NEW YORK – Emergency departments are seeing more pediatric and adolescent patients with autism spectrum disorder, and are struggling to meet their needs, experts say.

At the annual meeting of the American Academy of Child and Adolescent Psychiatry, researchers presented results from studies attempting to quantify and better understand the uptick in ED visits, while clinicians shared strategies aimed at improving care in a setting that, nearly all agreed, presents unique obstacles for treating children with ASD.

Bright lights, excess noise, frequently changing care staff, and a lack of training in nonverbal communication strategies were among the problems the clinicians highlighted.

“There’s been a huge increase in recent years in the number of children with ASD that are coming into the ED because of either behavioral crises or general pediatric medical concerns that require us to intervene,” said Eron Y. Friedlaender, MD, MPH, of Children’s Hospital of Philadelphia (CHOP). “Yet, we struggle to offer kids with challenging behaviors or communication vulnerabilities the same standard of care that we’re used to offering.”

John J. McGonigle, PhD, head of the autism center at the University of Pittsburgh, noted that incidents tied to safety issues, such as disruptive behavior, aggression, and self-injury, were occurring among young ASD patients in the ED. In 2015, he said, Pennsylvania’s statewide patient safety data reporting system reviewed hospital records from 2004 to 2014 and recorded 138 events in the ED involving patients with ASD, 86 of them involving children and adolescents.

Finding barriers to care

Dr. Friedlaender described a pilot study she and her colleagues conducted in her institution’s sedation unit that was designed to help them understand the barriers to optimal care for ASD patients, and to find ways around them. Many of the studies the investigators consulted “came from the dental literature, where there is a significant number of special-needs kids who need support during procedural care. [Dentists] were among the first to publish on how to make this a reasonable experience.”

One key insight gleaned from this literature, Dr. Friedlaender said, was that a simple screening question – whether the child could sit still for a haircut – proved sensitive in indicating a need for accommodation.

The CHOP researchers created a three-question universal screening tool that schedulers asked of all caregivers when a child presented to the ED. In addition to asking whether the child could sit still, schedulers asked whether he or she had a behavioral diagnosis or special communication needs. Of 458 families who completed the screening, 96 answered positively to at least one of the questions, and 79, or 17% of the cohort, indicated a behavioral diagnosis.

Such information previously had been missed, Dr. Friedlaender said, because “many families didn’t consider autism part of a medical history – if we didn’t ask about it, they didn’t share it.”

Her group also conducted a study on the effectiveness of self-reported pain scales in 43 verbal ASD children aged 6-17 who had undergone surgical procedures. Dr. Friedlaender said she suspected that it was impractical to ask children with ASD to use only pictures of facial expressions to indicate their pain.

The subjects were asked to circle images of faces with expressions corresponding to their pain. They also were asked to locate their pain by drawing it on tablet computers, and given poker chips to represent their degree of pain, with one chip the least and four the most. Caregivers were recruited to assist with questioning and interpreting responses.

All children in the study were able to describe and locate their pain. “We learned that there isn’t one universal pain tool that works for all kids,” Dr. Friedlaender said, “but that facial expressions and body language don’t often match pain scores” in ASD children. The study also revealed that parent or caregiver mediation is helpful in discerning the location and intensity of pain.

Why ED use is high

Other research presented at AACAP sought to grasp the scope of, and reasons behind, the increase in ASD youth seen in hospital emergency departments.

Michael J. Murray, MD, of Pennsylvania State University in Hershey, found using commercial insurance data from large employers showing that ED visits increased from 3% in 2005 to nearly 16% in 2013 among youth diagnosed with ASD, while a non-ASD comparison cohort saw a far more consistent rate of ED visits across the same time period, of about 3%. Adolescents with ASD were nearly five times more likely to have had an ED visit than were non-ASD adolescents (95% confidence interval, 4.678-4.875).

Dr. Murray said in an interview that the ASD cohort identified in his study “was smaller than it should have been,” compared with Centers for Disease Control and Prevention prevalence data. One likely reason is that not all the insurers had to cover ASD in the first years of the study period. Dr. Murray said he thinks a new study using public insurance data might provide a fuller picture.

Dr. Murray and colleagues’ study, which looked at youth aged 12-21, revealed that being older increased the likelihood of an ED visit. “We think it may have to do with the whole transition out of school,” he said. “This is the first generation with ASD that’s accustomed to having good school-based supports.” The transition to adulthood “is a really important time, and that’s when we’re pulling away from them.”

Sarah Lytle, MD, of University Hospitals Cleveland Medical Center, presented a literature review of ASD youth in the ED from 2006 through 2015. Dr. Lytle found that children with ASD were more likely to visit the ED than were those without ASD. In addition, the review showed a higher proportion of ED visits for psychiatric problems (13% of visits vs. 2% for non-ASD youth). Youth with ASD were more likely to be admitted to a psychiatric unit or medically boarded in the ED, she found. They also were more likely to have public insurance.

Dr. Lytle’s study drew from a dozen published studies in different age groups (subjects ranged from 0 to 24 years across studies). Though it was difficult to draw conclusions related to which saw the highest ED use, one study found the risk of ED use higher in adolescents, compared with younger children, she said. “One thing I see clinically is that when kids hit the age of 12, pediatric psychiatric units often won’t take them,” she said, as children are physically bigger and may be harder to manage. “And then they’re cycled into the ED,” she said.

Creating the ‘ASD care pathway’

Clinicians from New York shared their experiences designing and implementing an autism care pathway within the state’s only pediatric psychiatric emergency department.

At NYU Health and Hospitals/Bellevue, a public hospital, clinicians found themselves struggling to manage ASD patients, who comprise between 10% and 20% of children seen. “Most of our staff, and even our child psychiatrists, had previously had very little experience working with kids with autism, and that was true for most of our child psychiatrists as well,” said Ruth S. Gerson, MD, who oversees the hospital’s Children’s Comprehensive Psychiatric Emergency Program.

NEW YORK – Emergency departments are seeing more pediatric and adolescent patients with autism spectrum disorder, and are struggling to meet their needs, experts say.

At the annual meeting of the American Academy of Child and Adolescent Psychiatry, researchers presented results from studies attempting to quantify and better understand the uptick in ED visits, while clinicians shared strategies aimed at improving care in a setting that, nearly all agreed, presents unique obstacles for treating children with ASD.

Bright lights, excess noise, frequently changing care staff, and a lack of training in nonverbal communication strategies were among the problems the clinicians highlighted.

“There’s been a huge increase in recent years in the number of children with ASD that are coming into the ED because of either behavioral crises or general pediatric medical concerns that require us to intervene,” said Eron Y. Friedlaender, MD, MPH, of Children’s Hospital of Philadelphia (CHOP). “Yet, we struggle to offer kids with challenging behaviors or communication vulnerabilities the same standard of care that we’re used to offering.”

John J. McGonigle, PhD, head of the autism center at the University of Pittsburgh, noted that incidents tied to safety issues, such as disruptive behavior, aggression, and self-injury, were occurring among young ASD patients in the ED. In 2015, he said, Pennsylvania’s statewide patient safety data reporting system reviewed hospital records from 2004 to 2014 and recorded 138 events in the ED involving patients with ASD, 86 of them involving children and adolescents.

Finding barriers to care

Dr. Friedlaender described a pilot study she and her colleagues conducted in her institution’s sedation unit that was designed to help them understand the barriers to optimal care for ASD patients, and to find ways around them. Many of the studies the investigators consulted “came from the dental literature, where there is a significant number of special-needs kids who need support during procedural care. [Dentists] were among the first to publish on how to make this a reasonable experience.”

One key insight gleaned from this literature, Dr. Friedlaender said, was that a simple screening question – whether the child could sit still for a haircut – proved sensitive in indicating a need for accommodation.

The CHOP researchers created a three-question universal screening tool that schedulers asked of all caregivers when a child presented to the ED. In addition to asking whether the child could sit still, schedulers asked whether he or she had a behavioral diagnosis or special communication needs. Of 458 families who completed the screening, 96 answered positively to at least one of the questions, and 79, or 17% of the cohort, indicated a behavioral diagnosis.

Such information previously had been missed, Dr. Friedlaender said, because “many families didn’t consider autism part of a medical history – if we didn’t ask about it, they didn’t share it.”

Her group also conducted a study on the effectiveness of self-reported pain scales in 43 verbal ASD children aged 6-17 who had undergone surgical procedures. Dr. Friedlaender said she suspected that it was impractical to ask children with ASD to use only pictures of facial expressions to indicate their pain.

The subjects were asked to circle images of faces with expressions corresponding to their pain. They also were asked to locate their pain by drawing it on tablet computers, and given poker chips to represent their degree of pain, with one chip the least and four the most. Caregivers were recruited to assist with questioning and interpreting responses.

All children in the study were able to describe and locate their pain. “We learned that there isn’t one universal pain tool that works for all kids,” Dr. Friedlaender said, “but that facial expressions and body language don’t often match pain scores” in ASD children. The study also revealed that parent or caregiver mediation is helpful in discerning the location and intensity of pain.

Why ED use is high

Other research presented at AACAP sought to grasp the scope of, and reasons behind, the increase in ASD youth seen in hospital emergency departments.

Michael J. Murray, MD, of Pennsylvania State University in Hershey, found using commercial insurance data from large employers showing that ED visits increased from 3% in 2005 to nearly 16% in 2013 among youth diagnosed with ASD, while a non-ASD comparison cohort saw a far more consistent rate of ED visits across the same time period, of about 3%. Adolescents with ASD were nearly five times more likely to have had an ED visit than were non-ASD adolescents (95% confidence interval, 4.678-4.875).

Dr. Murray said in an interview that the ASD cohort identified in his study “was smaller than it should have been,” compared with Centers for Disease Control and Prevention prevalence data. One likely reason is that not all the insurers had to cover ASD in the first years of the study period. Dr. Murray said he thinks a new study using public insurance data might provide a fuller picture.

Dr. Murray and colleagues’ study, which looked at youth aged 12-21, revealed that being older increased the likelihood of an ED visit. “We think it may have to do with the whole transition out of school,” he said. “This is the first generation with ASD that’s accustomed to having good school-based supports.” The transition to adulthood “is a really important time, and that’s when we’re pulling away from them.”

Sarah Lytle, MD, of University Hospitals Cleveland Medical Center, presented a literature review of ASD youth in the ED from 2006 through 2015. Dr. Lytle found that children with ASD were more likely to visit the ED than were those without ASD. In addition, the review showed a higher proportion of ED visits for psychiatric problems (13% of visits vs. 2% for non-ASD youth). Youth with ASD were more likely to be admitted to a psychiatric unit or medically boarded in the ED, she found. They also were more likely to have public insurance.

Dr. Lytle’s study drew from a dozen published studies in different age groups (subjects ranged from 0 to 24 years across studies). Though it was difficult to draw conclusions related to which saw the highest ED use, one study found the risk of ED use higher in adolescents, compared with younger children, she said. “One thing I see clinically is that when kids hit the age of 12, pediatric psychiatric units often won’t take them,” she said, as children are physically bigger and may be harder to manage. “And then they’re cycled into the ED,” she said.

Creating the ‘ASD care pathway’

Clinicians from New York shared their experiences designing and implementing an autism care pathway within the state’s only pediatric psychiatric emergency department.

At NYU Health and Hospitals/Bellevue, a public hospital, clinicians found themselves struggling to manage ASD patients, who comprise between 10% and 20% of children seen. “Most of our staff, and even our child psychiatrists, had previously had very little experience working with kids with autism, and that was true for most of our child psychiatrists as well,” said Ruth S. Gerson, MD, who oversees the hospital’s Children’s Comprehensive Psychiatric Emergency Program.

NEW YORK – Emergency departments are seeing more pediatric and adolescent patients with autism spectrum disorder, and are struggling to meet their needs, experts say.

At the annual meeting of the American Academy of Child and Adolescent Psychiatry, researchers presented results from studies attempting to quantify and better understand the uptick in ED visits, while clinicians shared strategies aimed at improving care in a setting that, nearly all agreed, presents unique obstacles for treating children with ASD.

Bright lights, excess noise, frequently changing care staff, and a lack of training in nonverbal communication strategies were among the problems the clinicians highlighted.

“There’s been a huge increase in recent years in the number of children with ASD that are coming into the ED because of either behavioral crises or general pediatric medical concerns that require us to intervene,” said Eron Y. Friedlaender, MD, MPH, of Children’s Hospital of Philadelphia (CHOP). “Yet, we struggle to offer kids with challenging behaviors or communication vulnerabilities the same standard of care that we’re used to offering.”

John J. McGonigle, PhD, head of the autism center at the University of Pittsburgh, noted that incidents tied to safety issues, such as disruptive behavior, aggression, and self-injury, were occurring among young ASD patients in the ED. In 2015, he said, Pennsylvania’s statewide patient safety data reporting system reviewed hospital records from 2004 to 2014 and recorded 138 events in the ED involving patients with ASD, 86 of them involving children and adolescents.

Finding barriers to care

Dr. Friedlaender described a pilot study she and her colleagues conducted in her institution’s sedation unit that was designed to help them understand the barriers to optimal care for ASD patients, and to find ways around them. Many of the studies the investigators consulted “came from the dental literature, where there is a significant number of special-needs kids who need support during procedural care. [Dentists] were among the first to publish on how to make this a reasonable experience.”

One key insight gleaned from this literature, Dr. Friedlaender said, was that a simple screening question – whether the child could sit still for a haircut – proved sensitive in indicating a need for accommodation.

The CHOP researchers created a three-question universal screening tool that schedulers asked of all caregivers when a child presented to the ED. In addition to asking whether the child could sit still, schedulers asked whether he or she had a behavioral diagnosis or special communication needs. Of 458 families who completed the screening, 96 answered positively to at least one of the questions, and 79, or 17% of the cohort, indicated a behavioral diagnosis.

Such information previously had been missed, Dr. Friedlaender said, because “many families didn’t consider autism part of a medical history – if we didn’t ask about it, they didn’t share it.”

Her group also conducted a study on the effectiveness of self-reported pain scales in 43 verbal ASD children aged 6-17 who had undergone surgical procedures. Dr. Friedlaender said she suspected that it was impractical to ask children with ASD to use only pictures of facial expressions to indicate their pain.

The subjects were asked to circle images of faces with expressions corresponding to their pain. They also were asked to locate their pain by drawing it on tablet computers, and given poker chips to represent their degree of pain, with one chip the least and four the most. Caregivers were recruited to assist with questioning and interpreting responses.

All children in the study were able to describe and locate their pain. “We learned that there isn’t one universal pain tool that works for all kids,” Dr. Friedlaender said, “but that facial expressions and body language don’t often match pain scores” in ASD children. The study also revealed that parent or caregiver mediation is helpful in discerning the location and intensity of pain.

Why ED use is high

Other research presented at AACAP sought to grasp the scope of, and reasons behind, the increase in ASD youth seen in hospital emergency departments.

Michael J. Murray, MD, of Pennsylvania State University in Hershey, found using commercial insurance data from large employers showing that ED visits increased from 3% in 2005 to nearly 16% in 2013 among youth diagnosed with ASD, while a non-ASD comparison cohort saw a far more consistent rate of ED visits across the same time period, of about 3%. Adolescents with ASD were nearly five times more likely to have had an ED visit than were non-ASD adolescents (95% confidence interval, 4.678-4.875).

Dr. Murray said in an interview that the ASD cohort identified in his study “was smaller than it should have been,” compared with Centers for Disease Control and Prevention prevalence data. One likely reason is that not all the insurers had to cover ASD in the first years of the study period. Dr. Murray said he thinks a new study using public insurance data might provide a fuller picture.

Dr. Murray and colleagues’ study, which looked at youth aged 12-21, revealed that being older increased the likelihood of an ED visit. “We think it may have to do with the whole transition out of school,” he said. “This is the first generation with ASD that’s accustomed to having good school-based supports.” The transition to adulthood “is a really important time, and that’s when we’re pulling away from them.”

Sarah Lytle, MD, of University Hospitals Cleveland Medical Center, presented a literature review of ASD youth in the ED from 2006 through 2015. Dr. Lytle found that children with ASD were more likely to visit the ED than were those without ASD. In addition, the review showed a higher proportion of ED visits for psychiatric problems (13% of visits vs. 2% for non-ASD youth). Youth with ASD were more likely to be admitted to a psychiatric unit or medically boarded in the ED, she found. They also were more likely to have public insurance.

Dr. Lytle’s study drew from a dozen published studies in different age groups (subjects ranged from 0 to 24 years across studies). Though it was difficult to draw conclusions related to which saw the highest ED use, one study found the risk of ED use higher in adolescents, compared with younger children, she said. “One thing I see clinically is that when kids hit the age of 12, pediatric psychiatric units often won’t take them,” she said, as children are physically bigger and may be harder to manage. “And then they’re cycled into the ED,” she said.

Creating the ‘ASD care pathway’

Clinicians from New York shared their experiences designing and implementing an autism care pathway within the state’s only pediatric psychiatric emergency department.

At NYU Health and Hospitals/Bellevue, a public hospital, clinicians found themselves struggling to manage ASD patients, who comprise between 10% and 20% of children seen. “Most of our staff, and even our child psychiatrists, had previously had very little experience working with kids with autism, and that was true for most of our child psychiatrists as well,” said Ruth S. Gerson, MD, who oversees the hospital’s Children’s Comprehensive Psychiatric Emergency Program.

Approximately 600 cases of operating room (OR) fires are reported annually.¹ The incidence of OR fires in the United States equals that of wrong-site surgeries, and 20% of cases have associated morbidity.^1,2 The estimated mortality rate is 1 to 2 cases per year.^3-5 The most commonly involved anatomical regions are the airway (33%) and the face (28%).⁴ Most surgical fires are reported in anesthetized patients with open oxygen delivery systems during head, neck, and upper chest surgeries; electrosurgical instruments are the ignition source in 90% of these cases.⁶ Despite extensive fire safety education and training, complete elimination of OR fires still has not been achieved.

Each fire requires an ignition source, a fuel source, and an oxidizer.⁷ In the OR, the 2 most common oxidizers are oxygen and nitrous oxide. Head and neck surgeries have a high concentration of these gases near the working field and therefore a higher risk and incidence of fires. Furthermore, surgical drapes and equipment (eg, closed or semi-closed breathing systems, masks) may potentiate this risk by reducing ventilation in areas where gases can accumulate and ignite. Ignition sources provide the energy that starts fires; common sources are electrocautery, lasers, fiber-optic light cords, drills/burrs, and defibrillator paddles. Fires are propagated by fuel sources, which encompass any flammable material, including tracheal tubes, sponges, alcohol-based solutions, hair, gastrointestinal tract gases, gloves, and packaging materials.⁸ Of note, alcohol-based skin-preparation agents emit flammable vapors that can ignite.^9-14 Before draping or exposure to an ignition source, chlorhexidine gluconate-based preparations must be allowed to dry for at least 3 minutes after application to hairless skin and up to 1 hour after application to hair.¹⁵ Inadequate drying poses a risk of fire.¹⁰We present the case of an OR fire ignited by electrocautery near freshly applied bone cement. No patient information is disclosed in this report.

Case Report

Our patient was evaluated in clinic and scheduled for total knee arthroplasty (TKA). All preoperative safety checklists and time-out procedures were followed and documented at the start of surgery. The TKA was performed with a standard medial patellar arthrotomy. Tourniquet control was used after Esmarch exsanguination. The surgery proceeded uneventfully until just after the bone cement was applied to the tibial surface. The surgeon was using a Bovie to resect residual lateral meniscus tissue when a fire instantaneously erupted within the joint space. Fortunately, the surgeon quickly suffocated the fire with a dry towel. The ignited bone cement was removed, and the patient was examined. There was no injury to surrounding tissue or joint space. Surgery was resumed with application of new bone cement to the tibial surface. The artificial joint was then successfully implanted and the case completed without further incident. The patient was discharged from the hospital and followed up as an outpatient without any postoperative complications.

Discussion

Bone cement, which is commonly used in artificial joint anchoring, craniofacial reconstruction, and vertebroplasty, has liquid and powder components. The liquid monomer methyl methacrylate (MMA) is colorless and flammable and has a distinct odor.¹⁶ Exposure to heat or light can prematurely polymerize MMA, requiring the addition of hydroquinone to inhibit the reaction.¹⁶ The powder polymethylmethacrylate affords excellent structural support, radiopacity, and facility of use.¹⁷ Dibenzoyl peroxide and N,N-dimethyl-p-toluidine are added to the powder to facilitate the polymerization reaction at room temperature (ie, cold curing of cement). Premature application of unpolymerized cement increases the risk of fire from the volatile liquid component.

In the OR, bone cement is prepared by mixing together its powder and liquid components.¹⁸ The reaction is exothermic polymerization. The liquid is highly volatile and flammable in both liquid and vapor states.^16,19 The vapors are denser than air and can concentrate in poorly ventilated areas. The OR and the application site must be adequately ventilated to eliminate any pockets of vapor accumulation.¹⁶ A vacuum mixer can be used to minimize fume exposure, enhance cement strength, and reduce fire risk while combining the 2 components.

MMA’s flash point, the temperature at which the fumes could ignite in the presence of an ignition source, is 10.5ºC. The auto-ignition point, the temperature at which MMA spontaneously combusts, is 421ºC.²⁰ The OR is usually warmer than the flash point temperature, but the electrocautery tip can generate up to 1200ºC of heat.²¹ Therefore, bone cement is a potential fire hazard, and use of Bovies or other ignition sources in its vicinity must be avoided.

The Table lists the recommended times for preparing various bone cement products.^22,23Mix time is the time needed to combine the liquid and powder into a homogenous putty.

Approximately 600 cases of operating room (OR) fires are reported annually.¹ The incidence of OR fires in the United States equals that of wrong-site surgeries, and 20% of cases have associated morbidity.^1,2 The estimated mortality rate is 1 to 2 cases per year.^3-5 The most commonly involved anatomical regions are the airway (33%) and the face (28%).⁴ Most surgical fires are reported in anesthetized patients with open oxygen delivery systems during head, neck, and upper chest surgeries; electrosurgical instruments are the ignition source in 90% of these cases.⁶ Despite extensive fire safety education and training, complete elimination of OR fires still has not been achieved.

Each fire requires an ignition source, a fuel source, and an oxidizer.⁷ In the OR, the 2 most common oxidizers are oxygen and nitrous oxide. Head and neck surgeries have a high concentration of these gases near the working field and therefore a higher risk and incidence of fires. Furthermore, surgical drapes and equipment (eg, closed or semi-closed breathing systems, masks) may potentiate this risk by reducing ventilation in areas where gases can accumulate and ignite. Ignition sources provide the energy that starts fires; common sources are electrocautery, lasers, fiber-optic light cords, drills/burrs, and defibrillator paddles. Fires are propagated by fuel sources, which encompass any flammable material, including tracheal tubes, sponges, alcohol-based solutions, hair, gastrointestinal tract gases, gloves, and packaging materials.⁸ Of note, alcohol-based skin-preparation agents emit flammable vapors that can ignite.^9-14 Before draping or exposure to an ignition source, chlorhexidine gluconate-based preparations must be allowed to dry for at least 3 minutes after application to hairless skin and up to 1 hour after application to hair.¹⁵ Inadequate drying poses a risk of fire.¹⁰We present the case of an OR fire ignited by electrocautery near freshly applied bone cement. No patient information is disclosed in this report.

Case Report

Our patient was evaluated in clinic and scheduled for total knee arthroplasty (TKA). All preoperative safety checklists and time-out procedures were followed and documented at the start of surgery. The TKA was performed with a standard medial patellar arthrotomy. Tourniquet control was used after Esmarch exsanguination. The surgery proceeded uneventfully until just after the bone cement was applied to the tibial surface. The surgeon was using a Bovie to resect residual lateral meniscus tissue when a fire instantaneously erupted within the joint space. Fortunately, the surgeon quickly suffocated the fire with a dry towel. The ignited bone cement was removed, and the patient was examined. There was no injury to surrounding tissue or joint space. Surgery was resumed with application of new bone cement to the tibial surface. The artificial joint was then successfully implanted and the case completed without further incident. The patient was discharged from the hospital and followed up as an outpatient without any postoperative complications.

Discussion

Bone cement, which is commonly used in artificial joint anchoring, craniofacial reconstruction, and vertebroplasty, has liquid and powder components. The liquid monomer methyl methacrylate (MMA) is colorless and flammable and has a distinct odor.¹⁶ Exposure to heat or light can prematurely polymerize MMA, requiring the addition of hydroquinone to inhibit the reaction.¹⁶ The powder polymethylmethacrylate affords excellent structural support, radiopacity, and facility of use.¹⁷ Dibenzoyl peroxide and N,N-dimethyl-p-toluidine are added to the powder to facilitate the polymerization reaction at room temperature (ie, cold curing of cement). Premature application of unpolymerized cement increases the risk of fire from the volatile liquid component.

In the OR, bone cement is prepared by mixing together its powder and liquid components.¹⁸ The reaction is exothermic polymerization. The liquid is highly volatile and flammable in both liquid and vapor states.^16,19 The vapors are denser than air and can concentrate in poorly ventilated areas. The OR and the application site must be adequately ventilated to eliminate any pockets of vapor accumulation.¹⁶ A vacuum mixer can be used to minimize fume exposure, enhance cement strength, and reduce fire risk while combining the 2 components.

MMA’s flash point, the temperature at which the fumes could ignite in the presence of an ignition source, is 10.5ºC. The auto-ignition point, the temperature at which MMA spontaneously combusts, is 421ºC.²⁰ The OR is usually warmer than the flash point temperature, but the electrocautery tip can generate up to 1200ºC of heat.²¹ Therefore, bone cement is a potential fire hazard, and use of Bovies or other ignition sources in its vicinity must be avoided.

The Table lists the recommended times for preparing various bone cement products.^22,23Mix time is the time needed to combine the liquid and powder into a homogenous putty.

Approximately 600 cases of operating room (OR) fires are reported annually.¹ The incidence of OR fires in the United States equals that of wrong-site surgeries, and 20% of cases have associated morbidity.^1,2 The estimated mortality rate is 1 to 2 cases per year.^3-5 The most commonly involved anatomical regions are the airway (33%) and the face (28%).⁴ Most surgical fires are reported in anesthetized patients with open oxygen delivery systems during head, neck, and upper chest surgeries; electrosurgical instruments are the ignition source in 90% of these cases.⁶ Despite extensive fire safety education and training, complete elimination of OR fires still has not been achieved.

Each fire requires an ignition source, a fuel source, and an oxidizer.⁷ In the OR, the 2 most common oxidizers are oxygen and nitrous oxide. Head and neck surgeries have a high concentration of these gases near the working field and therefore a higher risk and incidence of fires. Furthermore, surgical drapes and equipment (eg, closed or semi-closed breathing systems, masks) may potentiate this risk by reducing ventilation in areas where gases can accumulate and ignite. Ignition sources provide the energy that starts fires; common sources are electrocautery, lasers, fiber-optic light cords, drills/burrs, and defibrillator paddles. Fires are propagated by fuel sources, which encompass any flammable material, including tracheal tubes, sponges, alcohol-based solutions, hair, gastrointestinal tract gases, gloves, and packaging materials.⁸ Of note, alcohol-based skin-preparation agents emit flammable vapors that can ignite.^9-14 Before draping or exposure to an ignition source, chlorhexidine gluconate-based preparations must be allowed to dry for at least 3 minutes after application to hairless skin and up to 1 hour after application to hair.¹⁵ Inadequate drying poses a risk of fire.¹⁰We present the case of an OR fire ignited by electrocautery near freshly applied bone cement. No patient information is disclosed in this report.

Case Report

Our patient was evaluated in clinic and scheduled for total knee arthroplasty (TKA). All preoperative safety checklists and time-out procedures were followed and documented at the start of surgery. The TKA was performed with a standard medial patellar arthrotomy. Tourniquet control was used after Esmarch exsanguination. The surgery proceeded uneventfully until just after the bone cement was applied to the tibial surface. The surgeon was using a Bovie to resect residual lateral meniscus tissue when a fire instantaneously erupted within the joint space. Fortunately, the surgeon quickly suffocated the fire with a dry towel. The ignited bone cement was removed, and the patient was examined. There was no injury to surrounding tissue or joint space. Surgery was resumed with application of new bone cement to the tibial surface. The artificial joint was then successfully implanted and the case completed without further incident. The patient was discharged from the hospital and followed up as an outpatient without any postoperative complications.

Discussion

Bone cement, which is commonly used in artificial joint anchoring, craniofacial reconstruction, and vertebroplasty, has liquid and powder components. The liquid monomer methyl methacrylate (MMA) is colorless and flammable and has a distinct odor.¹⁶ Exposure to heat or light can prematurely polymerize MMA, requiring the addition of hydroquinone to inhibit the reaction.¹⁶ The powder polymethylmethacrylate affords excellent structural support, radiopacity, and facility of use.¹⁷ Dibenzoyl peroxide and N,N-dimethyl-p-toluidine are added to the powder to facilitate the polymerization reaction at room temperature (ie, cold curing of cement). Premature application of unpolymerized cement increases the risk of fire from the volatile liquid component.

In the OR, bone cement is prepared by mixing together its powder and liquid components.¹⁸ The reaction is exothermic polymerization. The liquid is highly volatile and flammable in both liquid and vapor states.^16,19 The vapors are denser than air and can concentrate in poorly ventilated areas. The OR and the application site must be adequately ventilated to eliminate any pockets of vapor accumulation.¹⁶ A vacuum mixer can be used to minimize fume exposure, enhance cement strength, and reduce fire risk while combining the 2 components.

MMA’s flash point, the temperature at which the fumes could ignite in the presence of an ignition source, is 10.5ºC. The auto-ignition point, the temperature at which MMA spontaneously combusts, is 421ºC.²⁰ The OR is usually warmer than the flash point temperature, but the electrocautery tip can generate up to 1200ºC of heat.²¹ Therefore, bone cement is a potential fire hazard, and use of Bovies or other ignition sources in its vicinity must be avoided.

The Table lists the recommended times for preparing various bone cement products.^22,23Mix time is the time needed to combine the liquid and powder into a homogenous putty.

Fear and anxiety, economic disadvantage, and recent psychosocial adversity contribute significantly to the onset of major depressive disorder in children and adolescents with a strong family history of the condition.

A 4-year longitudinal study followed the offspring of 279 families in which one parent had experienced at least two episodes of major depressive disorder (MDD) and in which there was a biologically related child living with that index parent.

Fear and anxiety showed a strong and significant association with new-onset major depressive disorder, as did irritability. Furthermore, the association between the two symptoms was low but significant, suggesting that they do not often co-occur (JAMA Psychiatry. 2016 Dec 7. doi: 10.1001/jamapsychiatry.2016.3140).

“The results suggested that generalized anxiety symptoms were driving the predictive effect of fear/anxiety on new-onset MDD and that fear/anxiety (and not irritability) predicted an especially early MDD onset,” wrote Frances Rice, PhD, of the division of psychological medicine and clinical neurosciences at Cardiff University, Wales, and coauthors.

Recent psychosocial adversity – stressful events such as the death of a friend, illness, bullying, or parents fighting – also showed a strong association with new-onset major depressive disorder, while economic disadvantage had a lesser but still significant contribution. Both of these also were associated with fear and anxiety, and irritability.

Greater family history and more severe parental depression also contributed significantly to the emergence of depression in the offspring, although those factors were not associated with the clinical antecedents such as fear and anxiety.

“Therefore, the indicators of social risk predicted MDD independent of correlated familial risk, parental depression severity, and clinical antecedents in the child,” the authors wrote. “This result has important implications for treatment and prevention and highlights the need to resolve not only clinical phenomena in the child but also wider contextual difficulties.”

The study also suggested that neither disruptive behavior nor low mood were significantly associated with new-onset MDD in children and adolescents.

The children and adolescents in the study had a mean of 1.85 DSM-IV major depressive disorder symptoms at follow-up, and 20 of them – six males and 14 females – had new-onset MDD, with a mean age of onset of 14.4 years.

“Our findings suggest that primary prevention methods for depression in groups with high familial risk will need to include effective treatment of parental depression, irritability, and fear/anxiety in the child and consider social risk factors,” Dr. Rice and her coauthors wrote.

The research and researchers were supported by the Sir Jules Thorn Charitable Trust, the Medical Research Council, the Economic and Social Research Council, the British Academy, and the British Medical Association. No conflicts of interest were declared.

Fear and anxiety, economic disadvantage, and recent psychosocial adversity contribute significantly to the onset of major depressive disorder in children and adolescents with a strong family history of the condition.

A 4-year longitudinal study followed the offspring of 279 families in which one parent had experienced at least two episodes of major depressive disorder (MDD) and in which there was a biologically related child living with that index parent.

Fear and anxiety showed a strong and significant association with new-onset major depressive disorder, as did irritability. Furthermore, the association between the two symptoms was low but significant, suggesting that they do not often co-occur (JAMA Psychiatry. 2016 Dec 7. doi: 10.1001/jamapsychiatry.2016.3140).

“The results suggested that generalized anxiety symptoms were driving the predictive effect of fear/anxiety on new-onset MDD and that fear/anxiety (and not irritability) predicted an especially early MDD onset,” wrote Frances Rice, PhD, of the division of psychological medicine and clinical neurosciences at Cardiff University, Wales, and coauthors.

Recent psychosocial adversity – stressful events such as the death of a friend, illness, bullying, or parents fighting – also showed a strong association with new-onset major depressive disorder, while economic disadvantage had a lesser but still significant contribution. Both of these also were associated with fear and anxiety, and irritability.

Greater family history and more severe parental depression also contributed significantly to the emergence of depression in the offspring, although those factors were not associated with the clinical antecedents such as fear and anxiety.

“Therefore, the indicators of social risk predicted MDD independent of correlated familial risk, parental depression severity, and clinical antecedents in the child,” the authors wrote. “This result has important implications for treatment and prevention and highlights the need to resolve not only clinical phenomena in the child but also wider contextual difficulties.”

The study also suggested that neither disruptive behavior nor low mood were significantly associated with new-onset MDD in children and adolescents.

The children and adolescents in the study had a mean of 1.85 DSM-IV major depressive disorder symptoms at follow-up, and 20 of them – six males and 14 females – had new-onset MDD, with a mean age of onset of 14.4 years.

“Our findings suggest that primary prevention methods for depression in groups with high familial risk will need to include effective treatment of parental depression, irritability, and fear/anxiety in the child and consider social risk factors,” Dr. Rice and her coauthors wrote.

The research and researchers were supported by the Sir Jules Thorn Charitable Trust, the Medical Research Council, the Economic and Social Research Council, the British Academy, and the British Medical Association. No conflicts of interest were declared.

Fear and anxiety, economic disadvantage, and recent psychosocial adversity contribute significantly to the onset of major depressive disorder in children and adolescents with a strong family history of the condition.

A 4-year longitudinal study followed the offspring of 279 families in which one parent had experienced at least two episodes of major depressive disorder (MDD) and in which there was a biologically related child living with that index parent.

Fear and anxiety showed a strong and significant association with new-onset major depressive disorder, as did irritability. Furthermore, the association between the two symptoms was low but significant, suggesting that they do not often co-occur (JAMA Psychiatry. 2016 Dec 7. doi: 10.1001/jamapsychiatry.2016.3140).

“The results suggested that generalized anxiety symptoms were driving the predictive effect of fear/anxiety on new-onset MDD and that fear/anxiety (and not irritability) predicted an especially early MDD onset,” wrote Frances Rice, PhD, of the division of psychological medicine and clinical neurosciences at Cardiff University, Wales, and coauthors.

Recent psychosocial adversity – stressful events such as the death of a friend, illness, bullying, or parents fighting – also showed a strong association with new-onset major depressive disorder, while economic disadvantage had a lesser but still significant contribution. Both of these also were associated with fear and anxiety, and irritability.

Greater family history and more severe parental depression also contributed significantly to the emergence of depression in the offspring, although those factors were not associated with the clinical antecedents such as fear and anxiety.

“Therefore, the indicators of social risk predicted MDD independent of correlated familial risk, parental depression severity, and clinical antecedents in the child,” the authors wrote. “This result has important implications for treatment and prevention and highlights the need to resolve not only clinical phenomena in the child but also wider contextual difficulties.”

The study also suggested that neither disruptive behavior nor low mood were significantly associated with new-onset MDD in children and adolescents.

The children and adolescents in the study had a mean of 1.85 DSM-IV major depressive disorder symptoms at follow-up, and 20 of them – six males and 14 females – had new-onset MDD, with a mean age of onset of 14.4 years.

“Our findings suggest that primary prevention methods for depression in groups with high familial risk will need to include effective treatment of parental depression, irritability, and fear/anxiety in the child and consider social risk factors,” Dr. Rice and her coauthors wrote.

The research and researchers were supported by the Sir Jules Thorn Charitable Trust, the Medical Research Council, the Economic and Social Research Council, the British Academy, and the British Medical Association. No conflicts of interest were declared.

After older patients undergo lung resection for stage I non–small-cell lung cancer, they are actually at greater risk of death from something other than lung cancer for up to 2.5 years, according to researchers at Memorial Sloan Kettering Cancer Center, New York. The findings were published online in the Journal of Clinical Oncology (2016;34: doi: 10.1200/JCO.2016.69.0834).

“As age increases, the risk of competing events increases, such as death from noncancer diseases,” wrote Takashi Eguchi, MD, and coauthors. “In this era of personalized cancer therapy, important to the stratification of individualized treatments is the determination of how both cancer and noncancer risk factors – specifically, comorbidities associated with increasing age – contribute to the risk of death.”

The researchers examined outcomes in three different age groups: younger than 65, 65-74, and 75 and older. The study focused on 2,186 patients with pathologic stage I non–small-cell lung cancer (NSCLC) among a population of 5,371 consecutive patients who had resection for primary lung cancer from 2000 to 2011. Seventy percent of patients in the study group were 65 and older, and 29.2% were 75 and older.

In all age groups, the calculated 5-year cumulative incidence of death (CID) for lung cancer–specific causes exceeded that for noncancer causes, but at significant intervals the 65-and-over groups were more likely to die from the latter. For the overall study group, noncancer-specific causes accounted for a higher CID through 18 months after surgery, when the CID for both cancer and noncancer causes crossed at around 2.9. At 5 years, the overall lung cancer–specific CID was 10.4 vs. 5.3 for noncancer specific causes.

However, in the older age groups, those trends were more pronounced. In those aged 65-74, CID for both causes met at around 3.15 at 18 months (10.7 for lung cancer–specific and 4.9 for noncancer specific at 5 years), whereas for those 75 and older, CID for noncancer causes exceeded that for lung cancer–related causes for 2.5 years, when both were around 6; reaching 13.2 for lung cancer–specific and 9 for noncancer-specific at 5 years.

In the 65-and-younger group, lung cancer– and noncancer-specific CIDs were equal for about 3 months after surgery, when the lung cancer deaths tracked upward and the trends diverged (at 5 years, CID was 7.5 for lung cancer–specific and 1 for noncancer specific).

“We have shown that in patients with stage I NSCLC, the majority of postoperative severe morbidity, 1-year mortality, and 5-year noncancer-specific mortality were attributable to cardiorespiratory diseases,” Dr. Eguchi and colleagues said.

“We have also shown that short-term mortality is primarily attributable to noncancer-specific diseases.” The findings underscore the importance of screening older patients for noncancer-specific diseases that could alter outcomes, the researchers said.

Of the 2,186 stage I NSCLC patients in the study, 167 developed severe morbidities after surgery; 68.3% developed respiratory problems and 18.6% went on to develop cardiovascular problems. Patients who had lobectomy were more likely to develop respiratory problems than were those who had sublobar resection, Dr. Eguchi and coauthors said.

Respiratory and cardiovascular diseases were the most frequent causes of death early after surgery. At 30 days, respiratory disease accounted for 5 deaths and cardiovascular disease 7 of 15 total deaths at 30 days; and at 90 days, 11 and 7, respectively, of 27 overall deaths. Even at 1 year, noncancer issues were the leading cause of death (50%), followed by lung cancer–specific causes (27.8%) and other cancer specific disease (13.3%).

“Noncancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Dr. Eguchi and coauthors said. “These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status and help determine patients’ optimal treatment options.”

The study received financial support from coauthor Prasad S. Adusumilli, MD. Dr. Eguchi and Dr. Adusumilli and the other coauthors had no relevant financial disclosures.

After older patients undergo lung resection for stage I non–small-cell lung cancer, they are actually at greater risk of death from something other than lung cancer for up to 2.5 years, according to researchers at Memorial Sloan Kettering Cancer Center, New York. The findings were published online in the Journal of Clinical Oncology (2016;34: doi: 10.1200/JCO.2016.69.0834).

“As age increases, the risk of competing events increases, such as death from noncancer diseases,” wrote Takashi Eguchi, MD, and coauthors. “In this era of personalized cancer therapy, important to the stratification of individualized treatments is the determination of how both cancer and noncancer risk factors – specifically, comorbidities associated with increasing age – contribute to the risk of death.”

The researchers examined outcomes in three different age groups: younger than 65, 65-74, and 75 and older. The study focused on 2,186 patients with pathologic stage I non–small-cell lung cancer (NSCLC) among a population of 5,371 consecutive patients who had resection for primary lung cancer from 2000 to 2011. Seventy percent of patients in the study group were 65 and older, and 29.2% were 75 and older.

In all age groups, the calculated 5-year cumulative incidence of death (CID) for lung cancer–specific causes exceeded that for noncancer causes, but at significant intervals the 65-and-over groups were more likely to die from the latter. For the overall study group, noncancer-specific causes accounted for a higher CID through 18 months after surgery, when the CID for both cancer and noncancer causes crossed at around 2.9. At 5 years, the overall lung cancer–specific CID was 10.4 vs. 5.3 for noncancer specific causes.

However, in the older age groups, those trends were more pronounced. In those aged 65-74, CID for both causes met at around 3.15 at 18 months (10.7 for lung cancer–specific and 4.9 for noncancer specific at 5 years), whereas for those 75 and older, CID for noncancer causes exceeded that for lung cancer–related causes for 2.5 years, when both were around 6; reaching 13.2 for lung cancer–specific and 9 for noncancer-specific at 5 years.

In the 65-and-younger group, lung cancer– and noncancer-specific CIDs were equal for about 3 months after surgery, when the lung cancer deaths tracked upward and the trends diverged (at 5 years, CID was 7.5 for lung cancer–specific and 1 for noncancer specific).

“We have shown that in patients with stage I NSCLC, the majority of postoperative severe morbidity, 1-year mortality, and 5-year noncancer-specific mortality were attributable to cardiorespiratory diseases,” Dr. Eguchi and colleagues said.

“We have also shown that short-term mortality is primarily attributable to noncancer-specific diseases.” The findings underscore the importance of screening older patients for noncancer-specific diseases that could alter outcomes, the researchers said.

Of the 2,186 stage I NSCLC patients in the study, 167 developed severe morbidities after surgery; 68.3% developed respiratory problems and 18.6% went on to develop cardiovascular problems. Patients who had lobectomy were more likely to develop respiratory problems than were those who had sublobar resection, Dr. Eguchi and coauthors said.

Respiratory and cardiovascular diseases were the most frequent causes of death early after surgery. At 30 days, respiratory disease accounted for 5 deaths and cardiovascular disease 7 of 15 total deaths at 30 days; and at 90 days, 11 and 7, respectively, of 27 overall deaths. Even at 1 year, noncancer issues were the leading cause of death (50%), followed by lung cancer–specific causes (27.8%) and other cancer specific disease (13.3%).

“Noncancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Dr. Eguchi and coauthors said. “These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status and help determine patients’ optimal treatment options.”

The study received financial support from coauthor Prasad S. Adusumilli, MD. Dr. Eguchi and Dr. Adusumilli and the other coauthors had no relevant financial disclosures.

After older patients undergo lung resection for stage I non–small-cell lung cancer, they are actually at greater risk of death from something other than lung cancer for up to 2.5 years, according to researchers at Memorial Sloan Kettering Cancer Center, New York. The findings were published online in the Journal of Clinical Oncology (2016;34: doi: 10.1200/JCO.2016.69.0834).

“As age increases, the risk of competing events increases, such as death from noncancer diseases,” wrote Takashi Eguchi, MD, and coauthors. “In this era of personalized cancer therapy, important to the stratification of individualized treatments is the determination of how both cancer and noncancer risk factors – specifically, comorbidities associated with increasing age – contribute to the risk of death.”

The researchers examined outcomes in three different age groups: younger than 65, 65-74, and 75 and older. The study focused on 2,186 patients with pathologic stage I non–small-cell lung cancer (NSCLC) among a population of 5,371 consecutive patients who had resection for primary lung cancer from 2000 to 2011. Seventy percent of patients in the study group were 65 and older, and 29.2% were 75 and older.

In all age groups, the calculated 5-year cumulative incidence of death (CID) for lung cancer–specific causes exceeded that for noncancer causes, but at significant intervals the 65-and-over groups were more likely to die from the latter. For the overall study group, noncancer-specific causes accounted for a higher CID through 18 months after surgery, when the CID for both cancer and noncancer causes crossed at around 2.9. At 5 years, the overall lung cancer–specific CID was 10.4 vs. 5.3 for noncancer specific causes.

However, in the older age groups, those trends were more pronounced. In those aged 65-74, CID for both causes met at around 3.15 at 18 months (10.7 for lung cancer–specific and 4.9 for noncancer specific at 5 years), whereas for those 75 and older, CID for noncancer causes exceeded that for lung cancer–related causes for 2.5 years, when both were around 6; reaching 13.2 for lung cancer–specific and 9 for noncancer-specific at 5 years.

In the 65-and-younger group, lung cancer– and noncancer-specific CIDs were equal for about 3 months after surgery, when the lung cancer deaths tracked upward and the trends diverged (at 5 years, CID was 7.5 for lung cancer–specific and 1 for noncancer specific).

“We have shown that in patients with stage I NSCLC, the majority of postoperative severe morbidity, 1-year mortality, and 5-year noncancer-specific mortality were attributable to cardiorespiratory diseases,” Dr. Eguchi and colleagues said.

“We have also shown that short-term mortality is primarily attributable to noncancer-specific diseases.” The findings underscore the importance of screening older patients for noncancer-specific diseases that could alter outcomes, the researchers said.

Of the 2,186 stage I NSCLC patients in the study, 167 developed severe morbidities after surgery; 68.3% developed respiratory problems and 18.6% went on to develop cardiovascular problems. Patients who had lobectomy were more likely to develop respiratory problems than were those who had sublobar resection, Dr. Eguchi and coauthors said.

Respiratory and cardiovascular diseases were the most frequent causes of death early after surgery. At 30 days, respiratory disease accounted for 5 deaths and cardiovascular disease 7 of 15 total deaths at 30 days; and at 90 days, 11 and 7, respectively, of 27 overall deaths. Even at 1 year, noncancer issues were the leading cause of death (50%), followed by lung cancer–specific causes (27.8%) and other cancer specific disease (13.3%).

“Noncancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Dr. Eguchi and coauthors said. “These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status and help determine patients’ optimal treatment options.”

The study received financial support from coauthor Prasad S. Adusumilli, MD. Dr. Eguchi and Dr. Adusumilli and the other coauthors had no relevant financial disclosures.

Young children and infants who require cardiac valve replacement are limited to fixed-diameter prostheses that cannot accommodate their growth, but researchers at Boston Children’s Hospital have reinforced an expandable bovine jugular vein graft using an external stent and implanted it in 42 patients with acceptable short-term results, according to a report in the Journal of Thoracic and Cardiovascular Surgery.

In 4 years, the modified Melody valve (Medtronic) has proved amenable to enlargement via catheterization as the child grows, Sitaram M. Emani, MD, and coauthors said. “The valve was competent with low gradient acutely postoperatively in all patients,” Dr. Emani and his coauthors said (J Thorac Cardiovasc Surg. 2016 Dec;152[6]:1514-23).

Young children and infants who require cardiac valve replacement are limited to fixed-diameter prostheses that cannot accommodate their growth, but researchers at Boston Children’s Hospital have reinforced an expandable bovine jugular vein graft using an external stent and implanted it in 42 patients with acceptable short-term results, according to a report in the Journal of Thoracic and Cardiovascular Surgery.

In 4 years, the modified Melody valve (Medtronic) has proved amenable to enlargement via catheterization as the child grows, Sitaram M. Emani, MD, and coauthors said. “The valve was competent with low gradient acutely postoperatively in all patients,” Dr. Emani and his coauthors said (J Thorac Cardiovasc Surg. 2016 Dec;152[6]:1514-23).

Young children and infants who require cardiac valve replacement are limited to fixed-diameter prostheses that cannot accommodate their growth, but researchers at Boston Children’s Hospital have reinforced an expandable bovine jugular vein graft using an external stent and implanted it in 42 patients with acceptable short-term results, according to a report in the Journal of Thoracic and Cardiovascular Surgery.

In 4 years, the modified Melody valve (Medtronic) has proved amenable to enlargement via catheterization as the child grows, Sitaram M. Emani, MD, and coauthors said. “The valve was competent with low gradient acutely postoperatively in all patients,” Dr. Emani and his coauthors said (J Thorac Cardiovasc Surg. 2016 Dec;152[6]:1514-23).

At the recent Launch Pad: Pathways to Cancer Innovation, November 29, 2016, Federal Practitioner sat down for an exclusive interview with VA Under Secretary of Health David J. Shulkin, MD.  The below video that discusses ongoing efforts to improve coordination of care with community providers, the VA’s commitment to expanding the scope of practice for advanced practice registered nurses (APRNs), and the recruitment challenges for filling more than 46,000 health care vacancies. Dr. Shulkin also discussed VA progress over the past 18 months.

At the recent Launch Pad: Pathways to Cancer Innovation, November 29, 2016, Federal Practitioner sat down for an exclusive interview with VA Under Secretary of Health David J. Shulkin, MD.  The below video that discusses ongoing efforts to improve coordination of care with community providers, the VA’s commitment to expanding the scope of practice for advanced practice registered nurses (APRNs), and the recruitment challenges for filling more than 46,000 health care vacancies. Dr. Shulkin also discussed VA progress over the past 18 months.

At the recent Launch Pad: Pathways to Cancer Innovation, November 29, 2016, Federal Practitioner sat down for an exclusive interview with VA Under Secretary of Health David J. Shulkin, MD.  The below video that discusses ongoing efforts to improve coordination of care with community providers, the VA’s commitment to expanding the scope of practice for advanced practice registered nurses (APRNs), and the recruitment challenges for filling more than 46,000 health care vacancies. Dr. Shulkin also discussed VA progress over the past 18 months.

Low-dose aspirin is recommended to help prevent colorectal cancer and vascular disease as well as to reduce mortality. Research suggests that low-dose aspirin also can be useful as an adjunct treatment in established cancers. The potential, however, is offset by concerns about bleeding.

Are the concerns valid? When gauging the risks vs benefits of aspirin for patients at risk for bleeding, considering not only the severity of events, but also the frequency is important, say researchers from Cardiff University, Hywel Dda University, University of Cambridge, Harvard, University of Zaragoza, University of South Wales, Swansea University, National University of Singapore, and University of Leicester.

Related: A Better Way to Predict Colorectal Cancer Relapse?

 They point out that most estimates of harm from aspirin are based on the frequency of “major” gastrointestinal (GI) bleeding together with cerebral bleeding. But they also note that although GI bleeds can be severe, they’re “acute events usually followed by recovery without sequelae.” Strokes, on the other hand, can have lasting effects in survivors; and people who survive heart attacks or cancer may require complex and lifelong interventions.

The researchers suggest weighing the risk of fatal bleeds attributable to aspirin with the severity of the disease events prevented. And the distinction between GI bleeding and fatal bleeding isn’t trivial, they contend. Studies have already shown that the risk of death from aspirin-related GI bleeds is lower than that of spontaneous GI bleeding.

To put the discussion on a more even footing, the research team looked at 11 long-term, randomized controlled trials of aspirin prophylaxis with data on fatal adverse effects (AEs). They also incorporated new data from direct e-mail contact with the authors of some of the studies.

They found that although aspirin increases the risk of GI bleeding by about 60%, low-dose aspirin is associated with a lower risk of fatality among the patients who develop GI bleeding. The researchers note that no report mentioned the use of gastric protection by proton pump inhibitor or other treatment.

Most important, the researchers say, is the finding that among all the subjects who were taking aspirin, there was no increase in death from GI bleeding compared with those randomized to take no aspirin.

Related: Colorectal Screening: Available but Underused

Also important, they add, is to bear in mind the duration of aspirin taking. Almost all studies of cancer prevention, they note, show a 3- to 5-year delay before the benefits of aspirin are clinically apparent (because the effects on cells take a while to show up, that is, as the absence of a tumor).

However, the incidence of GI bleeding attributable to aspirin seems to drop over time: Within the first month of aspirin taking, the risk increases more than 4-fold, but then declines rapidly. After about 3 to 5 years of taking aspirin, there seems to be no excess in GI bleeds. Similarly, most deaths from bleeding happen with the first month, implying underlying untreated gastric pathology, the researchers say.

GI bleeds are still the majority of the AEs caused by aspirin, but thanks to better treatments, GI bleeding and fatal bleeding have declined as much as 20% to 50% in some countries, such as Scotland, Spain, U.S., and Wales. In the risk-benefit analysis, however, the researchers say, the “undesirable effect” of prophylactic aspirin as serious as a vascular event or cancer is rare: Low-dose aspirin is associated with 1 death and 1 disabling hemorrhagic stroke per year in every 10,000 people, and that number could be lower if hypertension is treated adequately.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Source:
Elwood PC, Morgan G, Galante J, et al. PLoS One. 2016;11(11): e0166166.
doi: 10.1371/journal.pone.0166166.

Low-dose aspirin is recommended to help prevent colorectal cancer and vascular disease as well as to reduce mortality. Research suggests that low-dose aspirin also can be useful as an adjunct treatment in established cancers. The potential, however, is offset by concerns about bleeding.

Are the concerns valid? When gauging the risks vs benefits of aspirin for patients at risk for bleeding, considering not only the severity of events, but also the frequency is important, say researchers from Cardiff University, Hywel Dda University, University of Cambridge, Harvard, University of Zaragoza, University of South Wales, Swansea University, National University of Singapore, and University of Leicester.

Related: A Better Way to Predict Colorectal Cancer Relapse?

 They point out that most estimates of harm from aspirin are based on the frequency of “major” gastrointestinal (GI) bleeding together with cerebral bleeding. But they also note that although GI bleeds can be severe, they’re “acute events usually followed by recovery without sequelae.” Strokes, on the other hand, can have lasting effects in survivors; and people who survive heart attacks or cancer may require complex and lifelong interventions.

The researchers suggest weighing the risk of fatal bleeds attributable to aspirin with the severity of the disease events prevented. And the distinction between GI bleeding and fatal bleeding isn’t trivial, they contend. Studies have already shown that the risk of death from aspirin-related GI bleeds is lower than that of spontaneous GI bleeding.

To put the discussion on a more even footing, the research team looked at 11 long-term, randomized controlled trials of aspirin prophylaxis with data on fatal adverse effects (AEs). They also incorporated new data from direct e-mail contact with the authors of some of the studies.

They found that although aspirin increases the risk of GI bleeding by about 60%, low-dose aspirin is associated with a lower risk of fatality among the patients who develop GI bleeding. The researchers note that no report mentioned the use of gastric protection by proton pump inhibitor or other treatment.

Most important, the researchers say, is the finding that among all the subjects who were taking aspirin, there was no increase in death from GI bleeding compared with those randomized to take no aspirin.

Related: Colorectal Screening: Available but Underused

Also important, they add, is to bear in mind the duration of aspirin taking. Almost all studies of cancer prevention, they note, show a 3- to 5-year delay before the benefits of aspirin are clinically apparent (because the effects on cells take a while to show up, that is, as the absence of a tumor).

However, the incidence of GI bleeding attributable to aspirin seems to drop over time: Within the first month of aspirin taking, the risk increases more than 4-fold, but then declines rapidly. After about 3 to 5 years of taking aspirin, there seems to be no excess in GI bleeds. Similarly, most deaths from bleeding happen with the first month, implying underlying untreated gastric pathology, the researchers say.

GI bleeds are still the majority of the AEs caused by aspirin, but thanks to better treatments, GI bleeding and fatal bleeding have declined as much as 20% to 50% in some countries, such as Scotland, Spain, U.S., and Wales. In the risk-benefit analysis, however, the researchers say, the “undesirable effect” of prophylactic aspirin as serious as a vascular event or cancer is rare: Low-dose aspirin is associated with 1 death and 1 disabling hemorrhagic stroke per year in every 10,000 people, and that number could be lower if hypertension is treated adequately.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Source:
Elwood PC, Morgan G, Galante J, et al. PLoS One. 2016;11(11): e0166166.
doi: 10.1371/journal.pone.0166166.

Low-dose aspirin is recommended to help prevent colorectal cancer and vascular disease as well as to reduce mortality. Research suggests that low-dose aspirin also can be useful as an adjunct treatment in established cancers. The potential, however, is offset by concerns about bleeding.

Are the concerns valid? When gauging the risks vs benefits of aspirin for patients at risk for bleeding, considering not only the severity of events, but also the frequency is important, say researchers from Cardiff University, Hywel Dda University, University of Cambridge, Harvard, University of Zaragoza, University of South Wales, Swansea University, National University of Singapore, and University of Leicester.

Related: A Better Way to Predict Colorectal Cancer Relapse?

 They point out that most estimates of harm from aspirin are based on the frequency of “major” gastrointestinal (GI) bleeding together with cerebral bleeding. But they also note that although GI bleeds can be severe, they’re “acute events usually followed by recovery without sequelae.” Strokes, on the other hand, can have lasting effects in survivors; and people who survive heart attacks or cancer may require complex and lifelong interventions.

The researchers suggest weighing the risk of fatal bleeds attributable to aspirin with the severity of the disease events prevented. And the distinction between GI bleeding and fatal bleeding isn’t trivial, they contend. Studies have already shown that the risk of death from aspirin-related GI bleeds is lower than that of spontaneous GI bleeding.

To put the discussion on a more even footing, the research team looked at 11 long-term, randomized controlled trials of aspirin prophylaxis with data on fatal adverse effects (AEs). They also incorporated new data from direct e-mail contact with the authors of some of the studies.

They found that although aspirin increases the risk of GI bleeding by about 60%, low-dose aspirin is associated with a lower risk of fatality among the patients who develop GI bleeding. The researchers note that no report mentioned the use of gastric protection by proton pump inhibitor or other treatment.

Most important, the researchers say, is the finding that among all the subjects who were taking aspirin, there was no increase in death from GI bleeding compared with those randomized to take no aspirin.

Related: Colorectal Screening: Available but Underused

Also important, they add, is to bear in mind the duration of aspirin taking. Almost all studies of cancer prevention, they note, show a 3- to 5-year delay before the benefits of aspirin are clinically apparent (because the effects on cells take a while to show up, that is, as the absence of a tumor).

However, the incidence of GI bleeding attributable to aspirin seems to drop over time: Within the first month of aspirin taking, the risk increases more than 4-fold, but then declines rapidly. After about 3 to 5 years of taking aspirin, there seems to be no excess in GI bleeds. Similarly, most deaths from bleeding happen with the first month, implying underlying untreated gastric pathology, the researchers say.

GI bleeds are still the majority of the AEs caused by aspirin, but thanks to better treatments, GI bleeding and fatal bleeding have declined as much as 20% to 50% in some countries, such as Scotland, Spain, U.S., and Wales. In the risk-benefit analysis, however, the researchers say, the “undesirable effect” of prophylactic aspirin as serious as a vascular event or cancer is rare: Low-dose aspirin is associated with 1 death and 1 disabling hemorrhagic stroke per year in every 10,000 people, and that number could be lower if hypertension is treated adequately.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Source:
Elwood PC, Morgan G, Galante J, et al. PLoS One. 2016;11(11): e0166166.
doi: 10.1371/journal.pone.0166166.

Federal Practitioner recently sat down with VA Deputy Under Secretary for Health for Policy and Services Jennifer Lee, MD, at the recent Launch Pad: Pathways to Cancer Innovation summit, November 29, 2016. In the interview, Dr. Lee discussed access to clinical trials for veterans, research, and the importance of partnering with other agencies, industry, and nonprofits to further veteran cancer care.

In the year since taking over for Madhulika Agarwal, MD, MPH, in the position, Dr. Lee has provided guidance to the Under Secretary for Health on matters related to health care policy, strategic objectives, and policy requirements for legislatively mandated health care delivery programs. She also directs research and other health policy and services programs within the VHA.

Federal Practitioner recently sat down with VA Deputy Under Secretary for Health for Policy and Services Jennifer Lee, MD, at the recent Launch Pad: Pathways to Cancer Innovation summit, November 29, 2016. In the interview, Dr. Lee discussed access to clinical trials for veterans, research, and the importance of partnering with other agencies, industry, and nonprofits to further veteran cancer care.

In the year since taking over for Madhulika Agarwal, MD, MPH, in the position, Dr. Lee has provided guidance to the Under Secretary for Health on matters related to health care policy, strategic objectives, and policy requirements for legislatively mandated health care delivery programs. She also directs research and other health policy and services programs within the VHA.

Federal Practitioner recently sat down with VA Deputy Under Secretary for Health for Policy and Services Jennifer Lee, MD, at the recent Launch Pad: Pathways to Cancer Innovation summit, November 29, 2016. In the interview, Dr. Lee discussed access to clinical trials for veterans, research, and the importance of partnering with other agencies, industry, and nonprofits to further veteran cancer care.

In the year since taking over for Madhulika Agarwal, MD, MPH, in the position, Dr. Lee has provided guidance to the Under Secretary for Health on matters related to health care policy, strategic objectives, and policy requirements for legislatively mandated health care delivery programs. She also directs research and other health policy and services programs within the VHA.

 

 

HSCT preparation

Photo by Chad McNeeley

 

SAN DIEGO—Researchers believe they have identified patients with chronic myeloid leukemia (CML) who are likely to derive long-term benefit from allogeneic hematopoietic stem cell transplant (allo-HSCT).

The researchers found that CML patients have a low risk of long-term morbidity if they undergo HSCT before the age of 45, are conditioned with busulfan and cyclophosphamide (Bu/Cy), and receive a graft from a matched, related donor (MRD).

Jessica Wu, of the University of Alabama at Birmingham, presented these findings at the 2016 ASH Annual Meeting (abstract 823*).

Wu noted that allogeneic HSCT is potentially curative for CML, but this method of treatment has been on the decline since the introduction of tyrosine kinase inhibitors (TKIs). And today, few CML patients undergo allo-HSCT.

She said that although TKIs can induce remission in CML patients, the drugs also fail to eradicate leukemia, can produce side effects that impact patients’ quality of life, and come with a significant financial burden (estimated at $92,000 to $138,000 per patient per year).

With this in mind, Wu and her colleagues set out to determine if certain CML patients might benefit from allo-HSCT long-term. The team also wanted to quantify overall and cause-specific late mortality after allo-HSCT and the long-term burden of severe/life-threatening chronic health conditions after allo-HSCT.

Patient population

The researchers studied 637 CML patients treated with allo-HSCT between 1981 and 2010 at City of Hope in Duarte, California, or the University of Minnesota in Minneapolis/Saint Paul. The patients had to have survived at least 2 years post-transplant.

About 60% of patients were male, and 67% were non-Hispanic white. Their median age at HSCT was 36.4 years, and 65% received an MRD graft. Nineteen percent of patients were transplanted in 1980-1989, 52% were transplanted in 1990-1999, and 29% were transplanted in 2000-2010.

Fifty-eight percent of patients received Cy/total body irradiation (TBI), 18% received Bu/Cy, and 3% received reduced-intensity conditioning (RIC).

Sixty-one percent of patients had chronic graft-vs-host disease (cGVHD), and 32% had high-risk disease at the time of HSCT.

Survival

The patients were followed for a median of 16.7 years. Thirty percent (n=192) died after surviving at least 2 years post-HSCT.

The median time to death was 8.3 years (range, 2-29.5), and the median age at death was 49.2 (range, 7.8-69.8). At 20 years from HSCT, the overall survival was 68.6%.

HSCT recipients had a 4.4-fold increased risk of death compared with the age-, sex-, and race-matched general population.

“Non-relapse mortality was the major contributor to late mortality, with infection, second malignancies, and cGVHD being the most common causes of death,” Wu said.

Non-relapse mortality was 20%, and relapse-related mortality was 4%. Eight percent of patients died of infection, 6.3% died of cGVHD, and 3.7% died of second malignancies.

Health outcomes

Patients who were still alive at the time of the study were asked to complete the BMTSS-2 health questionnaire, which was used to examine the risk of grade 3/4 chronic health conditions.


A total of 288 patients completed the questionnaire, as did a sibling comparison group of 404 individuals.

Among the patients, the median age at allo-HSCT was 37.5 (range, 3.6-71.4), and the median duration of follow-up was 13.9 years (range, 2-34.6).

Sixty-two percent of patients received an MRD graft, and 38% had a matched, unrelated donor. Eighty-three percent of patients had TBI-based conditioning, 16% received Bu/Cy, and 2.7% received RIC.

The prevalence of grade 3/4 chronic health conditions was significantly higher among patients than among siblings—38% and 24%, respectively (P<0.0001).

The odds ratio (OR)—adjusted for age, sex, race, and socioeconomic status—was 2.7 (P<0.0001).

The cumulative incidence of any grade 3/4 condition at 20 years after HSCT was 47.2% among patients. Common conditions were diabetes (14.9%), second malignancies (12.6%), and coronary artery disease (10%).

The researchers found the risk of grade 3/4 morbidity was significantly higher for the following patient groups:

• Those age 45 and older (hazard ratio [HR]=3.3, P<0.0001)
• Patients with a matched, unrelated donor (HR=3.0, P<0.0001)
• Those who received peripheral blood or cord blood grafts as opposed to bone marrow (HR=2.7, P=0.006).

(This analysis was adjusted for race/ethnicity, sex, education, household income, insurance, cGVHD, and conditioning regimen).

Lower risk

To identify subpopulations with a reduced risk of long-term morbidity, the researchers calculated the risk in various CML patient groups compared to siblings.

The overall OR for CML patients compared with siblings was 2.7 (P<0.0001).

The OR for patients in first chronic phase who underwent HSCT before the age of 45 and had an MRD was 1.5 (P=0.1).

The OR for CML patients in first chronic phase who underwent HSCT before the age of 45, had an MRD, and received Bu/Cy conditioning was 0.8 (P=0.7).

“[W]e found that patients who received a matched, related donor transplant under the age of 45, with busulfan/cyclophosphamide, carried the same burden of morbidity as the sibling cohort,” Wu said. “These findings could help inform decisions regarding therapeutic options for the management of CML.”

Wu noted that the limited sample size in this study prevented the researchers from examining outcomes with RIC. And a lack of data at analysis prevented them from examining pre-HSCT and post-HSCT management of CML, the interval between diagnosis and HSCT, and the life-long economic burden of allo-HSCT.

However, she said data collection is ongoing, and the researchers hope to address some of these limitations.

*Information presented at the meeting differs from the abstract.

 

 

HSCT preparation

Photo by Chad McNeeley

 

SAN DIEGO—Researchers believe they have identified patients with chronic myeloid leukemia (CML) who are likely to derive long-term benefit from allogeneic hematopoietic stem cell transplant (allo-HSCT).

The researchers found that CML patients have a low risk of long-term morbidity if they undergo HSCT before the age of 45, are conditioned with busulfan and cyclophosphamide (Bu/Cy), and receive a graft from a matched, related donor (MRD).

Jessica Wu, of the University of Alabama at Birmingham, presented these findings at the 2016 ASH Annual Meeting (abstract 823*).

Wu noted that allogeneic HSCT is potentially curative for CML, but this method of treatment has been on the decline since the introduction of tyrosine kinase inhibitors (TKIs). And today, few CML patients undergo allo-HSCT.

She said that although TKIs can induce remission in CML patients, the drugs also fail to eradicate leukemia, can produce side effects that impact patients’ quality of life, and come with a significant financial burden (estimated at $92,000 to $138,000 per patient per year).

With this in mind, Wu and her colleagues set out to determine if certain CML patients might benefit from allo-HSCT long-term. The team also wanted to quantify overall and cause-specific late mortality after allo-HSCT and the long-term burden of severe/life-threatening chronic health conditions after allo-HSCT.

Patient population

The researchers studied 637 CML patients treated with allo-HSCT between 1981 and 2010 at City of Hope in Duarte, California, or the University of Minnesota in Minneapolis/Saint Paul. The patients had to have survived at least 2 years post-transplant.

About 60% of patients were male, and 67% were non-Hispanic white. Their median age at HSCT was 36.4 years, and 65% received an MRD graft. Nineteen percent of patients were transplanted in 1980-1989, 52% were transplanted in 1990-1999, and 29% were transplanted in 2000-2010.

Fifty-eight percent of patients received Cy/total body irradiation (TBI), 18% received Bu/Cy, and 3% received reduced-intensity conditioning (RIC).

Sixty-one percent of patients had chronic graft-vs-host disease (cGVHD), and 32% had high-risk disease at the time of HSCT.

Survival

The patients were followed for a median of 16.7 years. Thirty percent (n=192) died after surviving at least 2 years post-HSCT.

The median time to death was 8.3 years (range, 2-29.5), and the median age at death was 49.2 (range, 7.8-69.8). At 20 years from HSCT, the overall survival was 68.6%.

HSCT recipients had a 4.4-fold increased risk of death compared with the age-, sex-, and race-matched general population.

“Non-relapse mortality was the major contributor to late mortality, with infection, second malignancies, and cGVHD being the most common causes of death,” Wu said.

Non-relapse mortality was 20%, and relapse-related mortality was 4%. Eight percent of patients died of infection, 6.3% died of cGVHD, and 3.7% died of second malignancies.

Health outcomes

Patients who were still alive at the time of the study were asked to complete the BMTSS-2 health questionnaire, which was used to examine the risk of grade 3/4 chronic health conditions.


A total of 288 patients completed the questionnaire, as did a sibling comparison group of 404 individuals.

Among the patients, the median age at allo-HSCT was 37.5 (range, 3.6-71.4), and the median duration of follow-up was 13.9 years (range, 2-34.6).

Sixty-two percent of patients received an MRD graft, and 38% had a matched, unrelated donor. Eighty-three percent of patients had TBI-based conditioning, 16% received Bu/Cy, and 2.7% received RIC.

The prevalence of grade 3/4 chronic health conditions was significantly higher among patients than among siblings—38% and 24%, respectively (P<0.0001).

The odds ratio (OR)—adjusted for age, sex, race, and socioeconomic status—was 2.7 (P<0.0001).

The cumulative incidence of any grade 3/4 condition at 20 years after HSCT was 47.2% among patients. Common conditions were diabetes (14.9%), second malignancies (12.6%), and coronary artery disease (10%).

The researchers found the risk of grade 3/4 morbidity was significantly higher for the following patient groups:

• Those age 45 and older (hazard ratio [HR]=3.3, P<0.0001)
• Patients with a matched, unrelated donor (HR=3.0, P<0.0001)
• Those who received peripheral blood or cord blood grafts as opposed to bone marrow (HR=2.7, P=0.006).

(This analysis was adjusted for race/ethnicity, sex, education, household income, insurance, cGVHD, and conditioning regimen).

Lower risk

To identify subpopulations with a reduced risk of long-term morbidity, the researchers calculated the risk in various CML patient groups compared to siblings.

The overall OR for CML patients compared with siblings was 2.7 (P<0.0001).

The OR for patients in first chronic phase who underwent HSCT before the age of 45 and had an MRD was 1.5 (P=0.1).

The OR for CML patients in first chronic phase who underwent HSCT before the age of 45, had an MRD, and received Bu/Cy conditioning was 0.8 (P=0.7).

“[W]e found that patients who received a matched, related donor transplant under the age of 45, with busulfan/cyclophosphamide, carried the same burden of morbidity as the sibling cohort,” Wu said. “These findings could help inform decisions regarding therapeutic options for the management of CML.”

Wu noted that the limited sample size in this study prevented the researchers from examining outcomes with RIC. And a lack of data at analysis prevented them from examining pre-HSCT and post-HSCT management of CML, the interval between diagnosis and HSCT, and the life-long economic burden of allo-HSCT.

However, she said data collection is ongoing, and the researchers hope to address some of these limitations.

*Information presented at the meeting differs from the abstract.

 

 

HSCT preparation

Photo by Chad McNeeley

 

SAN DIEGO—Researchers believe they have identified patients with chronic myeloid leukemia (CML) who are likely to derive long-term benefit from allogeneic hematopoietic stem cell transplant (allo-HSCT).

The researchers found that CML patients have a low risk of long-term morbidity if they undergo HSCT before the age of 45, are conditioned with busulfan and cyclophosphamide (Bu/Cy), and receive a graft from a matched, related donor (MRD).

Jessica Wu, of the University of Alabama at Birmingham, presented these findings at the 2016 ASH Annual Meeting (abstract 823*).

Wu noted that allogeneic HSCT is potentially curative for CML, but this method of treatment has been on the decline since the introduction of tyrosine kinase inhibitors (TKIs). And today, few CML patients undergo allo-HSCT.

She said that although TKIs can induce remission in CML patients, the drugs also fail to eradicate leukemia, can produce side effects that impact patients’ quality of life, and come with a significant financial burden (estimated at $92,000 to $138,000 per patient per year).

With this in mind, Wu and her colleagues set out to determine if certain CML patients might benefit from allo-HSCT long-term. The team also wanted to quantify overall and cause-specific late mortality after allo-HSCT and the long-term burden of severe/life-threatening chronic health conditions after allo-HSCT.

Patient population

The researchers studied 637 CML patients treated with allo-HSCT between 1981 and 2010 at City of Hope in Duarte, California, or the University of Minnesota in Minneapolis/Saint Paul. The patients had to have survived at least 2 years post-transplant.

About 60% of patients were male, and 67% were non-Hispanic white. Their median age at HSCT was 36.4 years, and 65% received an MRD graft. Nineteen percent of patients were transplanted in 1980-1989, 52% were transplanted in 1990-1999, and 29% were transplanted in 2000-2010.

Fifty-eight percent of patients received Cy/total body irradiation (TBI), 18% received Bu/Cy, and 3% received reduced-intensity conditioning (RIC).

Sixty-one percent of patients had chronic graft-vs-host disease (cGVHD), and 32% had high-risk disease at the time of HSCT.

Survival

The patients were followed for a median of 16.7 years. Thirty percent (n=192) died after surviving at least 2 years post-HSCT.

The median time to death was 8.3 years (range, 2-29.5), and the median age at death was 49.2 (range, 7.8-69.8). At 20 years from HSCT, the overall survival was 68.6%.

HSCT recipients had a 4.4-fold increased risk of death compared with the age-, sex-, and race-matched general population.

“Non-relapse mortality was the major contributor to late mortality, with infection, second malignancies, and cGVHD being the most common causes of death,” Wu said.

Non-relapse mortality was 20%, and relapse-related mortality was 4%. Eight percent of patients died of infection, 6.3% died of cGVHD, and 3.7% died of second malignancies.

Health outcomes

Patients who were still alive at the time of the study were asked to complete the BMTSS-2 health questionnaire, which was used to examine the risk of grade 3/4 chronic health conditions.


A total of 288 patients completed the questionnaire, as did a sibling comparison group of 404 individuals.

Among the patients, the median age at allo-HSCT was 37.5 (range, 3.6-71.4), and the median duration of follow-up was 13.9 years (range, 2-34.6).

Sixty-two percent of patients received an MRD graft, and 38% had a matched, unrelated donor. Eighty-three percent of patients had TBI-based conditioning, 16% received Bu/Cy, and 2.7% received RIC.

The prevalence of grade 3/4 chronic health conditions was significantly higher among patients than among siblings—38% and 24%, respectively (P<0.0001).

The odds ratio (OR)—adjusted for age, sex, race, and socioeconomic status—was 2.7 (P<0.0001).

The cumulative incidence of any grade 3/4 condition at 20 years after HSCT was 47.2% among patients. Common conditions were diabetes (14.9%), second malignancies (12.6%), and coronary artery disease (10%).

The researchers found the risk of grade 3/4 morbidity was significantly higher for the following patient groups:

• Those age 45 and older (hazard ratio [HR]=3.3, P<0.0001)
• Patients with a matched, unrelated donor (HR=3.0, P<0.0001)
• Those who received peripheral blood or cord blood grafts as opposed to bone marrow (HR=2.7, P=0.006).

(This analysis was adjusted for race/ethnicity, sex, education, household income, insurance, cGVHD, and conditioning regimen).

Lower risk

To identify subpopulations with a reduced risk of long-term morbidity, the researchers calculated the risk in various CML patient groups compared to siblings.

The overall OR for CML patients compared with siblings was 2.7 (P<0.0001).

The OR for patients in first chronic phase who underwent HSCT before the age of 45 and had an MRD was 1.5 (P=0.1).

The OR for CML patients in first chronic phase who underwent HSCT before the age of 45, had an MRD, and received Bu/Cy conditioning was 0.8 (P=0.7).

“[W]e found that patients who received a matched, related donor transplant under the age of 45, with busulfan/cyclophosphamide, carried the same burden of morbidity as the sibling cohort,” Wu said. “These findings could help inform decisions regarding therapeutic options for the management of CML.”

Wu noted that the limited sample size in this study prevented the researchers from examining outcomes with RIC. And a lack of data at analysis prevented them from examining pre-HSCT and post-HSCT management of CML, the interval between diagnosis and HSCT, and the life-long economic burden of allo-HSCT.

However, she said data collection is ongoing, and the researchers hope to address some of these limitations.

*Information presented at the meeting differs from the abstract.

Antihemophilic factor

Health Canada has approved the use of lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy, in hemophilia A patients of all ages.

Lonoctocog alfa is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand treatment to control bleeding episodes, and for perioperative management of bleeding (surgical prophylaxis).

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

Health Canada’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July.*

*Stasyshyn O et al; rVIII-SingleChain, results of the pivotal efficacy data from a phase III PK, efficacy and safety clinical study in children less than 12 years of age with severe hemophilia A; WFH 2016 World Congress, July 2016.

Antihemophilic factor

Health Canada has approved the use of lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy, in hemophilia A patients of all ages.

Lonoctocog alfa is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand treatment to control bleeding episodes, and for perioperative management of bleeding (surgical prophylaxis).

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

Health Canada’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July.*

*Stasyshyn O et al; rVIII-SingleChain, results of the pivotal efficacy data from a phase III PK, efficacy and safety clinical study in children less than 12 years of age with severe hemophilia A; WFH 2016 World Congress, July 2016.

Antihemophilic factor

Health Canada has approved the use of lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy, in hemophilia A patients of all ages.

Lonoctocog alfa is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand treatment to control bleeding episodes, and for perioperative management of bleeding (surgical prophylaxis).

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

Health Canada’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July.*

*Stasyshyn O et al; rVIII-SingleChain, results of the pivotal efficacy data from a phase III PK, efficacy and safety clinical study in children less than 12 years of age with severe hemophilia A; WFH 2016 World Congress, July 2016.