT.

“We did not find any evidence for a beneficial effect on functional outcome,” investigator Wouter van der Steen, MD, research physician and PhD student at Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization. The possibility that a positive effect would be observed if the trial were continued was considered negligible, he added.

The researchers stopped the trial for safety reasons and recommend avoiding the evaluated dosages of both medications during EVT for ischemic stroke, said Dr. van der Steen.

He presented the findings from the MR CLEAN-MED trial at the European Stroke Organisation Conference (ESOC) 2021, which was held online.
 

Trial stopped for safety

Previous research has supported the safety and efficacy of EVT for ischemic stroke. Still, more than 30% of patients do not recover, despite fast and complete recanalization. Incomplete microvascular reperfusion (IMR) could explain this incomplete recovery, the researchers note.

Microthrombi, which occlude distal vessels, and neutrophil extracellular traps can cause IMR. This problem can be reduced through treatment with ASA, which has an antithrombotic effect, or with heparin, which dissolves neutrophil extracellular traps, they add. Although these drugs are associated with good clinical outcomes, they entail an increased risk for sICH.

The investigators conducted the multicenter, randomized controlled MR CLEAN-MED trial to evaluate the effect of intravenous (IV) ASA and heparin, alone or in combination, during EVT for acute ischemic stroke. Treatment was open label, but outcome assessment was blinded. Eligible participants were adults with a National Institutes of Health Stroke Scale (NIHSS) score of greater than or equal to 2 and an anterior circulation large-vessel occlusion for whom EVT could be initiated in fewer than 6 hours.

Investigators randomly assigned patients to receive or not to receive ASA. Within each of these two treatment groups, patients were randomly assigned to receive no heparin, low-dose heparin, or moderate-dose heparin.

ASA was given in a loading dose of 300 mg. Patients who were given low-dose heparin received a loading dose of 5,000 IU followed by 500 IU/h for 6 hours. Patients who received moderate-dose heparin were given a loading dose of 5,000 IU followed by 1,250 IU/h for 6 hours.

The study’s primary outcome was Modified Rankin Scale (mRS) score at 90 days. Secondary outcomes were NIHSS score at 24 hours, NIHSS score at 5 to 7 days, and recanalization grade at 24 hours on CT angiography or MRI. The primary safety outcomes were sICH and death within 90 days.

An independent, unblinded data and safety monitoring board (DSMB) assessed the risk for the primary safety outcomes throughout the trial. The board performed interim analyses of safety and efficacy for every 300 patients.

After the fourth safety assessment, the DSMB recommended that enrollment in the moderate-dose heparin arm be discontinued for safety reasons. Enrollment in other arms continued.

After the second interim analysis, the DSMB advised that the trial steering committee be unblinded to decide whether to stop or continue the trial. The steering committee decided to stop the trial for reasons of safety.
 

Increased risk for sICH

In all, 628 patients were included in the study. The ASA groups included 310 patients, and the no-ASA groups included 318 patients. In all, 332 participants received heparin, and 296 received no heparin.

The demographic characteristics were well balanced between groups. The population’s median age was 73 years, and about 53% were men. The median baseline NIHSS score was approximately 15. About 74% of patients received IV thrombolysis. The median baseline Alberta Stroke Program Early CT Scan score was 9.

The investigators observed a slight shift toward worse outcome in the ASA group, compared with the no-ASA group (adjusted OR, 0.91). In addition, the ASA group had a significantly increased risk for sICH, compared with the no-ASA group (14% vs. 7.2%; aOR, 1.95).

Patients in the ASA group were less likely to have good functional outcome (mRS of 0 to 2; aOR, 0.76), and the mortality rate tended to be higher.

The researchers found a nonsignificant shift toward a worse functional outcome in the heparin group, compared with the no-heparin group (aOR, 0.81). The risk for sICH was significantly higher in the heparin group, compared with the no-heparin group (13% vs. 7.4%; aOR, 2.00).

Patients in the heparin group were also less likely to have a good functional outcome (aOR, 0.78), and there was a nonsignificant increase in risk for death among those patients.

The rate of sICH was 11% in the group that received low-dose heparin; it was 26% in the group that received moderate-dose heparin (aOR, 6.05). The mortality rate was 23% in the low-dose group and 47% in the moderate-dose group (aOR, 5.45).

There was no significant interaction between ASA and heparin on the primary outcome and on sICH occurrence.
 

‘A unique trial’

“MR CLEAN-MED is a unique trial because it investigated a widely used treatment but until now without any proof of effectiveness,” said Dr. van der Steen. The researchers expect that their findings will have a strong impact on the management of patients with acute ischemic stroke. They suggest that the administration of antithrombotic agents during EVT be avoided.

“We consider it probable that the increased risk of sICH explains at least a part of the nonsignificant shift towards a worse functional outcome,” co-investigator Bob Roozenbeek, MD, PhD, a neurologist at the Erasmus Medical Center, said in an interview. “However, to make more definite statements, we will have to do more in-depth analyses.”

It remains unclear whether the periprocedural use of lower dosages of antithrombotic agents or of a single bolus of heparin could be safe and effective, said Dr. van der Steen.

To gain insight into these questions, the investigators will evaluate the effect of the medications and dosages examined in this trial on primary hemostasis and coagulation activity in the trial population. They also plan to examine the effect of primary hemostasis and coagulation activity on risk for sICH and functional outcome.

Enhancing the effectiveness of thrombectomy for acute ischemic stroke continues to be an important goal for stroke therapy, said Mark Fisher, MD, professor of neurology and pathology and laboratory medicine at the University of California, Irvine, who commented on the findings for this news organization.

At least three strategies are available: The use of ancillary antithrombotic medications, neuroprotection, and modulation of the vasoconstrictive properties of the microcirculation.

“Results of MR CLEAN-MED argue against the antithrombotic strategy,” said Dr. Fisher. “The alternate strategies remain viable, and results of interventions using those approaches are awaited with great interest.”

The study was funded by the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative and the Brain Foundation Netherlands. Funding also was provided by Stryker, Medtronic, and Cerenovus. Dr. van der Steen and Dr. Fisher have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Moderna has released new data that it said support the argument for COVID-19 booster shots – specifically showing that people who received a first shot of their mRNA vaccine a median of 13 months ago are more likely to experience a breakthrough infection compared to individuals who received a first shot a median of 8 months ago.

Geber86/Getty Images

The findings come from the ongoing phase 3 COVE clinical trial, the results of which the Food and Drug Administration considered in granting emergency use authorization for the vaccine. In the initial stage of the trial, people were randomly assigned to receive the company’s mRNA vaccine or placebo.

Participants in COVE who were immunized more recently were 36% less likely to experience a breakthrough infection, according to the analysis of the open-label extension of the study during which placebo participants could cross over and get immunized as well.  

The updated COVE trial data show that 88 breakthrough cases of COVID-19 occurred among 11,431 participants vaccinated between December 2020 and March 2021 (49.0 cases per 1,000 person-years).

In contrast, there were 162 breakthrough cases among 14,746 people vaccinated between July and October 2020 (77.1 cases per 1,000 person-years).

The breakthrough infections include 19 severe cases. Although not statically different, there was a trend toward fewer severe cases among the more recently vaccinated, at a rate of 3.3 per 1,000 person-years, compared with 6.2 per 1,000 person-years in the group vaccinated in 2020

The findings were posted as a preprint to the medRxiv server and have not yet been peer reviewed.

“The increased risk of breakthrough infections in COVE study participants who were vaccinated last year compared to more recently illustrates the impact of waning immunity and supports the need for a booster to maintain high levels of protection,” Moderna CEO Stéphane Bancel said in a company statement.

An FDA advisory committee is meeting Sept. 17 to look at the available evidence on boosters to help the agency decide whether the additional shots are warranted.

There is still a lot of debate in the medical community about the need for boosters. U.S. physicians and nurses are divided about the need for them and about how the country should prioritize its vaccine supplies, according to a Medscape poll of more than 1,700 clinicians that collected responses from Aug. 25 to Sept. 6, 2020.

The research was funded by Moderna, and also supported by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, and by the National Institute of Allergy and Infectious Diseases.

A version of this article first appeared on Medscape.com.

Moderna has released new data that it said support the argument for COVID-19 booster shots – specifically showing that people who received a first shot of their mRNA vaccine a median of 13 months ago are more likely to experience a breakthrough infection compared to individuals who received a first shot a median of 8 months ago.

Geber86/Getty Images

The findings come from the ongoing phase 3 COVE clinical trial, the results of which the Food and Drug Administration considered in granting emergency use authorization for the vaccine. In the initial stage of the trial, people were randomly assigned to receive the company’s mRNA vaccine or placebo.

Participants in COVE who were immunized more recently were 36% less likely to experience a breakthrough infection, according to the analysis of the open-label extension of the study during which placebo participants could cross over and get immunized as well.  

The updated COVE trial data show that 88 breakthrough cases of COVID-19 occurred among 11,431 participants vaccinated between December 2020 and March 2021 (49.0 cases per 1,000 person-years).

In contrast, there were 162 breakthrough cases among 14,746 people vaccinated between July and October 2020 (77.1 cases per 1,000 person-years).

The breakthrough infections include 19 severe cases. Although not statically different, there was a trend toward fewer severe cases among the more recently vaccinated, at a rate of 3.3 per 1,000 person-years, compared with 6.2 per 1,000 person-years in the group vaccinated in 2020

The findings were posted as a preprint to the medRxiv server and have not yet been peer reviewed.

“The increased risk of breakthrough infections in COVE study participants who were vaccinated last year compared to more recently illustrates the impact of waning immunity and supports the need for a booster to maintain high levels of protection,” Moderna CEO Stéphane Bancel said in a company statement.

An FDA advisory committee is meeting Sept. 17 to look at the available evidence on boosters to help the agency decide whether the additional shots are warranted.

There is still a lot of debate in the medical community about the need for boosters. U.S. physicians and nurses are divided about the need for them and about how the country should prioritize its vaccine supplies, according to a Medscape poll of more than 1,700 clinicians that collected responses from Aug. 25 to Sept. 6, 2020.

The research was funded by Moderna, and also supported by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, and by the National Institute of Allergy and Infectious Diseases.

A version of this article first appeared on Medscape.com.

Moderna has released new data that it said support the argument for COVID-19 booster shots – specifically showing that people who received a first shot of their mRNA vaccine a median of 13 months ago are more likely to experience a breakthrough infection compared to individuals who received a first shot a median of 8 months ago.

Geber86/Getty Images

The findings come from the ongoing phase 3 COVE clinical trial, the results of which the Food and Drug Administration considered in granting emergency use authorization for the vaccine. In the initial stage of the trial, people were randomly assigned to receive the company’s mRNA vaccine or placebo.

Participants in COVE who were immunized more recently were 36% less likely to experience a breakthrough infection, according to the analysis of the open-label extension of the study during which placebo participants could cross over and get immunized as well.  

The updated COVE trial data show that 88 breakthrough cases of COVID-19 occurred among 11,431 participants vaccinated between December 2020 and March 2021 (49.0 cases per 1,000 person-years).

In contrast, there were 162 breakthrough cases among 14,746 people vaccinated between July and October 2020 (77.1 cases per 1,000 person-years).

The breakthrough infections include 19 severe cases. Although not statically different, there was a trend toward fewer severe cases among the more recently vaccinated, at a rate of 3.3 per 1,000 person-years, compared with 6.2 per 1,000 person-years in the group vaccinated in 2020

The findings were posted as a preprint to the medRxiv server and have not yet been peer reviewed.

“The increased risk of breakthrough infections in COVE study participants who were vaccinated last year compared to more recently illustrates the impact of waning immunity and supports the need for a booster to maintain high levels of protection,” Moderna CEO Stéphane Bancel said in a company statement.

An FDA advisory committee is meeting Sept. 17 to look at the available evidence on boosters to help the agency decide whether the additional shots are warranted.

There is still a lot of debate in the medical community about the need for boosters. U.S. physicians and nurses are divided about the need for them and about how the country should prioritize its vaccine supplies, according to a Medscape poll of more than 1,700 clinicians that collected responses from Aug. 25 to Sept. 6, 2020.

The research was funded by Moderna, and also supported by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, and by the National Institute of Allergy and Infectious Diseases.

A version of this article first appeared on Medscape.com.

Objectivity is tough, but essential: a critical part of patient care, allowing you to make appropriate decisions based on facts and circumstances, not emotions. We’re supposed to be compassionate Vulcans – able to logically weigh possibilities and treatment options under pressure, and at the same time exhibit empathy and sensitivity.

For the most part, all of us become very good at this juggling act. But we’re only human, and once the ability to do that with a given person is lost, it’s gone for good.

Have you ever lost objectivity with a patient? I have. Generally it involves the patient being so difficult, unpleasant, or dislikable that it exceeds my ability to remain impartial and pragmatic in their care.

I don’t know any physician it hasn’t happened to. And when it does, ending the doctor-patient relationship is the only effective answer.

It’s never easy sending that letter, telling someone that they need to seek care elsewhere, and often the specific reason is harder to define. In patients who are overtly rude or noncompliant it’s easy. But often a loss in objectivity is from something less tangible, such as the vagaries of personal chemistry.

I try to get along with all my patients. I really do. That’s part of the job. But sometimes, for whatever reason, it’s just an impossible task. Too many conflicts and differences of opinion over treatments, tests, diagnosis, what they read on Facebook … whatever. When these differences reach a point where they’re an impediment to good patient care … it’s time for both of us to move on.

Regardless of cause, professionalism requires that it be the end of the road. If I can’t objectively weigh a patient’s symptoms and treatment options, then I’m not going to be able to do my very best for them. And my very best is what every patient deserves.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Objectivity is tough, but essential: a critical part of patient care, allowing you to make appropriate decisions based on facts and circumstances, not emotions. We’re supposed to be compassionate Vulcans – able to logically weigh possibilities and treatment options under pressure, and at the same time exhibit empathy and sensitivity.

For the most part, all of us become very good at this juggling act. But we’re only human, and once the ability to do that with a given person is lost, it’s gone for good.

Have you ever lost objectivity with a patient? I have. Generally it involves the patient being so difficult, unpleasant, or dislikable that it exceeds my ability to remain impartial and pragmatic in their care.

I don’t know any physician it hasn’t happened to. And when it does, ending the doctor-patient relationship is the only effective answer.

It’s never easy sending that letter, telling someone that they need to seek care elsewhere, and often the specific reason is harder to define. In patients who are overtly rude or noncompliant it’s easy. But often a loss in objectivity is from something less tangible, such as the vagaries of personal chemistry.

I try to get along with all my patients. I really do. That’s part of the job. But sometimes, for whatever reason, it’s just an impossible task. Too many conflicts and differences of opinion over treatments, tests, diagnosis, what they read on Facebook … whatever. When these differences reach a point where they’re an impediment to good patient care … it’s time for both of us to move on.

Regardless of cause, professionalism requires that it be the end of the road. If I can’t objectively weigh a patient’s symptoms and treatment options, then I’m not going to be able to do my very best for them. And my very best is what every patient deserves.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Objectivity is tough, but essential: a critical part of patient care, allowing you to make appropriate decisions based on facts and circumstances, not emotions. We’re supposed to be compassionate Vulcans – able to logically weigh possibilities and treatment options under pressure, and at the same time exhibit empathy and sensitivity.

For the most part, all of us become very good at this juggling act. But we’re only human, and once the ability to do that with a given person is lost, it’s gone for good.

Have you ever lost objectivity with a patient? I have. Generally it involves the patient being so difficult, unpleasant, or dislikable that it exceeds my ability to remain impartial and pragmatic in their care.

I don’t know any physician it hasn’t happened to. And when it does, ending the doctor-patient relationship is the only effective answer.

It’s never easy sending that letter, telling someone that they need to seek care elsewhere, and often the specific reason is harder to define. In patients who are overtly rude or noncompliant it’s easy. But often a loss in objectivity is from something less tangible, such as the vagaries of personal chemistry.

I try to get along with all my patients. I really do. That’s part of the job. But sometimes, for whatever reason, it’s just an impossible task. Too many conflicts and differences of opinion over treatments, tests, diagnosis, what they read on Facebook … whatever. When these differences reach a point where they’re an impediment to good patient care … it’s time for both of us to move on.

Regardless of cause, professionalism requires that it be the end of the road. If I can’t objectively weigh a patient’s symptoms and treatment options, then I’m not going to be able to do my very best for them. And my very best is what every patient deserves.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.