NEW ORLEANS – Nearly half of all children with autism spectrum disorder wander off from safe supervision at some point in their childhood or adolescence, reported Paul Lipkin, MD, at the annual meeting of the American Academy of Pediatrics.

Though such behavior is developmentally normal in toddlers, it’s rarer for older children to leave a supervised, safe space for a longer period than just running away for a bit, he said.

Far more than an inconvenience, wandering, also called elopement, puts these children at high risk for injury or victimization. In fact, statistics from a survey by the National Autism Foundation suggest that nearly a third of autism-related wandering cases resulted in death or serious enough injury to require medical attention, said Dr. Lipkin, an associate professor of pediatrics at the Kennedy Krieger Institute and Johns Hopkins Medicine in Baltimore.

“Drowning is overwhelmingly the main cause of death in children with autism,” he said, sharing the data from National Autism Association, which relied on parent report and media reports. In that data, 71% of deaths from autistic children who wandered from 2011-2016 were drowning, and of those deaths, 76% of the drownings occurred in a natural body of water or drainage water. At a distant second, 18% of deaths were traffic accidents. The remaining causes were being hit by a train (4%), hypothermia or hyperthermia (3%), falling (1%) or other trauma (3%) (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Academic research has found similar statistics to those from the National Autism Association. In one study, 53% of autistic youth who attempted to run off succeeded and were missing long enough to cause safety concerns (Pediatrics. 2012 Nov;130[5]:870-7). Among these youth – representing about a quarter of all families surveyed in the study – the police were called in 31% of cases. In addition, 65% had a “close call” with a traffic injury and 24% had a close call with drowning.

The children wandered off in various settings, including home; another’s home; a store or other public place; or school, daycare or camp. A 2019 study found that 70% of parents reported their children wandering off from home at least once in the past 2 years (J Autism Dev Disorders. 2019 Mar 5; doi: 10.1107/s10803-019-03961-x).

Although most cases occur in children and teens, with the highest rate of death among children aged 5-9, the National Autism Association has received reports of wandering occur throughout autistic people’s lifetime.

Yet this issue doesn’t appear to be on the radar of many pediatricians, and those who are aware of it may not know the best strategies to share with parents to prevent wandering and subsequent injury, Dr Lipkin explained. In one study, only one-third of parents reported receiving guidance from a health provider related to wandering (J Dev Behav Pediatr. 2018 Sep;39[7]:538-46).

That research found that only 10% received advice from a pediatrician or other primary care provider, 12% received advice from a developmental pediatrician or neurologist and 10% received advance from a psychologist or psychiatrist. The largest source of guidance in that study was autism advocacy organizations, whom 22% of parents cited. Others included a teacher or other school staff member (15%), a personal contact (13%), law enforcement (8%) or another source (1%).
 

Role of the pediatrician

Pediatricians have an important role to play in prevention of elopement, Dr Lipkin said. They can screen autistic patients for wandering and elopement during visits, work with community stakeholders such as schools and law enforcement, advocate for awareness, and provider education and resources for families.

Perhaps the most valuable resource, he said, is the Big Red Safety Box, available from the National Autism Association. This resource, sponsored by more than a half dozen autism advocacy organizations, includes three digital safety toolkits: one for caregivers, one for first responders, and one for teachers. Parents can therefore share the toolkits for first responders and teachers with those respective community members.

Pediatricians can also help families develop a Family Wandering Emergency Plan (FWEP), a template for which is in the Big Red Safety Box. Parents and community members should know the steps to take if someone wanders: Stay calm, call 911, search nearby water first and then implement the FWEP.

It’s first helpful to understand why these youth wander off. In the National Autism Association survey, the most common reasons were to escape an anxious situation, particularly for those with Asperger’s, or simply to run, explore, or go to a favorite place, particularly among those with autism or pervasive developmental disorder-not otherwise specified (PDD-NOS).

Researchers have found similar reasons: 43% of elopement situations occurred when children were trying to escape an anxious situation, 39% left while in a stressful environment, and 24% were in an environment with conflict, found one study (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Sensory overload was also a trigger, with 38% of elopements occurring when it was too noisy, and 34% when it was a generally uncomfortable sensory experience. Just over a quarter (27%) of children left when they were understimulated or in a “boring” environment, Dr Lipkin reported. The remaining reason was goal-directed: 27% left to pursue a special interest, 18% sought a place where they enjoyed playing, and 11% were after their favorite food.
 

Prevention Strategies

Most data about effective strategies to prevent wandering comes from research that relies on parents, Dr Lipkin said. In general, environmental interventions tend to be the most effective, and medication tends to be the least effective.

One study on elopement prevention found that 96% of caregivers use at least some type of intervention, and the vast majority (83%) were using environmental interventions such as dead bolts (51%), latches (49%) and gates (36%). An equal proportion used behavioral services (83%), such as a behavioral psychologist (41%), social stories (40%) or an aide (39%). Just under a third used an ID bracelet or shoe tag (31%), and 19% used GPS trackers, according to Dr. Lipkin.

Although parents reported environmental interventions to be very effective, 68% said they were highly burdensome, though the median cost over 2 years was less than $1,000. The least expensive intervention was home behavioral specialists (when covered by insurance) and school aides, and the most expensive and burdensome – albeit highly effective – was a service animal.

Interventions with the least cost effectiveness included security cameras and GPS trackers, which only 15% of parents reported as being effective.

Although nearly half of parents reported their child had taken any psychiatric medication (48%), only 16% had taken medication explicitly to prevent wandering. Few reported the medication was very effective, however. Among the small number who did (less than 10), lorazepam, diazepam and atomoxetine appeared best.

Teaching children survival skills, as developmentally appropriate and possible, can also help. These include swimming lessons as well as learning how to interact in traffic, knowing their home address, and learning how to navigate around their neighborhood.

Dr. Lipkin no disclosures and used no external funding for this presentation.

NEW ORLEANS – Nearly half of all children with autism spectrum disorder wander off from safe supervision at some point in their childhood or adolescence, reported Paul Lipkin, MD, at the annual meeting of the American Academy of Pediatrics.

Though such behavior is developmentally normal in toddlers, it’s rarer for older children to leave a supervised, safe space for a longer period than just running away for a bit, he said.

Far more than an inconvenience, wandering, also called elopement, puts these children at high risk for injury or victimization. In fact, statistics from a survey by the National Autism Foundation suggest that nearly a third of autism-related wandering cases resulted in death or serious enough injury to require medical attention, said Dr. Lipkin, an associate professor of pediatrics at the Kennedy Krieger Institute and Johns Hopkins Medicine in Baltimore.

“Drowning is overwhelmingly the main cause of death in children with autism,” he said, sharing the data from National Autism Association, which relied on parent report and media reports. In that data, 71% of deaths from autistic children who wandered from 2011-2016 were drowning, and of those deaths, 76% of the drownings occurred in a natural body of water or drainage water. At a distant second, 18% of deaths were traffic accidents. The remaining causes were being hit by a train (4%), hypothermia or hyperthermia (3%), falling (1%) or other trauma (3%) (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Academic research has found similar statistics to those from the National Autism Association. In one study, 53% of autistic youth who attempted to run off succeeded and were missing long enough to cause safety concerns (Pediatrics. 2012 Nov;130[5]:870-7). Among these youth – representing about a quarter of all families surveyed in the study – the police were called in 31% of cases. In addition, 65% had a “close call” with a traffic injury and 24% had a close call with drowning.

The children wandered off in various settings, including home; another’s home; a store or other public place; or school, daycare or camp. A 2019 study found that 70% of parents reported their children wandering off from home at least once in the past 2 years (J Autism Dev Disorders. 2019 Mar 5; doi: 10.1107/s10803-019-03961-x).

Although most cases occur in children and teens, with the highest rate of death among children aged 5-9, the National Autism Association has received reports of wandering occur throughout autistic people’s lifetime.

Yet this issue doesn’t appear to be on the radar of many pediatricians, and those who are aware of it may not know the best strategies to share with parents to prevent wandering and subsequent injury, Dr Lipkin explained. In one study, only one-third of parents reported receiving guidance from a health provider related to wandering (J Dev Behav Pediatr. 2018 Sep;39[7]:538-46).

That research found that only 10% received advice from a pediatrician or other primary care provider, 12% received advice from a developmental pediatrician or neurologist and 10% received advance from a psychologist or psychiatrist. The largest source of guidance in that study was autism advocacy organizations, whom 22% of parents cited. Others included a teacher or other school staff member (15%), a personal contact (13%), law enforcement (8%) or another source (1%).
 

Role of the pediatrician

Pediatricians have an important role to play in prevention of elopement, Dr Lipkin said. They can screen autistic patients for wandering and elopement during visits, work with community stakeholders such as schools and law enforcement, advocate for awareness, and provider education and resources for families.

Perhaps the most valuable resource, he said, is the Big Red Safety Box, available from the National Autism Association. This resource, sponsored by more than a half dozen autism advocacy organizations, includes three digital safety toolkits: one for caregivers, one for first responders, and one for teachers. Parents can therefore share the toolkits for first responders and teachers with those respective community members.

Pediatricians can also help families develop a Family Wandering Emergency Plan (FWEP), a template for which is in the Big Red Safety Box. Parents and community members should know the steps to take if someone wanders: Stay calm, call 911, search nearby water first and then implement the FWEP.

It’s first helpful to understand why these youth wander off. In the National Autism Association survey, the most common reasons were to escape an anxious situation, particularly for those with Asperger’s, or simply to run, explore, or go to a favorite place, particularly among those with autism or pervasive developmental disorder-not otherwise specified (PDD-NOS).

Researchers have found similar reasons: 43% of elopement situations occurred when children were trying to escape an anxious situation, 39% left while in a stressful environment, and 24% were in an environment with conflict, found one study (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Sensory overload was also a trigger, with 38% of elopements occurring when it was too noisy, and 34% when it was a generally uncomfortable sensory experience. Just over a quarter (27%) of children left when they were understimulated or in a “boring” environment, Dr Lipkin reported. The remaining reason was goal-directed: 27% left to pursue a special interest, 18% sought a place where they enjoyed playing, and 11% were after their favorite food.
 

Prevention Strategies

Most data about effective strategies to prevent wandering comes from research that relies on parents, Dr Lipkin said. In general, environmental interventions tend to be the most effective, and medication tends to be the least effective.

One study on elopement prevention found that 96% of caregivers use at least some type of intervention, and the vast majority (83%) were using environmental interventions such as dead bolts (51%), latches (49%) and gates (36%). An equal proportion used behavioral services (83%), such as a behavioral psychologist (41%), social stories (40%) or an aide (39%). Just under a third used an ID bracelet or shoe tag (31%), and 19% used GPS trackers, according to Dr. Lipkin.

Although parents reported environmental interventions to be very effective, 68% said they were highly burdensome, though the median cost over 2 years was less than $1,000. The least expensive intervention was home behavioral specialists (when covered by insurance) and school aides, and the most expensive and burdensome – albeit highly effective – was a service animal.

Interventions with the least cost effectiveness included security cameras and GPS trackers, which only 15% of parents reported as being effective.

Although nearly half of parents reported their child had taken any psychiatric medication (48%), only 16% had taken medication explicitly to prevent wandering. Few reported the medication was very effective, however. Among the small number who did (less than 10), lorazepam, diazepam and atomoxetine appeared best.

Teaching children survival skills, as developmentally appropriate and possible, can also help. These include swimming lessons as well as learning how to interact in traffic, knowing their home address, and learning how to navigate around their neighborhood.

Dr. Lipkin no disclosures and used no external funding for this presentation.

NEW ORLEANS – Nearly half of all children with autism spectrum disorder wander off from safe supervision at some point in their childhood or adolescence, reported Paul Lipkin, MD, at the annual meeting of the American Academy of Pediatrics.

Though such behavior is developmentally normal in toddlers, it’s rarer for older children to leave a supervised, safe space for a longer period than just running away for a bit, he said.

Far more than an inconvenience, wandering, also called elopement, puts these children at high risk for injury or victimization. In fact, statistics from a survey by the National Autism Foundation suggest that nearly a third of autism-related wandering cases resulted in death or serious enough injury to require medical attention, said Dr. Lipkin, an associate professor of pediatrics at the Kennedy Krieger Institute and Johns Hopkins Medicine in Baltimore.

“Drowning is overwhelmingly the main cause of death in children with autism,” he said, sharing the data from National Autism Association, which relied on parent report and media reports. In that data, 71% of deaths from autistic children who wandered from 2011-2016 were drowning, and of those deaths, 76% of the drownings occurred in a natural body of water or drainage water. At a distant second, 18% of deaths were traffic accidents. The remaining causes were being hit by a train (4%), hypothermia or hyperthermia (3%), falling (1%) or other trauma (3%) (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Academic research has found similar statistics to those from the National Autism Association. In one study, 53% of autistic youth who attempted to run off succeeded and were missing long enough to cause safety concerns (Pediatrics. 2012 Nov;130[5]:870-7). Among these youth – representing about a quarter of all families surveyed in the study – the police were called in 31% of cases. In addition, 65% had a “close call” with a traffic injury and 24% had a close call with drowning.

The children wandered off in various settings, including home; another’s home; a store or other public place; or school, daycare or camp. A 2019 study found that 70% of parents reported their children wandering off from home at least once in the past 2 years (J Autism Dev Disorders. 2019 Mar 5; doi: 10.1107/s10803-019-03961-x).

Although most cases occur in children and teens, with the highest rate of death among children aged 5-9, the National Autism Association has received reports of wandering occur throughout autistic people’s lifetime.

Yet this issue doesn’t appear to be on the radar of many pediatricians, and those who are aware of it may not know the best strategies to share with parents to prevent wandering and subsequent injury, Dr Lipkin explained. In one study, only one-third of parents reported receiving guidance from a health provider related to wandering (J Dev Behav Pediatr. 2018 Sep;39[7]:538-46).

That research found that only 10% received advice from a pediatrician or other primary care provider, 12% received advice from a developmental pediatrician or neurologist and 10% received advance from a psychologist or psychiatrist. The largest source of guidance in that study was autism advocacy organizations, whom 22% of parents cited. Others included a teacher or other school staff member (15%), a personal contact (13%), law enforcement (8%) or another source (1%).
 

Role of the pediatrician

Pediatricians have an important role to play in prevention of elopement, Dr Lipkin said. They can screen autistic patients for wandering and elopement during visits, work with community stakeholders such as schools and law enforcement, advocate for awareness, and provider education and resources for families.

Perhaps the most valuable resource, he said, is the Big Red Safety Box, available from the National Autism Association. This resource, sponsored by more than a half dozen autism advocacy organizations, includes three digital safety toolkits: one for caregivers, one for first responders, and one for teachers. Parents can therefore share the toolkits for first responders and teachers with those respective community members.

Pediatricians can also help families develop a Family Wandering Emergency Plan (FWEP), a template for which is in the Big Red Safety Box. Parents and community members should know the steps to take if someone wanders: Stay calm, call 911, search nearby water first and then implement the FWEP.

It’s first helpful to understand why these youth wander off. In the National Autism Association survey, the most common reasons were to escape an anxious situation, particularly for those with Asperger’s, or simply to run, explore, or go to a favorite place, particularly among those with autism or pervasive developmental disorder-not otherwise specified (PDD-NOS).

Researchers have found similar reasons: 43% of elopement situations occurred when children were trying to escape an anxious situation, 39% left while in a stressful environment, and 24% were in an environment with conflict, found one study (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Sensory overload was also a trigger, with 38% of elopements occurring when it was too noisy, and 34% when it was a generally uncomfortable sensory experience. Just over a quarter (27%) of children left when they were understimulated or in a “boring” environment, Dr Lipkin reported. The remaining reason was goal-directed: 27% left to pursue a special interest, 18% sought a place where they enjoyed playing, and 11% were after their favorite food.
 

Prevention Strategies

Most data about effective strategies to prevent wandering comes from research that relies on parents, Dr Lipkin said. In general, environmental interventions tend to be the most effective, and medication tends to be the least effective.

One study on elopement prevention found that 96% of caregivers use at least some type of intervention, and the vast majority (83%) were using environmental interventions such as dead bolts (51%), latches (49%) and gates (36%). An equal proportion used behavioral services (83%), such as a behavioral psychologist (41%), social stories (40%) or an aide (39%). Just under a third used an ID bracelet or shoe tag (31%), and 19% used GPS trackers, according to Dr. Lipkin.

Although parents reported environmental interventions to be very effective, 68% said they were highly burdensome, though the median cost over 2 years was less than $1,000. The least expensive intervention was home behavioral specialists (when covered by insurance) and school aides, and the most expensive and burdensome – albeit highly effective – was a service animal.

Interventions with the least cost effectiveness included security cameras and GPS trackers, which only 15% of parents reported as being effective.

Although nearly half of parents reported their child had taken any psychiatric medication (48%), only 16% had taken medication explicitly to prevent wandering. Few reported the medication was very effective, however. Among the small number who did (less than 10), lorazepam, diazepam and atomoxetine appeared best.

Teaching children survival skills, as developmentally appropriate and possible, can also help. These include swimming lessons as well as learning how to interact in traffic, knowing their home address, and learning how to navigate around their neighborhood.

Dr. Lipkin no disclosures and used no external funding for this presentation.

Emicizumab (Hemlibra) is well tolerated and has substantial, clinically meaningful efficacy in pediatric patients with hemophilia A and factor VIII inhibitors, according to an analysis of data from the HAVEN 2 trial in this bispecific humanized monoclonal antibody.

Among those receiving once-weekly emicizumab prophylaxis, 77% had no treated bleeding events and 100% of evaluable target joints resolved in the HAVEN 2 study, which investigators say is the largest prospective study so far of bleed prevention in pediatric patients with hemophilia A and inhibitors.

Moreover, emicizumab resulted in a 99% reduction in bleeding rate versus previous bypassing agent prophylaxis, subsequent, according to an intraindividual comparison described in the report.

Based on these results, emicizumab stands to become the “next-generation standard of care” for pediatric patients with hemophilia A and factor VIII inhibitors, reported Guy Young, MD, of Children’s Hospital Los Angeles and University of Southern California Keck School of Medicine, and his coinvestigators.

“Despite a rapidly evolving treatment landscape in hemophilia, children have been largely excluded from recent trials of novel agents,” they said in the report, which appears in the journal Blood.

Before emicizumab, current treatment options for pediatric patients with factor VIII inhibitors were limited to immune tolerance induction, or use of bypassing agents with efficacy that “can be suboptimal and unpredictable,” said Dr. Young and colleagues.

“More effective prophylactic options with reduced treatment burden are needed,” they said.

Emicizumab works in hemophilia A by bridging activated factor IX and factor X, restoring the function of missing factor VIIIa, according to the report.

A total of 88 male pediatric patients with congenital hemophilia A were enrolled in HAVEN 2, an ongoing phase 3 multicenter study that is nonrandomized and open label. The median age of patients was 7 years (range, 1-15 years). Most participants (97%) had severe hemophilia A, 72% had previously undergone immune tolerance induction, and 75% were receiving treatment with prophylactic bypassing agents.

Most participants received 4 once-weekly loading doses of 3 mg/kg body weight of emicizumab subcutaneously, followed by a maintenance regimen of 1.5 mg/kg weekly.

The annualized bleed rate was 0.3, with 77% of participants having zero bleeding events, for the 65 participants in the trial who were under 12 and received emicizumab 1.5 mg/kg weekly, according to the report.

In the subset of those patients with target joints, the mean annualized bleed rate was 3.3 for the first 24 weeks, and 0 for the next 24 weeks; these findings suggest that bleed rates decrease over time with continuing emicizumab treatment “even in patients with a more severe phenotype,” the investigators wrote.

For 15 patients younger than 12 years of age receiving bypassing agent prophylaxis, emicizumab 1.5 mg/kg once weekly resulted in an annualized bleed rate of 0.3, compared to 21.1 for the prior bypassing agent, which translates into a 99% reduction in bleeding risk, according to investigators.

Annualized bleed rates for patients receiving emicizumab 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks were 0.2 and 2.2, respectively; hover, the numerically higher annualized bleed rate in the 6 mg/kg every-4-weeks group was based on 2 out of the 10 patients treated with that maintenance regimen, including one who had 6 target joint bleeds in the 24 weeks before enrolling in the study, and another who developed antidrug antibodies within the first 8 weeks of emicizumab treatment.

Out of 23 patients who had target joints and received emicizumab prophylaxis for at least 52 weeks, 100% (45 of 45) target joints resolved, according to the report.

“Notably, this is the first report of a treatment resolving target joints in an inhibitor population, which until now has only been reported when using factor VIII products in patients without inhibitors,” Dr. Young and colleagues said.

The most common of the 721 adverse events reported in HAVEN 2 were nasopharyngitis and injection-site reactions. Of 21 serious adverse events, only 1 (antidrug antibodies with neutralizing potential) was thought by investigators to be related to emicizumab.

The Food and Drug Administration (FDA) initially approved emicizumab in November 2017 on the basis of the HAVEN 2 pediatric trial, and on HAVEN 1, a randomized, multicenter, open-label, phase 3 trial including 109 adult and adolescent males with hemophilia A and FVIII inhibitors. The indication for emicizumab was expanded to include patients without inhibitors in October 2018, on the basis of the HAVEN 3 and HAVEN 4 randomized phase 3 trials.

Dr. Young reported disclosures related to Alnylam, Bayer, Bioverativ, CSL Behring, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Shire, Spark, and uniQure.

SOURCE: Young G, et al. Blood. 2019 Oct 10. doi: 10.1182/blood.2019001869.

Emicizumab (Hemlibra) is well tolerated and has substantial, clinically meaningful efficacy in pediatric patients with hemophilia A and factor VIII inhibitors, according to an analysis of data from the HAVEN 2 trial in this bispecific humanized monoclonal antibody.

Among those receiving once-weekly emicizumab prophylaxis, 77% had no treated bleeding events and 100% of evaluable target joints resolved in the HAVEN 2 study, which investigators say is the largest prospective study so far of bleed prevention in pediatric patients with hemophilia A and inhibitors.

Moreover, emicizumab resulted in a 99% reduction in bleeding rate versus previous bypassing agent prophylaxis, subsequent, according to an intraindividual comparison described in the report.

Based on these results, emicizumab stands to become the “next-generation standard of care” for pediatric patients with hemophilia A and factor VIII inhibitors, reported Guy Young, MD, of Children’s Hospital Los Angeles and University of Southern California Keck School of Medicine, and his coinvestigators.

“Despite a rapidly evolving treatment landscape in hemophilia, children have been largely excluded from recent trials of novel agents,” they said in the report, which appears in the journal Blood.

Before emicizumab, current treatment options for pediatric patients with factor VIII inhibitors were limited to immune tolerance induction, or use of bypassing agents with efficacy that “can be suboptimal and unpredictable,” said Dr. Young and colleagues.

“More effective prophylactic options with reduced treatment burden are needed,” they said.

Emicizumab works in hemophilia A by bridging activated factor IX and factor X, restoring the function of missing factor VIIIa, according to the report.

A total of 88 male pediatric patients with congenital hemophilia A were enrolled in HAVEN 2, an ongoing phase 3 multicenter study that is nonrandomized and open label. The median age of patients was 7 years (range, 1-15 years). Most participants (97%) had severe hemophilia A, 72% had previously undergone immune tolerance induction, and 75% were receiving treatment with prophylactic bypassing agents.

Most participants received 4 once-weekly loading doses of 3 mg/kg body weight of emicizumab subcutaneously, followed by a maintenance regimen of 1.5 mg/kg weekly.

The annualized bleed rate was 0.3, with 77% of participants having zero bleeding events, for the 65 participants in the trial who were under 12 and received emicizumab 1.5 mg/kg weekly, according to the report.

In the subset of those patients with target joints, the mean annualized bleed rate was 3.3 for the first 24 weeks, and 0 for the next 24 weeks; these findings suggest that bleed rates decrease over time with continuing emicizumab treatment “even in patients with a more severe phenotype,” the investigators wrote.

For 15 patients younger than 12 years of age receiving bypassing agent prophylaxis, emicizumab 1.5 mg/kg once weekly resulted in an annualized bleed rate of 0.3, compared to 21.1 for the prior bypassing agent, which translates into a 99% reduction in bleeding risk, according to investigators.

Annualized bleed rates for patients receiving emicizumab 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks were 0.2 and 2.2, respectively; hover, the numerically higher annualized bleed rate in the 6 mg/kg every-4-weeks group was based on 2 out of the 10 patients treated with that maintenance regimen, including one who had 6 target joint bleeds in the 24 weeks before enrolling in the study, and another who developed antidrug antibodies within the first 8 weeks of emicizumab treatment.

Out of 23 patients who had target joints and received emicizumab prophylaxis for at least 52 weeks, 100% (45 of 45) target joints resolved, according to the report.

“Notably, this is the first report of a treatment resolving target joints in an inhibitor population, which until now has only been reported when using factor VIII products in patients without inhibitors,” Dr. Young and colleagues said.

The most common of the 721 adverse events reported in HAVEN 2 were nasopharyngitis and injection-site reactions. Of 21 serious adverse events, only 1 (antidrug antibodies with neutralizing potential) was thought by investigators to be related to emicizumab.

The Food and Drug Administration (FDA) initially approved emicizumab in November 2017 on the basis of the HAVEN 2 pediatric trial, and on HAVEN 1, a randomized, multicenter, open-label, phase 3 trial including 109 adult and adolescent males with hemophilia A and FVIII inhibitors. The indication for emicizumab was expanded to include patients without inhibitors in October 2018, on the basis of the HAVEN 3 and HAVEN 4 randomized phase 3 trials.

Dr. Young reported disclosures related to Alnylam, Bayer, Bioverativ, CSL Behring, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Shire, Spark, and uniQure.

SOURCE: Young G, et al. Blood. 2019 Oct 10. doi: 10.1182/blood.2019001869.

Emicizumab (Hemlibra) is well tolerated and has substantial, clinically meaningful efficacy in pediatric patients with hemophilia A and factor VIII inhibitors, according to an analysis of data from the HAVEN 2 trial in this bispecific humanized monoclonal antibody.

Among those receiving once-weekly emicizumab prophylaxis, 77% had no treated bleeding events and 100% of evaluable target joints resolved in the HAVEN 2 study, which investigators say is the largest prospective study so far of bleed prevention in pediatric patients with hemophilia A and inhibitors.

Moreover, emicizumab resulted in a 99% reduction in bleeding rate versus previous bypassing agent prophylaxis, subsequent, according to an intraindividual comparison described in the report.

Based on these results, emicizumab stands to become the “next-generation standard of care” for pediatric patients with hemophilia A and factor VIII inhibitors, reported Guy Young, MD, of Children’s Hospital Los Angeles and University of Southern California Keck School of Medicine, and his coinvestigators.

“Despite a rapidly evolving treatment landscape in hemophilia, children have been largely excluded from recent trials of novel agents,” they said in the report, which appears in the journal Blood.

Before emicizumab, current treatment options for pediatric patients with factor VIII inhibitors were limited to immune tolerance induction, or use of bypassing agents with efficacy that “can be suboptimal and unpredictable,” said Dr. Young and colleagues.

“More effective prophylactic options with reduced treatment burden are needed,” they said.

Emicizumab works in hemophilia A by bridging activated factor IX and factor X, restoring the function of missing factor VIIIa, according to the report.

A total of 88 male pediatric patients with congenital hemophilia A were enrolled in HAVEN 2, an ongoing phase 3 multicenter study that is nonrandomized and open label. The median age of patients was 7 years (range, 1-15 years). Most participants (97%) had severe hemophilia A, 72% had previously undergone immune tolerance induction, and 75% were receiving treatment with prophylactic bypassing agents.

Most participants received 4 once-weekly loading doses of 3 mg/kg body weight of emicizumab subcutaneously, followed by a maintenance regimen of 1.5 mg/kg weekly.

The annualized bleed rate was 0.3, with 77% of participants having zero bleeding events, for the 65 participants in the trial who were under 12 and received emicizumab 1.5 mg/kg weekly, according to the report.

In the subset of those patients with target joints, the mean annualized bleed rate was 3.3 for the first 24 weeks, and 0 for the next 24 weeks; these findings suggest that bleed rates decrease over time with continuing emicizumab treatment “even in patients with a more severe phenotype,” the investigators wrote.

For 15 patients younger than 12 years of age receiving bypassing agent prophylaxis, emicizumab 1.5 mg/kg once weekly resulted in an annualized bleed rate of 0.3, compared to 21.1 for the prior bypassing agent, which translates into a 99% reduction in bleeding risk, according to investigators.

Annualized bleed rates for patients receiving emicizumab 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks were 0.2 and 2.2, respectively; hover, the numerically higher annualized bleed rate in the 6 mg/kg every-4-weeks group was based on 2 out of the 10 patients treated with that maintenance regimen, including one who had 6 target joint bleeds in the 24 weeks before enrolling in the study, and another who developed antidrug antibodies within the first 8 weeks of emicizumab treatment.

Out of 23 patients who had target joints and received emicizumab prophylaxis for at least 52 weeks, 100% (45 of 45) target joints resolved, according to the report.

“Notably, this is the first report of a treatment resolving target joints in an inhibitor population, which until now has only been reported when using factor VIII products in patients without inhibitors,” Dr. Young and colleagues said.

The most common of the 721 adverse events reported in HAVEN 2 were nasopharyngitis and injection-site reactions. Of 21 serious adverse events, only 1 (antidrug antibodies with neutralizing potential) was thought by investigators to be related to emicizumab.

The Food and Drug Administration (FDA) initially approved emicizumab in November 2017 on the basis of the HAVEN 2 pediatric trial, and on HAVEN 1, a randomized, multicenter, open-label, phase 3 trial including 109 adult and adolescent males with hemophilia A and FVIII inhibitors. The indication for emicizumab was expanded to include patients without inhibitors in October 2018, on the basis of the HAVEN 3 and HAVEN 4 randomized phase 3 trials.

Dr. Young reported disclosures related to Alnylam, Bayer, Bioverativ, CSL Behring, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Shire, Spark, and uniQure.

SOURCE: Young G, et al. Blood. 2019 Oct 10. doi: 10.1182/blood.2019001869.

WASHINGTON – People may differ in their susceptibility to different influenza subtypes based in part on the year when they were born and the flu strains that circulated during their birth year, according to infection patterns during a recent U.S. flu season.

“Our findings may indicate protection against H1 [influenza] viruses in age groups with early exposure to H1N1pdm09 during the 2009 pandemic or to older, antigenically similar H1N1 viruses,” Shikha Garg, MD, said at an annual scientific meeting on infectious diseases. If results from further studies confirm this relationship it could have implications for flu vaccine effectiveness in various age groups and influence the composition of flu vaccines based on the ages of the people who will receive them, said Dr. Garg, a medical epidemiologist with the Centers for Disease Control and Prevention in Atlanta.

The analysis she reported using data collected by the CDC’s Influenza Hospitalization Surveillance Network on 18,699 people hospitalized for influenza infection during the 2018-2019 season, Oct. 1, 2018–April 30, 2019. The database provides a representative sampling of patients hospitalized for influenza at more than 250 acute care hospitals in 13 states. During the season studied, both the H1N1 and H3N2 subtypes circulated and caused similar cumulative rates of infections, with H1N1 causing about 32 confirmed cases per 100,000 people and H3N2 causing about 29 cases/100,000.

But a more granular analysis that divided the hospitalized patients by their birth year showed an excess of H1N1 infections in two demographic slices: those born during 2010-2019 (corresponding to children 0-9 years old), in whom H1N1 accounted for roughly 60% of cases; and also in those born during 1948-1995 (people aged 24-70 years old) in whom H1N1 caused roughly 70% or more of all infections in some for some birth-year groups in this demographic range. In contrast, infection with the circulating H3N2 strain in the 2018-2019 season dominated among those born during 1996-2009 (people aged 10-23), as well as in those born in 1947 or earlier (those who were at least 71 years old). Some age groups within those born in 1996-2009 had H3N2 infection rates that made up 70% or more of all flu infections, and among nonagenarians well over three-quarters of flu infection were by the H3N2 subtype.

Dr. Garg also showed a similar pattern of predominant flu subtype by age using U.S. influenza hospitalization data for the 2017-2018 season, as well as for all types of 2018-2019 U.S. influenza infections that underwent strain typing including outpatients as well as in patients. All of these findings support the hypothesis and extend the data published earlier this year by Dr. Garg and several of her CDC colleagues that described a pattern of “antigen imprinting” that appeared caused by influenza exposure during the first year of life (J Infect Dis. 2019 Sep 1;220[5]:820-9). However, more data are needed to better assess time trends for children who were first exposed to H1N1 influenza during the 2009 pandemic, Dr. Garg said.

mzoler@mdedge.com

SOURCE: Garg S. ID Week 2019, Abstract LB19.

WASHINGTON – People may differ in their susceptibility to different influenza subtypes based in part on the year when they were born and the flu strains that circulated during their birth year, according to infection patterns during a recent U.S. flu season.

“Our findings may indicate protection against H1 [influenza] viruses in age groups with early exposure to H1N1pdm09 during the 2009 pandemic or to older, antigenically similar H1N1 viruses,” Shikha Garg, MD, said at an annual scientific meeting on infectious diseases. If results from further studies confirm this relationship it could have implications for flu vaccine effectiveness in various age groups and influence the composition of flu vaccines based on the ages of the people who will receive them, said Dr. Garg, a medical epidemiologist with the Centers for Disease Control and Prevention in Atlanta.

The analysis she reported using data collected by the CDC’s Influenza Hospitalization Surveillance Network on 18,699 people hospitalized for influenza infection during the 2018-2019 season, Oct. 1, 2018–April 30, 2019. The database provides a representative sampling of patients hospitalized for influenza at more than 250 acute care hospitals in 13 states. During the season studied, both the H1N1 and H3N2 subtypes circulated and caused similar cumulative rates of infections, with H1N1 causing about 32 confirmed cases per 100,000 people and H3N2 causing about 29 cases/100,000.

But a more granular analysis that divided the hospitalized patients by their birth year showed an excess of H1N1 infections in two demographic slices: those born during 2010-2019 (corresponding to children 0-9 years old), in whom H1N1 accounted for roughly 60% of cases; and also in those born during 1948-1995 (people aged 24-70 years old) in whom H1N1 caused roughly 70% or more of all infections in some for some birth-year groups in this demographic range. In contrast, infection with the circulating H3N2 strain in the 2018-2019 season dominated among those born during 1996-2009 (people aged 10-23), as well as in those born in 1947 or earlier (those who were at least 71 years old). Some age groups within those born in 1996-2009 had H3N2 infection rates that made up 70% or more of all flu infections, and among nonagenarians well over three-quarters of flu infection were by the H3N2 subtype.

Dr. Garg also showed a similar pattern of predominant flu subtype by age using U.S. influenza hospitalization data for the 2017-2018 season, as well as for all types of 2018-2019 U.S. influenza infections that underwent strain typing including outpatients as well as in patients. All of these findings support the hypothesis and extend the data published earlier this year by Dr. Garg and several of her CDC colleagues that described a pattern of “antigen imprinting” that appeared caused by influenza exposure during the first year of life (J Infect Dis. 2019 Sep 1;220[5]:820-9). However, more data are needed to better assess time trends for children who were first exposed to H1N1 influenza during the 2009 pandemic, Dr. Garg said.

mzoler@mdedge.com

SOURCE: Garg S. ID Week 2019, Abstract LB19.

WASHINGTON – People may differ in their susceptibility to different influenza subtypes based in part on the year when they were born and the flu strains that circulated during their birth year, according to infection patterns during a recent U.S. flu season.

“Our findings may indicate protection against H1 [influenza] viruses in age groups with early exposure to H1N1pdm09 during the 2009 pandemic or to older, antigenically similar H1N1 viruses,” Shikha Garg, MD, said at an annual scientific meeting on infectious diseases. If results from further studies confirm this relationship it could have implications for flu vaccine effectiveness in various age groups and influence the composition of flu vaccines based on the ages of the people who will receive them, said Dr. Garg, a medical epidemiologist with the Centers for Disease Control and Prevention in Atlanta.

The analysis she reported using data collected by the CDC’s Influenza Hospitalization Surveillance Network on 18,699 people hospitalized for influenza infection during the 2018-2019 season, Oct. 1, 2018–April 30, 2019. The database provides a representative sampling of patients hospitalized for influenza at more than 250 acute care hospitals in 13 states. During the season studied, both the H1N1 and H3N2 subtypes circulated and caused similar cumulative rates of infections, with H1N1 causing about 32 confirmed cases per 100,000 people and H3N2 causing about 29 cases/100,000.

But a more granular analysis that divided the hospitalized patients by their birth year showed an excess of H1N1 infections in two demographic slices: those born during 2010-2019 (corresponding to children 0-9 years old), in whom H1N1 accounted for roughly 60% of cases; and also in those born during 1948-1995 (people aged 24-70 years old) in whom H1N1 caused roughly 70% or more of all infections in some for some birth-year groups in this demographic range. In contrast, infection with the circulating H3N2 strain in the 2018-2019 season dominated among those born during 1996-2009 (people aged 10-23), as well as in those born in 1947 or earlier (those who were at least 71 years old). Some age groups within those born in 1996-2009 had H3N2 infection rates that made up 70% or more of all flu infections, and among nonagenarians well over three-quarters of flu infection were by the H3N2 subtype.

Dr. Garg also showed a similar pattern of predominant flu subtype by age using U.S. influenza hospitalization data for the 2017-2018 season, as well as for all types of 2018-2019 U.S. influenza infections that underwent strain typing including outpatients as well as in patients. All of these findings support the hypothesis and extend the data published earlier this year by Dr. Garg and several of her CDC colleagues that described a pattern of “antigen imprinting” that appeared caused by influenza exposure during the first year of life (J Infect Dis. 2019 Sep 1;220[5]:820-9). However, more data are needed to better assess time trends for children who were first exposed to H1N1 influenza during the 2009 pandemic, Dr. Garg said.

mzoler@mdedge.com

SOURCE: Garg S. ID Week 2019, Abstract LB19.

PHILADELPHIA – For patients transitioning to home after a heart failure hospitalization, substituting in-person visits with virtual, video-based visits is feasible, safe, and may reduce appointment no-show rates, results of a randomized study suggest.

Connecting patients with clinicians over secure video cut no-show rates at 7 days post-discharge by about one-third, with no difference in risk of readmission, emergency department visits, or death, compared with the traditional in-person follow-up visit, investigator Eiran Z. Gorodeski, MD, MPH, reported here at the annual scientific meeting of the Heart Failure Society of America.

There is currently no way to bill insurance companies for this type of visit, Dr. Gorodeski said when asked what initial barriers other institutions might have implementing a similar approach.

In the randomized, single-center clinical trial Dr. Gorodeski presented here at the HFSA meeting, called VIV-HF (Virtual Visits in Heart Failure Care Transitions), a total of 108 patients were randomized to the virtual visit (52 patients) or an in-person visit (56 patients).

The majority of patients (over 60%) had heart failure with reduced ejection fraction, according to the reported study results.

No-show rates were 50% for the in-person visit, and 34.6% for the virtual visit, for a relative risk reduction of 31%. However, this difference did not reach statistical significance, likely because the study was underpowered, according to Dr. Gorodeski.

“This strategy may reduce postdischarge appointment no-show rates, and this needs to be studied further in larger and appropriately powered clinical trials,” he said in presenting the results.

The 7-day postdischarge outpatient clinic visit is recommended in guidelines and viewed as a way to increase care engagement while reducing risk of poor outcomes, according to VIV-HF investigators.

Support for the study came from the Hunnell Fund. Dr. Gorodeski reported being a consultant and advisor to Abbott.

cardnews@mdedge

SOURCE: Gorodeski EZ, et al. HFSA 2019. Late-Breaking Clinical Trials session.

PHILADELPHIA – For patients transitioning to home after a heart failure hospitalization, substituting in-person visits with virtual, video-based visits is feasible, safe, and may reduce appointment no-show rates, results of a randomized study suggest.

Connecting patients with clinicians over secure video cut no-show rates at 7 days post-discharge by about one-third, with no difference in risk of readmission, emergency department visits, or death, compared with the traditional in-person follow-up visit, investigator Eiran Z. Gorodeski, MD, MPH, reported here at the annual scientific meeting of the Heart Failure Society of America.

There is currently no way to bill insurance companies for this type of visit, Dr. Gorodeski said when asked what initial barriers other institutions might have implementing a similar approach.

In the randomized, single-center clinical trial Dr. Gorodeski presented here at the HFSA meeting, called VIV-HF (Virtual Visits in Heart Failure Care Transitions), a total of 108 patients were randomized to the virtual visit (52 patients) or an in-person visit (56 patients).

The majority of patients (over 60%) had heart failure with reduced ejection fraction, according to the reported study results.

No-show rates were 50% for the in-person visit, and 34.6% for the virtual visit, for a relative risk reduction of 31%. However, this difference did not reach statistical significance, likely because the study was underpowered, according to Dr. Gorodeski.

“This strategy may reduce postdischarge appointment no-show rates, and this needs to be studied further in larger and appropriately powered clinical trials,” he said in presenting the results.

The 7-day postdischarge outpatient clinic visit is recommended in guidelines and viewed as a way to increase care engagement while reducing risk of poor outcomes, according to VIV-HF investigators.

Support for the study came from the Hunnell Fund. Dr. Gorodeski reported being a consultant and advisor to Abbott.

cardnews@mdedge

SOURCE: Gorodeski EZ, et al. HFSA 2019. Late-Breaking Clinical Trials session.

PHILADELPHIA – For patients transitioning to home after a heart failure hospitalization, substituting in-person visits with virtual, video-based visits is feasible, safe, and may reduce appointment no-show rates, results of a randomized study suggest.

Connecting patients with clinicians over secure video cut no-show rates at 7 days post-discharge by about one-third, with no difference in risk of readmission, emergency department visits, or death, compared with the traditional in-person follow-up visit, investigator Eiran Z. Gorodeski, MD, MPH, reported here at the annual scientific meeting of the Heart Failure Society of America.

There is currently no way to bill insurance companies for this type of visit, Dr. Gorodeski said when asked what initial barriers other institutions might have implementing a similar approach.

In the randomized, single-center clinical trial Dr. Gorodeski presented here at the HFSA meeting, called VIV-HF (Virtual Visits in Heart Failure Care Transitions), a total of 108 patients were randomized to the virtual visit (52 patients) or an in-person visit (56 patients).

The majority of patients (over 60%) had heart failure with reduced ejection fraction, according to the reported study results.

No-show rates were 50% for the in-person visit, and 34.6% for the virtual visit, for a relative risk reduction of 31%. However, this difference did not reach statistical significance, likely because the study was underpowered, according to Dr. Gorodeski.

“This strategy may reduce postdischarge appointment no-show rates, and this needs to be studied further in larger and appropriately powered clinical trials,” he said in presenting the results.

The 7-day postdischarge outpatient clinic visit is recommended in guidelines and viewed as a way to increase care engagement while reducing risk of poor outcomes, according to VIV-HF investigators.

Support for the study came from the Hunnell Fund. Dr. Gorodeski reported being a consultant and advisor to Abbott.

cardnews@mdedge

SOURCE: Gorodeski EZ, et al. HFSA 2019. Late-Breaking Clinical Trials session.

NEW ORLEANS – Accidental firearm-related injuries among children occur more frequently in rural than in urban locations, and nearly 60% of such cases are potentially preventable, results from a single-center study suggest.

Furthermore, these gun injuries carry the same mortality and disability risk.

“Firearm-related injury is an understudied topic,” lead study author Amelia Lucisano, MD, said in an interview in advance of the annual meeting of the American Academy of Pediatrics. “In particular there is a lack of granular level research on firearm-related injury in the population.”

At the meeting, she presented findings from an analysis which set out to investigate the location, preventability, and temporal trends of pediatric firearm-related injury in 184 patients age 18 and younger who were treated in the pediatric trauma program at University of Pittsburgh Medical Center during 2008-2017. Dr. Lucisano, a surgical resident at the university, and her colleagues focused their work on efforts to illustrate the differences and similarities in the demographics, injury-related characteristics, and outcomes between the rural and urban populations of children who are injured by firearms in Southwestern Pennsylvania. They classified the location as rural if the injury occurred outside the region’s central metropolitan county, and classified the injury as potentially preventable if the firearm was not stored securely and was used without permission. Statistical analyses included Wilcoxon rank-sum and chi-square analyses.

Of the 184 children who sustained a firearm-related injury during the study period, 43% occurred in a rural location. Compared with children who were injured in an urban setting, those who were injured in a rural setting were younger (a mean of 13 vs. 14 years; P = 0.0003), were more frequently white (81% vs. 14%; P less than 0.0001), and were more frequently injured by accident (70% vs. 15%; P less than 0.0001). They were also more likely to be injured by rifle or shotgun (24.1% vs. 6.67%; P = 0.001).

The rates of death or disability and lengths of stay did not differ significantly based on location of injury, occurring in 16.5% of rural and 13.3% of urban patients.

Nearly three-quarters of accidental injuries (72%) occurred on the gun-owner’s property and 58% were considered by the researchers to be potentially preventable.

“As expected, rural injuries are more frequently unintentional while urban injuries are more frequently assaults,” Dr. Lucisano said. “However, markers of injury severity and outcomes are equivalent between the groups, meaning that morbidity and mortality of injuries in the rural setting are similar to those in the urban setting.”

She emphasized that while clinician bias may be to consider rural firearm-based injuries as less severe, “our study shows that they carry the same burden of morbidity and mortality as urban injuries and thus should be cared for with the same intensity and anticipation of a possible poor outcome. Furthermore, the large number of potentially preventable injuries among those that were unintentional represents a significant burden of morbidity and mortality that could have been avoided through safer firearm storage. Programs to promote safe firearm storage should be targeted to populations that have high rates of potentially preventable injuries.”

Dr. Lucisano and her colleagues observed that the rates of all forms of firearm-related injury appear to be on the rise in both rural and urban areas: accidental, self-inflicted, and assault, in particular. She acknowledged certain limitations of the study, including its retrospective, single-center design. “We did not capture children who died in the field or who were treated at other hospitals, though as our center is the only pediatric Level 1 trauma center, we capture a large majority of pediatric trauma patients in the region,” she said.

The researchers reported having no disclosures.

dbrunk@mdedge.com

SOURCE: Lucisano A. AAP 2019, Section on Surgery program.

NEW ORLEANS – Accidental firearm-related injuries among children occur more frequently in rural than in urban locations, and nearly 60% of such cases are potentially preventable, results from a single-center study suggest.

Furthermore, these gun injuries carry the same mortality and disability risk.

“Firearm-related injury is an understudied topic,” lead study author Amelia Lucisano, MD, said in an interview in advance of the annual meeting of the American Academy of Pediatrics. “In particular there is a lack of granular level research on firearm-related injury in the population.”

At the meeting, she presented findings from an analysis which set out to investigate the location, preventability, and temporal trends of pediatric firearm-related injury in 184 patients age 18 and younger who were treated in the pediatric trauma program at University of Pittsburgh Medical Center during 2008-2017. Dr. Lucisano, a surgical resident at the university, and her colleagues focused their work on efforts to illustrate the differences and similarities in the demographics, injury-related characteristics, and outcomes between the rural and urban populations of children who are injured by firearms in Southwestern Pennsylvania. They classified the location as rural if the injury occurred outside the region’s central metropolitan county, and classified the injury as potentially preventable if the firearm was not stored securely and was used without permission. Statistical analyses included Wilcoxon rank-sum and chi-square analyses.

Of the 184 children who sustained a firearm-related injury during the study period, 43% occurred in a rural location. Compared with children who were injured in an urban setting, those who were injured in a rural setting were younger (a mean of 13 vs. 14 years; P = 0.0003), were more frequently white (81% vs. 14%; P less than 0.0001), and were more frequently injured by accident (70% vs. 15%; P less than 0.0001). They were also more likely to be injured by rifle or shotgun (24.1% vs. 6.67%; P = 0.001).

The rates of death or disability and lengths of stay did not differ significantly based on location of injury, occurring in 16.5% of rural and 13.3% of urban patients.

Nearly three-quarters of accidental injuries (72%) occurred on the gun-owner’s property and 58% were considered by the researchers to be potentially preventable.

“As expected, rural injuries are more frequently unintentional while urban injuries are more frequently assaults,” Dr. Lucisano said. “However, markers of injury severity and outcomes are equivalent between the groups, meaning that morbidity and mortality of injuries in the rural setting are similar to those in the urban setting.”

She emphasized that while clinician bias may be to consider rural firearm-based injuries as less severe, “our study shows that they carry the same burden of morbidity and mortality as urban injuries and thus should be cared for with the same intensity and anticipation of a possible poor outcome. Furthermore, the large number of potentially preventable injuries among those that were unintentional represents a significant burden of morbidity and mortality that could have been avoided through safer firearm storage. Programs to promote safe firearm storage should be targeted to populations that have high rates of potentially preventable injuries.”

Dr. Lucisano and her colleagues observed that the rates of all forms of firearm-related injury appear to be on the rise in both rural and urban areas: accidental, self-inflicted, and assault, in particular. She acknowledged certain limitations of the study, including its retrospective, single-center design. “We did not capture children who died in the field or who were treated at other hospitals, though as our center is the only pediatric Level 1 trauma center, we capture a large majority of pediatric trauma patients in the region,” she said.

The researchers reported having no disclosures.

dbrunk@mdedge.com

SOURCE: Lucisano A. AAP 2019, Section on Surgery program.

NEW ORLEANS – Accidental firearm-related injuries among children occur more frequently in rural than in urban locations, and nearly 60% of such cases are potentially preventable, results from a single-center study suggest.

Furthermore, these gun injuries carry the same mortality and disability risk.

“Firearm-related injury is an understudied topic,” lead study author Amelia Lucisano, MD, said in an interview in advance of the annual meeting of the American Academy of Pediatrics. “In particular there is a lack of granular level research on firearm-related injury in the population.”

At the meeting, she presented findings from an analysis which set out to investigate the location, preventability, and temporal trends of pediatric firearm-related injury in 184 patients age 18 and younger who were treated in the pediatric trauma program at University of Pittsburgh Medical Center during 2008-2017. Dr. Lucisano, a surgical resident at the university, and her colleagues focused their work on efforts to illustrate the differences and similarities in the demographics, injury-related characteristics, and outcomes between the rural and urban populations of children who are injured by firearms in Southwestern Pennsylvania. They classified the location as rural if the injury occurred outside the region’s central metropolitan county, and classified the injury as potentially preventable if the firearm was not stored securely and was used without permission. Statistical analyses included Wilcoxon rank-sum and chi-square analyses.

Of the 184 children who sustained a firearm-related injury during the study period, 43% occurred in a rural location. Compared with children who were injured in an urban setting, those who were injured in a rural setting were younger (a mean of 13 vs. 14 years; P = 0.0003), were more frequently white (81% vs. 14%; P less than 0.0001), and were more frequently injured by accident (70% vs. 15%; P less than 0.0001). They were also more likely to be injured by rifle or shotgun (24.1% vs. 6.67%; P = 0.001).

The rates of death or disability and lengths of stay did not differ significantly based on location of injury, occurring in 16.5% of rural and 13.3% of urban patients.

Nearly three-quarters of accidental injuries (72%) occurred on the gun-owner’s property and 58% were considered by the researchers to be potentially preventable.

“As expected, rural injuries are more frequently unintentional while urban injuries are more frequently assaults,” Dr. Lucisano said. “However, markers of injury severity and outcomes are equivalent between the groups, meaning that morbidity and mortality of injuries in the rural setting are similar to those in the urban setting.”

She emphasized that while clinician bias may be to consider rural firearm-based injuries as less severe, “our study shows that they carry the same burden of morbidity and mortality as urban injuries and thus should be cared for with the same intensity and anticipation of a possible poor outcome. Furthermore, the large number of potentially preventable injuries among those that were unintentional represents a significant burden of morbidity and mortality that could have been avoided through safer firearm storage. Programs to promote safe firearm storage should be targeted to populations that have high rates of potentially preventable injuries.”

Dr. Lucisano and her colleagues observed that the rates of all forms of firearm-related injury appear to be on the rise in both rural and urban areas: accidental, self-inflicted, and assault, in particular. She acknowledged certain limitations of the study, including its retrospective, single-center design. “We did not capture children who died in the field or who were treated at other hospitals, though as our center is the only pediatric Level 1 trauma center, we capture a large majority of pediatric trauma patients in the region,” she said.

The researchers reported having no disclosures.

dbrunk@mdedge.com

SOURCE: Lucisano A. AAP 2019, Section on Surgery program.

PHILADELPHIA – Ovarian tissue cryopreservation should no longer be considered experimental, Sherman J. Silber, MD, said at the annual meeting of the American Society for Reproductive Medicine.

That claim is based on more than 20 years of experience at his center performing the procedure and results he presented from patients for whom frozen ovarian tissue has been reimplanted resulting in a spontaneous pregnancy.

“For prepubertal girls with cancer and for patients who have already had a preliminary round of chemotherapy, ovarian tissue freezing is the only method available to preserve their fertility,” said Dr. Silber, of the Infertility Center of St. Louis in Chesterfield, Missouri. “It is also the only method available to preserve their fertility.”

“I have very strong feelings about this,” he added. “It has huge societal implications for insurance payments.”

Dr. Silber presented results of ovarian tissue freezing and reimplantation at his center beginning in 1997, where 115 patients between the ages of 2 and 35 years underwent the procedure using the same technique. Of these patients, 14 women came back years later to have their frozen ovary cortex reimplanted. Dr. Silber and his group followed these patients monthly for more than 2 years after reimplantation for signs of return of menses, hormonal changes, pregnancy, and live birth.

Most of the patients who chose ovarian tissue freezing had cancer. Eight patients underwent the procedure after being diagnosed with solid tissue cancer and three had leukemia, while two patients underwent ovarian tissue freezing due to premature ovarian failure, and one because of multiple sclerosis. Patients who underwent reimplantation were menopausal for at least 3 years, said Dr. Silber.

Dr. Silber also described the technique used for reimplantation. After the cortical tissue was thawed, the tissue was quilted into one piece from three to five slices using 9-0 nylon interrupted sutures. The quilted tissue was then sutured to the medulla after the surgeon completely removed the dead cortex from the other ovary. “Hemostasis was achieved with micro bipolar forceps,” said Dr. Silber. “Constant irrigation was employed with pulsed heparinized media because we wanted to avoid adhesions, and we wanted to try for spontaneous pregnancy rather than IVF.”

“Then, we put [the quilted ovarian slices] on to the medulla on the other side in such a way that the fallopian tube would be able to reach and catch any egg that’s ovulated during that time,” he added.

Dr. Silber and his group found that, over time, follicle-stimulating hormone (FSH) levels sharply decreased to normal or near-normal levels between 69 days and 133 days after the procedure while Anti-Müllerian hormone (AMH) levels dramatically rose to higher levels between 133 days and 227 days post-procedure before dropping to very low levels, “and the AMH remained at low levels despite the fact that [transplants] would last 8 to 10 years,” said Dr. Silber.

Of the 14 cases where frozen ovarian tissue was reimplanted, 11 patients (78%) achieved pregnancy, 10 patients (71%) delivered healthy babies, and 1 patient (9%) experienced a miscarriage. All patients had spontaneous pregnancies, and none used in vitro fertilization (IVF), noted Dr. Silber. There were 2 patients who had four children from transplanted ovarian tissue, and 2 of 3 patients with leukemia had a total of five children.

Additionally, Dr. Silber’s group examined the literature for other examples of ovarian tissue reimplantation after cryopreservation to determine how many live births resulted from the procedure. They found an additional 170 live births in addition to the 15 live births at their center, with a pregnancy rate ranging from 31% to 71% in different studies. Cancer was not transmitted from mother to child in any case, said Dr. Silber.

Compared with egg freezing, there is a benefit to performing ovarian tissue freezing, even after chemotherapy has begun, noted Dr. Silber. The cost of ovarian tissue freezing is also roughly one-tenth that of egg freezing, and the procedure is less burdensome than multiple cycles with the potential for ovarian hyperstimulation, and it restores the hormone function and the fertility of eggs after reimplantation.

“Because the greater primordial follicle recruitment decreases as the ovarian reserve decreases, you can put a piece of ovary tissue back every 8 years, and a woman can have endocrine function until she’s 100 years old,” said Dr. Silber.

Dr. Silber reported no relevant conflicts of interest.

obnews@mdedge.com

SOURCE: Silber SJ. ASRM 2019. Abstract O-203.

PHILADELPHIA – Ovarian tissue cryopreservation should no longer be considered experimental, Sherman J. Silber, MD, said at the annual meeting of the American Society for Reproductive Medicine.

That claim is based on more than 20 years of experience at his center performing the procedure and results he presented from patients for whom frozen ovarian tissue has been reimplanted resulting in a spontaneous pregnancy.

“For prepubertal girls with cancer and for patients who have already had a preliminary round of chemotherapy, ovarian tissue freezing is the only method available to preserve their fertility,” said Dr. Silber, of the Infertility Center of St. Louis in Chesterfield, Missouri. “It is also the only method available to preserve their fertility.”

“I have very strong feelings about this,” he added. “It has huge societal implications for insurance payments.”

Dr. Silber presented results of ovarian tissue freezing and reimplantation at his center beginning in 1997, where 115 patients between the ages of 2 and 35 years underwent the procedure using the same technique. Of these patients, 14 women came back years later to have their frozen ovary cortex reimplanted. Dr. Silber and his group followed these patients monthly for more than 2 years after reimplantation for signs of return of menses, hormonal changes, pregnancy, and live birth.

Most of the patients who chose ovarian tissue freezing had cancer. Eight patients underwent the procedure after being diagnosed with solid tissue cancer and three had leukemia, while two patients underwent ovarian tissue freezing due to premature ovarian failure, and one because of multiple sclerosis. Patients who underwent reimplantation were menopausal for at least 3 years, said Dr. Silber.

Dr. Silber also described the technique used for reimplantation. After the cortical tissue was thawed, the tissue was quilted into one piece from three to five slices using 9-0 nylon interrupted sutures. The quilted tissue was then sutured to the medulla after the surgeon completely removed the dead cortex from the other ovary. “Hemostasis was achieved with micro bipolar forceps,” said Dr. Silber. “Constant irrigation was employed with pulsed heparinized media because we wanted to avoid adhesions, and we wanted to try for spontaneous pregnancy rather than IVF.”

“Then, we put [the quilted ovarian slices] on to the medulla on the other side in such a way that the fallopian tube would be able to reach and catch any egg that’s ovulated during that time,” he added.

Dr. Silber and his group found that, over time, follicle-stimulating hormone (FSH) levels sharply decreased to normal or near-normal levels between 69 days and 133 days after the procedure while Anti-Müllerian hormone (AMH) levels dramatically rose to higher levels between 133 days and 227 days post-procedure before dropping to very low levels, “and the AMH remained at low levels despite the fact that [transplants] would last 8 to 10 years,” said Dr. Silber.

Of the 14 cases where frozen ovarian tissue was reimplanted, 11 patients (78%) achieved pregnancy, 10 patients (71%) delivered healthy babies, and 1 patient (9%) experienced a miscarriage. All patients had spontaneous pregnancies, and none used in vitro fertilization (IVF), noted Dr. Silber. There were 2 patients who had four children from transplanted ovarian tissue, and 2 of 3 patients with leukemia had a total of five children.

Additionally, Dr. Silber’s group examined the literature for other examples of ovarian tissue reimplantation after cryopreservation to determine how many live births resulted from the procedure. They found an additional 170 live births in addition to the 15 live births at their center, with a pregnancy rate ranging from 31% to 71% in different studies. Cancer was not transmitted from mother to child in any case, said Dr. Silber.

Compared with egg freezing, there is a benefit to performing ovarian tissue freezing, even after chemotherapy has begun, noted Dr. Silber. The cost of ovarian tissue freezing is also roughly one-tenth that of egg freezing, and the procedure is less burdensome than multiple cycles with the potential for ovarian hyperstimulation, and it restores the hormone function and the fertility of eggs after reimplantation.

“Because the greater primordial follicle recruitment decreases as the ovarian reserve decreases, you can put a piece of ovary tissue back every 8 years, and a woman can have endocrine function until she’s 100 years old,” said Dr. Silber.

Dr. Silber reported no relevant conflicts of interest.

obnews@mdedge.com

SOURCE: Silber SJ. ASRM 2019. Abstract O-203.

PHILADELPHIA – Ovarian tissue cryopreservation should no longer be considered experimental, Sherman J. Silber, MD, said at the annual meeting of the American Society for Reproductive Medicine.

That claim is based on more than 20 years of experience at his center performing the procedure and results he presented from patients for whom frozen ovarian tissue has been reimplanted resulting in a spontaneous pregnancy.

“For prepubertal girls with cancer and for patients who have already had a preliminary round of chemotherapy, ovarian tissue freezing is the only method available to preserve their fertility,” said Dr. Silber, of the Infertility Center of St. Louis in Chesterfield, Missouri. “It is also the only method available to preserve their fertility.”

“I have very strong feelings about this,” he added. “It has huge societal implications for insurance payments.”

Dr. Silber presented results of ovarian tissue freezing and reimplantation at his center beginning in 1997, where 115 patients between the ages of 2 and 35 years underwent the procedure using the same technique. Of these patients, 14 women came back years later to have their frozen ovary cortex reimplanted. Dr. Silber and his group followed these patients monthly for more than 2 years after reimplantation for signs of return of menses, hormonal changes, pregnancy, and live birth.

Most of the patients who chose ovarian tissue freezing had cancer. Eight patients underwent the procedure after being diagnosed with solid tissue cancer and three had leukemia, while two patients underwent ovarian tissue freezing due to premature ovarian failure, and one because of multiple sclerosis. Patients who underwent reimplantation were menopausal for at least 3 years, said Dr. Silber.

Dr. Silber also described the technique used for reimplantation. After the cortical tissue was thawed, the tissue was quilted into one piece from three to five slices using 9-0 nylon interrupted sutures. The quilted tissue was then sutured to the medulla after the surgeon completely removed the dead cortex from the other ovary. “Hemostasis was achieved with micro bipolar forceps,” said Dr. Silber. “Constant irrigation was employed with pulsed heparinized media because we wanted to avoid adhesions, and we wanted to try for spontaneous pregnancy rather than IVF.”

“Then, we put [the quilted ovarian slices] on to the medulla on the other side in such a way that the fallopian tube would be able to reach and catch any egg that’s ovulated during that time,” he added.

Dr. Silber and his group found that, over time, follicle-stimulating hormone (FSH) levels sharply decreased to normal or near-normal levels between 69 days and 133 days after the procedure while Anti-Müllerian hormone (AMH) levels dramatically rose to higher levels between 133 days and 227 days post-procedure before dropping to very low levels, “and the AMH remained at low levels despite the fact that [transplants] would last 8 to 10 years,” said Dr. Silber.

Of the 14 cases where frozen ovarian tissue was reimplanted, 11 patients (78%) achieved pregnancy, 10 patients (71%) delivered healthy babies, and 1 patient (9%) experienced a miscarriage. All patients had spontaneous pregnancies, and none used in vitro fertilization (IVF), noted Dr. Silber. There were 2 patients who had four children from transplanted ovarian tissue, and 2 of 3 patients with leukemia had a total of five children.

Additionally, Dr. Silber’s group examined the literature for other examples of ovarian tissue reimplantation after cryopreservation to determine how many live births resulted from the procedure. They found an additional 170 live births in addition to the 15 live births at their center, with a pregnancy rate ranging from 31% to 71% in different studies. Cancer was not transmitted from mother to child in any case, said Dr. Silber.

Compared with egg freezing, there is a benefit to performing ovarian tissue freezing, even after chemotherapy has begun, noted Dr. Silber. The cost of ovarian tissue freezing is also roughly one-tenth that of egg freezing, and the procedure is less burdensome than multiple cycles with the potential for ovarian hyperstimulation, and it restores the hormone function and the fertility of eggs after reimplantation.

“Because the greater primordial follicle recruitment decreases as the ovarian reserve decreases, you can put a piece of ovary tissue back every 8 years, and a woman can have endocrine function until she’s 100 years old,” said Dr. Silber.

Dr. Silber reported no relevant conflicts of interest.

obnews@mdedge.com

SOURCE: Silber SJ. ASRM 2019. Abstract O-203.

PARIS – Fewer than half of commercial drivers who received implantable cardioverter-defibrillators (ICDs) recalled being told they should never drive professionally again, according to a recent Danish survey. Further, about a third of patients overall reported that they began driving soon after they received an ICD, during the period when guidelines recommend refraining from driving.

“These devices, they save lives – so what’s not to like?” lead investigator Jenny Bjerre, MD, asked at the annual congress of the European Society of Cardiology. “Well, if you are a patient qualifying for an ICD, you also automatically qualify for some driving restrictions.” These are put in place because of the concern for an arrhythmia causing a loss of consciousness behind the wheel, she said.

A European consensus statement calls for a 3-month driving moratorium when an ICD is implanted for secondary prevention or after an appropriate ICD shock, and a 4-week restriction when an ICD is placed for primary prevention. All these restrictions apply to personal driver’s licenses; anyone with an ICD is permanently restricted from commercial driving according to the consensus statement, said Dr. Bjerre, of the University Hospital, Copenhagen.

“As you can imagine, these restrictions are not that popular with the patients,” she said. She related the story of a patient, a taxi driver who had returned to a full range of physically taxing activities after his ICD implantation, but whose livelihood had been taken away from him.

Dr. Bjerre said she sought to understand the perspective of this patient, who said, “Sometimes I wish I hadn’t been resuscitated!” She saw that the loss of freedom and a meaningful occupation had profoundly affected the daily life of this patient, and she became curious about adherence to driving restrictions in patients with ICDs.

Using the nationwide Danish medical record database, Dr. Bjerre and her colleagues looked at a nationwide cohort of ICD patients to see they remembered hearing about restrictions on personal and commercial driving activities after ICD implantation. They also investigated adherence to restrictions, and sought to identify what factors were associated with nonadherence.

The questionnaire developed by Dr. Bjerre and her colleagues was made available to the ICD cohort both electronically and in a paper version. Questionnaires received were linked with a variety of nationwide registries through each participant’s unique national identification number, she explained. They obtained information about comorbidities, pharmacotherapies, and socioeconomic status. Not only did this linkage give more precise and complete data than would a questionnaire alone, but it also allowed the investigators to see how responders differed from nonresponders – important in questionnaire research, said Dr. Bjerre.

The investigators were able to locate and distribute questionnaires to a total of 3,913 living adults who had received first-time ICDs during the 3-year study period. In the end, even after excluding 31 responses for missing data, 2,741 responses were used for analysis – a response rate of over 70%.

The median age of respondents was 67, and 83% were male. About half – 46% – of respondents had an ICD implanted for primary prevention. Compared with those who did respond, said Dr. Bjerre, the nonresponders “were younger, sicker, more likely to be female, had lower socioeconomic status, and were less likely to be on guideline-directed therapy.”

Over 90% of respondents held a private driver’s license at the time of their ICD implantation, and just 7% were actively using a commercial license prior to implantation. Participants had a variety of commercial driving occupations, including driving trucks, buses, and taxis.

“Only 43% of primary prevention patients and 64% of secondary prevention patients stated that they had been informed about any driving restrictions,” said Dr. Bjerre. The figure was slightly better for patients after an ICD shock was delivered – 72% of these patients recalled hearing about driving restrictions.

“Among professional drivers – who are never supposed to drive again – only 45% said they had been informed about any professional driving restrictions,” she added.

What did patients report about their actual driving behaviors? Of patients receiving an ICD for primary prevention, 34% resumed driving within one week of ICD implantation. For those receiving an ICD for secondary prevention and those who had received an appropriate ICD shock, 43% and 30%, respectively, began driving before the recommended 3 months had elapsed.

The driving behavior of those with commercial licenses didn’t differ from the cohort as a whole: 35% of this group had resumed commercial driving.

In all the study’s subgroups, nonadherence to driving restrictions was more likely if the participant didn’t recall having been informed of the restrictions, with an odds ratio (OR) of 3.34 for nonadherence. However, noted Dr. Bjerre, at least 20% of patients in all subgroups who said they’d been told not to drive still resumed driving in contravention of restrictions. “So it seems that information can’t explain everything,” she said.

Additional predictors of nonadherence included male sex, with an OR of 1.53, being the only driver in the household (OR 1.29), and being at least 60 years old (OR, 1.20). Those receiving an ICD for secondary prevention had an OR of 2.20 for nonadherence, as well.

The study had a large cohort of real-life ICD patients and the response rate was high, said Dr. Bjerre. However, there was a risk of recall bias; additionally, nonresponders differed from responders, limiting full generalizability of the data. Finally, she observed that participants may have given the answers they thought were socially desirable.

“I want to get back to our friend the taxi driver,” who was adherent to restrictions, but who kept wanting to know what the actual chances were that he’d harm someone if he resumed driving. Realizing she couldn’t give him a very precise answer, Dr. Bjerre concluded, “I do think we owe it to our patients to provide more evidence on the absolute risk of traffic accidents in these patients.”

Dr. Bjerre reported that she had no conflicts of interest.

koakes@mdedge.com

PARIS – Fewer than half of commercial drivers who received implantable cardioverter-defibrillators (ICDs) recalled being told they should never drive professionally again, according to a recent Danish survey. Further, about a third of patients overall reported that they began driving soon after they received an ICD, during the period when guidelines recommend refraining from driving.

“These devices, they save lives – so what’s not to like?” lead investigator Jenny Bjerre, MD, asked at the annual congress of the European Society of Cardiology. “Well, if you are a patient qualifying for an ICD, you also automatically qualify for some driving restrictions.” These are put in place because of the concern for an arrhythmia causing a loss of consciousness behind the wheel, she said.

A European consensus statement calls for a 3-month driving moratorium when an ICD is implanted for secondary prevention or after an appropriate ICD shock, and a 4-week restriction when an ICD is placed for primary prevention. All these restrictions apply to personal driver’s licenses; anyone with an ICD is permanently restricted from commercial driving according to the consensus statement, said Dr. Bjerre, of the University Hospital, Copenhagen.

“As you can imagine, these restrictions are not that popular with the patients,” she said. She related the story of a patient, a taxi driver who had returned to a full range of physically taxing activities after his ICD implantation, but whose livelihood had been taken away from him.

Dr. Bjerre said she sought to understand the perspective of this patient, who said, “Sometimes I wish I hadn’t been resuscitated!” She saw that the loss of freedom and a meaningful occupation had profoundly affected the daily life of this patient, and she became curious about adherence to driving restrictions in patients with ICDs.

Using the nationwide Danish medical record database, Dr. Bjerre and her colleagues looked at a nationwide cohort of ICD patients to see they remembered hearing about restrictions on personal and commercial driving activities after ICD implantation. They also investigated adherence to restrictions, and sought to identify what factors were associated with nonadherence.

The questionnaire developed by Dr. Bjerre and her colleagues was made available to the ICD cohort both electronically and in a paper version. Questionnaires received were linked with a variety of nationwide registries through each participant’s unique national identification number, she explained. They obtained information about comorbidities, pharmacotherapies, and socioeconomic status. Not only did this linkage give more precise and complete data than would a questionnaire alone, but it also allowed the investigators to see how responders differed from nonresponders – important in questionnaire research, said Dr. Bjerre.

The investigators were able to locate and distribute questionnaires to a total of 3,913 living adults who had received first-time ICDs during the 3-year study period. In the end, even after excluding 31 responses for missing data, 2,741 responses were used for analysis – a response rate of over 70%.

The median age of respondents was 67, and 83% were male. About half – 46% – of respondents had an ICD implanted for primary prevention. Compared with those who did respond, said Dr. Bjerre, the nonresponders “were younger, sicker, more likely to be female, had lower socioeconomic status, and were less likely to be on guideline-directed therapy.”

Over 90% of respondents held a private driver’s license at the time of their ICD implantation, and just 7% were actively using a commercial license prior to implantation. Participants had a variety of commercial driving occupations, including driving trucks, buses, and taxis.

“Only 43% of primary prevention patients and 64% of secondary prevention patients stated that they had been informed about any driving restrictions,” said Dr. Bjerre. The figure was slightly better for patients after an ICD shock was delivered – 72% of these patients recalled hearing about driving restrictions.

“Among professional drivers – who are never supposed to drive again – only 45% said they had been informed about any professional driving restrictions,” she added.

What did patients report about their actual driving behaviors? Of patients receiving an ICD for primary prevention, 34% resumed driving within one week of ICD implantation. For those receiving an ICD for secondary prevention and those who had received an appropriate ICD shock, 43% and 30%, respectively, began driving before the recommended 3 months had elapsed.

The driving behavior of those with commercial licenses didn’t differ from the cohort as a whole: 35% of this group had resumed commercial driving.

In all the study’s subgroups, nonadherence to driving restrictions was more likely if the participant didn’t recall having been informed of the restrictions, with an odds ratio (OR) of 3.34 for nonadherence. However, noted Dr. Bjerre, at least 20% of patients in all subgroups who said they’d been told not to drive still resumed driving in contravention of restrictions. “So it seems that information can’t explain everything,” she said.

Additional predictors of nonadherence included male sex, with an OR of 1.53, being the only driver in the household (OR 1.29), and being at least 60 years old (OR, 1.20). Those receiving an ICD for secondary prevention had an OR of 2.20 for nonadherence, as well.

The study had a large cohort of real-life ICD patients and the response rate was high, said Dr. Bjerre. However, there was a risk of recall bias; additionally, nonresponders differed from responders, limiting full generalizability of the data. Finally, she observed that participants may have given the answers they thought were socially desirable.

“I want to get back to our friend the taxi driver,” who was adherent to restrictions, but who kept wanting to know what the actual chances were that he’d harm someone if he resumed driving. Realizing she couldn’t give him a very precise answer, Dr. Bjerre concluded, “I do think we owe it to our patients to provide more evidence on the absolute risk of traffic accidents in these patients.”

Dr. Bjerre reported that she had no conflicts of interest.

koakes@mdedge.com

PARIS – Fewer than half of commercial drivers who received implantable cardioverter-defibrillators (ICDs) recalled being told they should never drive professionally again, according to a recent Danish survey. Further, about a third of patients overall reported that they began driving soon after they received an ICD, during the period when guidelines recommend refraining from driving.

“These devices, they save lives – so what’s not to like?” lead investigator Jenny Bjerre, MD, asked at the annual congress of the European Society of Cardiology. “Well, if you are a patient qualifying for an ICD, you also automatically qualify for some driving restrictions.” These are put in place because of the concern for an arrhythmia causing a loss of consciousness behind the wheel, she said.

A European consensus statement calls for a 3-month driving moratorium when an ICD is implanted for secondary prevention or after an appropriate ICD shock, and a 4-week restriction when an ICD is placed for primary prevention. All these restrictions apply to personal driver’s licenses; anyone with an ICD is permanently restricted from commercial driving according to the consensus statement, said Dr. Bjerre, of the University Hospital, Copenhagen.

“As you can imagine, these restrictions are not that popular with the patients,” she said. She related the story of a patient, a taxi driver who had returned to a full range of physically taxing activities after his ICD implantation, but whose livelihood had been taken away from him.

Dr. Bjerre said she sought to understand the perspective of this patient, who said, “Sometimes I wish I hadn’t been resuscitated!” She saw that the loss of freedom and a meaningful occupation had profoundly affected the daily life of this patient, and she became curious about adherence to driving restrictions in patients with ICDs.

Using the nationwide Danish medical record database, Dr. Bjerre and her colleagues looked at a nationwide cohort of ICD patients to see they remembered hearing about restrictions on personal and commercial driving activities after ICD implantation. They also investigated adherence to restrictions, and sought to identify what factors were associated with nonadherence.

The questionnaire developed by Dr. Bjerre and her colleagues was made available to the ICD cohort both electronically and in a paper version. Questionnaires received were linked with a variety of nationwide registries through each participant’s unique national identification number, she explained. They obtained information about comorbidities, pharmacotherapies, and socioeconomic status. Not only did this linkage give more precise and complete data than would a questionnaire alone, but it also allowed the investigators to see how responders differed from nonresponders – important in questionnaire research, said Dr. Bjerre.

The investigators were able to locate and distribute questionnaires to a total of 3,913 living adults who had received first-time ICDs during the 3-year study period. In the end, even after excluding 31 responses for missing data, 2,741 responses were used for analysis – a response rate of over 70%.

The median age of respondents was 67, and 83% were male. About half – 46% – of respondents had an ICD implanted for primary prevention. Compared with those who did respond, said Dr. Bjerre, the nonresponders “were younger, sicker, more likely to be female, had lower socioeconomic status, and were less likely to be on guideline-directed therapy.”

Over 90% of respondents held a private driver’s license at the time of their ICD implantation, and just 7% were actively using a commercial license prior to implantation. Participants had a variety of commercial driving occupations, including driving trucks, buses, and taxis.

“Only 43% of primary prevention patients and 64% of secondary prevention patients stated that they had been informed about any driving restrictions,” said Dr. Bjerre. The figure was slightly better for patients after an ICD shock was delivered – 72% of these patients recalled hearing about driving restrictions.

“Among professional drivers – who are never supposed to drive again – only 45% said they had been informed about any professional driving restrictions,” she added.

What did patients report about their actual driving behaviors? Of patients receiving an ICD for primary prevention, 34% resumed driving within one week of ICD implantation. For those receiving an ICD for secondary prevention and those who had received an appropriate ICD shock, 43% and 30%, respectively, began driving before the recommended 3 months had elapsed.

The driving behavior of those with commercial licenses didn’t differ from the cohort as a whole: 35% of this group had resumed commercial driving.

In all the study’s subgroups, nonadherence to driving restrictions was more likely if the participant didn’t recall having been informed of the restrictions, with an odds ratio (OR) of 3.34 for nonadherence. However, noted Dr. Bjerre, at least 20% of patients in all subgroups who said they’d been told not to drive still resumed driving in contravention of restrictions. “So it seems that information can’t explain everything,” she said.

Additional predictors of nonadherence included male sex, with an OR of 1.53, being the only driver in the household (OR 1.29), and being at least 60 years old (OR, 1.20). Those receiving an ICD for secondary prevention had an OR of 2.20 for nonadherence, as well.

The study had a large cohort of real-life ICD patients and the response rate was high, said Dr. Bjerre. However, there was a risk of recall bias; additionally, nonresponders differed from responders, limiting full generalizability of the data. Finally, she observed that participants may have given the answers they thought were socially desirable.

“I want to get back to our friend the taxi driver,” who was adherent to restrictions, but who kept wanting to know what the actual chances were that he’d harm someone if he resumed driving. Realizing she couldn’t give him a very precise answer, Dr. Bjerre concluded, “I do think we owe it to our patients to provide more evidence on the absolute risk of traffic accidents in these patients.”

Dr. Bjerre reported that she had no conflicts of interest.

koakes@mdedge.com

MADRID – Serlopitant, an investigational once-daily oral neurokinin-1 receptor antagonist, resulted in clinically meaningful improvement in psoriatic itch in a phase 2, double-blind, placebo-controlled randomized trial, David M. Pariser, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The drug is not an effective stand alone treatment for psoriasis, though.

“The psoriasis itself did not improve during the trial. It’s the itch that improved. This drug is not designed for psoriasis; it’s going to be used for itching. If this does materialize as a treatment for psoriasis, it would be as an adjunct,” according to Dr. Pariser, a dermatologist at the Eastern Virginia School of Medicine, Norfolk.

Still, serlopitant addresses an unmet need for better treatment options for psoriatic itch. Up to 90% of psoriasis patients report experiencing pruritus, regardless of their disease severity.

“Although patients consider pruritus one of the most important, severe, and troublesome symptoms of psoriasis, clinicians have not historically recognized itch as a significant symptom, and treatments for psoriasis often don’t alleviate the associated pruritus,” he said.

Serlopitant has already shown efficacy and good tolerability in phase 2 studies in patients with prurigo nodularis and chronic pruritus.

The 8-week psoriatic itch trial included 204 adults with plaque psoriasis randomized to 5 mg of serlopitant once daily or placebo. Patients averaged 4.3% involved body surface area, and nearly two-thirds of them had moderate psoriasis by physician global assessment. The majority of patients rated their itch as severe; The average baseline score on the 0-10 Worst Itch Numeric Rating Scale was 8.2.

The primary study endpoint was achievement of at least a 4-point improvement on the Worst Itch Numeric Rating Scale. This was achieved in 33.9% of the serlopitant group and 21.1% of placebo-treated controls. The therapeutic benefit was consistent regardless of baseline body weight, gender, age, or extent of psoriasis-involved body surface area.

The safety data were consistent with what was seen in prior phase 2 studies for other dermatologic disorders. There were no serious adverse events, and the type and frequency of adverse events deemed related to treatment was similar in the two study arms.

“These results support the ongoing development of serlopitant across the spectrum of psoriatic disease,” Dr. Pariser declared.

The study was funded by Menlo Therapeutics. Dr. Pariser reported receiving research funding from and/or serving as a consultant to or advisory board member for roughly two dozen pharmaceutical companies.

bjancin@mdedge.com

MADRID – Serlopitant, an investigational once-daily oral neurokinin-1 receptor antagonist, resulted in clinically meaningful improvement in psoriatic itch in a phase 2, double-blind, placebo-controlled randomized trial, David M. Pariser, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The drug is not an effective stand alone treatment for psoriasis, though.

“The psoriasis itself did not improve during the trial. It’s the itch that improved. This drug is not designed for psoriasis; it’s going to be used for itching. If this does materialize as a treatment for psoriasis, it would be as an adjunct,” according to Dr. Pariser, a dermatologist at the Eastern Virginia School of Medicine, Norfolk.

Still, serlopitant addresses an unmet need for better treatment options for psoriatic itch. Up to 90% of psoriasis patients report experiencing pruritus, regardless of their disease severity.

“Although patients consider pruritus one of the most important, severe, and troublesome symptoms of psoriasis, clinicians have not historically recognized itch as a significant symptom, and treatments for psoriasis often don’t alleviate the associated pruritus,” he said.

Serlopitant has already shown efficacy and good tolerability in phase 2 studies in patients with prurigo nodularis and chronic pruritus.

The 8-week psoriatic itch trial included 204 adults with plaque psoriasis randomized to 5 mg of serlopitant once daily or placebo. Patients averaged 4.3% involved body surface area, and nearly two-thirds of them had moderate psoriasis by physician global assessment. The majority of patients rated their itch as severe; The average baseline score on the 0-10 Worst Itch Numeric Rating Scale was 8.2.

The primary study endpoint was achievement of at least a 4-point improvement on the Worst Itch Numeric Rating Scale. This was achieved in 33.9% of the serlopitant group and 21.1% of placebo-treated controls. The therapeutic benefit was consistent regardless of baseline body weight, gender, age, or extent of psoriasis-involved body surface area.

The safety data were consistent with what was seen in prior phase 2 studies for other dermatologic disorders. There were no serious adverse events, and the type and frequency of adverse events deemed related to treatment was similar in the two study arms.

“These results support the ongoing development of serlopitant across the spectrum of psoriatic disease,” Dr. Pariser declared.

The study was funded by Menlo Therapeutics. Dr. Pariser reported receiving research funding from and/or serving as a consultant to or advisory board member for roughly two dozen pharmaceutical companies.

bjancin@mdedge.com

MADRID – Serlopitant, an investigational once-daily oral neurokinin-1 receptor antagonist, resulted in clinically meaningful improvement in psoriatic itch in a phase 2, double-blind, placebo-controlled randomized trial, David M. Pariser, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The drug is not an effective stand alone treatment for psoriasis, though.

“The psoriasis itself did not improve during the trial. It’s the itch that improved. This drug is not designed for psoriasis; it’s going to be used for itching. If this does materialize as a treatment for psoriasis, it would be as an adjunct,” according to Dr. Pariser, a dermatologist at the Eastern Virginia School of Medicine, Norfolk.

Still, serlopitant addresses an unmet need for better treatment options for psoriatic itch. Up to 90% of psoriasis patients report experiencing pruritus, regardless of their disease severity.

“Although patients consider pruritus one of the most important, severe, and troublesome symptoms of psoriasis, clinicians have not historically recognized itch as a significant symptom, and treatments for psoriasis often don’t alleviate the associated pruritus,” he said.

Serlopitant has already shown efficacy and good tolerability in phase 2 studies in patients with prurigo nodularis and chronic pruritus.

The 8-week psoriatic itch trial included 204 adults with plaque psoriasis randomized to 5 mg of serlopitant once daily or placebo. Patients averaged 4.3% involved body surface area, and nearly two-thirds of them had moderate psoriasis by physician global assessment. The majority of patients rated their itch as severe; The average baseline score on the 0-10 Worst Itch Numeric Rating Scale was 8.2.

The primary study endpoint was achievement of at least a 4-point improvement on the Worst Itch Numeric Rating Scale. This was achieved in 33.9% of the serlopitant group and 21.1% of placebo-treated controls. The therapeutic benefit was consistent regardless of baseline body weight, gender, age, or extent of psoriasis-involved body surface area.

The safety data were consistent with what was seen in prior phase 2 studies for other dermatologic disorders. There were no serious adverse events, and the type and frequency of adverse events deemed related to treatment was similar in the two study arms.

“These results support the ongoing development of serlopitant across the spectrum of psoriatic disease,” Dr. Pariser declared.

The study was funded by Menlo Therapeutics. Dr. Pariser reported receiving research funding from and/or serving as a consultant to or advisory board member for roughly two dozen pharmaceutical companies.

bjancin@mdedge.com

PARIS – Though cardiovascular disease still accounts for 40% of deaths around the world, cancer is eclipsing cardiovascular disease as a cause of mortality in high income nations, according to new data from a global prospective study.

“Cancer deaths are becoming more frequent not because the rates of death from cancer are going up, but because we have decreased the deaths from cardiovascular disease,” said the study’s senior author, Salim Yusuf, MD, at the annual congress of the European Society of Cardiology.

A striking pattern emerged when cause of death was stratified by country income level, said fellow investigator Darryl P. Leong, MBBS, in presenting data regarding shifting global mortality patterns. Fully 55% of deaths in high-income nations were caused by cancer, compared with 30% in middle-income countries and 15% in low-income countries. In high-income countries, by contrast, cardiovascular disease (CVD) was the cause of death 23% of the time, while that figure was 42% and 43% for middle- and low-income countries, respectively.

Looking at the data slightly differently, the ratio of cardiovascular deaths to cancer deaths for high-income countries is 0.4; for middle-income countries, the ratio is 1.3, and “One is threefold more likely to die from cardiovascular disease as from cancer” in low-income countries, said Dr. Leong. Although the United States is not included in the PURE study, “recent data shows that some states in the U.S. also have higher cancer mortality than cardiovascular disease. This is a success story,” said Dr. Yusuf, since the shift is largely attributable to decreased mortality from CVD.

Dr. Leong and Dr. Yusuf each presented results from the PURE (Prospective Urban Rural Epidemiology) study, which has enrolled a total of 202,000 individuals from 27 countries on every inhabited continent but Australia. Follow-up data are available for 167,000 individuals in 21 countries. Canada, Russia, China, India, Brazil, and Chile are among the most populous national that are included. Their findings were published simultaneously in the Lancet with the congress presentations (2019 Sep 3; doi: 10.1016/S0140-6736(19)32008-2 and doi: 10.1016/S0140-6736(19)32007-0).

The INTERHEART risk score, an integrated cardiovascular risk score that uses non-laboratory values such as age, smoking status, family history, and comorbidities, was calculated for all participants. “We observed that the highest predicted cardiovascular risk is in high-income countries, and the lowest, in low-income countries,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Over the study period, 11,307 deaths occurred. Over 9,000 incident cardiovascular events were observed, as were over 5,000 new cancers.

“We have some interesting observations from these data,” said Dr. Leong. “Firstly, there is a gradient in the cardiovascular disease rates, moving from lowest in high-income countries – despite the fact that their INTERHEART risk score was highest – through to highest incident cardiovascular disease in low-income countries, despite their INTERHEART risk score being lowest.” This difference, said Dr. Leong, was driven by higher myocardial infarction rates in low-income countries and higher stroke rates in middle-income countries, when compared to high-income countries.

Once a participant was subject to one of the incident diseases, though, the patterns shifted. For CVD, cancer, chronic obstructive pulmonary disease, pneumonia, and injury, the likelihood of death within 1 year was highest in low-income countries – markedly higher, in the case of CVD. For all conditions, the one-year case-fatality rate after the occurrence of an incident disease was lowest in high-income countries.

“So we are seeing a new transition,” said Dr. Yusuf, the executive director of the Population Health Research Institute and Distinguished University Professor of Medicine, McMaster University, both in Hamilton, Ont. “The old transition was infectious diseases giving way to noncommunicable diseases. Now we are seeing a transition within noncommunicable diseases: In rich countries, cardiovascular disease is going down, perhaps due to better prevention, but I think even more importantly, due to better treatments.

“I want to hasten to add that the difference in risk between high-, middle-, and low-income countries in cardiovascular disease is not due to risk factors,” he went on. “Risk factors, if anything, are lower in the poor countries, compared to the higher-income countries.”

The shift away from cardiovascular disease mortality toward cancer mortality is also occurring in some countries that are in the upper tier of middle-income nations, including Chile, Argentina, Turkey, and Poland, said Dr. Yusuf, who presented data regarding the relative contributions of risk factors to cardiovascular disease and mortality.

Risk factors for cardiovascular disease in the PURE study were expressed by a measure called the population attributable fraction (PAF) that captures both the hazard ratio for a particular risk factor and the prevalence of the risk factor, explained Dr. Yusuf. “Hypertension, by far, was the biggest risk factor of cardiovascular disease globally,” he added, noting that the PAF for hypertension was over 20%. Hypertension far outstripped the next most significant risk factor, high non-HDL cholesterol, which had a PAF of less than 10%.

“This was a big surprise to us: Household pollution was a big factor,” said Dr. Yusuf, who later added that particulate matter from cooking, particularly with solid fuels such as wood or charcoal, was likely the source of much household air pollution, “a big problem in middle- and low-income countries.”

Tobacco usage is decreasing, as is its contribution to cardiovascular deaths, but other commonly cited culprits for cardiovascular disease were not significant contributors to cardiovascular disease in the PURE population.

“Abdominal obesity, and not BMI” contributes to cardiovascular risk. “BMI is not a good indicator of risk,” said Dr. Yusuf in a video interview. These results were presented separately at the congress.

“Grip strength is important; in fact, it is more important than low physical activity. People have focused on physical activity – how much you do. But strength seems to be more important…We haven’t focused on the importance of strength in the past.”

“Salt doesn’t figure in at all; salt has been exaggerated as a risk factor,” said Dr. Yusuf. “Diet needs to be rethought,” and conventional thinking challenged, he added, noting that consumption of full-fat dairy, nuts, and a moderate amount of meat all were protective among the PURE cohort.

Looking next at factors contributing to mortality in the global PURE population, low educational level had the highest attributable fraction of mortality of any single risk factor, at about 12%. “This has been ignored,” said Dr. Yusuf. “In most epidemiological studies, it’s been used as a covariate, or a stratifier,” rather than addressing low education itself as a risk factor, he said.

Tobacco use, low grip strength, and poor diet all had attributable fractions of just over 10%, said Dr. Yusuf, again noting that it wasn’t fat or meat consumption that made for the riskiest diet.

Overall, metabolic risk factors accounted for the largest fraction of risk of cardiovascular disease in the PURE population, with behavioral risk factors such as alcohol and tobacco use coming next. This held true across all income categories. However, in higher income nations where environmental factors and household air pollution are lower contributors to cardiovascular disease, metabolic and behavioral risk factors contributed more to cardiovascular disease risk.

Global differences in cardiovascular disease rates, stressed Dr. Yusuf, are not primarily attributable to metabolic risk factors. “The [World Health Organization] has focused on risk factors and has not focused on improved health care. Health care matters, and it matters in a big way.”

Adults aged 35-70 were recruited from 4 high-, 12 middle- and 5 low-income countries for PURE, and followed for a median 9.5 years. Cardiovascular disease and other health events salient to the study were documented both through direct contact and administrative record review, said Dr. Leong, and data about cardiovascular events and vital status were known for well over 90% of study participants.

Slightly less than half of participants were male, and over 108,000 participants were from middle income countries.

The PURE study was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Ontaario Ministry of Health and Long-Term Care, Astra Zeneca, Boehringer Ingelheim, Sanofi-Aentis, Servier Laboratories, and Glaxo Smith Kline. The study also received additional support in individual participating countries. Dr. Yusuf and Dr. Leon reported that they had no relevant conflicts of interest.

koakes@mdedge.com

PARIS – Though cardiovascular disease still accounts for 40% of deaths around the world, cancer is eclipsing cardiovascular disease as a cause of mortality in high income nations, according to new data from a global prospective study.

“Cancer deaths are becoming more frequent not because the rates of death from cancer are going up, but because we have decreased the deaths from cardiovascular disease,” said the study’s senior author, Salim Yusuf, MD, at the annual congress of the European Society of Cardiology.

A striking pattern emerged when cause of death was stratified by country income level, said fellow investigator Darryl P. Leong, MBBS, in presenting data regarding shifting global mortality patterns. Fully 55% of deaths in high-income nations were caused by cancer, compared with 30% in middle-income countries and 15% in low-income countries. In high-income countries, by contrast, cardiovascular disease (CVD) was the cause of death 23% of the time, while that figure was 42% and 43% for middle- and low-income countries, respectively.

Looking at the data slightly differently, the ratio of cardiovascular deaths to cancer deaths for high-income countries is 0.4; for middle-income countries, the ratio is 1.3, and “One is threefold more likely to die from cardiovascular disease as from cancer” in low-income countries, said Dr. Leong. Although the United States is not included in the PURE study, “recent data shows that some states in the U.S. also have higher cancer mortality than cardiovascular disease. This is a success story,” said Dr. Yusuf, since the shift is largely attributable to decreased mortality from CVD.

Dr. Leong and Dr. Yusuf each presented results from the PURE (Prospective Urban Rural Epidemiology) study, which has enrolled a total of 202,000 individuals from 27 countries on every inhabited continent but Australia. Follow-up data are available for 167,000 individuals in 21 countries. Canada, Russia, China, India, Brazil, and Chile are among the most populous national that are included. Their findings were published simultaneously in the Lancet with the congress presentations (2019 Sep 3; doi: 10.1016/S0140-6736(19)32008-2 and doi: 10.1016/S0140-6736(19)32007-0).

The INTERHEART risk score, an integrated cardiovascular risk score that uses non-laboratory values such as age, smoking status, family history, and comorbidities, was calculated for all participants. “We observed that the highest predicted cardiovascular risk is in high-income countries, and the lowest, in low-income countries,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Over the study period, 11,307 deaths occurred. Over 9,000 incident cardiovascular events were observed, as were over 5,000 new cancers.

“We have some interesting observations from these data,” said Dr. Leong. “Firstly, there is a gradient in the cardiovascular disease rates, moving from lowest in high-income countries – despite the fact that their INTERHEART risk score was highest – through to highest incident cardiovascular disease in low-income countries, despite their INTERHEART risk score being lowest.” This difference, said Dr. Leong, was driven by higher myocardial infarction rates in low-income countries and higher stroke rates in middle-income countries, when compared to high-income countries.

Once a participant was subject to one of the incident diseases, though, the patterns shifted. For CVD, cancer, chronic obstructive pulmonary disease, pneumonia, and injury, the likelihood of death within 1 year was highest in low-income countries – markedly higher, in the case of CVD. For all conditions, the one-year case-fatality rate after the occurrence of an incident disease was lowest in high-income countries.

“So we are seeing a new transition,” said Dr. Yusuf, the executive director of the Population Health Research Institute and Distinguished University Professor of Medicine, McMaster University, both in Hamilton, Ont. “The old transition was infectious diseases giving way to noncommunicable diseases. Now we are seeing a transition within noncommunicable diseases: In rich countries, cardiovascular disease is going down, perhaps due to better prevention, but I think even more importantly, due to better treatments.

“I want to hasten to add that the difference in risk between high-, middle-, and low-income countries in cardiovascular disease is not due to risk factors,” he went on. “Risk factors, if anything, are lower in the poor countries, compared to the higher-income countries.”

The shift away from cardiovascular disease mortality toward cancer mortality is also occurring in some countries that are in the upper tier of middle-income nations, including Chile, Argentina, Turkey, and Poland, said Dr. Yusuf, who presented data regarding the relative contributions of risk factors to cardiovascular disease and mortality.

Risk factors for cardiovascular disease in the PURE study were expressed by a measure called the population attributable fraction (PAF) that captures both the hazard ratio for a particular risk factor and the prevalence of the risk factor, explained Dr. Yusuf. “Hypertension, by far, was the biggest risk factor of cardiovascular disease globally,” he added, noting that the PAF for hypertension was over 20%. Hypertension far outstripped the next most significant risk factor, high non-HDL cholesterol, which had a PAF of less than 10%.

“This was a big surprise to us: Household pollution was a big factor,” said Dr. Yusuf, who later added that particulate matter from cooking, particularly with solid fuels such as wood or charcoal, was likely the source of much household air pollution, “a big problem in middle- and low-income countries.”

Tobacco usage is decreasing, as is its contribution to cardiovascular deaths, but other commonly cited culprits for cardiovascular disease were not significant contributors to cardiovascular disease in the PURE population.

“Abdominal obesity, and not BMI” contributes to cardiovascular risk. “BMI is not a good indicator of risk,” said Dr. Yusuf in a video interview. These results were presented separately at the congress.

“Grip strength is important; in fact, it is more important than low physical activity. People have focused on physical activity – how much you do. But strength seems to be more important…We haven’t focused on the importance of strength in the past.”

“Salt doesn’t figure in at all; salt has been exaggerated as a risk factor,” said Dr. Yusuf. “Diet needs to be rethought,” and conventional thinking challenged, he added, noting that consumption of full-fat dairy, nuts, and a moderate amount of meat all were protective among the PURE cohort.

Looking next at factors contributing to mortality in the global PURE population, low educational level had the highest attributable fraction of mortality of any single risk factor, at about 12%. “This has been ignored,” said Dr. Yusuf. “In most epidemiological studies, it’s been used as a covariate, or a stratifier,” rather than addressing low education itself as a risk factor, he said.

Tobacco use, low grip strength, and poor diet all had attributable fractions of just over 10%, said Dr. Yusuf, again noting that it wasn’t fat or meat consumption that made for the riskiest diet.

Overall, metabolic risk factors accounted for the largest fraction of risk of cardiovascular disease in the PURE population, with behavioral risk factors such as alcohol and tobacco use coming next. This held true across all income categories. However, in higher income nations where environmental factors and household air pollution are lower contributors to cardiovascular disease, metabolic and behavioral risk factors contributed more to cardiovascular disease risk.

Global differences in cardiovascular disease rates, stressed Dr. Yusuf, are not primarily attributable to metabolic risk factors. “The [World Health Organization] has focused on risk factors and has not focused on improved health care. Health care matters, and it matters in a big way.”

Adults aged 35-70 were recruited from 4 high-, 12 middle- and 5 low-income countries for PURE, and followed for a median 9.5 years. Cardiovascular disease and other health events salient to the study were documented both through direct contact and administrative record review, said Dr. Leong, and data about cardiovascular events and vital status were known for well over 90% of study participants.

Slightly less than half of participants were male, and over 108,000 participants were from middle income countries.

The PURE study was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Ontaario Ministry of Health and Long-Term Care, Astra Zeneca, Boehringer Ingelheim, Sanofi-Aentis, Servier Laboratories, and Glaxo Smith Kline. The study also received additional support in individual participating countries. Dr. Yusuf and Dr. Leon reported that they had no relevant conflicts of interest.

koakes@mdedge.com

PARIS – Though cardiovascular disease still accounts for 40% of deaths around the world, cancer is eclipsing cardiovascular disease as a cause of mortality in high income nations, according to new data from a global prospective study.

“Cancer deaths are becoming more frequent not because the rates of death from cancer are going up, but because we have decreased the deaths from cardiovascular disease,” said the study’s senior author, Salim Yusuf, MD, at the annual congress of the European Society of Cardiology.

A striking pattern emerged when cause of death was stratified by country income level, said fellow investigator Darryl P. Leong, MBBS, in presenting data regarding shifting global mortality patterns. Fully 55% of deaths in high-income nations were caused by cancer, compared with 30% in middle-income countries and 15% in low-income countries. In high-income countries, by contrast, cardiovascular disease (CVD) was the cause of death 23% of the time, while that figure was 42% and 43% for middle- and low-income countries, respectively.

Looking at the data slightly differently, the ratio of cardiovascular deaths to cancer deaths for high-income countries is 0.4; for middle-income countries, the ratio is 1.3, and “One is threefold more likely to die from cardiovascular disease as from cancer” in low-income countries, said Dr. Leong. Although the United States is not included in the PURE study, “recent data shows that some states in the U.S. also have higher cancer mortality than cardiovascular disease. This is a success story,” said Dr. Yusuf, since the shift is largely attributable to decreased mortality from CVD.

Dr. Leong and Dr. Yusuf each presented results from the PURE (Prospective Urban Rural Epidemiology) study, which has enrolled a total of 202,000 individuals from 27 countries on every inhabited continent but Australia. Follow-up data are available for 167,000 individuals in 21 countries. Canada, Russia, China, India, Brazil, and Chile are among the most populous national that are included. Their findings were published simultaneously in the Lancet with the congress presentations (2019 Sep 3; doi: 10.1016/S0140-6736(19)32008-2 and doi: 10.1016/S0140-6736(19)32007-0).

The INTERHEART risk score, an integrated cardiovascular risk score that uses non-laboratory values such as age, smoking status, family history, and comorbidities, was calculated for all participants. “We observed that the highest predicted cardiovascular risk is in high-income countries, and the lowest, in low-income countries,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Over the study period, 11,307 deaths occurred. Over 9,000 incident cardiovascular events were observed, as were over 5,000 new cancers.

“We have some interesting observations from these data,” said Dr. Leong. “Firstly, there is a gradient in the cardiovascular disease rates, moving from lowest in high-income countries – despite the fact that their INTERHEART risk score was highest – through to highest incident cardiovascular disease in low-income countries, despite their INTERHEART risk score being lowest.” This difference, said Dr. Leong, was driven by higher myocardial infarction rates in low-income countries and higher stroke rates in middle-income countries, when compared to high-income countries.

Once a participant was subject to one of the incident diseases, though, the patterns shifted. For CVD, cancer, chronic obstructive pulmonary disease, pneumonia, and injury, the likelihood of death within 1 year was highest in low-income countries – markedly higher, in the case of CVD. For all conditions, the one-year case-fatality rate after the occurrence of an incident disease was lowest in high-income countries.

“So we are seeing a new transition,” said Dr. Yusuf, the executive director of the Population Health Research Institute and Distinguished University Professor of Medicine, McMaster University, both in Hamilton, Ont. “The old transition was infectious diseases giving way to noncommunicable diseases. Now we are seeing a transition within noncommunicable diseases: In rich countries, cardiovascular disease is going down, perhaps due to better prevention, but I think even more importantly, due to better treatments.

“I want to hasten to add that the difference in risk between high-, middle-, and low-income countries in cardiovascular disease is not due to risk factors,” he went on. “Risk factors, if anything, are lower in the poor countries, compared to the higher-income countries.”

The shift away from cardiovascular disease mortality toward cancer mortality is also occurring in some countries that are in the upper tier of middle-income nations, including Chile, Argentina, Turkey, and Poland, said Dr. Yusuf, who presented data regarding the relative contributions of risk factors to cardiovascular disease and mortality.

Risk factors for cardiovascular disease in the PURE study were expressed by a measure called the population attributable fraction (PAF) that captures both the hazard ratio for a particular risk factor and the prevalence of the risk factor, explained Dr. Yusuf. “Hypertension, by far, was the biggest risk factor of cardiovascular disease globally,” he added, noting that the PAF for hypertension was over 20%. Hypertension far outstripped the next most significant risk factor, high non-HDL cholesterol, which had a PAF of less than 10%.

“This was a big surprise to us: Household pollution was a big factor,” said Dr. Yusuf, who later added that particulate matter from cooking, particularly with solid fuels such as wood or charcoal, was likely the source of much household air pollution, “a big problem in middle- and low-income countries.”

Tobacco usage is decreasing, as is its contribution to cardiovascular deaths, but other commonly cited culprits for cardiovascular disease were not significant contributors to cardiovascular disease in the PURE population.

“Abdominal obesity, and not BMI” contributes to cardiovascular risk. “BMI is not a good indicator of risk,” said Dr. Yusuf in a video interview. These results were presented separately at the congress.

“Grip strength is important; in fact, it is more important than low physical activity. People have focused on physical activity – how much you do. But strength seems to be more important…We haven’t focused on the importance of strength in the past.”

“Salt doesn’t figure in at all; salt has been exaggerated as a risk factor,” said Dr. Yusuf. “Diet needs to be rethought,” and conventional thinking challenged, he added, noting that consumption of full-fat dairy, nuts, and a moderate amount of meat all were protective among the PURE cohort.

Looking next at factors contributing to mortality in the global PURE population, low educational level had the highest attributable fraction of mortality of any single risk factor, at about 12%. “This has been ignored,” said Dr. Yusuf. “In most epidemiological studies, it’s been used as a covariate, or a stratifier,” rather than addressing low education itself as a risk factor, he said.

Tobacco use, low grip strength, and poor diet all had attributable fractions of just over 10%, said Dr. Yusuf, again noting that it wasn’t fat or meat consumption that made for the riskiest diet.

Overall, metabolic risk factors accounted for the largest fraction of risk of cardiovascular disease in the PURE population, with behavioral risk factors such as alcohol and tobacco use coming next. This held true across all income categories. However, in higher income nations where environmental factors and household air pollution are lower contributors to cardiovascular disease, metabolic and behavioral risk factors contributed more to cardiovascular disease risk.

Global differences in cardiovascular disease rates, stressed Dr. Yusuf, are not primarily attributable to metabolic risk factors. “The [World Health Organization] has focused on risk factors and has not focused on improved health care. Health care matters, and it matters in a big way.”

Adults aged 35-70 were recruited from 4 high-, 12 middle- and 5 low-income countries for PURE, and followed for a median 9.5 years. Cardiovascular disease and other health events salient to the study were documented both through direct contact and administrative record review, said Dr. Leong, and data about cardiovascular events and vital status were known for well over 90% of study participants.

Slightly less than half of participants were male, and over 108,000 participants were from middle income countries.

The PURE study was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Ontaario Ministry of Health and Long-Term Care, Astra Zeneca, Boehringer Ingelheim, Sanofi-Aentis, Servier Laboratories, and Glaxo Smith Kline. The study also received additional support in individual participating countries. Dr. Yusuf and Dr. Leon reported that they had no relevant conflicts of interest.

koakes@mdedge.com

NEW ORLEANS – Patients tended to recall the benefits of lung cancer screening much more than the risks in a recent survey, underscoring the need for ongoing patient education beyond the initial shared decision-making encounter, a researcher said.

While about 9 in 10 patients recalled key information on the benefits, only about 4 in 10 recalled information on risks, according to Erin Hirsch, MSPH, of the Colorado School of Public Health in Aurora.

“This may mean we need ongoing clinician involvement or continued education about this important information, especially if the patients aren’t screening annually,” Ms. Hirsch said in a podium presentation at the annual meeting of the American College of Chest Physicians.

Even fewer patients could correctly recall eligibility criteria for lung cancer screening, which suggests “ongoing clinician involvement” is needed to identify appropriate patients, Hirsch added in her presentation.

Shared decision making about lung cancer screening, which is supposed to entail a balanced patient-provider conversation about eligibility, risks, and benefits, is required by the Centers for Medicare & Medicaid Services to cover the cost of lung cancer screening as a preventative service, Hirsch noted in her presentation.

However, it’s largely unknown to what extent patients due for an annual screening recall information that should have been imparted in that initial discussion.

“The gap in knowledge centers around the fact that shared decision making is only required for baseline scan, but screening is recommended on an annual basis,” she said.

To test patient recall, Hirsch and colleagues developed a knowledge survey including 34 questions about lung cancer screening eligibility, risks, and benefits. The surveys went out by mail or email to 228 patients who had a baseline screening CT scan 6-12 months earlier; a total of 53 complete responses were included in the analysis, which focused on seven key questions about benefit, risk, and eligibility.

Recall was “excellent” for the benefit questions, Ms. Hirsch said, with 91% of patients able to recall that a computed tomography (CT) scan is better at detecting a possible lung cancer than a chest x-ray, while 87% recalled that without screening lung cancer is often found at a later stage when cure is less likely.

By contrast, a “moderate” amount (40%) remembered that a CT scan can suggest the patient has lung cancer when in fact they do not, she said, and only 38% recalled that radiation exposure was one of the harms of lung cancer screening, she added.

Eligibility recall was “poor,” she added, with only 21% affirming that not all current and former smokers need to be screened for lung cancer. Just 8% recalled that 55 years is the age at which beginning lung cancer screening is recommended, and 4% knew that 30 is the minimum number of pack-years required to be eligible for screening.

While these results may have clinical implications, Ms. Hirsch acknowledged a number of limitations to this pilot study. Among those was the fact that the content of the initial shared decision-making conversation could not be assessed: “We assumed that the patients were exposed to the information asked about in the survey ahead of time, but we can’t say for sure if that was true,” she explained.

Ms. Hirsch and coauthors disclosed no relationships relevant to their study.

SOURCE: Hirsch E et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.107.

NEW ORLEANS – Patients tended to recall the benefits of lung cancer screening much more than the risks in a recent survey, underscoring the need for ongoing patient education beyond the initial shared decision-making encounter, a researcher said.

While about 9 in 10 patients recalled key information on the benefits, only about 4 in 10 recalled information on risks, according to Erin Hirsch, MSPH, of the Colorado School of Public Health in Aurora.

“This may mean we need ongoing clinician involvement or continued education about this important information, especially if the patients aren’t screening annually,” Ms. Hirsch said in a podium presentation at the annual meeting of the American College of Chest Physicians.

Even fewer patients could correctly recall eligibility criteria for lung cancer screening, which suggests “ongoing clinician involvement” is needed to identify appropriate patients, Hirsch added in her presentation.

Shared decision making about lung cancer screening, which is supposed to entail a balanced patient-provider conversation about eligibility, risks, and benefits, is required by the Centers for Medicare & Medicaid Services to cover the cost of lung cancer screening as a preventative service, Hirsch noted in her presentation.

However, it’s largely unknown to what extent patients due for an annual screening recall information that should have been imparted in that initial discussion.

“The gap in knowledge centers around the fact that shared decision making is only required for baseline scan, but screening is recommended on an annual basis,” she said.

To test patient recall, Hirsch and colleagues developed a knowledge survey including 34 questions about lung cancer screening eligibility, risks, and benefits. The surveys went out by mail or email to 228 patients who had a baseline screening CT scan 6-12 months earlier; a total of 53 complete responses were included in the analysis, which focused on seven key questions about benefit, risk, and eligibility.

Recall was “excellent” for the benefit questions, Ms. Hirsch said, with 91% of patients able to recall that a computed tomography (CT) scan is better at detecting a possible lung cancer than a chest x-ray, while 87% recalled that without screening lung cancer is often found at a later stage when cure is less likely.

By contrast, a “moderate” amount (40%) remembered that a CT scan can suggest the patient has lung cancer when in fact they do not, she said, and only 38% recalled that radiation exposure was one of the harms of lung cancer screening, she added.

Eligibility recall was “poor,” she added, with only 21% affirming that not all current and former smokers need to be screened for lung cancer. Just 8% recalled that 55 years is the age at which beginning lung cancer screening is recommended, and 4% knew that 30 is the minimum number of pack-years required to be eligible for screening.

While these results may have clinical implications, Ms. Hirsch acknowledged a number of limitations to this pilot study. Among those was the fact that the content of the initial shared decision-making conversation could not be assessed: “We assumed that the patients were exposed to the information asked about in the survey ahead of time, but we can’t say for sure if that was true,” she explained.

Ms. Hirsch and coauthors disclosed no relationships relevant to their study.

SOURCE: Hirsch E et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.107.

NEW ORLEANS – Patients tended to recall the benefits of lung cancer screening much more than the risks in a recent survey, underscoring the need for ongoing patient education beyond the initial shared decision-making encounter, a researcher said.

While about 9 in 10 patients recalled key information on the benefits, only about 4 in 10 recalled information on risks, according to Erin Hirsch, MSPH, of the Colorado School of Public Health in Aurora.

“This may mean we need ongoing clinician involvement or continued education about this important information, especially if the patients aren’t screening annually,” Ms. Hirsch said in a podium presentation at the annual meeting of the American College of Chest Physicians.

Even fewer patients could correctly recall eligibility criteria for lung cancer screening, which suggests “ongoing clinician involvement” is needed to identify appropriate patients, Hirsch added in her presentation.

Shared decision making about lung cancer screening, which is supposed to entail a balanced patient-provider conversation about eligibility, risks, and benefits, is required by the Centers for Medicare & Medicaid Services to cover the cost of lung cancer screening as a preventative service, Hirsch noted in her presentation.

However, it’s largely unknown to what extent patients due for an annual screening recall information that should have been imparted in that initial discussion.

“The gap in knowledge centers around the fact that shared decision making is only required for baseline scan, but screening is recommended on an annual basis,” she said.

To test patient recall, Hirsch and colleagues developed a knowledge survey including 34 questions about lung cancer screening eligibility, risks, and benefits. The surveys went out by mail or email to 228 patients who had a baseline screening CT scan 6-12 months earlier; a total of 53 complete responses were included in the analysis, which focused on seven key questions about benefit, risk, and eligibility.

Recall was “excellent” for the benefit questions, Ms. Hirsch said, with 91% of patients able to recall that a computed tomography (CT) scan is better at detecting a possible lung cancer than a chest x-ray, while 87% recalled that without screening lung cancer is often found at a later stage when cure is less likely.

By contrast, a “moderate” amount (40%) remembered that a CT scan can suggest the patient has lung cancer when in fact they do not, she said, and only 38% recalled that radiation exposure was one of the harms of lung cancer screening, she added.

Eligibility recall was “poor,” she added, with only 21% affirming that not all current and former smokers need to be screened for lung cancer. Just 8% recalled that 55 years is the age at which beginning lung cancer screening is recommended, and 4% knew that 30 is the minimum number of pack-years required to be eligible for screening.

While these results may have clinical implications, Ms. Hirsch acknowledged a number of limitations to this pilot study. Among those was the fact that the content of the initial shared decision-making conversation could not be assessed: “We assumed that the patients were exposed to the information asked about in the survey ahead of time, but we can’t say for sure if that was true,” she explained.

Ms. Hirsch and coauthors disclosed no relationships relevant to their study.

SOURCE: Hirsch E et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.107.